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Sample records for histologic tumor grade

  1. Tumor tissue protein signatures reflect histological grade of breast cancer.

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    Skoog, Petter; Ohlsson, Mattias; Fernö, Mårten; Rydén, Lisa; Borrebaeck, Carl A K; Wingren, Christer

    2017-01-01

    Histological grade is one of the most commonly used prognostic factors for patients diagnosed with breast cancer. However, conventional grading has proven technically challenging, and up to 60% of the tumors are classified as histological grade 2, which represents a heterogeneous cohort less informative for clinical decision making. In an attempt to study and extend the molecular puzzle of histologically graded breast cancer, we have in this pilot project searched for additional protein biomarkers in a new space of the proteome. To this end, we have for the first time performed protein expression profiling of breast cancer tumor tissue, using recombinant antibody microarrays, targeting mainly immunoregulatory proteins. Thus, we have explored the immune system as a disease-specific sensor (clinical immunoproteomics). Uniquely, the results showed that several biologically relevant proteins reflecting histological grade could be delineated. In more detail, the tentative biomarker panels could be used to i) build a candidate model classifying grade 1 vs. grade 3 tumors, ii) demonstrate the molecular heterogeneity among grade 2 tumors, and iii) potentially re-classify several of the grade 2 tumors to more like grade 1 or grade 3 tumors. This could, in the long-term run, lead to improved prognosis, by which the patients could benefit from improved tailored care.

  2. Clinical staging in bitches with mammary tumors: Influence of type and histological grade.

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    Gundim, Lígia F; de Araújo, Camila P; Blanca, William T; Guimarães, Ednaldo C; Medeiros, Alessandra A

    2016-10-01

    Breast tumors are the most common tumors in dogs and the study of disease prognostic factors is important for establishing the appropriate treatment protocols. The purpose of this study was to clinically stage mammary tumors of bitches and correlate the stages with histological type and grade. The tumors of 63 dogs were clinically staged based on the findings of tumor sizing, lymph node evaluation, and radiographic examination. After surgical excision, the tumors were classified histologically and graded. The relationship between the tumor grade, stage, and histological type was evaluated using a binomial test. Stage I tumors were the most numerous (31.75%), followed by tumors at stages II, III, IV, and V. Animals with histological grade I carcinomas presented stage I, II, or III tumors more frequently and stage IV and V tumors less frequently. The number of animals with simple carcinomas that were at stage I of the disease was greater than that at stage V. Carcinomas in the mixed tumors were less aggressive; however, the small number of animals in stage V of the disease made any statistical association impossible. The complex carcinomas presented with the invasion of the lymph nodes and less cellular differentiation in a larger number of animals than did simple carcinomas. Histological grading proved to be the best parameter for the prognostic evaluation of the breast carcinomas.

  3. Preoperative lymphoscintigraphy and tumor histologic grade are associated with surgical detection of the sentinel lymph node.

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    Arias Ortega, M; Torres Sousa, M Y; González García, B; Pardo García, R; González López, A; Delgado Portela, M

    2014-01-01

    To study which variables involved in the process of selective sentinel node biopsy (SSNB) influence the intraoperative detection of the sentinel lymph node. This was a prospective cross-sectional study in 210 patients (mean age, 54 years) diagnosed with breast cancer who underwent SSNB. We recorded clinical, radiological, radioisotope administration, surgical, and histological data as well as follow-up data. We did a descriptive analysis of the data and an associative analysis using multivariable regression. Deep injection alone was the most common route of radioisotope administration (72.7%). Most lesions were palpable (57.1%), presented as nodules (67.1%), measured less than 2 cm in diameter (64.8%), were located in the upper outer quadrant (49.1%), were ductal carcinomas (85.7%), were accompanied by infiltration (66.2%), and had a histologic grade of differentiation of ii (44.8%). Preoperative scintigraphy detected the sentinel node in 97.6% of cases and 95.7% were detected during the operation. One axillary relapse was observed. In the associative study, the variables "preoperative lymphoscintigraphy" and "histologic grade of differentiation of the tumor" were significantly associated with the detection of the sentinel lymph node during the operation. The probability of not detecting the sentinel lymph node during the surgical intervention is higher in patients with high histologic grade tumors or in patients in whom preoperative lymphoscintigraphy failed to detect the sentinel node. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

  4. Expression of CAF-Related Proteins Is Associated with Histologic Grade of Breast Phyllodes Tumor

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    Hye Min Kim

    2016-01-01

    Full Text Available Purpose. The purpose of this study was to investigate the expression of cancer-associated fibroblast- (CAF- related proteins and the implications in breast phyllodes tumor (PT. Methods. Tissue microarrays of 194 PT cases (151 benign PT, 27 borderline PT, and 16 malignant PT were constructed. We performed immunohistochemical staining for CAF-related proteins (podoplanin, prolyl 4-hydroxylase, FAPα, S100A4, PDGFR α/β, and NG2 and analyzed the results according to clinicopathologic parameters. Results. Expression of PDGFRα and PDGFRβ in the stromal component increased with increasing histologic grade of PT (p=0.003 and p=0.034, resp.. Among clinicopathologic parameters, only expression of FAPα in stroma was associated with distant metastasis (p=0.002. In univariate analysis, stromal expression of PDGFRα was associated with shorter overall survival (p=0.002. In Cox multivariate analysis, stromal overgrowth and PDGFRα stromal positivity were associated with shorter overall survival (p=0.006 and p=0.050, resp.. Furthermore, expression of PDGFRβ in stroma was associated with shorter overall survival in patients with malignant PT (p=0.041. Conclusion. Stromal expression of PDGFRα and PDGFRβ increased with increasing histologic grade of PT. In addition, PDGFR stromal positivity was associated with shorter overall survival. These results suggest that CAFs are associated with breast PT progression.

  5. Expression of CAF-Related Proteins Is Associated with Histologic Grade of Breast Phyllodes Tumor

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    Kim, Hye Min; Lee, Yu Kyung

    2016-01-01

    Purpose. The purpose of this study was to investigate the expression of cancer-associated fibroblast- (CAF-) related proteins and the implications in breast phyllodes tumor (PT). Methods. Tissue microarrays of 194 PT cases (151 benign PT, 27 borderline PT, and 16 malignant PT) were constructed. We performed immunohistochemical staining for CAF-related proteins (podoplanin, prolyl 4-hydroxylase, FAPα, S100A4, PDGFR α/β, and NG2) and analyzed the results according to clinicopathologic parameters. Results. Expression of PDGFRα and PDGFRβ in the stromal component increased with increasing histologic grade of PT (p = 0.003 and p = 0.034, resp.). Among clinicopathologic parameters, only expression of FAPα in stroma was associated with distant metastasis (p = 0.002). In univariate analysis, stromal expression of PDGFRα was associated with shorter overall survival (p = 0.002). In Cox multivariate analysis, stromal overgrowth and PDGFRα stromal positivity were associated with shorter overall survival (p = 0.006 and p = 0.050, resp.). Furthermore, expression of PDGFRβ in stroma was associated with shorter overall survival in patients with malignant PT (p = 0.041). Conclusion. Stromal expression of PDGFRα and PDGFRβ increased with increasing histologic grade of PT. In addition, PDGFR stromal positivity was associated with shorter overall survival. These results suggest that CAFs are associated with breast PT progression. PMID:27881889

  6. Expression of CAF-Related Proteins Is Associated with Histologic Grade of Breast Phyllodes Tumor.

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    Kim, Hye Min; Lee, Yu Kyung; Koo, Ja Seung

    2016-01-01

    Purpose. The purpose of this study was to investigate the expression of cancer-associated fibroblast- (CAF-) related proteins and the implications in breast phyllodes tumor (PT). Methods. Tissue microarrays of 194 PT cases (151 benign PT, 27 borderline PT, and 16 malignant PT) were constructed. We performed immunohistochemical staining for CAF-related proteins (podoplanin, prolyl 4-hydroxylase, FAPα, S100A4, PDGFR α/β, and NG2) and analyzed the results according to clinicopathologic parameters. Results. Expression of PDGFRα and PDGFRβ in the stromal component increased with increasing histologic grade of PT (p = 0.003 and p = 0.034, resp.). Among clinicopathologic parameters, only expression of FAPα in stroma was associated with distant metastasis (p = 0.002). In univariate analysis, stromal expression of PDGFRα was associated with shorter overall survival (p = 0.002). In Cox multivariate analysis, stromal overgrowth and PDGFRα stromal positivity were associated with shorter overall survival (p = 0.006 and p = 0.050, resp.). Furthermore, expression of PDGFRβ in stroma was associated with shorter overall survival in patients with malignant PT (p = 0.041). Conclusion. Stromal expression of PDGFRα and PDGFRβ increased with increasing histologic grade of PT. In addition, PDGFR stromal positivity was associated with shorter overall survival. These results suggest that CAFs are associated with breast PT progression.

  7. Expression of M-CSF and CSF-1R is correlated with histological grade in soft tissue tumors.

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    Richardsen, Elin; Sørbye, Sveinung Wergeland; Crowe, John Phil; Yang, Jia-Lin; Busund, Lill-Tove

    2009-10-01

    Macrophage colony stimulating factor (M-CSF) binds to colony-stimulating factor-1 receptor (CSF-1R) and thereby stimulates the proliferation, differentiation and behaviour of monocytes, macrophages and their bone marrow progenitors. Previous studies have suggested that high expression of these markers is correlated with poor prognosis. M-CSF, CSF-1R and CD68 protein expression was examined by immunohistochemistry in paraffin embedded sections of soft tissue tumor specimens from 46 patients. The proportion of positive cells and the expression intensity of M-CSF, CSF-1R and CD68 in both the tumor cell areas and the adjacent stromal areas were correlated to the histological grade. In the high grade tumors M-CSF and CSF-1R were more highly expressed than in the low grade tumors. This was seen in both the tumor cell areas and the adjacent stromal areas. No differences in CD68 expression between the high and low grade tumors were found either in the tumor cell areas or the stromal areas. The expression of M-CSF and CSF-1R in tumor cell areas and adjacent stromal areas correlate with the histological grade of soft tissue tumors.

  8. Histological type and grade of breast cancer tumors by parity, age at birth, and time since birth: a register-based study in Norway

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    Heuch Ivar

    2010-05-01

    Full Text Available Abstract Background Some studies have indicated that reproductive factors affect the risk of histological types of breast cancer differently. The long-term protective effect of a childbirth is preceded by a short-term adverse effect. Few studies have examined whether tumors diagnosed shortly after birth have specific histological characteristics. Methods In the present register-based study, comprising information for 22,867 Norwegian breast cancer cases (20-74 years, we examined whether histological type (9 categories and grade of tumor (2 combined categories differed by parity or age at first birth. Associations with time since birth were evaluated among 9709 women diagnosed before age 50 years. Chi-square tests were applied for comparing proportions, whereas odds ratios (each histological type vs. ductal, or grade 3-4 vs. grade 1-2 were estimated in polytomous and binary logistic regression analyses. Results Ductal tumors, the most common histological type, accounted for 81.4% of all cases, followed by lobular tumors (6.3% and unspecified carcinomas (5.5%. Other subtypes accounted for 0.4%-1.5% of the cases each. For all histological types, the proportions differed significantly by age at diagnoses. The proportion of mucinous and tubular tumors decreased with increasing parity, whereas Paget disease and medullary tumors were most common in women of high parity. An increasing trend with increasing age at first birth was most pronounced for lobular tumors and unspecified carcinomas; an association in the opposite direction was seen in relation to medullary and tubular tumors. In age-adjusted analyses, only the proportions of unspecified carcinomas and lobular tumors decreased significantly with increasing time since first and last birth. However, ductal tumors, and malignant sarcomas, mainly phyllodes tumors, seemed to occur at higher frequency in women diagnosed Conclusion Our results support previous observations that reproductive factors

  9. Tumor Grade

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    ... is used to grade prostate cancer ( 1 ). The Gleason score is based on biopsy samples taken from the ... two grades are then added to give a Gleason score. The American Joint Committee on Cancer recommends grouping ...

  10. Neuroendocrine Tumor, Well Differentiated, of the Breast: A Relatively High-Grade Case in the Histological Subtype

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    Shogo Tajima

    2013-01-01

    Full Text Available Primary neuroendocrine carcinoma of the breast is a rare entity, comprising <1% of breast carcinomas. Described here is the case of a 78-year-old woman who developed an invasive tumor in the left breast measuring 2.0 cm x 1.5 cm x 1.2 cm. The tumor was composed of only endocrine elements in the invasive part. It infiltrated in a nested fashion with no tubular formation. Intraductal components were present both inside and outside of the invasive portion. Almost all carcinoma cells consisting of invasive and intraductal parts were positive for synaptophysin and neuron-specific enolase. According to the World Health Organization classification 2012, this tumor was subclassified as neuroendocrine tumor, well-differentiated. Among the subgroup, this tumor was relatively high-grade because it was grade 3 tumor with a few mitotic figures. Vascular and lymphatic permeation and lymph node metastases were noted. In the lymph nodes, the morphology of the tumor was similar to the primary site. No distant metastasis and no relapse was seen for one year after surgery. The prognosis of neuroendocrine carcinomas is thought to be worse than invasive mammary carcinomas, not otherwise specified. Therefore, immunohistochemistry for neuroendocrine markers is important in the routine practice to prevent overlooking neuroendocrine carcinomas.

  11. [Histologic findings in kidney tumors].

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    Hora, M; Ouda, Z; Schejbalová, E; Chudácek, Z; Mukensnabl, P

    1997-01-01

    The authors present a group of 304 adult patients (with the exception of one child with a Wilms tumour) from 1988-95 with the diagnosis of a primary renal tumour treated by surgery and subsequently subjected to histological examination. The tumours were in 83.9% clear renal cell tumours (Grawitz carcinoma), 4.3% were papillary carcinomas, 3.3% renal cortical adenomas, 3.9% oncocytomas and 2.0% non-differentiated carcinomas, 0.7% angiomyolipomas, 0.7% chromophobe cell renal carcinomas, 0.7% secondaries (carcinoma of the breast and testis), 0.7% multilocular cysts, one case each (0.3%) Wilms tumour, malignant lymphoma, necrotic histologically not classifiable tumour. The authors give a more detailed account of multilocular cystic RCC (which accounts for 5.9% Grawitz tumours), papillary tumours, chromophobe cell renal carcinoma, oncoytoma and angiomyolipoma. The authors correlate briefly the histological findings with preoperative graphic examinations. They are very sceptical as regards assessment of the histological type of tumour from preoperative graphic examination (with the exception of angiomyolipoma). Finally the authors suggest classification of renal expansions from the urologists aspect-in the first place from preoperative graphic examinations for non-neoplastic lesions (in particular cysts and hypertrophy of the columna Bertini), parenchymatous tumours and tumours of the renal pelvis and secondly (mainly in parenchymatous tumours) histological classification is taken into account.

  12. Histological Grading of Hepatocellular Carcinoma—A Systematic Review of Literature

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    Sebastiao N. Martins-Filho

    2017-11-01

    Full Text Available BackgroundHistological grading typically reflects the biological behavior of solid tumors, thus providing valuable prognostic information. This is also expected in hepatocellular carcinoma (HCC, although limited access to biopsy samples and a lack of standardization might hinder its full predictive value in this cancer.ObjectivesIn order to better understand the current practices of histological grading in HCC, we examined the latest publications addressing its impact on the outcome of patients following surgical treatment.MethodsWe searched the PubMed (MEDLINE database under the headings “hepatocellular carcinoma,” “grade OR grading,” and “prognosis.” Qualitative and quantitative assessment of publications was performed according to the reference they used to grade their tumors (e.g., Edmondson–Steiner, World Health Organization.ResultsWe reviewed a total of 216 articles: 114 enclosed adequate information and were included herein. Among these, we found divergences and inaccuracies in the histological grade assessment of this cancer, which might have led to a non-standardized grade distribution, with further impact on data analysis. Nevertheless, in most of them, poor tumor differentiation correlated with worse prognosis, expressed by lower overall and/or disease-free survival.ConclusionWhile histological grading of HCC has an important prognostic role, there is an unsatisfactory heterogeneity on the microscopic assessment of this tumor, urging for a movement toward standardization.

  13. Histologic and molecular analysis of patient derived xenografts of high-grade serous ovarian carcinoma

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    Ruifen Dong

    2016-09-01

    Full Text Available Abstract Background Patient derived xenografts (PDX are generated by transplanting the original patient’s tumor tissue into immune-deficient mice. Unlike xenograft models derived from cell lines, PDX models can better preserve the histopathology from the original patient and molecular pathways. High-grade serous carcinoma (HGSC is a deadly form of ovarian/fallopian tube cancer whose response to current chemotherapies varies widely due to patient variability. Therefore, a PDX model can provide a valuable tool to study and test treatment options for each individual patient. Methods In this study, over 200 PDX tumors from nine HGSC were analyzed to investigate the nature and behavior of PDX tumors originating from HGSC. PDX tumors were serially passaged (from P0 to P4 and tumors were grafted orthotopically under the ovarian bursa or subcutaneously. Results Comparative analysis of the histology and molecular markers of tumors from over 200 PDX tumor-bearing mice, revealed that the tumors maintained similar histologies, stem cell populations, and expression for the majority of the tested oncogenic markers, compared to the primary tumors. However, a significant loss of steroid hormone receptors and altered expression of immunoresponsive genes in PDX tumors were also noted. Conclusion Our findings provide substantial new information about PDX tumor characteristics from HGSC which will be valuable towards the development of personalized therapy and new drug development for HGSC.

  14. Large-scale computations on histology images reveal grade-differentiating parameters for breast cancer

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    Katsinis Constantine

    2006-10-01

    Full Text Available Abstract Background Tumor classification is inexact and largely dependent on the qualitative pathological examination of the images of the tumor tissue slides. In this study, our aim was to develop an automated computational method to classify Hematoxylin and Eosin (H&E stained tissue sections based on cancer tissue texture features. Methods Image processing of histology slide images was used to detect and identify adipose tissue, extracellular matrix, morphologically distinct cell nuclei types, and the tubular architecture. The texture parameters derived from image analysis were then applied to classify images in a supervised classification scheme using histologic grade of a testing set as guidance. Results The histologic grade assigned by pathologists to invasive breast carcinoma images strongly correlated with both the presence and extent of cell nuclei with dispersed chromatin and the architecture, specifically the extent of presence of tubular cross sections. The two parameters that differentiated tumor grade found in this study were (1 the number density of cell nuclei with dispersed chromatin and (2 the number density of tubular cross sections identified through image processing as white blobs that were surrounded by a continuous string of cell nuclei. Classification based on subdivisions of a whole slide image containing a high concentration of cancer cell nuclei consistently agreed with the grade classification of the entire slide. Conclusion The automated image analysis and classification presented in this study demonstrate the feasibility of developing clinically relevant classification of histology images based on micro- texture. This method provides pathologists an invaluable quantitative tool for evaluation of the components of the Nottingham system for breast tumor grading and avoid intra-observer variability thus increasing the consistency of the decision-making process.

  15. Histologic distribution of borderline ovarian tumors worldwide: a systematic review

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    Song, Taejong; Lee, Yoo-Young; Choi, Chel Hun; Kim, Tae-Joong; Lee, Jeong-Won; Bae, Duk-Soo; Kim, Byoung-Gie

    2013-01-01

    Objective The histologic types of borderline ovarian tumors (BOTs) exhibit striking differences in clinical behavior and prognosis. Yet, there is no information available on the histologic distribution of BOTs according to geographic region. The purpose of this study was to systematically review this issue worldwide. Methods A comprehensive search of the literature was conducted using electronic databases. Studies were eligible if BOTs were investigated and the histologic distribution of the ...

  16. Histological grade of hepatocellular carcinoma correlates with arterial enhancement on gadoxetic acid-enhanced and diffusion-weighted MR images.

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    Chang, Wei-Chou; Chen, Ran-Chou; Chou, Chen-Te; Lin, Chun-Yi; Yu, Chih-Yung; Liu, Chang-Hsien; Chou, Jung-Mao; Hsu, Hsian-He; Huang, Guo-Shu

    2014-12-01

    To retrospectively determine the correlation between heptic tumor signal intensity on gadoxetic acid-enhanced and diffusion-weighted MR images and histopathological grading of hepatocellular carcinoma (HCC). We retrospectively reviewed the MR images of 79 patients with 141 surgically resected HCCs. The signal intensity and its relationship with histopathological grade were assessed. We measured the apparent diffusion correlation (ADC) values and calculated arterial enhancement ratios, washout ratios, and relative intensity ratios of HCCs relative to the surrounding liver parenchyma in gadoxetic-enhanced MR images in order to determine their relationship to the histological grade. Morphological evaluation showed that larger tumor size and extrahepatic extension were associated with higher histologic grade (p enhancement on gadoxetic acid-enhanced MR images and low ADC are predictive of worse histological grades of HCC.

  17. Soft tissue tumors of the pelvis: Technical and histological considerations.

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    Mullen, John T; van Houdt, Winan

    2017-12-19

    In this review, we first address the anatomic and technical considerations in the resection of pelvic soft tissue tumors, including the challenges unique to these tumors, such as the narrow anatomic confines of the bony pelvis, the often locally aggressive nature of these tumors, as well as the major functional deficits that may result from their resection. We then review the optimal, multidisciplinary, histology-driven treatment approach to pelvic tumors. © 2017 Wiley Periodicals, Inc.

  18. Lipomatous tumors of soft tissue: MR appearance with histological correlation

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    Drevelegas, A. E-mail: adrev@med.auth.gr; Pilavaki, M.; Chourmouzi, D

    2004-06-01

    There is a broad spectrum of lipomatous tumors that involve soft tissues including ordinary lipomas, variants of lipomas, heterotopic lipomas, lipomatosis, hibernomas and liposarcomas. The recognition of these tumors is important to avoid diagnostic pitfalls. The MR imaging appearance of the lesion, including location, shape and internal architecture, suggests the diagnosis of lipomatous tumors. The signal intensity on T1-, T2-, fat-suppressed T2-weighted (FS-T2) images or short tau inversion recovery (STIR), T1- and fat-suppressed T1-weighted images after Gd-DTPA administration can be a useful aid in distinguishing between biologically different types of lipomatous tumors. The imaging features are often characteristic and reflect the histological pattern of the tumors. We present an overview of the lipomatous tumors and we correlate MR imaging appearance with histological findings.

  19. Seizure prognosis of patients with low-grade tumors.

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    Kahlenberg, Cynthia A; Fadul, Camilo E; Roberts, David W; Thadani, Vijay M; Bujarski, Krzysztof A; Scott, Rod C; Jobst, Barbara C

    2012-09-01

    Seizures frequently impact the quality of life of patients with low grade tumors. Management is often based on best clinical judgment. We examined factors that correlate with seizure outcome to optimize seizure management. Patients with supratentorial low-grade tumors evaluated at a single institution were retrospectively reviewed. Using multiple regression analysis the patient characteristics and treatments were correlated with seizure outcome using Engel's classification. Of the 73 patients with low grade tumors and median follow up of 3.8 years (range 1-20 years), 54 (74%) patients had a seizure ever and 46 (63%) had at least one seizure before tumor surgery. The only factor significantly associated with pre-surgical seizures was tumor histology. Of the 54 patients with seizures ever, 25 (46.3%) had a class I outcome at last follow up. There was no difference in seizure outcome between grade II gliomas (astrocytoma grade II, oligodendroglioma grade II, mixed oligo-astrocytoma grade II) and other pathologies (pilocytic astrocytoma, ependymomas, DNET, gangliocytoma and ganglioglioma). Once seizures were established seizure prognosis was similar between different pathologies. Chemotherapy (p=0.03) and radiation therapy (p=0.02) had a positive effect on seizure outcome. No other parameter including significant tumor growth during the follow up period predicted seizure outcome. Only three patients developed new-onset seizures after tumor surgery that were non-perioperative. Anticonvulsant medication was tapered in 14 patients with seizures and 10 had no further seizures. Five patients underwent additional epilepsy surgery with a class I outcome in four. Two patients received a vagal nerve stimulator with >50% seizure reduction. Seizures at presentation are the most important factor associated with continued seizures after tumor surgery. Pathology does not influence seizure outcome. Use of long term prophylactic anticonvulsants is unwarranted. Chemotherapy and

  20. Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation

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    Plaga, Alexis; Shields, Lisa B.E. [Norton Neuroscience Institute, Louisville, KY (United States); Sun, David A.; Vitaz, Todd W. [Norton Neuroscience Institute, Louisville, KY (United States); Brain Tumor Center, Norton Healthcare, Louisville, KY (United States); Spalding, Aaron C., E-mail: acspalding1@gmail.com [Brain Tumor Center, Norton Healthcare, Louisville, KY (United States); Norton Cancer Institute, Radiation Center, Kosair Children' s Hospital, Louisville, KY (United States)

    2012-10-01

    Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority given to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study

  1. Histological outcomes of anal high-grade cytopredictions.

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    Roberts, Jennifer Margaret; Jin, Fengyi; Poynten, Isobel Mary; Law, Carmella; Templeton, David James; Thurloe, Julia Kathleen; Garland, Suzanne Marie; Grulich, Andrew Edwin; Farnsworth, Annabelle; Hillman, Richard John

    2017-10-20

    Longitudinal studies of histological outcomes after anal cytological screening in men who have sex with men (MSM) are rare. This study measured the positive predictive values (PPVs) of each level of baseline cytological abnormality in MSM in Sydney, Australia, over a 12-month period. The Study of the Prevention of Anal Cancer is a 3-year prospective study of the natural history of anal human papillomavirus infection in MSM at least 35 years old. For each participant with a baseline cytological abnormality, the worst histology was recorded at the baseline high-resolution anoscopy and at 6 and 12 months. PPVs for a histological high-grade squamous intraepithelial lesion (HSIL) diagnosis were calculated for each level of baseline cytological abnormality at each time point. Among 424 men who completed 3 visits, the PPV of a cytological HSIL increased from 71.6% at the baseline to 86.4% at 6 months and to 92.6% at 12 months (P < .001). For cytological atypical squamous cells, cannot rule out high-grade squamous intraepithelial lesion (ASC-H), the PPV increased from 51.5% at the baseline to 69.7% at 6 months and to 75.8% at 12 months (P = .004). At each time point, the PPV of a cytological HSIL was significantly higher than the PPV of ASC-H. The PPV of low-grade cytology reports was significantly lower than the PPV of ASC-H at each time point. In a cohort of MSM, a baseline histological HSIL diagnosis after an HSIL cytoprediction is high, and it increases with further examinations over the course of 12 months. Lower levels of cytological abnormalities have significantly lower PPVs. These data can inform patient management and the quality assessment of each aspect of the screening pathway. Cancer Cytopathol 2017. © 2017 American Cancer Society. © 2017 American Cancer Society.

  2. Parametrization histological grade white adipose tissue of the breast by the cubic spline interpolation

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    Martinez, Leslie A.; Narea, Freddy J.; Cedeño, Fernando; Muñoz, Aaron A.; Reigosa, Aldo; Bravo, Kelly

    2013-11-01

    The noninvasive optical techniques have attracted considerable interest in recent years, because these techniques provide lot of information on the structure and composition of biological tissues more quickly and painlessly, in this study classifies the degrees of histological differentiation of neoplastic tissue of the breast in white adipose tissue samples through numerical pametrización of the diffuse reflection spectra using the Fourier series approximation. The white adipose tissue is irradiated with the spectrophotometer MiniScan XEplus and it from a mastectomy of patients with aged 38 and 50 who have a cancer lesion in the breast. The samples were provided by the pathologist with theirs medical report, it which we indicate the histological grade of tumor. We performed a parameterization algorithm where the classification criterion is the modulus of the minimum difference between the numerical approximation coefficients ai and average numerical approximation coefficients obtained for each histological grade ¯ al. Is confirmed that the cubic spline interpolation this low-power computing lets classified into histological grades with 91% certainty the tissues under study from |ai - ¯ al|

  3. Cytological grading: An alternative to histological grading in oral squamous cell carcinoma

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    Srilekha Namala

    2016-01-01

    Full Text Available Background: Micronuclei (MN in oral exfoliative cells have been shown to indicate a disparaging change in genetic information of the cell. Recent studies showed correlation between the frequency of MN and severity of this damage. Grading of lesions can be used to determine the austerity of this damage. Aims: The aim of this study is to compare the MN frequency in oral exfoliated cells of normal and oral squamous cell carcinoma (OSCC individuals and to cytologically grade the frequency of MN in cytological smears and to correlate it with histological grading. The objective is to ascertain whether MN frequency in oral exfoliated cells can be a parameter for grading of OSCC. Settings and Design: The study group comprises of 40 subjects (20 controls and 20 OSCC patients in the age group of 45-85 years. Materials and Methods: The cytosmear was obtained from each group and stained with Papanicolaou (PAP stain. Twenty cells from each slide were counted for MN and cytological grade of OSCC was assigned based on the average frequency of MN. Cytological grade was correlated with histological grading and the data were recorded. Student′s t-test and Spearman′s correlation were used for the analysis of the data. Results: Average frequency of MN was 2.5 times higher in OSCC patients when compared to that in controls and the difference was found to be highly significant. Sixty percent correlation was found between cytological grade and histological grade of OSCC and the difference between them was not significant. Conclusions: Cytological grading can be used in grading OSCC, and MN insinuates genotoxic damage occurring in the epithelial cells.

  4. Histologically confirmed intracranial tumors managed at Enugu, Nigeria

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    Chika Anele Ndubuisi

    2017-01-01

    Full Text Available Background: There is controversy about the global distribution of intracranial tumors (ICTs. The previous reports from Africa suggested low frequency and different pattern of distribution of brain tumors from what obtains in other continents. The limitations at that time, including paucity of diagnostic facilities and personnel, have improved. Objective: The objective of this study is to analyze the current trend and distribution of histology confirmed brain tumors managed in Enugu, in a decade. Methods: A retrospective analysis of ICTs managed between 2006 and 2015 at Memfys Hospital, Enugu. Only cases with conclusive histology report were analyzed. The World Health Organization ICT classification was used. Results: This study reviewed 252 patients out of 612 neuroimaging diagnosed brain tumors. Mean age was 42.8 years and male-to-female ratio was 1.2:1.0. Annual frequency increased from 11 in 2006 to 55 in 2015. Metastatic brain tumors accounted for 5.6%, and infratentorial tumors represented 16.3%. Frequency of the common primary tumors were meningioma (32.9%, glioma (23.8%, pituitary adenomas (13.5%, and craniopharyngioma (7.5% (P = 0.001. Vestibular schwannoma accounted for 1.2%. Meningioma did not have gender difference (P = 0.714. Medulloblastoma, glioma, and craniopharyngioma were the most common pediatric tumors. About 8.7% presented unconscious (P < 0.001. There was no significant difference between radiology and histology diagnosis (P = 0.932. Conclusion: Meningioma is the most frequent tumor with increasing male incidence, but the frequency of glioma is increasing. Metastasis, acoustic schwannoma, lymphoma, and germ cell tumors seem to be uncommon. Late presentation is the rule.

  5. Analysis of angiogenic factors and cyclooxygenase-2 expression in cartilaginous tumors: clinical and histological correlation

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    Francisco Fontes Cintra

    2011-01-01

    Full Text Available OBJECTIVES: To study the role of angiogenesis and cyclooxygenase-2 expression in cartilaginous tumors and correlate these factors with prognosis. INTRODUCTION: For chondrosarcoma, the histological grade is the current standard for predicting tumor outcome. However, a low-grade chondrosarcoma can follow an aggressive course-as monitored by sequential imaging techniques-even when it is histologically indistinguishable from an enchondroma. Therefore, additional tools are needed to help identify the biological potential of these tumors. The degree of angiogenesis that is induced by the tumor could assist in this task. Angiogenesis can be quantified by measuring the expression of vascular endothelial growth factor and CD34, and cyclooxygenase-2 can induce angiogenesis by stimulating the production of proangiogenic factors. METHODS: In total, 21 enchondromas and 58 conventional chondrosarcomas were studied by examining the clinical and histopathological findings in conjunction with the immunostaining markers of angiogenesis and cyclooxygenase- 2 expression. RESULTS: The significant variables that were associated with poor outcome were 1 higher-grade chondrosarcomas, 2 tumors that developed in flat bones, and 3 over-expression of CD34 (with a median count that was higher than 5.9 vessels in 5 high power fields. Moreover, CD34 expression (measured using the Chalkley method revealed significantly higher microvessel density in flat bone chondrosarcomas. DISCUSSION: Previous studies have shown a positive correlation between Chalkley microvessel density and histological grade; however, in our sample, we found that the former is predictive of the outcome. Chondrosarcomas in flat bones have been shown to correlate with a poor prognosis. We also found that CD34 microvessel density values were significantly higher in flat-bone chondrosarcomas. This could explain-at least in part-the more aggressive biological course that is taken by these tumors. CONCLUSIONS

  6. Stimulated Raman scattering microscopy for rapid brain tumor histology

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    Yifan Yang

    2017-09-01

    Full Text Available Rapid histology of brain tissues with sufficient diagnostic information has the great potential to aid neurosurgeons during operations. Stimulated Raman Scattering (SRS microscopy is an emerging label-free imaging technique, with the intrinsic chemical resolutions to delineate brain tumors from normal tissues without the need of time-consuming tissue processing. Growing number of studies have shown SRS as a “virtual histology” tool for rapid diagnosis of various types of brain tumors. In this review, we focus on the basic principles and current developments of SRS microscopy, as well as its applications for brain tumor imaging.

  7. Histologic distribution of borderline ovarian tumors worldwide: a systematic review.

    Science.gov (United States)

    Song, Taejong; Lee, Yoo-Young; Choi, Chel Hun; Kim, Tae-Joong; Lee, Jeong-Won; Bae, Duk-Soo; Kim, Byoung-Gie

    2013-01-01

    The histologic types of borderline ovarian tumors (BOTs) exhibit striking differences in clinical behavior and prognosis. Yet, there is no information available on the histologic distribution of BOTs according to geographic region. The purpose of this study was to systematically review this issue worldwide. A comprehensive search of the literature was conducted using electronic databases. Studies were eligible if BOTs were investigated and the histologic distribution of the data was shown. The studies were grouped by geographic region and totaled by country. Of 487 potentially relevant studies, 51 met our inclusion criteria, as follows: 8 studies from North America (2 countries); 26 studies from Europe (14 countries); 7 studies from the Middle East (3 countries); and 10 studies from East Asia (5 countries). The histologic distribution of BOTs was considerably different in different parts of the world, but follows specific patterns. In general, serous-type BOTs were the predominantly identified histology in North America, the Middle East, and Europe, while mucinous-type BOTs predominated in East Asia. Significant geographic variation is evident among BOT histology in different parts of the world. More research is needed to understand this phenomenon.

  8. [Incidence of anaplastic tumor in structure of other histologic forms of the thyroid gland cancer].

    Science.gov (United States)

    Vinnik, Iu A; Gorbenko, V N; Vas'ko, A R; Kikhtenko, E V; Gargin, V V

    2014-01-01

    The degrees of invasiveness, proliferative activity, morphofunctional activity of nuclei in the thyroidal gland tumors were studied, while analyzing material, obtained in 1343 patients, suffering thyroidal gland cancer (THGC) and operated on in 2000-2013 yrs. Morphological point quantity of malignancy (as a criterion of the tumor progression grade) and mitotic activity in cellular population were determined in various kinds of THGC. Undifferentiated (anaplastic carcinoma) type of THGC is the most malignant one. There were determined a spindle-like, giant-cell and squamous-cell forms of undifferentiated THGC. The presence of sites of differentiated cancer in 33% of histological preparations witnesses the interrelationship with the earlier existed pathological process.

  9. New Software for Preoperative Diagnostics of Meningeal Tumor Histologic Types.

    Science.gov (United States)

    Krivoshapkin, Alexey L; Sergeev, Gleb S; Kalneus, Leonid E; Gaytan, Alekey S; Murtazin, Vladimir I; Kurbatov, Vladislav P; Volkov, Alexander M; Kostromskaya, Diana V; Pyatov, Sergey M; Amelin, Michael E; Duishobaev, Abdyrakman R

    2016-06-01

    Meningeal tumors are neoplasms with different histologic manifestations of both benign and malignant types that determine the prognosis of tumor recurrence and its consistency. The risk of surgical treatment depends on the location, size, and consistency of the tumor. Magnetic resonance imaging (MRI) sequences can be used to identify the features of tumors, but these MRI characteristics are not well understood. The present study describes an advanced mathematical algorithm to analyze MRI data and distinguish histologic types of meningeal tumors before surgery. Forty-eight patients underwent surgical removal of meningeal brain tumor. All patients had preoperative MRI with a 1.5-T scanner. One radiologist and 2 neurosurgeons evaluated MRI histogram peaks of the whole tumor volume using the advanced computer algorithm. Three specialists received the following mean value of histogram peaks: 15.99 ± 0.23 (± standard error of the mean [SEM]) for meningoteliomatous meningiomas; 21.24 ± 0.3 (±SEM) for fibroplastic meningiomas; 19.0 ± 0.28 (±SEM) for transitional meningiomas; 10.7 ± 0.27 (±SEM) for anatypical, anaplastic meningiomas, 11.03 ± 0.51 (±SEM) for primary intracranial fibrosarcomas and 25.72 ± 0.29 (±SEM) for meningeal hemangiopericytomas. A one-way analysis of variance test proved the difference between group means: F = 70.138, P < 0.01. The Tukey test and the Games-Howell test indicated that the difference between the tumor groups was significant. Mean deviation in agreement index between specialists was 0.98 ± 0.007 (±SEM). The advanced algorithm proved high specificity, sensitivity, and interoperator repeatability. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Diffusion-weighted MRI of epithelial ovarian cancers: correlation of apparent diffusion coefficient values with histologic grade and surgical stage.

    Science.gov (United States)

    Oh, Ji-Won; Rha, Sung Eun; Oh, Soon Nam; Park, Michael Yong; Byun, Jae Young; Lee, Ahwon

    2015-04-01

    The purpose of this article is to correlate the apparent diffusion coefficient (ADC) values of epithelial ovarian cancers with histologic grade and surgical stage. We enrolled 43 patients with pathologically proven epithelial ovarian cancers for this retrospective study. All patients underwent preoperative pelvic magnetic resonance imaging (MRI) including diffusion-weighted images with b value of 0 and 1000 s/mm2 at 3.0-T unit. The mean ADC values of the solid portion of the tumor were measured and compared among different histologic grades and surgical stages. The mean ADC values of epithelial ovarian cancers differed significantly between grade 1 (well-differentiated) and grade 2 (moderately-differentiated) (P=0.013) as well as between grade 1 and grade 3 (poorly-differentiated) (P=0.01); however, no statistically significant difference existed between grade 2 and grade 3 (P=0.737). The receiver-operating characteristic analysis indicated that a cutoff ADC value of less than or equal to 1.09×10(-3)mm2/s was associated with 94.4% sensitivity and 85.7% specificity in distinguishing grade 1 and grade 2/3 cancer. The difference in mean ADC values was statistically significant for early stage (FIGO stage I) and advanced stage (FIGO stage II-IV) cancer (P=0.011). The interobserver agreement for the mean ADC values of epithelial ovarian cancers was excellent. The mean ADC values of the solid portion of epithelial ovarian cancers negatively correlated to histologic grade and surgical stage. The mean ADC values may be useful imaging biomarkers for assessment of tumor grade of epithelial ovarian cancer. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. 3D analysis of apparent diffusion coefficient histograms in hepatocellular carcinoma: correlation with histological grade.

    Science.gov (United States)

    Moriya, Tomohisa; Saito, Kazuhiro; Tajima, Yu; Harada, Taiyo L; Araki, Yoichi; Sugimoto, Katsutoshi; Tokuuye, Koichi

    2017-01-05

    To evaluate the usefulness of differentiation of histological grade in hepatocellular carcinoma (HCC) using three-dimensional (3D) analysis of apparent diffusion coefficient (ADC) histograms retrospectively. The subjects consisted of 53 patients with 56 HCCs. The subjects included 12 well-differentiated, 35 moderately differentiated, and nine poorly differentiated HCCs. Diffusion-weighted imaging (b-values of 100 and 800 s/mm(2)) were obtained within 3 months before surgery. Regions of interest (ROIs) covered the entire tumor. The data acquired from each slice were summated to derive voxel-by-voxel ADCs for the entire tumor. The following parameters were derived from the ADC histogram: mean, standard deviation, minimum, maximum, mode, percentiles (5th, 10th, 25th, 50th, 75th, and 90th), skew, and kurtosis. These parameters were analyzed according to histological grade. After eliminating steatosis lesions, these parameters were re-analyzed. A weak correlation was observed in minimum ADC and 5th percentile for each histological grade (r = -0.340 and r = -0.268, respectively). The minimum ADCs of well, moderately, and poorly differentiated HCC were 585 ± 388, 411 ± 278, and 235 ± 102 × 10(-6) mm(2)/s, respectively. Minimum ADC showed significant differences among tumor histological grades (P = 0.009). The minimum ADC of poorly differentiated HCC and that of combined well and moderately differentiated HCC were 236 ± 102 and 437 ± 299 × 10(-6) mm(2)/s. The minimum ADC of poorly differentiated HCC was significantly lower than that of combined well and moderately differentiated HCC (P = 0.001). The sensitivity and specificity, when a minimum ADC of 400 × 10(-6) mm(2)/s or lower was considered to be poorly differentiated HCC, were 100 and 54%, respectively. After exclusion of the effect of steatosis, the sensitivity and specificity did not change, although the statistical differences became strong (P < 0

  12. Influence of tumor histology on preoperative staging accuracy of breast metastases to the axilla.

    Science.gov (United States)

    Hackney, Lisa; Williams, Susan; Bajwa, Saba; Morley-Davies, Adrian J; Kirby, Robert M; Britton, Ingrid

    2013-01-01

    Histologic confirmation of axillary nodal metastases preoperatively avoids a sentinel node biopsy and enables a one step surgical procedure. The aim of this study was to establish the local positive predictive value of axillary ultrasound (AUS) and guided needle core biopsy (NCB) in axillary staging of breast cancer, and to identify factors influencing yield. A prospective audit of 142 consecutive patients (screening and symptomatic) presenting from 1st December 2008-31st May 2009 with breast lesions categorized R4-R5, who underwent a preoperative AUS, and proceeded to surgery was undertaken. Ultrasound-guided NCB was performed on nodes radiologically classified R3-R5. Lymph node size, number, and morphological features were documented. Yield was correlated with tumor size, grade, and histologic type. AUS/NCB was correlated with post surgical pathologic findings to determine sensitivity, specificity, positive and negative predictive value of AUS and NCB. A total of 142 patients underwent surgery, of whom 52 (37%) had lymph node metastases on histology. All had a preoperative AUS, 51 (36%) had abnormal ultrasound findings. 46 (90%) underwent axillary node NCB of which 24 (52%) were positive. The smallest tumor size associated with positive nodes at surgery was 11.5 mm. The sensitivity of AUS was 65%. Specificity was 81%, with a positive predictive value (PPV) of 67% and negative predictive (NPV) value of 80%. Sensitivity of U/S-guided NCB was 75%, with a specificity of 100%, PPV 100% and NPV 64%. Sensitivity of AUS for lobular carcinoma was 36% versus 76% for all other histologies. Sensitivity of NCB for lobular cancer was 33% versus 79% for all other histologies. The most significant factor producing discordance between preoperative AUS and definitive histologic evidence of lymph node metastasis was tumor type. Accurate preoperative lymph node staging was prejudiced by lobular histology (p < 0.0019). © 2012 Wiley Periodicals, Inc.

  13. Serological and histological indices of hepatocellular carcinoma and tumor volume doubling time

    Science.gov (United States)

    SHINGAKI, NAOKI; TAMAI, HIDEYUKI; MORI, YOSHIYUKI; MORIBATA, KOSAKU; ENOMOTO, SHOTARO; DEGUCHI, HISANOBU; UEDA, KAZUKI; INOUE, IZUMI; MAEKITA, TAKAO; IGUCHI, MIKITAKA; KATO, JUN; ICHINOSE, MASAO

    2013-01-01

    Hepatocellular carcinoma (HCC) frequently develops in cirrhotic liver and is one of the most common malignancies worldwide. The tumor volume doubling time (TVDT) reflects the natural tumor growth rate and is an indicator of the biological malignant potential of a tumor. The present study aimed to elucidate the association between the serological and histological indices of HCC and TVDT. TVDT was analyzed for 53 HCCs by measuring the enlargement of the tumor diameter on dynamic computed tomography. Differences in TVDT were compared among histological grades of HCC differentiation. The α-fetoprotein (AFP) doubling time (T2AFP) for 44 HCCs with AFP levels >200 ng/ml was calculated and the differences in T2AFP were compared according to the histological grade of HCC differentiation and positivity for Lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3). Among these 44 HCCs, the correlation between T2AFP and TVDT was analyzed for the 27 tumors for which TVDT could be calculated. The mean ± standard deviation (SD) TVDT in Edmondson grade 1 (Ed1), Ed2 and Ed3 HCC was 138.3±110.3, 94.9±91.5 and 32.2±20.8 days, respectively (P<0.05). The mean ± SD T2AFP in Ed2 and Ed3 HCC was 121.0±167.5 and 37.3±24.6 days, respectively (P<0.01). TVDT and T2AFP decreased with histological dedifferentiation of HCC. The mean ± SD T2AFP in the AFP-L3-positive and -negative groups was 63.2±101.2 and 191.9±209.9 days, respectively, with a statistically significant difference between the groups (P<0.01). A significant correlation was observed between T2AFP and TVDT (correlation coefficient, 0.70; P<0.01). A significant correlation was also observed among TVDT, serological indices and histological grades of HCC differentiation. A short T2AFP and/or AFP-L3-positivity were shown to reflect a poorly differentiated HCC histopathology and a higher malignant potential. PMID:24649280

  14. Mammary analog secretory carcinoma of salivary gland with high-grade histology arising in hard palate, report of a case and review of literature

    Science.gov (United States)

    Luo, Wenyi; Lindley, Sarah W; Lindley, Peter H; Krempl, Gregory A; Seethala, Raja R; Fung, Kar-Ming

    2014-01-01

    Mammary gland analog secretary carcinoma (MASC) of salivary gland is typically a tumor of low histologic grade and behaves as a low-grade malignancy with relatively benign course. This tumor shares histologic features, immunohistochemical profile, and a highly specific genetic translocation, ETV6-NTRK3, with secretory carcinoma of breast. Histologically, it is often mistaken as acinic cell carcinoma, adenocarcinoma not otherwise specified, and other primary salivary gland tumors. Here we report a case of MASC with high-grade transformation and cervical lymph node metastases confirmed with ETV6-NTRK3 translocation arising in the hard palate of a 41 year-old adult. Interestingly, the metastatic carcinoma has lower grade than the original tumor which strongly support malignant transformation of the original tumor. Most commonly, MASC arises from the parotid gland and less often in minor salivary glands. Metastasis is relatively uncommon and high-grade histology has only been reported in four cases with three of them arising from the parotid gland and the location of the fourth one has not been reported. This is the first case with high grade histology that arise from minor salivary gland and it emphasizes the importance of molecular screening of salivary gland tumor with high-grade histology for ETV6-NTRK3 translocation. In our literature of 115 cases that includes the current case, MASC occurred predominantly in adult with only a few cases under 18 years of age and a male to female ratio of 1.2:1. Parotid gland is more commonly affected but there is also significant occurrence in minor salivary glands. Except for the cases with high grade histology, the overall prognosis is good. PMID:25674280

  15. Endometrial cancer: correlation of apparent diffusion coefficient (ADC) with tumor cellularity and tumor grade.

    Science.gov (United States)

    Kishimoto, Keiko; Tajima, Shinya; Maeda, Ichiro; Takagi, Masayuki; Ueno, Takahiko; Suzuki, Nao; Nakajima, Yasuo

    2016-08-01

    Diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) are widely used for detecting uterine endometrial cancer. The relationships between ADC values and pathological features of endometrial cancer have not yet been established. To investigate whether ADC values of endometrial cancer vary according to histologic tumor cellularity and tumor grade. We retrospectively reviewed 30 pathologically confirmed endometrial cancers. All patients underwent conventional non-enhanced magnetic resonance imaging (MRI) and DWI procedures, and ADC values were calculated. Tumor cellularity was evaluated by counting cancer cells in three high-power ( × 400) fields. The correlation between ADC values and tumor cellularity was assessed using Pearson's correlation coefficient test for statistical analysis. The mean ± standard deviation (SD) ADC value ( ×10(-3) mm(2)/s) of endometrial cancer was 0.85 ± 0.22 (range, 0.55-1.71). The mean ± SD tumor cellularity was 528.36 ± 16.89 (range, 298.0-763.6). ADC values were significantly inversely correlated with tumor cellularity. No significant relationship was observed between ADC values and tumor grade (mean ADC values: G1, 0.88 ± 0.265 × 10(-3) mm(2)/s; G2, 0.80 ± 0.178 × 10(-3) mm(2)/s; G3, 0.81 ± 0.117 × 10(-3) mm(2)/s). There is a significant inverse relationship between ADC values and tumor cellularity in endometrial cancer. No significant differences in average ADC value were observed between G1, G2, and G3 tumors. However, the lower the tumor grade, the wider the SD. © The Foundation Acta Radiologica 2015.

  16. Early genetic changes involved in low-grade astrocytic tumor development.

    Science.gov (United States)

    Arjona, Dolores; Rey, Juan Antonio; Taylor, Shirley M

    2006-09-01

    Astrocytomas represent the most common form of glial tumors. The most malignant grade of these tumors, glioblastoma multiforme, may arise as a malignant progression from low-grade astrocytoma through anaplastic astrocytoma to secondary GBM, or else it may arise "de novo" as primary GBM. Both types of glioblastoma are usually histologically indistinguishable. However, distinct molecular alterations have been described between them that potentially allow differentiation between the two mechanisms of origin. Since malignant transformation is a multistep process, we summarize in this review the earliest genetic changes that seem to be involved in the appearance and development of low-grade astrocytic tumors, where early detection and treatment could be possible.

  17. Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants.

    Science.gov (United States)

    Pareja, Fresia; Geyer, Felipe C; Marchiò, Caterina; Burke, Kathleen A; Weigelt, Britta; Reis-Filho, Jorge S

    2016-01-01

    Triple-negative breast cancers (TNBCs), defined by lack of expression of estrogen receptor, progesterone receptor and HER2, account for 12-17% of breast cancers and are clinically perceived as a discrete breast cancer subgroup. Nonetheless, TNBC has been shown to constitute a vastly heterogeneous disease encompassing a wide spectrum of entities with marked genetic, transcriptional, histological and clinical differences. Although most TNBCs are high-grade tumors, there are well-characterized low-grade TNBCs that have an indolent clinical course, whose natural history, molecular features and optimal therapy vastly differ from those of high-grade TNBCs. Secretory and adenoid cystic carcinomas are two histologic types of TNBCs underpinned by specific fusion genes; these tumors have an indolent clinical behavior and lack all of the cardinal molecular features of high-grade triple-negative disease. Recent studies of rare entities, including lesions once believed to constitute mere benign breast disease (e.g., microglandular adenosis), have resulted in the identification of potential precursors of TNBC and suggested the existence of a family of low-grade triple-negative lesions that, despite having low-grade morphology and indolent clinical behavior, have been shown to harbor the complex genomic landscape of common forms of TNBC, and may progress to high-grade disease. In this review, we describe the heterogeneity of TNBC and focus on the histologic and molecular features of low-grade forms of TNBC. Germane to addressing the challenges posed by the so-called triple-negative disease is the realization that TNBC is merely a descriptive term, and that low-grade types of TNBC may be driven by distinct sets of genetic alterations.

  18. Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants

    Science.gov (United States)

    Pareja, Fresia; Geyer, Felipe C; Marchiò, Caterina; Burke, Kathleen A; Weigelt, Britta; Reis-Filho, Jorge S

    2016-01-01

    Triple-negative breast cancers (TNBCs), defined by lack of expression of estrogen receptor, progesterone receptor and HER2, account for 12–17% of breast cancers and are clinically perceived as a discrete breast cancer subgroup. Nonetheless, TNBC has been shown to constitute a vastly heterogeneous disease encompassing a wide spectrum of entities with marked genetic, transcriptional, histological and clinical differences. Although most TNBCs are high-grade tumors, there are well-characterized low-grade TNBCs that have an indolent clinical course, whose natural history, molecular features and optimal therapy vastly differ from those of high-grade TNBCs. Secretory and adenoid cystic carcinomas are two histologic types of TNBCs underpinned by specific fusion genes; these tumors have an indolent clinical behavior and lack all of the cardinal molecular features of high-grade triple-negative disease. Recent studies of rare entities, including lesions once believed to constitute mere benign breast disease (e.g., microglandular adenosis), have resulted in the identification of potential precursors of TNBC and suggested the existence of a family of low-grade triple-negative lesions that, despite having low-grade morphology and indolent clinical behavior, have been shown to harbor the complex genomic landscape of common forms of TNBC, and may progress to high-grade disease. In this review, we describe the heterogeneity of TNBC and focus on the histologic and molecular features of low-grade forms of TNBC. Germane to addressing the challenges posed by the so-called triple-negative disease is the realization that TNBC is merely a descriptive term, and that low-grade types of TNBC may be driven by distinct sets of genetic alterations. PMID:28721389

  19. Diffusion-weighted MRI of epithelial ovarian cancers: Correlation of apparent diffusion coefficient values with histologic grade and surgical stage

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Ji-Won, E-mail: fromentin@naver.com [Department of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701 (Korea, Republic of); Rha, Sung Eun, E-mail: serha@catholic.ac.kr [Department of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701 (Korea, Republic of); Oh, Soon Nam, E-mail: hiohsn@catholic.ac.kr [Department of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701 (Korea, Republic of); Park, Michael Yong, E-mail: digirave@kmle.com [Department of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701 (Korea, Republic of); Byun, Jae Young, E-mail: jybyun@catholic.ac.kr [Department of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701 (Korea, Republic of); Lee, Ahwon, E-mail: klee@catholic.ac.kr [Department of Hospital Pathology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701 (Korea, Republic of)

    2015-04-15

    Highlights: •The solid component of all invasive epithelial cancers showed high b{sub 1000} signal intensity. •ADCs can predict the histologic grade of epithelial ovarian cancer. •ADCs correlate negatively to the surgical stage of epithelial ovarian cancer. •ADCs may be useful imaging biomarkers to assess epithelial ovarian cancer. -- Abstract: Objective: The purpose of this article is to correlate the apparent diffusion coefficient (ADC) values of epithelial ovarian cancers with histologic grade and surgical stage. Materials and methods: We enrolled 43 patients with pathologically proven epithelial ovarian cancers for this retrospective study. All patients underwent preoperative pelvic magnetic resonance imaging (MRI) including diffusion-weighted images with b value of 0 and 1000 s/mm{sup 2} at 3.0-T unit. The mean ADC values of the solid portion of the tumor were measured and compared among different histologic grades and surgical stages. Results: The mean ADC values of epithelial ovarian cancers differed significantly between grade 1 (well-differentiated) and grade 2 (moderately-differentiated) (P = 0.013) as well as between grade 1 and grade 3 (poorly-differentiated) (P = 0.01); however, no statistically significant difference existed between grade 2 and grade 3 (P = 0.737). The receiver-operating characteristic analysis indicated that a cutoff ADC value of less than or equal to 1.09 × 10{sup −3} mm{sup 2}/s was associated with 94.4% sensitivity and 85.7% specificity in distinguishing grade 1 and grade 2/3 cancer. The difference in mean ADC values was statistically significant for early stage (FIGO stage I) and advanced stage (FIGO stage II-IV) cancer (P = 0.011). The interobserver agreement for the mean ADC values of epithelial ovarian cancers was excellent. Conclusion: The mean ADC values of the solid portion of epithelial ovarian cancers negatively correlated to histologic grade and surgical stage. The mean ADC values may be useful imaging

  20. Respective prognostic value of genomic grade and histological proliferation markers in early stage (pN0 breast carcinoma.

    Directory of Open Access Journals (Sweden)

    Fabien Reyal

    Full Text Available BACKGROUND: Genomic grade (GG is a 97-gene signature which improves the accuracy and prognostic value of histological grade (HG in invasive breast carcinoma. Since most of the genes included in the GG are involved in cell proliferation, we performed a retrospective study to compare the prognostic value of GG, Mitotic Index and Ki67 score. METHODS: A series of 163 consecutive breast cancers was retained (pT1-2, pN0, pM0, 10-yr follow-up. GG was computed using MapQuant Dx(R. RESULTS: GG was low (GG-1 in 48%, high (GG-3 in 31% and equivocal in 21% of cases. For HG-2 tumors, 50% were classified as GG-1, 18% as GG-3 whereas 31% remained equivocal. In a subgroup of 132 ER+/HER2- tumors GG was the most significant prognostic factor in multivariate Cox regression analysis adjusted for age and tumor size (HR = 5.23, p = 0.02. CONCLUSIONS: In a reference comprehensive cancer center setting, compared to histological grade, GG added significant information on cell proliferation in breast cancers. In patients with HG-2 carcinoma, applying the GG to guide the treatment scheme could lead to a reduction in adjuvant therapy prescription. However, based on the results observed and considering (i the relatively close prognostic values of GG and Ki67, (ii the reclassification of about 30% of HG-2 tumors as Equivocal GG and (iii the economical and technical requirements of the MapQuant micro-array GG test, the availability in the near future of a PCR-based Genomic Grade test with improved performances may lead to an introduction in clinical routine of this test for histological grade 2, ER positive, HER2 negative breast carcinoma.

  1. Respective prognostic value of genomic grade and histological proliferation markers in early stage (pN0) breast carcinoma.

    Science.gov (United States)

    Reyal, Fabien; Bollet, Marc A; Caly, Martial; Gentien, David; Carpentier, Sabrina; Peyro-Saint-Paul, Hélène; Pierga, Jean-Yves; Cottu, Paul; Dieras, Véronique; Sigal-Zafrani, Brigitte; Vincent-Salomon, Anne; Sastre-Garau, Xavier

    2012-01-01

    Genomic grade (GG) is a 97-gene signature which improves the accuracy and prognostic value of histological grade (HG) in invasive breast carcinoma. Since most of the genes included in the GG are involved in cell proliferation, we performed a retrospective study to compare the prognostic value of GG, Mitotic Index and Ki67 score. A series of 163 consecutive breast cancers was retained (pT1-2, pN0, pM0, 10-yr follow-up). GG was computed using MapQuant Dx(R). GG was low (GG-1) in 48%, high (GG-3) in 31% and equivocal in 21% of cases. For HG-2 tumors, 50% were classified as GG-1, 18% as GG-3 whereas 31% remained equivocal. In a subgroup of 132 ER+/HER2- tumors GG was the most significant prognostic factor in multivariate Cox regression analysis adjusted for age and tumor size (HR = 5.23, p = 0.02). In a reference comprehensive cancer center setting, compared to histological grade, GG added significant information on cell proliferation in breast cancers. In patients with HG-2 carcinoma, applying the GG to guide the treatment scheme could lead to a reduction in adjuvant therapy prescription. However, based on the results observed and considering (i) the relatively close prognostic values of GG and Ki67, (ii) the reclassification of about 30% of HG-2 tumors as Equivocal GG and (iii) the economical and technical requirements of the MapQuant micro-array GG test, the availability in the near future of a PCR-based Genomic Grade test with improved performances may lead to an introduction in clinical routine of this test for histological grade 2, ER positive, HER2 negative breast carcinoma.

  2. Histological-subtypes and anatomical location correlated in meningeal brain tumors (meningiomas

    Directory of Open Access Journals (Sweden)

    Abdul Rashid Bhat

    2014-01-01

    Full Text Available Context: Not enough literature is available to suggest a link between the histological subtypes of intracranial meningeal brain tumors, called ′meningiomas′ and their location of origin. Aim: The evidence of correlation between the anatomical location of the intracranial meningiomas and the histopathological grades will facilitate specific diagnosis and accurate treatment. Materials and Methods: The retrospective study was conducted in a single high-patient-inflow Neurosurgical Center, under a standard and uniform medical protocol, over a period of 30 years from December 1982 to December 2012. The records of all the operated 729 meningiomas were analyzed from the patient files in the Medical Records Department. The biodata, x-rays, angiography, computed tomography (CT scans, imaging, histopathological reports, and mortality were evaluated and results drawn. Results: The uncommon histopathological types of meningiomas (16.88% had common locations of origin in the sphenoid ridge, posterior parafalcine, jugular foramen, peritorcular and intraventricular regions, cerebellopontine angle, and tentorial and petroclival areas. The histopathological World Health Organization (WHO Grade I (Benign Type meningiomas were noted in 89.30%, WHO Grade II (Atypical Type in 5.90%, and WHO Grade III (Malignant Type in 4.80% of all meningiomas. Meningiomas of 64.60% were found in females, 47.32% were in the age group of 41-50 years, and 3.43% meningiomas were found in children. An overall mortality of 6.04% was noted. WHO Grade III (malignant meningiomas carried a high mortality (25.71% and the most common sites of meningiomas with high mortality were: The cerebellopontine angles, intraventricular region, sphenoid ridge, tuberculum sellae, and the posterior parafalcine areas. Conclusion: The correlation between the histological subtypes and the anatomical location of intracranial meningeal brain tumors, called meningiomas, is evident, but further research is

  3. Diffusion-weighted MRI in renal cell carcinoma: A surrogate marker for predicting nuclear grade and histological subtype

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    Goyal, Ankur; Sharma, Raju; Bhalla, Ashu S.; Gamanagatti, Shivanand (Dept. of Radiodiagnosis, All India Inst. of Medical Sciences (AIIMS), New Delhi (India)), Email: raju152@yahoo.com; Seth, Amlesh (Dept. of Urology, All India Inst. of Medical Sciences (AIIMS), New Delhi (India)); Iyer, Venkateswaran K.; Das, Prasenjit (Dept. of Pathology, All India Inst. of Medical Sciences (AIIMS), New Delhi (India))

    2012-04-15

    Background: Though previous investigators have attempted to evaluate its utility in characterization of focal renal lesions, diffusion-weighted MR imaging (DW MRI) in renal diseases is still an evolving field and its role in predicting the aggressiveness of renal cell carcinoma (RCC) is yet to be established. Purpose: To assess whether apparent diffusion coefficient (ADC) values can be used to determine the nuclear grade and histological subtype of RCCs and to identify the tumor attributes contributing to variation in ADC values. Material and Methods: The institutional ethics committee waived the requirement of informed consent for this retrospective study. The study cohort consisted of 33 patients who underwent MRI (with diffusion-weighted imaging at b values of 0 and 500 s/mm2) and were found to have 36 pathologically-proven RCCs. ADC values were determined for solid portions of RCC, cystic/hemorrhagic areas, and normal renal parenchyma. Histological subtype, nuclear grade, and cell count were determined for each lesion. ADC values were compared between different grades and subtypes and correlation with cell count was investigated. Receiver operating characteristic curves were drawn to establish cut-off ADC values. Results: There were 23 low grade (grades I and II) and 13 high grade tumors (grades III and IV). There were 32 clear-cell and four non-clear-cell RCCs. A decreasing trend of ADC values was seen with increasing grade and mean ADC of high grade RCC was significantly lower than low grade (1.3145 vs 1.6982 x 10-3 mm2/s) (P = 0.005). Mean ADC for clear-cell RCC was significantly higher than non-clear-cell RCC (1.6245 vs. 1.0412 x 10-3 mm2/s) (P = 0.005). ADC values higher than 1.7960 x 10-3 mm2/s were seen only with low grade and values greater than 1.4904 x 10-3 mm2/s were seen only with clear-cell RCC. Conclusion: ADC values provide a non-invasive means to predict the nuclear grade and histological subtype of RCC. Cellularity and morphology are other

  4. Pretreatment Biopsy for Histological Diagnosis and Induction Therapy in Thymic Tumors

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    Jie YUE

    2016-07-01

    Full Text Available Background and objective The aim of this study is to investigate the value of pretreatment biopsy for histological diagnosis and induction therapies in the management of locally advanced thymic malignancies. Methods The clinical pathological data of patients with thymic tumors in the Chinese Alliance for Research in Thymomas (ChART who underwent biopsy before treatment from 1994 to December 2012 were retrospectively reviewed. The application trend of preoperative histological diagnosis and its influence on treatment outcome were analyzed. Results Of 1,902 cases of thymic tumors, 336 (17.1% had undergone biopsy for histological diagnosis before therapeutic decision was decided. In recent years, percentage of pretreatment histological diagnosis significantly increased in the later ten years than the former during the study period (P=0.008. There was also a significant increase in thoracoscopy/mediastinoscopy/endobronchial ultrasound (E-BUS biopsy as compared to open biopsy (P=0.029. Survival in Patients with preoperative biopsy for histology had significantly higher stage lesions (P<0.001 and higher grade malignancy (P<0.001, thus a significantly lower complete resection rate (P<0.001 and therefore a significantly worse survival than those without preoperative biopsy (P=0.001. In the biopsied 336 patients, those who received upfront surgery had significantly better survival than those received surgery after induction therapy (P=0.001. In stage III and IVa diseases, the R0 resection rate after induction therapies increased significantly as compared to the surgery upfront cases (65.5% vs 46.2%, P=0.025. Tumors downstaged after induction had similar outcomes as those having upfront surgery (92.3% vs 84.2%, P=0.51. However, tumors not downstaged by induction had significantly worse prognosis than those downstaged (P=0.004, and fared even worse than those having definitive chemoradiation without surgery (37.2% vs 62.4%, P=0.216. Conclusion It is

  5. Histology image analysis for carcinoma detection and grading.

    Science.gov (United States)

    He, Lei; Long, L Rodney; Antani, Sameer; Thoma, George R

    2012-09-01

    This paper presents an overview of the image analysis techniques in the domain of histopathology, specifically, for the objective of automated carcinoma detection and classification. As in other biomedical imaging areas such as radiology, many computer assisted diagnosis (CAD) systems have been implemented to aid histopathologists and clinicians in cancer diagnosis and research, which have been attempted to significantly reduce the labor and subjectivity of traditional manual intervention with histology images. The task of automated histology image analysis is usually not simple due to the unique characteristics of histology imaging, including the variability in image preparation techniques, clinical interpretation protocols, and the complex structures and very large size of the images themselves. In this paper we discuss those characteristics, provide relevant background information about slide preparation and interpretation, and review the application of digital image processing techniques to the field of histology image analysis. In particular, emphasis is given to state-of-the-art image segmentation methods for feature extraction and disease classification. Four major carcinomas of cervix, prostate, breast, and lung are selected to illustrate the functions and capabilities of existing CAD systems. Published by Elsevier Ireland Ltd.

  6. Grading glioma tumors using OWL-DL and NCI Thesaurus.

    Science.gov (United States)

    Marquet, Gwenaëlle; Dameron, Olivier; Saikali, Stephan; Mosser, Jean; Burgun, Anita

    2007-10-11

    Brain tumors' treatment and prognosis depend to a large extent on their grades. Grading tumors follows a set of rules that refers to domain knowledge. Developing an automatic grading system requires explicit and formal representation of the domain. The NCI Thesaurus is the major ontological resource in the cancer domain. However, the description of brain tumors and grades in the NCI Thesaurus does not enable automatic grading. We have developed an ontology based on the NCI Thesaurus for automatic classification of glioma tumors based on a reference grading system. Two sets of tests have been done. The first one has been automatically generated and the second one consists of eleven pathology reports. The resulting ontology contains 243 classes, among which 234 correspond to NCI Thesaurus classes. Because all of the generated tests were correctly classified, we believe our system to be correct. Ten clinical reports are correctly graded and one is graded incompletely.

  7. Can the apparent diffusion coefficient differentiate the grade of endometrioid adenocarcinoma and the histological subtype of endometrial cancer?

    Science.gov (United States)

    Yan, Bin; Zhao, Tingting; Liang, Xiufen; Niu, Chen; Ding, Caixia

    2018-03-01

    Background Diffusion-weighted imaging (DWI) provides useful information for the identification of benign and malignant uterine lesions. However, the use of the apparent diffusion coefficient (ADC) for histopathological grading of endometrial cancer is controversial. Purpose To explore the use of ADC values in differentiating the preoperative tumor grading of endometrioid adenocarcinomas and investigate the relationship between the ADC values of endometrial cancer and the histological tumor subtype. Material and Methods We retrospectively evaluated 98 patients with endometrial cancers, including both endometrioid adenocarcinomas (n = 80) and non-endometrioid adenocarcinomas (n = 18). All patients underwent DWI procedures and ADC values were calculated. The Kruskal-Wallis test and the independent samples Mann-Whitney U test were used to compare differences in the ADC values between different tumor grades and different histological subtypes. Results The mean ADC values (ADCmean) for high-grade endometrioid adenocarcinomas were significantly lower than the values for low-grade tumors (0.800 versus 0.962 × 10 -3  mm 2 /s) ( P = 0.002). However, no significant differences in ADCmean and minimum ADC values (ADCmin) were found between tumor grades (G1, G2, and G3) of endometrial cancer. Compared with endometrioid adenocarcinomas, the adenocarcinoma with squamous differentiation showed lower ADC values (mean/minimum = 0.863/0.636 versus 0.962/0.689 × 10 -3  mm 2 /s), but the differences were not significant ( P mean  = 0.074, P min  = 0.441). Moreover, ADCmean for carcinosarcomas was significantly higher than the value for G3 non-carcinosarcoma endometrial cancers (1.047 versus 0.823 × 10 -3  mm 2 /s) ( P = 0.001). Conclusion The ADCmean was useful for identifying high-grade and low-grade endometrioid adenocarcinomas. Additionally, squamous differentiation may decrease ADCmean and ADCmin of endometrioid adenocarcinoma, and

  8. Comparative molecular and histological grading of epithelial dysplasia of the oral cavity and the oropharynx

    NARCIS (Netherlands)

    Tabor, M.P.; Braakhuis, B.J.M.; van der Wal, J.E.; van Diest, P.J.; Leemans, C.R.; Brakenhoff, R.H.; Kummer, J.A.

    2003-01-01

    Histological grading of epithelial dysplasia in the oral cavity and oropharynx is used to predict the risk for cancer and to determine the treatment strategy. This grading, however, is subjective and not well reproducible. Recent publications have shown that molecular markers are promising in cancer

  9. Computer-aided evaluation of neuroblastoma on whole-slide histology images: Classifying grade of neuroblastic differentiation.

    Science.gov (United States)

    Kong, J; Sertel, O; Shimada, H; Boyer, K L; Saltz, J H; Gurcan, M N

    2009-06-01

    Neuroblastoma (NB) is one of the most frequently occurring cancerous tumors in children. The current grading evaluations for patients with this disease require pathologists to identify certain morphological characteristics with microscopic examinations of tumor tissues. Thanks to the advent of modern digital scanners, it is now feasible to scan cross-section tissue specimens and acquire whole-slide digital images. As a result, computerized analysis of these images can generate key quantifiable parameters and assist pathologists with grading evaluations. In this study, image analysis techniques are applied to histological images of haematoxylin and eosin (H&E) stained slides for identifying image regions associated with different pathological components. Texture features derived from segmented components of tissues are extracted and processed by an automated classifier group trained with sample images with different grades of neuroblastic differentiation in a multi-resolution framework. The trained classification system is tested on 33 whole-slide tumor images. The resulting whole-slide classification accuracy produced by the computerized system is 87.88%. Therefore, the developed system is a promising tool to facilitate grading whole-slide images of NB biopsies with high throughput.

  10. Mammographic findings of infiltrating ductal carcinoma: correlation with histologic grading and age

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    Shin, Kue Hee; Lee, Ki Yeol; Kang, Eun Young [Korea Univ. College of Medicine, Seoul (Korea, Republic of)

    1997-11-01

    To investigate the correlation between mammographic findings of infiltrating ductal carcinoma (IDC), patient age and pathologic grading. The study included 103 cases of infiltrating ductal carcinoma in 102 women who during the preceding three years had undergone mammography and surgery. The mammograms were retrospectively reviewed by two radiologists. The mean age of the patients was 45.2 (range 26 - 74) years and the age distribution was seven in the 3rd decade, 37 in the 4th, 29 in the 5th, 24 in the 6th, and six in the 7th or above. Thirty-three lesions were histologic. Grade 1, 59 were Grade 2 and 11 were Grade 3. Ten (9.7%) of 103 cases, all of whom were younger than 50, were missed during mammographic diagnosis. On mammograms, primary findings of breast malignancy were found in 54 (74%) of 73 patients younger than 50 and 27 (90%) of 30 patients older than 51. Mass with or without microcalcification was found in 45 patients (62%) younger than 50 and in 26 (87%) older than 51. Nine (12%) and 3 (10%) in each age group showed secondary findings. There was no correlation between age distribution and histologic grading. Seventy-three percent of Grade 1 lesions and 78% of those of Grade 3 showed primary findings. Five lesions in each of Grade 1 and 2 were missed at mammographic interpretation, but this was not statistically significant (p=0.250). In all 11 Grade 3 cases, breast cancer were manifested as primary findings, but this was not statistically significant (p=0.203). The majority of IDC were detected by mammography, but 9.7% of IDC patients, all younger than 50, were misdiagnosed. Most IDC was manifested as primary findings, particularly in patients aged over 51. There were no differences in pathologic grading according to age distribution. All histologic Grade 3 lesions were detected by mammography.

  11. A survival analysis comparing women with ovarian low-grade serous carcinoma to those with high-grade histology

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    Chen M

    2014-10-01

    Full Text Available Ming Chen,1 Ying Jin,1 Yalan Bi,2 Jie Yin,1 Yongxue Wang,1 Lingya Pan1 1Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; 2Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China Abstract: Ovarian low-grade serous carcinoma (LGSC and high-grade serous carcinoma have distinct molecular profiles, clinical behaviors, and treatment responses. The survival advantage for patients with low-grade carcinoma compared with patients with high-grade histology remains controversial. We retrospectively reviewed the medical charts of 381 patients with ovarian serous carcinoma at Peking Union Medical College Hospital from 2007 to 2010. Patients were classified into two groups according to MD Anderson two-tier system: 35 (9.2% cases with LGSC and 346 with high-grade serous carcinoma. Patients with low-grade serous ovarian cancer had a significantly younger age at diagnosis (46 versus 56 years, P=0.046, and their median progression-free survival (PFS and overall survival values were 35.0 and 54.0 months, respectively. A multivariate analysis showed that, for serous ovarian cancer, the histological grade was a significant prognostic factor for PFS but not for overall survival (P=0.022 and P=0.0566, respectively. When stratified by the existence of a residual disease, patients with low-grade disease who underwent cytoreductive surgery without macroscopic residual disease (>1 cm had a significantly improved median PFS time (36.0 months compared with that of patients with high-grade carcinoma who received optimal cytoreductive surgery (16.0 months, P=0.017. Conversely, patients with low-grade and high-grade carcinoma who were left with macroscopic residue (>1 cm experienced a similarly shorter median PFS (10.0 and 13

  12. P27/SKP-2 histochemical profile is relevant to malignant salivary gland tumors (MST) histogenesis and tumor grade.

    Science.gov (United States)

    Akrish, Sharon; Ben-Izhak, Ofer; Peled, Micha

    2012-06-01

    Malignant salivary gland tumors (MST) represent over more than 24 distinct morphological subtypes. Most high grade tumors arise from the excretory duct portion of the salivary gland apparatus; the remainder from the intercalated duct portion. Altered p27/skp-2 expression has been associated with tumor aggressiveness and histologic differentiation. In our study, we analyzed p27/skp-2 expression proteins on series of malignant salivary gland tumors in order to assess their value as a histogenetic marker, which is relevant to tumor grade. 61 MST cases were segregated by proposed histogenesis and immunohistochemistry was performed using antibodies directed against p27 and skp-2. MST of proposed intercalated duct origin (n=27) showed strong p27 expression (n=25/27; 93%) in the vast majority of cases and all cases weakly expressed skp-2. MST of proposed excretory duct origin (n=32) showed strong p27 expression (n=18/32; 56%) and moderately strong/strong skp-2 expression (n=18/32; 56%), respectively, in over half the cases. MST of intercalated duct origin showed evident p27/skp-2 inverse correlation. Differences in p27/skp-2 expression among the MST subtypes correlated with histogenesis and tumor grade, which reinforces the notion that tumor behavior is relevant to the portion of the salivary gland unit from which they arise. MST of proposed intercalated duct origin strongly expressed p27, and not skp-2, unlike MST of proposed excretory duct origin. The immunohistochemical profile of high grade mucoepidermoid carcinoma was distinct from its low/intermediate grade counterparts, suggesting a separate identity. These results may influence future decision making when formulating workable MST categorization schemes. Further studies on a larger series of MST are warranted in order to support the value of our findings.

  13. Imaging of brain tumors with histological correlations. 2. ed.

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    Drevelegas, Antonios (ed.)

    2011-07-01

    This volume provides a deeper understanding of the diagnosis of brain tumors by correlating radiographic imaging features with the underlying pathological abnormalities. All modern imaging modalities are used to complete a diagnostic overview of brain tumors with emphasis on recent advances in diagnostic neuroradiology. High-quality illustrations depicting common and uncommon imaging characteristics of a wide range of brain tumors are presented and analysed, drawing attention to the ways in which these characteristics reflect different aspects of pathology. Important theoretical considerations are also discussed. Since the first edition, chapters have been revised and updated and new material has been added, including detailed information on the clinical application of functional MRI and diffusion tensor imaging. Radiologists and other clinicians interested in the current diagnostic approach to brain tumors will find this book to be an invaluable and enlightening clinical tool. (orig.)

  14. Histological Regression of Giant Cell Tumor of Bone Following RANK Ligand Inhibition

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    Martin F. Dietrich MD, PhD

    2014-11-01

    Full Text Available Lung metastases are a rare complication of giant cell tumors of bone. We herein describe an interesting case of histological regression and size reduction of lung metastases originating from a primary giant cell tumor of bone in response to the RANK ligand inhibitor denosumab.

  15. Oncocytoma-Like Renal Tumor With Transformation Toward High-Grade Oncocytic Carcinoma

    Science.gov (United States)

    Sirintrapun, Sahussapont J.; Geisinger, Kim R.; Cimic, Adela; Snow, Anthony; Hagenkord, Jill; Monzon, Federico; Legendre, Benjamin L.; Ghazalpour, Anatole; Bender, Ryan P.; Gatalica, Zoran

    2014-01-01

    Abstract Renal oncocytoma is a benign tumor with characteristic histologic findings. We describe an oncocytoma-like renal tumor with progression to high-grade oncocytic carcinoma and metastasis. A 74-year-old man with no family history of cancer presented with hematuria. Computed tomography showed an 11 cm heterogeneous multilobulated mass in the right kidney lower pole, enlarged aortocaval lymph nodes, and multiple lung nodules. In the nephrectomy specimen, approximately one third of the renal tumor histologically showed regions classic for benign oncocytoma transitioning to regions of high-grade carcinoma without sharp demarcation. With extensive genomic investigation using single nucleotide polymorphism-based array virtual karyotyping, multiregion sequencing, and expression array analysis, we were able to show a common lineage between the benign oncocytoma and high-grade oncocytic carcinoma regions in the tumor. We were also able to show karyotypic differences underlying this progression. The benign oncocytoma showed no chromosomal aberrations, whereas the high-grade oncocytic carcinoma showed loss of the 17p region housing FLCN (folliculin [Birt–Hogg–Dubé protein]), loss of 8p, and gain of 8q. Gene expression patterns supported dysregulation and activation of phosphoinositide 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homolog (Akt), mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK), and mechanistic target of rapamycin (serine/threonine kinase) (mTOR) pathways in the high-grade oncocytic carcinoma regions. This was partly attributable to FLCN underexpression but further accentuated by overexpression of numerous genes on 8q. In the high-grade oncocytic carcinoma region, vascular endothelial growth factor A along with metalloproteinases matrix metallopeptidase 9 and matrix metallopeptidase 12 were overexpressed, facilitating angiogenesis and invasiveness. Genetic molecular testing provided evidence for the

  16. [Transrectal biopsy scheme can predict incorrect histological grading in prostate cancer].

    Science.gov (United States)

    Nieto-Morales, M L; Fernández-Ramos, J; Pérez-Méndez, L; Alventosa-Fernández, E; Pastor-Santoveña, M S; Aguirre-Jaime, A

    2014-01-01

    To identify factors that might explain why a prostate with a Gleason score (GS) <7 in the biopsy specimen can turn out to have a GS ≥7 in the surgical specimen. We compared the GS of biopsy specimens with the GS of surgical specimens in 185 patients who underwent surgery for prostate cancer. We calculated the sensitivity, specificity, and predictive values for the GS of the biopsy specimens. We used Cohen's kappa to determine the degree of concordance between a GS of <7 and ≥7 for the biopsy specimen and the surgical specimen. Age, a family history of prostate cancer, total prostate-specific antigen (tPSA), digital rectal examination, prostate structure and volume, and the number of biopsy cores (biopsy scheme) were analyzed using multivariable logistic regression. Histological study of biopsy specimens yielded high sensitivity (98%) but low specificity (49%) for GS ≤6 and low sensitivity (35, 26%) and high specificity (93, 99%) for GS=7 and GS ≥7, respectively. Cohen's kappa for the GS from the biopsy and surgical specimens was 0.43 (95% CI=30-56%). The biopsy scheme was the only predictor of discordance in the GS between the two techniques. Among the other variables included in the model, only tPSA showed a slightly significant association. Taking a scheme with less than 7 cores as a reference, we found no difference with 8 to 9 cores but we did find a difference with 10 to 11 cores and with 12 or more cores, with a prevalence ratio of 0.138 (95% CI=0.030-0.513) and 0.277 (95% CI=0.091-0.806), respectively. The GS of the biopsy depends on the scheme. This factor must be taken into account when choosing a treatment option in patients with low tumor grade in biopsy specimens. Copyright © 2011 SERAM. Published by Elsevier Espana. All rights reserved.

  17. A Grading System Combining Tumor Budding and Nuclear Diameter Predicts Prognosis in Resected Lung Squamous Cell Carcinoma.

    Science.gov (United States)

    Kadota, Kyuichi; Miyai, Yumi; Katsuki, Naomi; Kushida, Yoshio; Matsunaga, Toru; Okuda, Masaya; Yokomise, Hiroyasu; Kanaji, Nobuhiro; Bandoh, Shuji; Haba, Reiji

    2017-06-01

    For lung squamous cell carcinomas, there are no histologic findings that have been universally accepted as prognostic factors. Tumor budding and nuclear grade have been recognized as prognostic factors in other carcinomas. In this study, we investigated whether pathologic findings could determine clinical outcome in Japanese patients with lung squamous cell carcinomas. Tumor slides from surgically resected lung squamous cell carcinomas (1999 to 2012) were reviewed (n=216). Tumors were evaluated for histologic subtypes, differentiation, tumor budding, nuclear diameter, and mitosis. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the log-rank test and the Cox proportional hazards model. Tumor budding and large nuclei were independent prognostic factors of a worse RFS (P<0.001 and P=0.002, respectively) and a worse OS (P<0.001 and P=0.038, respectively) on multivariate analysis after adjustment for pathologic stage and lymphatic invasion. However, histologic subtypes, differentiation, and mitotic count did not correlate with prognosis. A grading system combining tumor budding and nuclear diameter was an independent prognostic factors of a worse RFS (grade 2 vs. 1, hazard ratio [HR]=2.91; P<0.001, and grade 3 vs. 1, HR=7.60, P<0.001) and a worse OS (grade 2 vs. 1, HR=2.15; P=0.014, and grade 3 vs. 1, HR=4.54, P<0.001). We found that a grading system combining tumor budding and nuclear diameter was a significant prognostic factor among Japanese patients with resected lung squamous cell carcinoma.

  18. The impact of stage, grade, and mucinous histology on the efficacy of systemic chemotherapy in adenocarcinomas of the appendix: Analysis of the National Cancer Data Base.

    Science.gov (United States)

    Asare, Elliot A; Compton, Carolyn C; Hanna, Nader N; Kosinski, Lauren A; Washington, Mary Kay; Kakar, Sanjay; Weiser, Martin R; Overman, Michael J

    2016-01-15

    Adenocarcinomas of the appendix represent a heterogeneous disease depending on the presence of mucinous histology, histologic grade, and stage. In the current study, the authors sought to explore the interplay of these factors with systemic chemotherapy in a large population data set. Patients in the National Cancer Data Base (NCDB) who were diagnosed with mucinous, nonmucinous, and signet ring cell-type appendiceal neoplasms from 1985 through 2006 were selected. Multivariable Cox proportional hazards regression models were developed. A total of 11,871 patients met the inclusion criteria for the current study: 50.3% had mucinous neoplasms, 40.5% had nonmucinous neoplasms, and 9.2% had signet ring cell-type neoplasms. The 5-year overall survival (OS) stratified by grade was similar among patients with American Joint Committee on Cancer stage I to stage III disease but not for those with stage IV disease. The median OS for patients with stage IV mucinous and nonmucinous tumors was 6.4 years and 2.3 years, respectively, for those with well differentiated histology (P<.0001) and was 1.5 years and 0.8 years, respectively, for those with poorly differentiated histology (P<.0001). In multivariable modeling for stage I to III disease, adjuvant chemotherapy improved OS for both mucinous and nonmucinous histologies, with hazard ratios (HRs) of 0.78 (95% confidence interval [95% CI], 0.68-0.89 [P = .0002]) and 0.83 (95% CI, 0.74-0.94 [P = .002]), respectively. For patients with stage IV disease, systemic chemotherapy significantly improved OS for those with nonmucinous (HR, 0.72; 95% CI, 0.64-0.82 [P<.0001]) but not mucinous (HR, 0.95; 95% CI, 0.86-1.04 [P = .2) histologies, although this was grade-dependent. The median OS for chemotherapy versus no chemotherapy was 6.4 years versus 6.5 years (P value not significant) for patients with mucinous, well-differentiated tumors and 1.6 years versus 1.0 years (P = .0007) for patients with mucinous, poorly

  19. Value of normalized apparent diffusion coefficient for estimating histological grade of vesical urothelial carcinoma.

    Science.gov (United States)

    Wang, H J; Pui, M H; Guo, Y; Li, S R; Liu, M J; Guan, J; Zhang, X L; Feng, Y

    2014-07-01

    To compare the efficacy of apparent diffusion coefficient (ADC) and normalized ADC (nADC) for estimating the histological grade of vesical urothelial carcinoma and to identify an optimal reference for nADC calculation. Thirty patients with histologically confirmed vesical urothelial carcinomas underwent preoperative diffusion-weighted magnetic resonance imaging (DW-MRI) of the pelvis. nADC of the tumour was calculated as ADC (tumour)/ADC (reference) using urine in the bladder lumen, and the obturator internus and gluteus maximus muscles as reference. Receiver operating characteristic (ROC) curves were constructed and compared to identify an optimal reference for nADC calculation. Both ADC and nADC of low-grade tumours (1.112 ± 0.159 × 10(-3) mm(2)/s, 0.403 ± 0.047 × 10(-3) mm(2)/s) were significantly (p obturator internus (0.960) and gluteus maximus (0.945). nADC is superior to ADC for estimating the histological grade of bladder carcinoma using urine in the bladder lumen as an optimal reference for nADC calculation. Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  20. Tumor grade-related NDRG2 gene expression in primary and recurrent intracranial meningiomas.

    Science.gov (United States)

    Skiriute, Daina; Tamasauskas, Sarunas; Asmoniene, Virginija; Saferis, Viktoras; Skauminas, Kestutis; Deltuva, Vytenis; Tamasauskas, Arimantas

    2011-03-01

    Approximately 30% of all primary CNS tumors are meningiomas. Depending on histological type, meningiomas can recur as follows: benign--with five-year recurrence of 5%, atypical--recurrence approximately 40%, and anaplastic with recurrence of 50-80%. In an attempt to understand the molecular mechanism of meningioma recurrence we investigated the N-Myc downstream-regulated gene 2 (NDRG2), which has recently been described as important in suppressing cellular carcinogenesis in different types of cancer. The objective of the study was to investigate NDRG2 gene expression at the mRNA level in primary and recurrent meningiomas as a potential marker of tumor aggressiveness, malignancy, and recurrence. Primary and recurrent meningiomas of WHO grades I, II, and III from 35 patients operated on between 2005 and 2008 year at the Department of Neurosurgery of Kaunas Medical University Hospital (Lithuania) were studied. Using the qRT-PCR method we measured NDRG2 gene expression at the mRNA level in primary (n = 24) and recurrent (n = 11) meningiomas. Statistically significant differences in NDRG2 gene expression level were observed between primary and recurrent meningioma groups (P grade I) and atypical (WHO grade II) meningiomas (P 0.05) among histological subtypes of benign (WHO grade I) meningiomas: fibrous, meningothelial, and transitional. In accordance with our results, reduction of NDRG2 gene expression at the mRNA level could help to explain malignant progression and predisposition to recurrence in meningiomas.

  1. The new histologic classification of lung primary adenocarcinoma subtypes is a reliable prognostic marker and identifies tumors with different mutation status: the experience of a French cohort.

    Science.gov (United States)

    Mansuet-Lupo, Audrey; Bobbio, Antonio; Blons, Hélène; Becht, Etienne; Ouakrim, Hanane; Didelot, Audrey; Charpentier, Marie-Christine; Bain, Serge; Marmey, Béatrice; Bonjour, Patricia; Biton, Jérôme; Cremer, Isabelle; Dieu-Nosjean, Marie-Caroline; Sautès-Fridman, Catherine; Régnard, Jean-François; Laurent-Puig, Pierre; Alifano, Marco; Damotte, Diane

    2014-09-01

    Histologic classification of lung adenocarcinoma subtype has a prognostic value in most studies. However, lung adenocarcinoma characteristics differ across countries. Here, we aimed at validating the prognostic value of this classification in a large French series of lung adenocarcinoma. We reviewed 407 consecutive lung adenocarcinomas operated on between 2001 and 2005 and reclassified them according to the International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification and subsequently graded them into low, intermediate, and high grade. We analyzed the relevance of this classification according to clinical, pathologic, and molecular analysis. Patients (median age, 61 years; 288 men) underwent lobectomy (n = 378) or pneumonectomy (n = 29). Patients' overall survival at 5 and 10 years was 53.2% and 32.6%, respectively. Union for International Cancer Control stage distribution was 189 stage I, 104 stage II, 107 stage III, and seven stage IV. Low-grade tumor was found in one patient, intermediate grade in 275 patients, and high grade in 131 patients. KRAS and EGFR mutations were detected in 34% and 9.6%, respectively. Histologic grade was significantly correlated with extent of resection (P = .01), thyroid transcriptional factor-1 expression (P = .00000001), vascular emboli (P = .03), and EGFR mutations (P = .01). Mucinous adenocarcinomas were associated with KRAS mutations (P = .003). At univariate analysis, age, extent of resection, histologic grade, pleural invasion, vascular emboli, pathologic T and N, and stage were predictive of survival. At multivariate analysis, age (P = .0001), histologic grade (P = .03), and stage (P = .000003) were independent prognostic factors. IASLC/ATS/ERS classification of lung adenocarcinomas predicts survival in French population. Histologic grade correlates with clinical, pathologic and molecular parameters suggesting different oncogenic pathways.

  2. Textural analysis of pre-therapeutic [18F]-FET-PET and its correlation with tumor grade and patient survival in high-grade gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Pyka, Thomas; Hiob, Daniela; Wester, Hans-Juergen [Klinikum Rechts der Isar der TU Muenchen, Department of Nuclear Medicine, Munich (Germany); Gempt, Jens; Ringel, Florian; Meyer, Bernhard [Klinikum Rechts der Isar der TU Muenchen, Neurosurgic Department, Munich (Germany); Schlegel, Juergen [Klinikum Rechts der Isar der TU Muenchen, Institute of Pathology and Neuropathology, Munich (Germany); Bette, Stefanie [Klinikum Rechts der Isar der TU Muenchen, Neuroradiologic department, Munich (Germany); Foerster, Stefan [Klinikum Rechts der Isar der TU Muenchen, Department of Nuclear Medicine, Munich (Germany); Klinikum Rechts der Isar der TU Muenchen, TUM Neuroimaging Center (TUM-NIC), Munich (Germany)

    2016-01-15

    Amino acid positron emission tomography (PET) with [18F]-fluoroethyl-L-tyrosine (FET) is well established in the diagnostic work-up of malignant brain tumors. Analysis of FET-PET data using tumor-to-background ratios (TBR) has been shown to be highly valuable for the detection of viable hypermetabolic brain tumor tissue; however, it has not proven equally useful for tumor grading. Recently, textural features in 18-fluorodeoxyglucose-PET have been proposed as a method to quantify the heterogeneity of glucose metabolism in a variety of tumor entities. Herein we evaluate whether textural FET-PET features are of utility for grading and prognostication in patients with high-grade gliomas. One hundred thirteen patients (70 men, 43 women) with histologically proven high-grade gliomas were included in this retrospective study. All patients received static FET-PET scans prior to first-line therapy. TBR (max and mean), volumetric parameters and textural parameters based on gray-level neighborhood difference matrices were derived from static FET-PET images. Receiver operating characteristic (ROC) and discriminant function analyses were used to assess the value for tumor grading. Kaplan-Meier curves and univariate and multivariate Cox regression were employed for analysis of progression-free and overall survival. All FET-PET textural parameters showed the ability to differentiate between World Health Organization (WHO) grade III and IV tumors (p < 0.001; AUC 0.775). Further improvement in discriminatory power was possible through a combination of texture and metabolic tumor volume, classifying 85 % of tumors correctly (AUC 0.830). TBR and volumetric parameters alone were correlated with tumor grade, but showed lower AUC values (0.644 and 0.710, respectively). Furthermore, a correlation of FET-PET texture but not TBR was shown with patient PFS and OS, proving significant in multivariate analysis as well. Volumetric parameters were predictive for OS, but this correlation did not

  3. Comparison of histological grading and large-scale genomic status (DNA ploidy) as prognostic tools in oral dysplasia.

    Science.gov (United States)

    Sudbø, J; Bryne, M; Johannessen, A C; Kildal, W; Danielsen, H E; Reith, A

    2001-07-01

    Approximately one in ten oral white patches (leukoplakia) are histologically classified as dysplasia, with a well-documented potential for developing into oral squamous cell carcinoma (OSCC). Histological grading in oral dysplasia has limited prognostic value, whereas large-scale genomic status (DNA ploidy, nuclear DNA content) is an early marker of malignant transformation in several tissues. Biopsies from 196 patients with oral leukoplakia histologically typed as dysplasia were investigated. Inter-observer agreement among four experienced pathologists performing a simplified grading was assessed by Cohen's kappa values. For 150 of the 196 cases, it was also possible to assess large-scale genomic status and compare its prognostic impact with that of histological grading. Disease-free survival was estimated by life-table methods, with a mean follow-up time of 103 months (range 4-165 months). The primary considered end-point was the subsequent occurrence of OSCC. For grading of the total of 196 cases, kappa values ranged from 0.17 to 0.33 when three grading groups (mild, moderate, and severe dysplasia) were considered, and from 0.21 to 0.32 when two groups (low grade and high grade) were considered (p=0.41). For the 150 cases in which large-scale genomic status was also assessed, kappa values for the histological grading ranged from 0.21 to 0.33 for three grading groups and from 0.27 to 0.34 for two grading groups (p=0.47). In survival analysis, histological grading was without significant prognostic value for any of the four observers (p 0.14-0.44), in contrast to DNA ploidy (p=0.001). It is concluded that DNA ploidy in oral dysplasia has a practical prognostic value, unlike histological grading of the same lesions. Copyright 2001 John Wiley & Sons, Ltd.

  4. Quantitative free-breathing dynamic contrast-enhanced MRI in hepatocellular carcinoma using gadoxetic acid: correlations with Ki67 proliferation status, histological grades, and microvascular density.

    Science.gov (United States)

    Chen, Jie; Chen, Chenyang; Xia, Chunchao; Huang, Zixing; Zuo, Panli; Stemmer, Alto; Song, Bin

    2017-09-22

    To validate a free-breathing dynamic contrast-enhanced-MRI (DCE-MRI) in hepatocellular carcinoma (HCC) patients using gadoxetic acid, and to determine the relationship between DCE-MRI parameters and histological results. Thirty-four HCC patients were included in this prospective study. Free-breathing DCE-MRI data was acquired preoperatively on a 3.0 Tesla scanner. Perfusion parameters (K (trans), K ep, V e and the semi-quantitative parameter of initial area under the gadolinium concentration-time curve, iAUC) were calculated and compared with tumor enhancement at contrast-enhanced CT. The relationship between DCE-MRI parameters and Ki67 indices, histological grades and microvascular density (MVD) was determined by correlation analysis. Differences of perfusion parameters between different histopathological groups were compared. Receiver operation characteristic (ROC) analysis of discriminating high-grades (grade III and IV) from low-grades (grade I and II) HCC was performed for perfusion parameters. Significant relationship was found between DCE-MRI and CT results. The DCE-MRI derived K (trans) were significantly negatively correlated with Ki-67 indices (rho = - 0.408, P = 0.017) and the histological grades (rho = - 0.444, P = 0.009) of HCC, and K ep and V e were significantly related with tumor MVD (rho = - 0.405, P = 0.017 for K ep; and rho = 0.385, P = 0.024 for V e). K (trans), K ep, and iAUC demonstrated moderate diagnostic performance (iAUC = 0.78, 0.77 and 0.80, respectively) for discriminating high-grades from low-grades HCC without significant differences. The DCE-MRI derived parameters demonstrated weak but significant correlations with tumor proliferation status, histological grades or microvascular density, respectively. This free-breathing DCE-MRI is technically feasible and offers a potential avenue toward non-invasive evaluation of HCC malignancy.

  5. Anechoic halo in solid liver tumors: sonographic, microangiographic, and histologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Marchal, G.J.; Pylyser, K.; Tshibwabwa-Tumba, E.A.; Verbeken, E.K.; Oyen, R.H.; Baert, A.L.; Lauweryns, J.M.

    1985-08-01

    The origin of the sonographic halo sign in liver metastases was studied after autopsy in 33 livers with macroscopic tumoral involvement. For 20 lesions a detailed comparison of findings from high-resolution 7.5- and 10-MHz sonography, microangiography, and histology was carried out. Histologic study focused on the tumor periphery and its relationship to the adjacent liver parenchyma. In particular, the type of tumor infiltration, the presence or absence of peritumoral fibrosis, and the degree of liver cell compression were assessed. In all but two cases the halo was extratumoral and was caused by peritumoral liver cell compression. In the remaining two cases the halo was tumoral and was caused by irregular fibrosis or vascularization.

  6. Diffusion Kurtosis Imaging of Gliomas Grades II and III - A Study of Perilesional Tumor Infiltration, Tumor Grades and Subtypes at Clinical Presentation.

    Science.gov (United States)

    Delgado, Anna F; Fahlström, Markus; Nilsson, Markus; Berntsson, Shala G; Zetterling, Maria; Libard, Sylwia; Alafuzoff, Irina; van Westen, Danielle; Lätt, Jimmy; Smits, Anja; Larsson, Elna-Marie

    2017-06-01

    Diffusion kurtosis imaging (DKI) allows for assessment of diffusion influenced by microcellular structures. We analyzed DKI in suspected low-grade gliomas prior to histopathological diagnosis. The aim was to investigate if diffusion parameters in the perilesional normal-appearing white matter (NAWM) differed from contralesional white matter, and to investigate differences between glioma malignancy grades II and III and glioma subtypes (astrocytomas and oligodendrogliomas). Forty-eight patients with suspected low-grade glioma were prospectively recruited to this institutional review board-approved study and investigated with preoperative DKI at 3T after written informed consent. Patients with histologically proven glioma grades II or III were further analyzed (n=35). Regions of interest (ROIs) were delineated on T2FLAIR images and co-registered to diffusion MRI parameter maps. Mean DKI data were compared between perilesional and contralesional NAWM (student's t-test for dependent samples, Wilcoxon matched pairs test). Histogram DKI data were compared between glioma types and glioma grades (multiple comparisons of mean ranks for all groups). The discriminating potential for DKI in assessing glioma type and grade was assessed with receiver operating characteristics (ROC) curves. There were significant differences in all mean DKI variables between perilesional and contralesional NAWM (p=grades II (n=23) and III (n=12) (p=0.003-0.048) and 10 variables differed significantly between ACs (n=18) and ODs (n=17) (p=0.011-0.050). ROC curves of the best discriminating variables had an area under the curve (AUC) of 0.657-0.815. Mean DKI variables in perilesional NAWM differ significantly from contralesional NAWM, suggesting altered microstructure by tumor infiltration not depicted on morphological MRI. Histogram analysis of DKI data identifies differences between glioma grades and subtypes.

  7. Low enhancement on multiphase contrast-enhanced CT images: an independent predictor of the presence of high tumor grade of clear cell renal cell carcinoma.

    Science.gov (United States)

    Zhu, Ye-Hua; Wang, Xun; Zhang, Jin; Chen, Yong-Hui; Kong, Wen; Huang, Yi-Ran

    2014-09-01

    The purpose of this study was to assess the relation between tumor enhancement on multiphase contrast-enhanced CT images and Fuhrman grade of clear cell renal cell carcinoma. A single-institution retrospective review was conducted on the records of 255 patients who underwent radical or partial nephrectomy and received a histologic diagnosis of clear cell renal cell carcinoma. Two radiologists recorded the radiographic features of each patient, including the attenuation value of the lesion, lesion size, calcification within the lesion, cystic versus solid appearance, and margin regularity. Parameters representing the extent of tumor enhancement were defined and calculated. The association between tumor enhancement and Fuhrman grade was analyzed, and multivariate analysis was performed to find independent predictors of high tumor grade. Significant differences existed in tumor enhancement among different Fuhrman grades (p enhancement (p enhancement parameter had a sensitivity of 0.84 and specificity of 0.93 in prediction of high tumor grade. In the multivariate analysis, more advanced age, irregular margin, and low tumor enhancement were the three independent predictors of high tumor grade. Tumor enhancement of clear cell renal cell carcinoma on multiphase contrast-enhanced CT images is associated with Fuhrman grade. Low tumor enhancement in the corticomedullary phase is an independent predictor of high tumor grade. This system may be helpful in clinical decision making about the care of patients treated by nonsurgical approaches.

  8. Pediatric High Grade Glioma (HGG: a Review and Update on Tumor Clinical Characteristics and Biology

    Directory of Open Access Journals (Sweden)

    Jason eFangusaro

    2012-08-01

    Full Text Available High grade gliomas (HGG are one of the most common central nervous system (CNS tumors encountered in adults, but they only represent approximately 8-12% of all pediatric CNS tumors. Historically, pediatric HGG were thought similar to adult HGG since they appear histologically identical; however, molecular, genetic, and biologic data reveal that they are distinct. Similar to adults, pediatric HGG are very aggressive and malignant lesions with few patients achieving long-term survival despite a variety of therapies. Initial treatment strategies typically consist of a gross total resection (GTR when feasible followed by focal radiotherapy combined with chemotherapy. Over the last few decades, a wealth of data has emerged from basic science and pre-clinical animal models helping to better define the common biologic, genetic and molecular make-up of these tumors. These data have not only provided a better understanding of tumor biology, but they have also provided new areas of research targeting molecular and genetic pathways with the potential for novel treatment strategies and improved patient outcomes. Here we provide a review of pediatric non-brainstem HGG, including epidemiology, presentation, histology, imaging characteristics, treatments, survival outcomes and an overview of both basic and translational research. An understanding of all relevant pre-clinical tumor models, including their strengths and pitfalls is essential in realizing improved patient outcomes in this population.

  9. Distinct Patterns of Stromal and Tumor Expression of ROR1 and ROR2 in Histological Subtypes of Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    C.E. Henry

    2017-06-01

    Full Text Available OBJECTIVE: The ROR1 and ROR2 receptor tyrosine kinases have both been implicated in ovarian cancer progression and have been shown to drive migration and invasion. There is an increasing importance of the role of stroma in ovarian cancer metastasis; however, neither ROR1 nor ROR2 expression in tumor or stromal cells has been analyzed in the same clinical cohort. AIM: To determine ROR1 and ROR2 expression in ovarian cancer and surrounding microenvironment and examine associations with clinicopathological characteristics. METHODS: Immunohistochemistry for ROR1 and ROR2 was used to assess receptor expression in a cohort of epithelial ovarian cancer patients (n = 178. Results were analyzed in relation to clinical and histopathological characteristics and survival. Matched patient sample case studies of normal, primary, and metastatic lesions were used to examine ROR expression in relation to ovarian cancer progression. RESULTS: ROR1 and ROR2 are abnormally expressed in malignant ovarian epithelium and stroma. Higher ROR2 tumor expression was found in early-stage, low-grade endometrioid carcinomas. ROR2 stromal expression was highest in the serous subtype. In matched patient case studies, metastatic samples had higher expression of ROR2 in the stroma, and a recurrent sample had the highest expression of ROR2 in both tumor and stroma. CONCLUSION: ROR1 and ROR2 are expressed in tumor-associated stroma in all histological subtypes of ovarian cancer and hold potential as therapeutic targets which may disrupt tumor and stroma interactions.

  10. Distinct Patterns of Stromal and Tumor Expression of ROR1 and ROR2 in Histological Subtypes of Epithelial Ovarian Cancer.

    Science.gov (United States)

    Henry, C E; Emmanuel, C; Lambie, N; Loo, C; Kan, B; Kennedy, C J; de Fazio, A; Hacker, N F; Ford, C E

    2017-06-01

    The ROR1 and ROR2 receptor tyrosine kinases have both been implicated in ovarian cancer progression and have been shown to drive migration and invasion. There is an increasing importance of the role of stroma in ovarian cancer metastasis; however, neither ROR1 nor ROR2 expression in tumor or stromal cells has been analyzed in the same clinical cohort. To determine ROR1 and ROR2 expression in ovarian cancer and surrounding microenvironment and examine associations with clinicopathological characteristics. Immunohistochemistry for ROR1 and ROR2 was used to assess receptor expression in a cohort of epithelial ovarian cancer patients (n=178). Results were analyzed in relation to clinical and histopathological characteristics and survival. Matched patient sample case studies of normal, primary, and metastatic lesions were used to examine ROR expression in relation to ovarian cancer progression. ROR1 and ROR2 are abnormally expressed in malignant ovarian epithelium and stroma. Higher ROR2 tumor expression was found in early-stage, low-grade endometrioid carcinomas. ROR2 stromal expression was highest in the serous subtype. In matched patient case studies, metastatic samples had higher expression of ROR2 in the stroma, and a recurrent sample had the highest expression of ROR2 in both tumor and stroma. ROR1 and ROR2 are expressed in tumor-associated stroma in all histological subtypes of ovarian cancer and hold potential as therapeutic targets which may disrupt tumor and stroma interactions. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Grading in soft tissue tumors: principles and problems

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, A.M.; Nascimento, A.G. [Div. of Anatomic Pathology, Mayo Clinic, Rochester, MN (United States)

    2001-10-01

    Histologic grading has been considered the most important prognostic factor for soft tissue sarcomas. Several grading systems have been proposed based on the assessment of morphologic features in heterogeneous groups of sarcomas. Currently, the French Federation of Cancer Centers (FNCLCC) and the National Cancer Institute (NCI) grading systems are the most commonly used. These systems are based on a few morphologic predictors of biologic behavior, which is justifiable because of the rarity of soft tissue sarcomas. Nonetheless, over- or underestimation of prognosis may occur because of an uneven representation of specific sarcomas with rather distinct biologic behaviors among studies of grading systems. In addition, lack of standardization of morphologic criteria and frequent omission of the influence of clinical factors on the final survival analyses preclude universal acceptance of a particular grading system. New advances in diagnostic imaging, quantitative morphometric technologies, cytogenetics, and molecular genetics, allied with alternative analytic data systems, may provide better validation, reproducibility, and prognostic capabilities for current and future grading systems. This article summarizes and critically analyzes the various important grading systems that have thus far been proposed and suggests alternatives for the elaboration of more reproducible systems with higher predictive capabilities. (orig.)

  12. Inherited variant on chromosome 11q23 increases susceptibility to IDH-mutated but not IDH-normal gliomas regardless of grade or histology.

    Science.gov (United States)

    Rice, Terri; Zheng, Shichun; Decker, Paul A; Walsh, Kyle M; Bracci, Paige; Xiao, Yuanyuan; McCoy, Lucie S; Smirnov, Ivan; Patoka, Joseph S; Hansen, Helen M; Hsuang, George; Wiemels, Joe L; Tihan, Tarik; Pico, Alexander R; Prados, Michael D; Chang, Susan M; Berger, Mitchel S; Caron, Alissa; Fink, Stephanie; Kollmeyer, Thomas; Rynearson, Amanda; Voss, Jesse; Kosel, Matthew L; Fridley, Brooke L; Lachance, Daniel H; Eckel-Passow, Jeanette E; Sicotte, Hugues; O'Neill, Brian Patrick; Giannini, Caterina; Wiencke, John K; Jenkins, Robert B; Wrensch, Margaret R

    2013-05-01

    Recent discoveries of inherited glioma risk loci and acquired IDH mutations are providing new insights into glioma etiology. IDH mutations are common in lower grade gliomas and secondary glioblastomas and uncommon in primary glioblastomas. Because the inherited variant in 11q23 has been associated with risk of lower grade glioma and not with glioblastomas, we hypothesized that this variant increases susceptibility to IDH-mutated gliomas, but not to IDH-wild-type gliomas. We tested this hypothesis in patients with glioma and controls from the San Francisco Adult Glioma Study, the Mayo Clinic, and Illumina controls (1102 total patients, 5299 total controls). Case-control additive associations of 11q23 risk alleles (rs498872, T allele) were calculated using logistic regression, stratified by tumor IDH status (mutated or wild-type) and by histology and grade. We also adjusted for the recently discovered 8q24 glioma risk locus rs55705857 G allele. The 11q23 glioma risk locus was associated with increased risk of IDH-mutated gliomas of all histologies and grades (odds ratio [OR] = 1.50; 95% confidence interval [CI] = 1.29-1.74; P = 1.3X10(-7)) but not with IDH-wild-type gliomas of any histology or grade (OR = 0.91; 95% CI = 0.81-1.03; P = 0.14). The associations were independent of the rs55705857 G allele. A variant at the 11q23 locus increases risk for IDH-mutated but not IDH-wild-type gliomas, regardless of grade or histology.

  13. Analysis of interobserver reproducibility in grading histological patterns of dysplastic nevi*

    Science.gov (United States)

    Nobre, Aretha Brito; Piñeiro-Maceira, Juan; Raggio Luiz, Ronir

    2013-01-01

    BACKGROUND Dysplastic nevi are among the most important cutaneous melanoma simulators. They are important risk markers for this neoplasia and can be its potential precursors. Some authors found a statistically significant relationship between the degree of dysplasia and the risk for developing melanoma. However, reproducibility of grading criteria ranged from poor to fair in the researched articles. OBJECTIVE To test the reproducibility of the grading criteria proposed by Sagebiel et al. regarding dysplastic nevi. METHODS Histological specimens of 75 dysplastic nevi were graded, independently and in a blinded fashion, according to preestablished criteria, by a panel of 10 pathologists with different levels of experience. Diagnostic agreement was calculated using weighted kappa and intraclass correlation coefficients. RESULTS The average of weighted kappa values was 0.13 for all observers, 0.12 for dermatopathologists, 0.18 for general pathologists and 0.05 for residents. Intraclass correlation coefficient values were 0.2 for all observers, 0.18 for dermatopathologists, 0.33 for general pathologists and 0.15 for residents. CONCLUSIONS: Histopathological grading for dysplastic nevi was not reproducible in this Brazilian series, so the criteria used are not a helpful histopathological parameter for clinicopathological correlation. PMID:23539000

  14. Non-Gaussian diffusion MR imaging of glioma: comparisons of multiple diffusion parameters and correlation with histologic grade and MIB-1 (Ki-67 labeling) index

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Ren; Haopeng, Pang; Xiaoyuan, Feng; Jiawen, Zhang; Zhenwei, Yao [Fudan University, Department of Radiology, Huashan Hospital, Shanghai (China); Jinsong, Wu; Chengjun, Yao; Tianming, Qiu [Fudan University, Department of Neurosurgery, Huashan Hospital, Shanghai (China); Ji, Xiong [Fudan University, Department of Neuropathology, Huashan Hospital, Shanghai (China); Mao, Sheng; Yueyue, Ding [Department of Imaging, Suzhou Children' s Hospital, Suzhou, Jiangsu (China); Yong, Zhang [MR Research, GE Healthcare, Shanghai (China); Jianfeng, Luo [Fudan University, Department of Biostatistics, Public Health School, Shanghai (China)

    2016-02-15

    This study was conducted to compare the association of Gaussian and non-Gaussian magnetic resonance imaging (MRI)-derived parameters with histologic grade and MIB-1 (Ki-67 labeling) index (MI) in brain glioma. Sixty-five patients with pathologically confirmed glioma, who underwent diffusion-weighted MRI with 2 b values (0, 1000 s/mm{sup 2}) and 22 b values (≤5000 s/mm{sup 2}), respectively, were divided into three groups of grade II (n = 35), grade III (n = 8), and grade IV (n = 22). Comparisons by two groups were made for apparent diffusion coefficient (ADC), slow diffusion coefficient (Dslow), distributed diffusion coefficient (DDC), and heterogeneity index α. Analyses of receiver operating characteristic (ROC) curve were performed to maximize the area under the curve (AUC) for differentiating grade III + IV (high-grade glioma, HGG) from grade II (low-grade glioma, LGG) and grade IV (glioblastoma multiforme, GBM) from grade II + III (other grade glioma, OGG). Correlations with MI were analyzed for the MRI parameters. On tumor regions, the values of ADC, Dslow, DDC, and α were significantly higher in grade II [(1.37 ± 0.29, 0.70 ± 0.11, 1.39 ± 0.34) (x 10{sup -3} mm{sup 2}/s) and 0.88 ± 0.05, respectively] than in grade III [(0.99 ± 0.13, 0.55 ± 0.07, 1.04 ± 0.20) (x 10{sup -3} mm{sup 2}/s) and 0.80 ± 0.03, respectively] and grade IV [(1.03 ± 0.14, 0.50 ± 0.05, 1.02 ± 0.16) (x 10{sup -3} mm{sup 2}/s) and 0.76 ± 0.04, respectively] (all P < 0.001). The parameter α showed the highest AUCs of 0.950 and 0.922 in discriminating HGG from LGG and GBM from OGG, respectively. Significant correlations with histologic grade and MI were observed for the MRI parameters. The non-Gaussian MRI-derived parameters α and Dslow are superior to ADC in glioma grading, which are comparable with ADC as reliable biomarkers in noninvasively predicting the proliferation level of glioma malignancy. (orig.)

  15. Volume-Based F-18 FDG PET/CT Imaging Markers Provide Supplemental Prognostic Information to Histologic Grading in Patients With High-Grade Bone or Soft Tissue Sarcoma

    DEFF Research Database (Denmark)

    Andersen, Kim Francis; Fuglo, Hanna Maria; Rasmussen, Sine Hvid

    2015-01-01

    to 2012 including 92 patients with histologically verified high-grade BS (N = 37) or STS (N = 55). All patients underwent a pretreatment F-18 FDG PET/CT scan. Clinical data were registered. Measurements of the accuracy of metabolic tumor volume with a preset threshold of 40% of the maximum standardized...... analysis. Kaplan-Meier survival estimates and log-rank test were used to compare the degree of equality of survival distributions. Prognostic variables with related hazard ratios (HR) were assessed using Cox proportional hazards regression analysis.Forty-one of 92 patients died during follow-up (45%; 12 BS.......05, HR 3.37 [95% CI 1.02-11.11]). No significant results were demonstrated for MTV40%.Volume-based F-18 FDG PET/CT imaging markers in terms of pretreatment estimation of TLG provide supplemental prognostic information to histologic grading, with significant independent properties for prediction...

  16. Aerobic Glycolysis as a Marker of Tumor Aggressiveness: Preliminary Data in High Grade Human Brain Tumors

    Directory of Open Access Journals (Sweden)

    Andrei G. Vlassenko

    2015-01-01

    Full Text Available Objectives. Glucose metabolism outside of oxidative phosphorylation, or aerobic glycolysis (AG, is a hallmark of active cancer cells that is not directly measured with standard 18F-fluorodeoxyglucose (FDG positron emission tomography (PET. In this study, we characterized tumor regions with elevated AG defined based on PET measurements of glucose and oxygen metabolism. Methods. Fourteen individuals with high-grade brain tumors underwent structural MR scans and PET measurements of cerebral blood flow (CBF, oxygen (CMRO2 and glucose (CMRGlu metabolism, and AG, using 15O-labeled CO, O2 and H2O, and FDG, and were compared to a normative cohort of 20 age-matched individuals. Results. Elevated AG was observed in most high-grade brain tumors and it was associated with decreased CMRO2 and CBF, but not with significant changes in CMRGlu. Elevated AG was a dramatic and early sign of tumor growth associated with decreased survival. AG changes associated with tumor growth were differentiated from the effects of nonneoplastic processes such as epileptic seizures. Conclusions. Our findings demonstrate that high-grade brain tumors exhibit elevated AG as a marker of tumor growth and aggressiveness. AG may detect areas of active tumor growth that are not evident on conventional FDG PET.

  17. Global incidence of malignant brain and other central nervous system tumors by histology, 2003-2007.

    Science.gov (United States)

    Leece, Rebecca; Xu, Jordan; Ostrom, Quinn T; Chen, Yanwen; Kruchko, Carol; Barnholtz-Sloan, Jill S

    2017-10-19

    Previous reports have shown that overall incidence of malignant brain and other central nervous system (CNS) tumors varied significantly by country. The aim of this study was to estimate histology-specific incidence rates by global region and assess incidence variation by histology and age. Using data from the Central Brain Tumor Registry of the United States (CBTRUS) and the International Agency for Research on Cancer's (IARC) Cancer Incidence in Five Continents X (including over 300 cancer registries), we calculated the age-adjusted incidence rates (AAIR) per 100000 person-years and 95% CIs for brain and other CNS tumors overall and by age groups and histology. There were significant differences in incidence by region. Overall incidence of malignant brain tumors per 100000 person-years in the US was 5.74 (95% CI = 5.71-5.78). Incidence was lowest in Southeast Asia (AAIR = 2.55, 95% CI = 2.44-2.66), India (AAIR = 2.85, 95% CI = 2.78-2.93), and East Asia (AAIR = 3.07, 95% CI = 3.02-3.12). Incidence was highest in Northern Europe (AAIR = 6.59, 95% CI = 6.52-6.66) and Canada (AAIR = 6.53, 95% CI = 6.41-6.66). Astrocytic tumors showed the broadest variation in incidence regionally across the globe. Brain and other CNS tumors are a significant source of cancer-related morbidity and mortality worldwide. Regional differences in incidence may provide clues toward genetic or environmental causes as well as a foundation for broadening knowledge of their epidemiology. Gaining a comprehensive understanding of the epidemiology of malignant brain tumors globally is critical to researchers, public health officials, disease interest groups, and clinicians and contributes to collaborative efforts in future research.

  18. Differential gene expression in tumor adjacent histologically normal prostatic tissue indicates field cancerization.

    Science.gov (United States)

    Haaland, C M; Heaphy, C M; Butler, K S; Fischer, E G; Griffith, J K; Bisoffi, M

    2009-09-01

    Field cancerization denotes the occurrence of aberrant cells in tumor adjacent histologically normal tissues (TAHN). To characterize field cancerization in prostate cancer, we used RNA from paired patient tumor and TAHN tissues excised at 1 cm from the tumor margin and subjected them to microarray expression analysis comparative to RNA from normal cancer-free prostatic tissues. Eleven novel transcripts were significantly up-regulated in TAHN tissues and also in tumors. Expression of early growth response protein 1, tristetraprolin, testican, and fatty acid synthase, mutually up-regulated at different levels in tumors and TAHN tissues was confirmed by quantitative reverse transcriptase PCR in the experimental and in an independent validation set. This study offers proof of expressional changes in field cancerized prostatic TAHN tissues at defined distances from tumor margins. Markers of field cancerized prostatic tissues could be early diagnostic indicators in biopsies after abnormal prostate-specific antigen and digital rectal examination and independent of cancerous histology and/or early targets for chemo-preventive intervention in pre-malignant disease.

  19. Grade Increases in Gastroenteropancreatic Neuroendocrine Tumor Metastases Compared to the Primary Tumor.

    Science.gov (United States)

    Grillo, Federica; Albertelli, Manuela; Brisigotti, Maria Pia; Borra, Tiziana; Boschetti, Mara; Fiocca, Roberto; Ferone, Diego; Mastracci, Luca

    2016-01-01

    The neuroendocrine tumor (NET) proliferation-based grading system (ENETS/WHO) for gastroenteropancreatic (GEP) tumors has proved reliable for prognostic stratification. To date, concerns exist regarding Ki-67 heterogeneity within the tumor and little is known on whether grade varies between primary and secondary sites. As tumor heterogeneity may have a significant impact on clinical management, our aim was to retrospectively evaluate Ki-67 on a series of GEP NETs in order to establish whether there is variability in different samples of the same lesion or between primary and metastatic disease (local/distant, synchronous/metachronous). Sixty patients with multiple samples of tumor were accrued from a total of 338 GEP NETs; 44 of them also had tissue from local/distant metastases and a further 5 had multiple metastatic foci from unknown primary tumors. Immunohistochemistry for Ki-67 was performed on all paraffin blocks from both primary and metastatic tumors. Intratumor Ki-67 heterogeneity sufficient to change grade at first diagnosis was seen in 3/60 cases (5%). Out of 49 patients with primary NETs and/or multiple metastases, discrepancy in grade between sites was identified in 19 (39%) cases and in particular in 11/47 (23%) and in 10/12 (83%) patients with synchronous and metachronous metastases, respectively (p = 0.0002). Change in grade was more frequent in distant compared to locoregional metastases (p = 0.024) and in particular in distant sites other than the liver (p = 0.006). NETs show frequent differences in grade between primary sites and their synchronous/metachronous metastases; assessment of Ki-67 at all sites may prove to be significant for patient management. © 2015 S. Karger AG, Basel.

  20. A Gastrointestinal Stromal Tumor of the Stomach Demonstrating a Stepwise Progression from Low- to High-Grade Malignancy

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    Takahiko Nakajima

    2012-01-01

    Full Text Available We report a case of a gastrointestinal stromal tumor (GIST of the stomach that demonstrated a stepwise progression from low- to high-grade malignancy. The patient had been followed for a small gastric submucosal tumor that had turned malignant after 8 years of indolence, manifested by tarry stools. The tumor was enucleated, and gastric GIST was diagnosed. The most significant histological finding was that the tumor comprised two clearly demarcated areas, one with less aggressive characteristics and the other with highly aggressive characteristics. The patient exhibited multiple liver metastases 24 months after surgery. Imatinib mesylate was not administered throughout the clinical course because it was not available for clinical use at that time. The patient followed an unfavorable clinical course and died of liver dysfunction 55 months after surgery. Autopsy was performed. By comparing the immunohistochemical profiles of primary and metastatic tumors, it was established that only the tumor cells with highly aggressive characteristics had metastasized.

  1. Identification of histological correlates of overall survival in lower grade gliomas using a bag-of-words paradigm: A preliminary analysis based on hematoxylin & eosin stained slides from the lower grade glioma cohort of the cancer genome Atlas

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    Reid Trenton Powell

    2017-01-01

    Full Text Available Background: Glioma, the most common primary brain neoplasm, describes a heterogeneous tumor of multiple histologic subtypes and cellular origins. At clinical presentation, gliomas are graded according to the World Health Organization guidelines (WHO, which reflect the malignant characteristics of the tumor based on histopathological and molecular features. Lower grade diffuse gliomas (LGGs (WHO Grade II–III have fewer malignant characteristics than high-grade gliomas (WHO Grade IV, and a better clinical prognosis, however, accurate discrimination of overall survival (OS remains a challenge. In this study, we aimed to identify tissue-derived image features using a machine learning approach to predict OS in a mixed histology and grade cohort of lower grade glioma patients. To achieve this aim, we used H and E stained slides from the public LGG cohort of The Cancer Genome Atlas (TCGA to create a machine learned dictionary of “image-derived visual words” associated with OS. We then evaluated the combined efficacy of using these visual words in predicting short versus long OS by training a generalized machine learning model. Finally, we mapped these predictive visual words back to molecular signaling cascades to infer potential drivers of the machine learned survival-associated phenotypes. Methods: We analyzed digitized histological sections downloaded from the LGG cohort of TCGA using a bag-of-words approach. This method identified a diverse set of histological patterns that were further correlated with OS, histology, and molecular signaling activity using Cox regression, analysis of variance, and Spearman correlation, respectively. A support vector machine (SVM model was constructed to discriminate patients into short and long OS groups dichotomized at 24-month. Results: This method identified disease-relevant phenotypes associated with OS, some of which are correlated with disease-associated molecular pathways. From these image

  2. High-grade histologic features of DCIS are associated with R5 rather than R3 calcifications in breast screening mammography.

    LENUS (Irish Health Repository)

    Hayes, Brian D

    2013-01-01

    Mammographic calcification is an important radiologic feature of early breast carcinoma whose index of suspicion for malignancy may be reported by a five-tier R-category system. This study aims to describe the histologic diagnoses underlying screen-detected mammographic calcifications using both digital and screen-film mammography, and to correlate these findings with radiologic R-categories. Patients attending the Merrion Breast Screening Unit in Dublin between 2000 and 2011 were identified, who underwent needle-core biopsy for assessment of mammographic calcifications without associated mass or architectural distortion. Radiologic R-category was correlated with biopsy and excision histology reports. A total of 776 cases of calcification were identified, involving 769 individual patients. The radiologic R-categories were as follows: R3 513 (66.1%), R4 192 (24.7%), R5 71 (9.1%). The positive predictive values for malignancy were R3 32.6%, R4 69.8%, R5 95.8%. Several histologic features of DCIS were associated with R5 rather than R3 radiology: high nuclear grade, solid or cribriform architecture, necrosis, periductal inflammation or fibrosis, and associated microinvasive or invasive carcinoma. Mammographic lesions and histologic whole and invasive tumors increased in size from R3 to R5. Radiologic size of calcifications correlated with whole (but not invasive) tumor size, although it tended to underestimate it by several millimeters. Digital-detected calcifications were more likely than screen-film detected to be categorized as R3 and less likely R4 or R5, and there was no significant difference in positive predictive value between the two imaging techniques in any R-category. In conclusion, histologic features of DCIS, in particular those associated with high grade, are associated with R5 radiology. There is no significant difference in positive predictive value for malignancy in any R-category between digital and screen-film mammography.

  3. Gadd45β expression in chondrosarcoma: A pilot study for diagnostic and biological implications in histological grading

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    Ishido Yasuhiro

    2010-10-01

    Full Text Available Abstract Background Although the diagnosis of chondrosarcoma, especially the distinction between enchondroma and low-grade chondrosarcoma or low-grade chondrosarcoma and high-grade chondrosarcoma, is pathologically difficult, differential diagnosis is very important because the treatment strategies for these diseases are completely different. The grading system is crucial in predicting biologic behavior and prognosis, however, exact pathological grading is difficult using only routine examinations because the criteria of the grading system are not necessarily definitive. Growth arrest and DNA damage-inducible protein 45β (GADD45β is an essential molecule for chondrocytes during terminal differentiation. In the present study, we investigated the immunohistochemical expression of GADD45β in enchondroma, and chondrosarcoma of histological grades I, II, and III, to clarify the diagnostic significance of GADD45β in pathological grading of chondrosarcoma. Methods Twenty samples (enchondroma = 6, chondrosarcoma grade I = 7, grade II = 6, grade III = 1 were used for immunohistochemical analysis to investigate the expression of GADD45β. Quantitative analysis was performed to compare the number of GADD45β positive cells and pathological grading. Results Over 70% of the cells in enchondromas expressed GADD45β. On the other hand, the expression of GADD45β decreased significantly according to the histological grade of chondrosarcoma (grade I: 45%; grade II: 13.8%; and grade III: 3.8%. Conclusions The association of GADD45β expression and pathological grading of chondrosarcoma in the present study suggests that the immunohistochemical study of GADD45β may be a specific diagnostic parameter for chondrosarcoma cell differentiation.

  4. MUC1 positive, Kras and Pten driven mouse gynecologic tumors replicate human tumors and vary in survival and nuclear grade based on anatomical location.

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    Tejas S Tirodkar

    Full Text Available Activating mutations of Kras oncogene and deletions of Pten tumor suppressor gene play important roles in cancers of the female genital tract. We developed here new preclinical models for gynecologic cancers, using conditional (Cre-loxP mice with floxed genetic alterations in Kras and Pten. The triple transgenic mice, briefly called MUC1KrasPten, express human MUC1 antigen as self and carry a silent oncogenic KrasG12D and Pten deletion mutation. Injection of Cre-encoding adenovirus (AdCre in the ovarian bursa, oviduct or uterus activates the floxed mutations and initiates ovarian, oviductal, and endometrial cancer, respectively. Anatomical site-specific Cre-loxP recombination throughout the genital tract of MUC1KrasPten mice leads to MUC1 positive genital tract tumors, and the development of these tumors is influenced by the anatomical environment. Endometrioid histology was consistently displayed in all tumors of the murine genital tract (ovaries, oviducts, and uterus. Tumors showed increased expression of MUC1 glycoprotein and triggered de novo antibodies in tumor bearing hosts, mimicking the immunobiology seen in patients. In contrast to the ovarian and endometrial tumors, oviductal tumors showed higher nuclear grade. Survival for oviduct tumors was significantly lower than for endometrial tumors (p = 0.0015, yet similar to survival for ovarian cancer. Oviducts seem to favor the development of high grade tumors, providing preclinical evidence in support of the postulated role of fallopian tubes as the originating site for high grade human ovarian tumors.

  5. Keratocystic odontogenic tumor with ossification and calcification: A case report with unusual histological findings

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    Swati Shrikant Gotmare

    2016-01-01

    Full Text Available The keratocystic odontogenic tumor (KCOT, formerly known as odontogenic keratocyst, is a benign developmental odontogenic tumor with many distinguishing clinical and histologic features. Hard tissue deposits, which usually take the form of dystrophic calcifications, cartilaginous tissue, or dentinoid, are uncommon findings in the connective tissue capsule of the KCOT. We report a case of a 33-year-old female with KCOT showing osseous tissue and calcified deposits close to its epithelial lining, which is an extremely rare occurrence. A brief review on the reported prevalence of hard tissue deposits in KCOTs and possible mechanisms that has been implicated in mineralization and bone formation has been discussed.

  6. A binary histologic grading system for ovarian serous carcinoma is an independent prognostic factor: a population-based study of 4317 women diagnosed in Denmark 1978-2006.

    Science.gov (United States)

    Hannibal, Charlotte Gerd; Vang, Russell; Junge, Jette; Kjaerbye-Thygesen, Anette; Kurman, Robert J; Kjaer, Susanne K

    2012-06-01

    To evaluate the prognostic significance of histologic grade on survival of ovarian serous cancer in Denmark during nearly 30 years. Using the nationwide Danish Pathology Data Bank, we evaluated 4317 women with ovarian serous carcinoma in 1978-2006. All pathology reports were scrutinized and tumors classified as either low-grade serous carcinomas (LGSC) or high-grade serous carcinomas (HGSC). Tumors in which the original pathology reports were described as well-differentiated were classified as LGSC, and those that were described as moderately or poorly differentiated were classified as HGSC. We obtained histologic slides from the pathology departments for women with a diagnosis of well-differentiated serous carcinoma during 1997-2006, which were then reviewed by expert gynecologic pathologists. Data were analyzed using Kaplan-Meier methods and Cox proportional hazards regression analysis with follow-up through June 2009. Women with HGSC had a significantly increased risk of dying (HR=1.9; 95% CI: 1.6-2.3) compared with women with LGSC while adjusting for age and stage. Expert review of 171 women originally classified as well-differentiated in 1997-2006 were interpreted as LGSC in 30% of cases, whereas 12% were interpreted as HGSC and 50% as serous borderline ovarian tumors (SBT). Compared with women with confirmed LGSC, women with SBT at review had a significantly lower risk of dying (HR=0.5; 95% CI: 0.22-0.99), and women with HGSC at review had a non-significantly increased risk of dying (HR=1.6; 95% CI: 0.7-3.4). A binary grading system is a significant predictor of survival for ovarian serous carcinoma. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Immunohistochemical expression of phosphatase and tensin homolog in histologic gradings of oral squamous cell carcinoma

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    Shiny S.R. Jasphin

    2016-01-01

    Full Text Available Context: Phosphatase and tensin homolog (PTEN is a tumor suppressor gene located on chromosome 10q23. PTEN has its major function in the regulation of cell adhesion, cell cycle arrest, migration, apoptosis programming, and differentiation. This genomic region suffers loss of heterozygosity in many human cancers. Aims: The aim of this study was to compare the immunohistochemical expression of PTEN in normal oral mucosa and oral squamous cell carcinoma (OSCC and to correlate the PTEN expression in gradings of OSCC. Materials and Methods: Thirty cases of paraffin tissue sections of previously diagnosed OSCC were taken. Of thirty cases, ten were well differentiated, ten were moderately differentiated, and ten were poorly differentiated. As a control, ten paraffin sections of oral normal mucosa tissue specimens were taken from patients undergoing extractions. The sections were stained for immunohistochemical expression of PTEN. The cells stained by PTEN antibody were counted, and an immunohistochemical score was obtained. Statistical Analysis Used: Statistical analysis was done using Mann–Whitney's test and Kruskal–Wallis test. Results: Statistical analysis revealed that there was a significant difference between normal mucosa and OSCC in immunohistochemistry staining. However, there was no significant difference in PTEN expression among gradings of OSCC. Conclusions: The study concluded that there was a decrease in PTEN expression in OSCC than normal mucosa. It also concluded that PTEN is a tumor suppressor gene which has a wide role in oral carcinogenesis.

  8. Histological grading of breast cancer on needle core biopsy: the role of immunohistochemical assessment of proliferation.

    Science.gov (United States)

    Kwok, T'ng Chang; Rakha, Emad A; Lee, Andrew H S; Grainge, Matthew; Green, Andrew R; Ellis, Ian O; Powe, Desmond G

    2010-08-01

    Histological grade assessed on needle core biopsy (NCB) moderately concurs with the grade in the surgical excision specimen (SES) (kappa-values between 0.35 and 0.65). A major cause of the discrepancy is underestimation of mitoses in the NCB specimen. The aim was to determine the best method of assessing proliferation on NCB. Proliferative activity of 101 invasive carcinomas of the breast on NCB and SES was assessed using mitotic counts on routine haematoxylin and eosin (H&E) sections and immunohistochemical markers Mib-1 and phosphorylated histone H3 (PPH3). H&E mitotic count in SES was considered as the gold standard. H&E mitotic count was found to be underestimated on NCB when compared with that in SES (P NCB and SES regarding Mib-1 (P = 0.13) or PPH3 (P = 0.073). Using receiver-operating characteristic curve, Mib-1 on NCB was found to agree with the gold standard significantly better than routine H&E on NCB. Immunohistochemical markers in NCB showed better concordance with H&E mitotic count in SES (gold standard) than routine H&E mitotic count in NCB. Further refinement of cut-offs and scoring methods is needed.

  9. A proposed grading system for standardizing tumor consistency of intracranial meningiomas.

    Science.gov (United States)

    Zada, Gabriel; Yashar, Parham; Robison, Aaron; Winer, Jesse; Khalessi, Alexander; Mack, William J; Giannotta, Steven L

    2013-12-01

    Tumor consistency plays an important and underrecognized role in the surgeon's ability to resect meningiomas, especially with evolving trends toward minimally invasive and keyhole surgical approaches. Aside from descriptors such as "hard" or "soft," no objective criteria exist for grading, studying, and conveying the consistency of meningiomas. The authors designed a practical 5-point scale for intraoperative grading of meningiomas based on the surgeon's ability to internally debulk the tumor and on the subsequent resistance to folding of the tumor capsule. Tumor consistency grades and features are as follows: 1) extremely soft tumor, internal debulking with suction only; 2) soft tumor, internal debulking mostly with suction, and remaining fibrous strands resected with easily folded capsule; 3) average consistency, tumor cannot be freely suctioned and requires mechanical debulking, and the capsule then folds with relative ease; 4) firm tumor, high degree of mechanical debulking required, and capsule remains difficult to fold; and 5) extremely firm, calcified tumor, approaches density of bone, and capsule does not fold. Additional grading categories included tumor heterogeneity (with minimum and maximum consistency scores) and a 3-point vascularity score. This grading system was prospectively assessed in 50 consecutive patients undergoing craniotomy for meningioma resection by 2 surgeons in an independent fashion. Grading scores were subjected to a linear weighted kappa analysis for interuser reliability. Fifty patients (100 scores) were included in the analysis. The mean maximal tumor diameter was 4.3 cm. The distribution of overall tumor consistency scores was as follows: Grade 1, 4%; Grade 2, 9%; Grade 3, 43%; Grade 4, 44%; and Grade 5, 0%. Regions of Grade 5 consistency were reported only focally in 14% of heterogeneous tumors. Tumors were designated as homogeneous in 68% and heterogeneous in 32% of grades. The kappa analysis score for overall tumor consistency

  10. Validation of the Diagnostic Value of Nuclear Matrix Protein 22 Depending on Tumoral Stage and Grade

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    Zoltán A. MIHÁLY

    2013-02-01

    Full Text Available Objectives: The aim of the present study was to validate the sensitivity and specificity of the NMP22® BladderChek® test in our group of patients according to the tumoral stage and grade and to identify the patient categories that might benefit from the non-invasive nature of NMP22® BladderChek® test. Methods: Voided urine samples from 266 patients with imagistic suspicion of bladder cancer were collected to perform the NMP22® BladderChek® test. The nuclear matrix protein 22 (NMP22 levels were measured by a lateral flow immunochromatographic qualitative assay, using 10 U/ml as the cut-off value. After this patients underwent transurethral resection of bladder tumors (TUR-BT follewed by histologic grading and tumor staging for a proper and optimal patient management. Sensitivity specificity and positive predictive value of the NMP22® BladderChek® test were defined for different tumoral stage and grade. Results: Two hundred thirty-eight of the 265 patients had urothelial malignancies (76 pTa, 81 pT1, 37 pT2, 32 pT3, 12 pT4, 27 pT0; 118 G1, 54 G2, 64 G3. The sensitivity was 0.629 [0.612; 0.629] for the NMP22® BladderChek® test while the specificity was equal to 1 [0.851; 1]. Positive predictive values was 1 [0.973; 1], and the negative predictive value was 0.235 [0.200; 0.235]. Conclusions: The results demonstrate that the even if the NMP22® BladderChek® is an easily applied test, giving diagnostic findings within 30 min, cannot be recommended for screening or surveillance in clinical routine use in non muscle invasive bladder cancer because of its poor sensitivity.

  11. DNA-fluorescence-cytometry and prognosis (grading) of meningiomas--a study of 104 surgically removed tumors.

    Science.gov (United States)

    Spaar, F W; Ahyai, A; Blech, M

    1987-01-01

    A total of 104 meningiomas of various histological types were examined microscopically and with flow fluorescence cytometry using the EBR staining technique and either an ICP 11 or an ICP 22 (PHYWE). Also tissue culture cells of 72 tumors were studied for their DNA content. There was a variable DNA distribution, which allowed a grading of malignancy according to a 3 or 4 grade scale. Useful information on the nature of a meningioma and its proliferative activity can be obtained during the surgical treatment. A majority of meningiomas show slowly proliferative DNA patterns typical for benign tumors. More than one third of the meningiomas show an intermediate configuration, probably associated with more or less semi-benign proliferative activity. 5.8% of our cases showed primary malignant tumors--except meningosarcomas.

  12. Molecular Transition of an Adult Low-Grade Brain Tumor to an Atypical Teratoid/Rhabdoid Tumor Over a Time-Course of 14 Years.

    Science.gov (United States)

    Schweizer, Yvonne; Meszaros, Zsolt; Jones, David T W; Koelsche, Christian; Boudalil, Miream; Fiesel, Petra; Schrimpf, Daniel; Piro, Rosario M; Brehmer, Stefanie; von Deimling, Andreas; Kerl, Ulrich; Seiz-Rosenhagen, Marcel; Capper, David

    2017-08-01

    Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system is a highly malignant, pediatric brain tumor typically arising de novo. Inactivation of SMARCB1 is a defining molecular event. We present here a rare case of an adult (35 years) low-grade SMARCB1-deleted brain tumor with transition into prototypical AT/RT over 14 years. Molecular analysis was performed for 3 tumor presentations including copy number analysis, DNA methylation analysis (450k), and whole exome sequencing. We detected the identical somatic SMARCB1 deletion at all 3 time-points. In an unsupervised hierarchical clustering of methylation data together with 127 reference cases comprising 9 brain tumor classes all 3 manifestations clustered with AT/RT. Exome sequencing revealed an increase of mutational burden over time. The acquired mutations and additional copy number changes did not affect known cancer genes. In conclusion, we demonstrate molecular changes associated with histological and clinical transition of a low-grade brain tumor to an adult AT/RT. Our observation of a stable disease course for nearly 10 years in a tumor with SMARCB1 loss and an AT/RT-like DNA methylation profile indicates that caution may be required in the diagnostic interpretation of such findings in adult patients. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

  13. Non-Gaussian diffusion MR imaging of glioma: comparisons of multiple diffusion parameters and correlation with histologic grade and MIB-1 (Ki-67 labeling) index.

    Science.gov (United States)

    Yan, Ren; Haopeng, Pang; Xiaoyuan, Feng; Jinsong, Wu; Jiawen, Zhang; Chengjun, Yao; Tianming, Qiu; Ji, Xiong; Mao, Sheng; Yueyue, Ding; Yong, Zhang; Jianfeng, Luo; Zhenwei, Yao

    2016-02-01

    This study was conducted to compare the association of Gaussian and non-Gaussian magnetic resonance imaging (MRI)-derived parameters with histologic grade and MIB-1 (Ki-67 labeling) index (MI) in brain glioma. Sixty-five patients with pathologically confirmed glioma, who underwent diffusion-weighted MRI with 2 b values (0, 1000 s/mm(2)) and 22 b values (≤5000 s/mm(2)), respectively, were divided into three groups of grade II (n = 35), grade III (n = 8), and grade IV (n = 22). Comparisons by two groups were made for apparent diffusion coefficient (ADC), slow diffusion coefficient (Dslow), distributed diffusion coefficient (DDC), and heterogeneity index α. Analyses of receiver operating characteristic (ROC) curve were performed to maximize the area under the curve (AUC) for differentiating grade III + IV (high-grade glioma, HGG) from grade II (low-grade glioma, LGG) and grade IV (glioblastoma multiforme, GBM) from grade II + III (other grade glioma, OGG). Correlations with MI were analyzed for the MRI parameters. On tumor regions, the values of ADC, Dslow, DDC, and α were significantly higher in grade II [(1.37 ± 0.29, 0.70 ± 0.11, 1.39 ± 0.34) (×10(-3) mm(2)/s) and 0.88 ± 0.05, respectively] than in grade III [(0.99 ± 0.13, 0.55 ± 0.07, 1.04 ± 0.20) (×10(-3) mm(2)/s) and 0.80 ± 0.03, respectively] and grade IV [(1.03 ± 0.14, 0.50 ± 0.05, 1.02 ± 0.16) (×10(-3) mm(2)/s) and 0.76 ± 0.04, respectively] (all P Gaussian MRI-derived parameters α and Dslow are superior to ADC in glioma grading, which are comparable with ADC as reliable biomarkers in noninvasively predicting the proliferation level of glioma malignancy.

  14. Influence of Helicobacter pylori Colonization on Histological Grading of Chronic Gastritis in Korean Patients with Peptic Ulcer

    Science.gov (United States)

    Park, Joongwon; Kim, Mi Kyung; Park, Sill Moo

    1995-01-01

    Objectives: We conducted an analysis of correlation between histological grading of chronic gastritis and the presence of H. pylori infection to investigate if H. pylori influences histological severity of chronic gastritis in Korean patients with peptic ulcers. Methods: Gastroscopic antral biopsy specimens and peripheral venous blood were taken from 80 patients with gastric or duodenal ulcers. H. pylori was identified microscopically in sections with Giemsa staining and quantitative grading of cultured H. pylori was reported on a scale 0 to 3. The histopathological features of biopsy specimens were reported according to the Sydney classification of chronic gastritis. Serum gastritis and pepsinogen concentrations were measured by radioimmunoassay. Results: H. pylori was identified in 62.5% (20 of 32 GU, 30 of 48 DU) of the study group. Gastric clonization rate of H. pylori did not increased with age. Forty of 50 biopsy specimens with H. pylori and also 23 of 30 biopsy specimens without H. pylori showed active chronic gastritis. There was no significant correlation overall between the presence of H. pylori and histological grading of chronic gastritis, including activity, and also no association was found between the quantitative grading of H. pylori and the histological grading of chronic gastritis. With and without H. pylori, a mean of serum gastritis concentration (79.4±43.0 pg/ml and 80.2±31.9 pg/ml) showed no significant difference, but a mean of serum pepsinogen concentration (87.7±41.6 ng/ml and 119±34.4 ng/ml) showed significant difference between the populations with and without H. pylori (p=0.001) Conclusions: The influence of H. pylori on histological grading of chronic gastritis in Korean is less than that in prior studies of Western countries, and further investigation of pathogenesis of H. pylori in chronic gastritis and peptic ulceration is necessary. PMID:7495770

  15. Colorectal carcinoma evaluated by incremental dynamic CT; Comparison of CT density, histology, and tumor size

    Energy Technology Data Exchange (ETDEWEB)

    Furukawa, Hiroyoshi; Hara, Tsuyoshi; Taniguchi, Tetsushi (Shimizu Kosei Hospital, Shizuoka (Japan))

    1992-06-01

    Evaluation of incremental dynamic CT scan and histologic findings were compared in order to clarify the cause of the differences in colorectal carcinoma as observed on CT after administration of contrast medium. In 48 cases demonstrated on postcontrast dynamic CT scan, the CT density of the tumor was homogeneous (Type 1) in 26 (54.2%) cases and heterogeneous (Type 2) in 22 (45.8%) cases. Well differentiated adenocarcinoma was seen as Type 1 in 11 of 13 (84.6%) cases while moderately differentiated adenocarcinoma was of Type 1 in 15 of 29 (51.7%) cases. Poorly differentiated and mucinous adenocarcinoma were detected as Type 2 in all cases. A comparison of CT types and tumor size showed that as tumor size increased, the number of Type 1 cases decreased while Type 2 cases increased. Histologically, high density areas consisted mainly of well-developed tubular, branching glands of adenocarcinoma, while low density areas were composed of fibrous or mucinous stroma or necrosis. Dynamic CT scans for colorectal cancer are useful not only for preoperative staging but also for tissue characterization. (author).

  16. Low-grade gliomas: six-month tumor growth predicts patient outcome better than admission tumor volume, relative cerebral blood volume, and apparent diffusion coefficient.

    Science.gov (United States)

    Brasil Caseiras, Gisele; Ciccarelli, Olga; Altmann, Daniel R; Benton, Christopher E; Tozer, Daniel J; Tofts, Paul S; Yousry, Tarek A; Rees, Jeremy; Waldman, Adam D; Jäger, Hans Rolf

    2009-11-01

    To prospectively compare tumor volume, relative cerebral blood volume (rCBV), and apparent diffusion coefficient (ADC) and short-term changes of these parameters as predictors of time to malignant transformation and time to death in patients with low-grade gliomas (LGGs). Patients gave written informed consent for this institutional ethics committee-approved study. Patients with histologically proved LGGs underwent conventional, perfusion-weighted, and diffusion-weighted magnetic resonance (MR) imaging at study entry and at 6 months. At both time points, tumor volume, maximum rCBV, and ADC histogram measures were calculated. Patient follow-up consisted of MR imaging every 6 months and clinical examinations. To investigate the association between MR imaging variables and time to progression and time to death, a Cox regression curve was applied at study entry and at 6 months. The models were corrected for age, sex, and histologic findings. Thirty-four patients (22 men, 12 women; mean age, 42 years) with histologically proved LGGs (eight oligodendrogliomas, 20 astrocytomas, and six oligoastrocytomas) were followed up clinically and radiologically for a median of 2.6 years (range, 0.4-5.5 years). Tumor growth over the course of 6 months was the best predictor of time to transformation, independent of rCBV, diffusion histogram parameters, age, sex, and histologic findings. When only single-time-point measurements were compared, tumor volume helped predict outcome best and was the only independent predictor of time to death (P < .02). Six-month tumor growth helps predict outcome in patients with LGG better than parameters derived from perfusion- or diffusion-weighed MR imaging. Tumor growth can readily be calculated from volume measurements on images acquired with standard MR imaging protocols and may well prove most useful among various MR imaging findings in clinical practice. (c) RSNA, 2009.

  17. Downregulation of transient receptor potential cation channel, subfamily C, member 1 contributes to drug resistance and high histological grade in ovarian cancer.

    Science.gov (United States)

    Liu, Xia; Zou, Jing; Su, Jie; Lu, Yi; Zhang, Jian; Li, Li; Yin, Fuqiang

    2016-01-01

    Transient receptor potential cation channel, subfamily C, member 1 (TRPC1) participates in many physiological functions but has also been implicated in cancer development. However, little is known about the role of TRPC1 in ovarian cancer (OC), including the drug resistance of these tumors. In the present study, a significant and consistent downregulation of TRPC1 in drug-resistant OC tissues/cells was determined using real-time quantitative polymerase chain reaction assays and the microarrays deposited in Oncomine and Gene Expression Omnibus (GEO) profiles. Protein/gene-protein/gene and protein-chemical interactions indicated that TRPC1 interacts with 14 proteins/genes and 6 chemicals, all of which are involved in the regulation of drug resistance in OC. Biological process annotation of TRPC1, OC, and drug resistance indicated a role for TRPC1 in drug-resistance-related functions in OC, mainly via the cell cycle, gene expression and cell growth and cell death. Analysis of mRNA-microRNA interactions showed that 8 out of 11 major pathways enriched from 38 predominant microRNAs targeting TRPC1 were involved in the regulation of drug resistance in OC, and 8 out of these top 10 microRNAs were implicated in the drug resistance in ovarian and other cancers. In a clinical analysis using data obtained from The Cancer Genome Atlas project (TCGA) cohort on 341 OC patients, TRPC1 expression was found to differ significantly between grade 2 and grade 3 tumors, with low-level expression correlating with higher tumor grade. This is the first report to show a potential association between the downregulation of TRPC1 and both drug resistance and high histological tumor grade in OC. Our results provide the basis for further investigations of the drug-resistance-related functions of TRPC1 in OC and other forms of cancer.

  18. Histologic classification of gliomas

    NARCIS (Netherlands)

    Perry, Arie; Wesseling, Pieter|info:eu-repo/dai/nl/157872866

    2016-01-01

    Gliomas form a heterogeneous group of tumors of the central nervous system (CNS) and are traditionally classified based on histologic type and malignancy grade. Most gliomas, the diffuse gliomas, show extensive infiltration in the CNS parenchyma. Diffuse gliomas can be further typed as astrocytic,

  19. Virtual microscopy: an evaluation of its validity and diagnostic performance in routine histologic diagnosis of skin tumors

    DEFF Research Database (Denmark)

    Nielsen, Patricia Switten; Lindebjerg, Jan; Rasmussen, Jan

    2010-01-01

    in routine histologic diagnosis of skin tumors. Our aim is to investigate whether conventional microscopy of skin tumors can be replaced by virtual microscopy. Ninety-six skin tumors and skin-tumor-like changes were consecutively gathered over a 1-week period. Specimens were routinely processed, and digital...... that it is feasible to make histologic diagnosis on the skin tumor types represented in this study using virtual microscopy after pathologists have completed a period of training. Larger studies should be conducted to verify whether virtual microscopy can replace conventional microscopy in routine practice.......Digitization of histologic slides is associated with many advantages, and its use in routine diagnosis holds great promise. Nevertheless, few articles evaluate virtual microscopy in routine settings. This study is an evaluation of the validity and diagnostic performance of virtual microscopy...

  20. Facing Contrast-Enhancing Gliomas: Perfusion MRI in Grade III and Grade IV Gliomas according to Tumor Area

    Directory of Open Access Journals (Sweden)

    Anna Luisa Di Stefano

    2014-01-01

    Full Text Available Tumoral neoangiogenesis characterizes high grade gliomas. Relative Cerebral Blood Volume (rCBV, calculated with Dynamic Susceptibility Contrast (DSC Perfusion-Weighted Imaging (PWI, allows for the estimation of vascular density over the tumor bed. The aim of the study was to characterize putative tumoral neoangiogenesis via the study of maximal rCBV with a Region of Interest (ROI approach in three tumor areas—the contrast-enhancing area, the nonenhancing tumor, and the high perfusion area on CBV map—in patients affected by contrast-enhancing glioma (grades III and IV. Twenty-one patients were included: 15 were affected by grade IV and 6 by grade III glioma. Maximal rCBV values for each patient were averaged according to glioma grade. Although rCBV from contrast-enhancement and from nonenhancing tumor areas was higher in grade IV glioma than in grade III (5.58 and 2.68; 3.01 and 2.2, resp., the differences were not significant. Instead, rCBV recorded in the high perfusion area on CBV map, independently of tumor compartment, was significantly higher in grade IV glioma than in grade III (7.51 versus 3.78, P=0.036. In conclusion, neoangiogenesis encompasses different tumor compartments and CBV maps appear capable of best characterizing the degree of neovascularization. Facing contrast-enhancing brain tumors, areas of high perfusion on CBV maps should be considered as the reference areas to be targeted for glioma grading.

  1. Quantifying expert diagnosis variability when grading tumor-infiltrating lymphocytes

    Science.gov (United States)

    Toro, Paula; Corredor, Germán.; Wang, Xiangxue; Arias, Viviana; Velcheti, Vamsidhar; Madabhushi, Anant; Romero, Eduardo

    2017-11-01

    Tumor-infiltrating lymphocytes (TILs) have proved to play an important role in predicting prognosis, survival, and response to treatment in patients with a variety of solid tumors. Unfortunately, currently, there are not a standardized methodology to quantify the infiltration grade. The aim of this work is to evaluate variability among the reports of TILs given by a group of pathologists who examined a set of digitized Non-Small Cell Lung Cancer samples (n=60). 28 pathologists answered a different number of histopathological images. The agreement among pathologists was evaluated by computing the Kappa index coefficient and the standard deviation of their estimations. Furthermore, TILs reports were correlated with patient's prognosis and survival using the Pearson's correlation coefficient. General results show that the agreement among experts grading TILs in the dataset is low since Kappa values remain below 0.4 and the standard deviation values demonstrate that in none of the images there was a full consensus. Finally, the correlation coefficient for each pathologist also reveals a low association between the pathologists' predictions and the prognosis/survival data. Results suggest the need of defining standardized, objective, and effective strategies to evaluate TILs, so they could be used as a biomarker in the daily routine.

  2. MALIGNANT TUMORS OF BONES. MORBIDITY, MORTALITY, INDEX ACCURACY, SURVIVAL OF PATIENTS ACCORDING TO HISTOLOGICAL FORMS

    Directory of Open Access Journals (Sweden)

    V. M. Merabishvili

    2015-01-01

    Full Text Available Introduction. Standardized (world standard incidence of malignant tumors of bones (S40,41 does not have has significant fluctuations. According to IARC among male population the most common incidence rates range from 1 to 2 cases per 100.000 and among female population – from 0.5 to 1.0 among women.  Purpose of study. To study dynamics of morbidity and mortality from malignant tumors of bones, the quality of estimation, observed and relative survival of patients according to histological forms. The work of this level is held in Russia for the first time. Material and methods of study. There were used an open world and domestic sources to estimate the prevalence of malignant tumors of bones, databases of population-based cancer registers, classical methods of population-based estimation of the prevalence of malignant tumors of bones. results of study. The basis of this work is data from the Population-based Cancer Registry of St. Petersburg and special studies being held before its establishing in 1993. Annually in St. Petersburg there are registered 40–60 primary cases of malignant tumors of bones (S40, 41. The level of morphological verification of these malignancies in Russia is 82.1 %, in St. Petersburg – 84.9 %. There is a high rate of undefined stage: in Russia – 19.7 %, in St. Petersburg – 24.5 %, in Moscow – 23.5 %. During the first year of observation 27.3 % of patients die in Russia, 21.7 % in St. Petersburg, and 11.1 % in Moscow. In comparison with the average data (Eurocare program the relative survival of patients in St. Petersburg is significantly lower: in men (St. Petersburg – 42.2–48.2 %, (Eurocare-3,4 – 55–58 %, in women (St. Petersburg – 32.2–54.6 % (Eurocare – 59–63 %. conclusion. Thus, in this work for the first time in Russia it is showed dynamics of absolute and relative incidence rates of malignant tumors of bones since 1980 by sex and age-specific indicators. It is presented a set of

  3. Ki-ras gene mutations are invariably present in low-grade mucinous tumors of the vermiform appendix.

    Science.gov (United States)

    Zauber, Peter; Berman, Errol; Marotta, Stephen; Sabbath-Solitare, Marlene; Bishop, Timothy

    2011-07-01

    Low-grade mucinous tumors of the appendix appear to have a simple histological structure. Paradoxically, reports have suggested a greater frequency of Ki-ras gene mutation in these lesions than in more complex lesions such as benign colonic adenomas and carcinomas. We assessed several molecular genetic changes, including Ki-ras gene mutations, in a large series of low-grade mucinous tumors of the appendix. We retrospectively ascertained low-grade mucinous tumors of the appendix from computerized pathology records. Extracted DNA was analyzed for APC and DCC gene loss of heterozygosity, microsatellite instability and for the presence of Ki-ras gene mutation using standard molecular techniques. Controls consisted of normal appendices, other appendiceal neoplasms, and ovarian mucinous cystadenomas. A total of 31 low-grade appendiceal mucinous tumors were identified. All were microsatellite stable and none demonstrated loss of heterozygosity for the APC or DCC genes. By contrast, all 31 lesions contained a Ki-ras gene mutation. The presence of a Ki-ras gene mutation in all lesions, with no other molecular changes identified, strongly suggests a possible etiological role of the Ki-ras mutation in the development of this particular lesion of the appendix. Based on other work regarding intestinal bacteria, we hypothesize a relationship between chronic inflammation of the appendix from bacterial overgrowth and Ki-ras gene mutation.

  4. Analysis of histological and immunohistochemical patterns of benign and malignant adrenocortical tumors by computerized morphometry.

    Science.gov (United States)

    Dalino Ciaramella, Paolo; Vertemati, Maurizio; Petrella, Duccio; Bonacina, Edgardo; Grossrubatscher, Erika; Duregon, Eleonora; Volante, Marco; Papotti, Mauro; Loli, Paola

    2017-07-01

    Diagnosis of benign and purely localized malignant adrenocortical lesions is still a complex issue. Moreover, histology-based diagnosis may suffer of a moment of subjectivity due to inter- and intra-individual variations. The aim of the present study was to assess, by computerized morphometry, the morphological features in benign and malignant adrenocortical neoplasms. Eleven adrenocortical adenomas (ACA) were compared with 18 adrenocortical cancers (ACC). All specimens were stained with H&E, cellular proliferation marker Ki-67 and reticulin. We generated a morphometric model based on the analysis of volume fractions occupied by Ki-67 positive and negative cells (nuclei and cytoplasm), vascular and inflammatory compartment; we also analyzed the surface fraction occupied by reticulin. We compared the quantitative data of Ki-67 obtained by morphometry with the quantification resulting from pathologist's visual reading. The volume fraction of Ki-67 positive cells in ACCs was higher than in ACAs. The volume fraction of nuclei in unit volume and the nuclear/cytoplasmic ratio in both Ki-67 negative cells and Ki-67 positive cells were prominent in ACCs. The surface fraction of reticulin was considerably lower in ACCs. Our computerized morphometric model is simple, reproducible and can be used by the pathologist in the histological workup of adrenocortical tumors to achieve precise and reader-independent quantification of several morphological characteristics of adrenocortical tumors. Copyright © 2017 Elsevier GmbH. All rights reserved.

  5. Quantification of tumor morphology via 3D histology: application to oral cavity cancers

    Science.gov (United States)

    Doyle, Scott; Brandwein-Gensler, Margaret; Tomaszewski, John

    2016-03-01

    Traditional histopathology quantifies disease through the study of glass slides, i.e. two-dimensional samples that are representative of the overall process. We hypothesize that 3D reconstruction can enhance our understanding of histopathologic interpretations. To test this hypothesis, we perform a pilot study of the risk model for oral cavity cancer (OCC), which stratifies patients into low-, intermediate-, and high-risk for locoregional disease-free survival. Classification is based on study of hematoxylin and eosin (H and E) stained tissues sampled from the resection specimens. In this model, the Worst Pattern of Invasion (WPOI) is assessed, representing specific architectural features at the interface between cancer and non-cancer tissue. Currently, assessment of WPOI is based on 2D sections of tissue, representing complex 3D structures of tumor growth. We believe that by reconstructing a 3D model of tumor growth and quantifying the tumor-host interface, we can obtain important diagnostic information that is difficult to assess in 2D. Therefore, we introduce a pilot study framework for visualizing tissue architecture and morphology in 3D from serial sections of histopathology. This framework can be used to enhance predictive models for diseases where severity is determined by 3D biological structure. In this work we utilize serial H and E-stained OCC resections obtained from 7 patients exhibiting WPOI-3 (low risk of recurrence) through WPOI-5 (high risk of recurrence). A supervised classifier automatically generates a map of tumor regions on each slide, which are then co-registered using an elastic deformation algorithm. A smooth 3D model of the tumor region is generated from the registered maps, which is suitable for quantitative tumor interface morphology feature extraction. We report our preliminary models created with this system and suggest further enhancements to traditional histology scoring mechanisms that take spatial architecture into consideration.

  6. Histological advantages of the tumor graft: a murine model involving transplantation of human pancreatic cancer tissue fragments.

    Science.gov (United States)

    Akashi, Yoshimasa; Oda, Tatsuya; Ohara, Yusuke; Miyamoto, Ryoichi; Hashimoto, Shinji; Enomoto, Tsuyoshi; Yamada, Keiichi; Kobayashi, Akihiko; Fukunaga, Kiyoshi; Ohkochi, Nobuhiro

    2013-11-01

    Experimental data based on cell line-derived xenograft models (cell xenograft) seldom reproduce the clinical situation, and therefore we demonstrated here the superiority of a murine model involving transplantation of human pancreatic cancer tissue fragments (tumor graft), focusing on the histological features and drug delivery characteristics. Tumor pieces from 10 pancreatic cancer patients were transplanted into SCID (severe combined immunodeficient) mice. Histological characteristics of tumor grafts, including morphology, desmoplastic reaction, and vascularization, were compared with those of cell xenografts. Drug delivery was evaluated by quantifying the concentrations of injected drug, and the results were compared with its histological features. Eight of the 10 transplanted tumors successfully engrafted. Histological comparisons between tumor grafts and cell xenografts revealed the following: the amount of stroma was more (22.9% ± 11.8% vs 10.8% ± 5.4%; P cancer cell distance was longer (35.3 ± 39.0 vs 3.9 ± 3.1 μm; P Pancreatic tumor grafts better reproduce the histological nature of clinical cancer and thus provide a more realistic model that is applicable for pharmacokinetic studies.

  7. Increased fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) uptake in childhood CNS tumors is correlated with malignancy grade

    DEFF Research Database (Denmark)

    Borgwardt, Lise; Højgaard, Liselotte; Carstensen, Henrik

    2005-01-01

    .89; P correlation with malignancy. Digitally performed PET/MRI coregistration increased information on tumor characterization in 90......-D-glucose (FDG) PET with (n = 16) or without (n = 22) H(2)(15)O-PET before therapy. Image processing included coregistration to magnetic resonance imaging (MRI) in all patients. The FDG uptake in tumors was semiquantitatively calculated by a region-of-interest-based tumor hotspot/brain index. Eight tumors...... of 12 grade 1 tumors had a mean index of -0.31 +/- 0.59. Eight patients with no histologic confirmation had a mean index of 1.04. For these 34 tumors, FDG uptake was positively correlated with malignancy grading (n = 34; r = 0.72; P

  8. Frequency of papillary tubal hyperplasia (PTH), salpingoliths and transition from adenoma to borderline ovarian tumors (BOT): A systematic analysis of 74 BOT with different histologic types.

    Science.gov (United States)

    Horn, Lars-Christian; Angermann, Karolin; Hentschel, Bettina; Einenkel, Jens; Höhn, Anne Kathrin

    2017-04-01

    Borderline ovarian tumors (BOT) arise from cystadenomas and represent a transition step within the development of low-grade ovarian carcinomas (Type I tumors). That pathway mirrors the adenoma-to-carcinoma sequence known for colorectal cancer. It has been suggested that papillary tubal hyperplasia (PTH) and salpingoliths may be associated with the development of BOT. To evaluate the frequency of the presence of benign cystadenoma and its transition to BOT in a given patient as well as the presence of PTH and salpingoliths we re-valuated in 74 consecutive cases of BOT with different histologic types. The majority of cases represented serous-BOT (60.8%), followed by mucinous BOT (25.7%), other histologic types were rare. 86.5% showed an adenoma-BOT sequence, which was seen in all mucinous BOT but was missed in 15.6% of serous BOT. Two cases had salpingoliths without associated PTH. PTH was seen in four out of the 74 (5.4%) BOT and occurred only in cases with serous histology. The vast majority of BOT represent a transition from benign cystadenoma to BOT in cases with mucinous and serous histology. Salpingoliths are rarely seen in association with BOT and occurred exclusively in BOT with serous histology. PTH may represent a distinct lesion but is rarely seen in association with BOT, especially in those with non-serous histology. Further studies are needed to evaluate the frequency and pathogenetic association of PTH with BOT. Copyright © 2017 Elsevier GmbH. All rights reserved.

  9. Common variants in the UBC9 gene encoding the SUMO-conjugating enzyme are associated with breast tumor grade.

    Science.gov (United States)

    Dünnebier, Thomas; Bermejo, Justo Lorenzo; Haas, Susanne; Fischer, Hans-Peter; Pierl, Christiane B; Justenhoven, Christina; Brauch, Hiltrud; Baisch, Christian; Gilbert, Michael; Harth, Volker; Spickenheuer, Anne; Rabstein, Sylvia; Pesch, Beate; Brüning, Thomas; Ko, Yon-Dschun; Hamann, Ute

    2009-08-01

    UBC9 encodes a protein that conjugates small ubiquitin-related modifier (SUMO) to target proteins resulting in a change of their localization, activity or stability. Genetic variability may affect expression and activity of UBC9 and may have an impact on breast tumor progression. We investigated associations between UBC9 genotypes and histopathological parameters in 1,021 breast cancer cases of the GENICA collection using a single nucleotide polymorphism (SNP) tagging approach. Genotyping analyses were performed by TaqMan(R) allelic discrimination. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by ordinal logistic regression. Multiple imputation based on HapMap data was applied to boost the power of the study. The study revealed significant associations of three UBC9 SNPs with histological grade (rs7187167, p(trend) = 0.001; rs11248866, p(trend) = 0.009; rs8052688, p(trend) = 0.008). Model selection identified a recessive penetrance model for rs7187167 as the best representation of tumor grade (global p = 0.001). This model did not improve by inclusion of additional SNPs in linkage disequilibrium. Imputation of SNPs in a 300 kb region around the genotyped SNPs supported rs7187167 as a major contributor to tumor grade. Compared with common allele carriers, rare homozygotes presented less frequently with high grade tumors (G3 vs. G1: OR 0.26, 95% CI 0.11-0.62; G3 vs. G2: OR 0.45, 95% CI 0.23-0.86). In addition to tumor size, nodal status and estrogen receptor status, multivariate analyses confirmed an independent role of rs7187167 as predictor of tumor grade (p = 0.0003). The present results underline the value of genetic variation in UBC9 for breast cancer prognosis.

  10. Diagnostic efficacy of smear cytology and Robinson’s cytological grading of canine mammary tumors with respect to histopathology, cytomorphometry, metastases and overall survival

    Science.gov (United States)

    Czopowicz, Michał; Gruk-Jurka, Anna; Wojtkowska, Agata; Sapierzyński, Rafał; Jurka, Piotr

    2018-01-01

    Cytology is a simple, rapid, and inexpensive method used for pre-operative diagnosis of canine mammary tumors (CMTs) in veterinary practice. Studies related to human breast cancer showed the Robinson’s grading system—established for invasive ductal carcinoma, not otherwise specified (IDC, NOS) and used on cytological material—to not only closely correspond to the histopathological grading but also be helpful in assessing prognosis and selecting most suitable treatments before surgery. The objectives of this study were: to evaluate the accuracy of cytological diagnosis and cytological Robinson’s grading system compared to the histopathological examination of CMTs; to compare of cytological features and cytomorphometric parameters with tumor behavior, as well as cytological and histological grading; and to determine an association of the Robinson’s grading system and cytological background details with metastases, and patients’ survival. We report substantial diagnostic accuracy in detecting simple types and high grade tumors. Cytological diagnosis of tumor behavior showed relatively low sensitivity and specificity compared to human studies, and this might be caused by the heterogeneous morphology of CMTs. The presence of mucosecretory material and extracellular matrix was not significantly associated with tumor behavior. We report a positive correlation between both grading systems and cytological features (included in Robinson’s grading), the presence of necrotic debris, inflammation, and red blood cells. A negative correlation was determined only for the presence of extracellular matrix. The univariate and multivariate analyses confirmed a significantly higher risk of developing metastasis and shorter overall survival for dogs with tumors of grade 2 or 3 on cytology. In addition, these tumors were the most common cause of CMT-related deaths in dogs. Taken together, our findings suggest that the Robinson’s method of cytological grading applied for

  11. Association between relative liver enhancement on gadoxetic acid enhanced magnetic resonance images and histologic grade of hepatocellular carcinoma.

    Science.gov (United States)

    Jin, Young-Joo; Cho, Soon Gu; Lee, Kun Young; Kim, Joon Mee; Lee, Jin Woo

    2017-07-01

    We evaluated the association between histologic grade of hepatocellular carcinoma (HCC) and degree of HCC enhancement on Gd-EOB-DTPA (Gadoxetic acid, Primovist)-enhanced magnetic resonance images (MRI) in HCC patients.A total of 121 patients who underwent curative surgical resection for HCC at our institution between January 2012 and March 2015 were retrospectively analyzed. Gadoxetic acid enhanced MRI was performed in all patients before surgery. Signal intensities of HCC and peri-HCC areas were measured using regions of interest. Relative intensity ratios of HCC lesions versus the surrounding non-HCC areas on unenhanced images (precontrast ratio) and on hepatobiliary phase images (postcontrast ratio) were calculated. Relative liver enhancement (RLE) ratios (post-contrast ratio/pre-contrast ratio) were also calculated. The Edmondson-Steiner (E-S) grading system was used to histologically grade HCC.E-S grades I, II, III, and IV were observed in 2 (1.7%), 14 (11.6%), 54 (44.6%), and 51 (42.1%) of the patients, respectively. For E-S grades I/II (n = 16), III (n = 54), and IV (n = 51), mean RLE (%) were 85.5, 84.9, and 71.2, respectively (P = .01), and for E-S grades I-III (n = 70) and IV (n = 51), mean RLE (%) were 85.1 and 71.2, respectively (P enhanced MR images of HCC patients.

  12. Usefulness of p16(INK4a) staining for managing histological high-grade squamous intraepithelial cervical lesions.

    Science.gov (United States)

    Miralpeix, Ester; Genovés, Jordi; Maria Solé-Sedeño, Josep; Mancebo, Gemma; Lloveras, Belen; Bellosillo, Beatriz; Alameda, Francesc; Carreras, Ramon

    2017-02-01

    p16(INK4a) (p16) tumor-suppressor protein is a biomarker of human papillomavirus (HPV) oncogenic activity that has revealed a high rate of positivity in histological high-gade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 2 (HSIL/CIN2) lesions. However, there is a paucity of data regarding p16 status as a surrogate marker of HSIL/CIN2 evolution. The aim of this study was to evaluate the outcome of HSIL/CIN2 patients followed up without treatment for 12 months according to p16 immunohistochemical staining. Patients diagnosed with HSIL/CIN2 colposcopy-directed biopsy, were recruited prospectively between December 2011 and October 2013. p16 staining was performed in all HSIL/CIN2 diagnostic biopsies. Follow-up was conducted every 4 months by cytology, colposcopy and biopsy if suspicion of progression and once the 12 months of follow-up completed. Complete regression, partial regression, persistence, and progression rates of HSIL/CIN2 were defined as a final outcome. A total of 96 patients were included in the analysis. The rate of spontaneous regression was 64%, while 28% had persistent disease, and 8% progressed at 12 months of follow-up. p16 was positive in 81 (84%) initial HSIL/CIN2 biopsies. Regression was observed in all 15 p16 negative cases and in 46 of 81 (57%) p16 positive cases (P=0.001). In conclusion, patients with p16 negative HSIL/CIN2 biopsy had a high rate of regression during first 12 months of follow-up. Status of p16 staining could be considered for HSIL/CIN2 management.

  13. Grading of complications of transurethral resection of bladder tumor using Clavien–Dindo classification system

    Directory of Open Access Journals (Sweden)

    Ankur Bansal

    2016-01-01

    Conclusions: Clavien–Dindo classification system can be easily applied to grade the complications of TURBT, and it is easily reproducible. We observed that TURBT was a safe procedure. Majority of complications were Grade 1–2 (90% and Grade 3–5 were rare (10%. Postoperative bleeding is the most common complication. A greater rate of complications of TURBT was associated with patient age, size of tumor, location of tumor, surgeon experience, resection time, and completion of tumor resection.

  14. Tumor Grade versus Expression of Invasion-Related Molecules in Astrocytoma.

    Science.gov (United States)

    Virga, József; Bognár, László; Hortobágyi, Tibor; Zahuczky, Gábor; Csősz, Éva; Kalló, Gergő; Tóth, Judit; Hutóczki, Gábor; Reményi-Puskár, Judit; Steiner, László; Klekner, Almos

    2018-01-01

    Peritumoral infiltration is characteristic of astrocytomas even in low-grade tumors. Tumor cells migrate to neighbouring tissue and cause recurrence. The extracellular matrix (ECM) plays a role in tumor invasion; expression levels of its components' have been linked to tumor invasion. This study determines the mRNA and protein expression of 20 invasion-related ECM components by examining non-tumor brain; grade I-II-III astrocytoma and glioblastoma samples. Expression levels were measured by QRT-PCR and mass-spectroscopy. The connection between the expression pattern and tumor grade is statistically analyzed. During the analysis of data, key molecules (brevican, cadherin-12, fibronectin and integrin-β1) correlating the most with tumor grade were selected. While the mRNA level of brevican, ErbB2, fibronectin, integrin-β1 and versican discriminates low-grade from high-grade gliomas, of proteins RHAMM, integrin-α1 and MMP2 seems important. The expression pattern was found to be distinctive for tumor grade, as statistical classifiers are capable of identifying an unknown sample's grade using them. Furthermore, normal brain and glioma expression patterns, along with low-grade astrocytoma and glioblastoma samples, differ the most. Determining the invasion-related molecules' expression profile provides extra information regarding the tumor's clinical behavior. Additionally, identifying molecules playing a key role in glioma invasion could uncover potential therapeutic targets in the future.

  15. Expression of neurotensin receptor 1 in endometrial adenocarcinoma is correlated with histological grade and clinical outcome.

    Science.gov (United States)

    Agopiantz, Mikaël; Forgez, Patricia; Casse, Jean-Matthieu; Lacomme, Stéphanie; Charra-Brunaud, Claire; Clerc-Urmès, Isabelle; Morel, Olivier; Bonnet, Céline; Guéant, Jean-Louis; Vignaud, Jean-Michel; Gompel, Anne; Gauchotte, Guillaume

    2017-10-01

    The promalignant effects of neurotensin (NTS) are sustained in many solid tumors, including hormone-dependent cancers. As the endometrium is also subjected to hormonal regulation, we evaluated the contribution of NTS to endometrial carcinogenesis. Neurotensin receptor 1 (NTSR1) expression and NTSR1 promoter methylation (HM450) were analyzed in 385 cases of endometrial carcinoma from The Cancer Genome Atlas (TCGA). Additionally, from a series of 100 endometrial carcinomas, and 66 benign endometrium samples, NTS and NTSR1 labeling was evaluated by immunohistochemistry. Using TCGA series, NTSR1 messenger RNA (mRNA) level was negatively correlated with overall survival (OS) and progression-free survival (PFS) (p = 0.0012 and p = 0.0116, respectively), and positively correlated with the grade (p = 0.0008). When including only endometrioid carcinomas, NTSR1 mRNA level continued to be negatively correlated with OS (log-rank: p endometrial cancer, highlighting the contribution of NTS in endometrial cancer progression and its uses as a prognostic marker, and as a potential therapeutic target.

  16. Smooth Muscle Hyperplasia/Hypertrophy is the Most Prominent Histological Change in Crohn's Fibrostenosing Bowel Strictures: A Semiquantitative Analysis by Using a Novel Histological Grading Scheme.

    Science.gov (United States)

    Chen, Wenqian; Lu, Cathy; Hirota, Christina; Iacucci, Marietta; Ghosh, Subrata; Gui, Xianyong

    2017-01-01

    The simplistically and ambiguously termed 'fibrostenosis' of bowel is a hallmark of severe Crohn's disease [CD] and a major contributor to medical treatment failure. Non-invasive imaging assessment and novel medical therapy targeting this condition are under investigation, which particularly requires a better understanding of the underlying histological basis. We analysed 48 patients with stricturing Crohn's ileitis or/and colitis that required surgical resection. The most representative sections of the fibrostenotic, non-stenotic and uninvolved regions were reviewed for histological analysis. For each layer of bowel wall (mucosa including muscularis mucosae [MU], submucosa [SM], muscularis propria [MP], subserosal adventitia [SS]), histological abnormalities were evaluated individually, including active and chronic inflammation, fibrosis, smooth muscle hyperplasia or hypertrophy, neuronal hypertrophy and adipocyte proliferation. A novel semiquantitative histological grading scheme was created. The most significant histopathological features characterizing the stricturing intestines were smooth muscle hyperplasia of SM, hypertrophy of MP and chronic inflammation. The muscular alteration was predominant in all layers. The overall muscular hyperplasia/hypertrophy was positively correlated with chronic inflammation and negatively correlated with fibrosis, whereas SM muscular hyperplasia was also associated with MU active inflammation. Similar changes, to a lesser extent, occurred in the adjacent non-stenotic inflamed bowel as well. In CD-associated 'fibrostenosis', it is the smooth muscle hyperplasia/hypertrophy that contributes most to the stricturing phenotype, whereas fibrosis is less significant. The 'inflammation-smooth muscle hyperplasia axis' may be the most important in the pathogenesis of Crohn's strictures. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please

  17. Histological grade as an alternative to the Ki67 labeling index is only available for luminal-type breast cancers.

    Science.gov (United States)

    Hayashi, Satoshi; Kitada, Masahiro; Sato, Kazuhiro; Matsuda, Yoshinari; Ishibashi, Kei; Oikawa, Kensuke; Miyokawa, Naoyuki; Hirata, Satoshi

    2014-01-01

    The 2011 St. Gallen Consensus Statement advocated using histological grade (HG) as a proliferation marker of breast cancer (BC) if reliable Ki67 labeling index (Ki67-LI) assessment is not available. However, it has been difficult to evaluate tumor aggressiveness in case of HG2. A total of 259 cases of BC were assessed for HG, Ki67-LI and other clinicopathological features. The cut point for Ki67-LI was interpreted as low and high using a 14% threshold. The average age at diagnosis was 58.2 years (range 28-86); 64.9% of the patients were postmenopausal. Of the 259 cases, 151 were stage I, 78 were stage II, 29 were stage III, and 1 was stage IV. The subtypes based on immunohistochemical staining were 60 cases of luminal A (LA) type (23.2%), 37 cases of luminal B (LB) (HER2-) type (14.3%), 91 cases of LB (HER2+) type (35.1%), 40 cases of human epidermal growth factor receptor 2 (HER2) type (15.4%) and 31 cases of triple negative (TN) type (12%). HG was 1 (89 cases, 34.4 %), 2 (117 cases, 45.2%) and 3 (53 cases, 20.5%). High Ki67-LI cases were observed in HG1 (37.1%), HG2 (56.4%) and HG3 (96.2%). Especially in cases of HG2, high Ki67-LI cases were observed in 0 % of LA type, 100% of LB (HER2-) type, 71.2% of LB (HER2+) type, 68.8% of HER2 type and 40.0% of TN type. The average Ki67-LI was 6.0 ± 3.8 (LA type), 31.4 ± 15.7 [LB (HER2-) type], 20.2 ± 14.8 [LB (HER2+) type], 32.7 ± 21.9 (HER2 type) and 55.7 ± 32.2 (TN type). All LA-type cases and 66.7% of LB (HER2+)-type cases were low Ki67-LI. Our study demonstrates that all LA-type cases and most HG1 of LB (HER2+)-type cases are low proliferative. However, HG was not informative enough for estimating tumor proliferation in cases of LB (HER2-), HER2 and TN types. It is necessary to add other proliferation tools such as the gene expression profiling tool and Ki67-LI except in LA and HG1 of LB (HER2+)-type cases.

  18. Computed tomography in the evaluation of malignant pleural mesothelioma-Association of tumor size to a sarcomatoid histology, a more advanced TNM stage and poor survival.

    Science.gov (United States)

    Paajanen, Juuso; Laaksonen, Sanna; Ilonen, Ilkka; Wolff, Henrik; Husgafvel-Pursiainen, Kirsti; Kuosma, Eeva; Ollila, Hely; Myllärniemi, Marjukka; Vehmas, Tapio

    2018-02-01

    Appropriate clinical staging of malignant pleural mesothelioma (MPM) is critical for correct treatment decisions. Newly revised TNM staging protocol has been released for MPM. We investigated baseline computed tomography (CT) characteristics of MPM patients, the new staging system and a simple tumor size (TS) assessment in terms of survival. As part of our study that included all MPM patients diagnosed in Finland 2000-2012, we retrospectively reviewed 161 CT scans of MPM patients diagnosed between 2007 and 2012 in the Hospital District of Helsinki and Uusimaa. TS was estimated by using the maximal tumor thickness and grading tumor extension along the chest wall. Cox Regression models were used to identify relationships between survival, clinicopathological factors and CT-findings. The median length of follow-up was 9.7 months and the median survival 9.1 months. The right sided tumors tended to be more advanced at baseline and had worse prognosis in the univariate analyses. In the multivariate survival model, TS, pleural effusion along with non-epithelioid histology were predictors of poor survival. Tumor size correlated significantly with a sarcomatoid histopathological finding and several parameters linked to a more advanced TNM stage. Most patients were diagnosed with locally advanced stage, while 12 (7%) had no sign of the tumor in CT. In this study, we demonstrate a novel approach for MPM tumor size evaluation that has a strong relationship with mortality, sarcomatoid histology and TNM stage groups. TS could be used for prognostic purposes and it may be a useful method for assessing therapy responses. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Evaluation of a new histologic staging and grading system for primary biliary cirrhosis in comparison with classical systems.

    Science.gov (United States)

    Kakuda, Yuko; Harada, Kenichi; Sawada-Kitamura, Seiko; Ikeda, Hiroko; Sato, Yasunori; Sasaki, Motoko; Okafuji, Hirofumi; Mizukoshi, Eishiro; Terasaki, Shuichi; Ohta, Hajime; Kasashima, Satomi; Kawashima, Atsuhiro; Kaizaki, Yasuharu; Kaneko, Shuichi; Nakanuma, Yasuni

    2013-06-01

    Recently, our research team proposed a new histologic staging and grading system for primary biliary cirrhosis (PBC) that takes into account necroinflammatory activity and histologic heterogeneity. The present study aimed to confirm the usefulness of the new evaluation system. A total of 152 liver biopsy specimens and clinical data (including outcomes in patients with PBC before treatment with ursodeoxycholic acid) were analyzed with respect to the new system. Staging was evaluated on the basis of 3 histologic components (fibrosis, bile duct loss, and deposition of orcein-positive granules), and grading was assessed on the basis of chronic cholangitis activity and hepatitis activity. Concurrently, the classical systems, that is, the Scheuer and Ludwig staging systems, were also assessed and compared with our new system. PBC cases showed different distributions in each stage of the 3 systems. The new staging and grading system reflected liver dysfunctions before specific treatment. This was on a par with the results obtained using the classical systems. Development of cirrhosis-related conditions correlated well with the new staging system compared with the 2 classical staging systems, and in particular, the amount of deposition of orcein-positive granules could reflect development of cirrhosis-related conditions (scores 0-1 versus scores 2-3 groups, P new PBC staging system was demonstrated to reflect clinicolaboratory features, and its progression was associated with the development of cirrhosis-related conditions. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Recurrent DGCR8, DROSHA, and SIX homeodomain mutations in favorable histology Wilms tumors | Office of Cancer Genomics

    Science.gov (United States)

    We report the most common single-nucleotide substitution/deletion mutations in favorable histology Wilms tumors (FHWTs) to occur within SIX1/2 (7% of 534 tumors) and microRNA processing genes (miRNAPGs) DGCR8 and DROSHA (15% of 534 tumors). Comprehensive analysis of 77 FHWTs indicates that tumors with SIX1/2 and/or miRNAPG mutations show a pre-induction metanephric mesenchyme gene expression pattern and are significantly associated with both perilobar nephrogenic rests and 11p15 imprinting aberrations.

  1. Correlation of serum intercellular adhesion molecule 1 and vascular endothelial growth factor with tumor grading and staging in breast cancer patients.

    Science.gov (United States)

    Haghi, Alireza Rastgoo; Vahedi, Amir; Shekarchi, Ali Akbar; Kamran, Aziz

    2017-01-01

    Breast cancer is the most common cancer among women. There are several prognostic factors for this disease. The aim of this article is to explore the correlation of serum level of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM1) with tumor, node, metastasis staging and grading of breast cancer. Serum samples of 51 patients with breast cancer were assessed with enzyme-linked immunosorbent assay for the level of VEGF and ICAM1 preoperatively. After the operation, histopathologic specimens stained with hematoxylin and eosin were evaluated for tumor size, histopathologic subtype, grade, lymph node, vascular and lymphatic involvement. Then, the correlation of tumor stage and grade and serum level of markers was analyzed. There was no significant correlation between serum level of markers with vascular invasions, lymph node involvement, and menstruation. There was a weak correlation between tumor size and serum level of ICAM1 with Pearson score correlation, but there was no significant correlation with VEGF. There was no significant correlation between tumor grading and staging with the level of markers. There was a significant correlation between the level of VEGF and ICAM1 and histologic type of tumors in invasive through in situ tumors. Levels of VEGF and ICAM1 can be used as a predictor of tumor invasion and also for target therapy.

  2. Relationship between the presence of liver metastases with histological grading, depth of invasion and nodal involvement in sporadic adenocarcinoma of the large intestine

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    Eduardo Cambruzzi

    2015-08-01

    Full Text Available ABSTRACTIntroduction:Large intestine adenocarcinoma (LIA is the most common cancer of the gastrointestinal tract, and corresponds to the fifth most common malignancy in Brazil. The main prognostic factors related to LIA are depth of tumor invasion and perivisceral lymph nodes status.Objective:To estimate the relationship between pathological findings and the presence of liver metastases (LM in LIA cases.Method:We evaluated 51 cases of LIA, previously submitted to surgical resection, in order to determine the following variables: topography, tumor size, macroscopic appearance, degree of differentiation, depth of invasion, nodal status, and presence of LM.Results:The average age was 64.8 years, with predominance of men (n = 26/51.0% and lesions in the sigmoid colon (n = 18/35.3%. The main general characteristics of the sample were ulcerative-vegetative lesions (n = 20/39.2%, no annular tumors (n = 3/64.7%, moderately differentiated tumor (n = 44/86.3%, absence of mucinous areas (n = 40/78.4%, and mesocolon invasion (n = 29/56.9%. LM were found in 14 cases (27.5%, and is associated with presence of nodal metastases (p = 0.005. Tumor size (p = 0.72, macroscopic appearance (p = 0.362, histological grade (p = 0.147, and depth of invasion (p = 0.195 showed no association with LM presence.Conclusion:LIA has a wide anatomical and pathological heterogeneity. In this study, the presence of LM associated with LIA was related to perivisceral lymph nodes status, with no relation to tumor size, degree of differentiation, and depth of invasion, which suggests that identifying neoplastic angiolymphatic invasion is a possible predictor of liver involvement.

  3. Familial breast cancer. Part II: Relationships with histology, staging, steroid receptors and serum tumor markers.

    Science.gov (United States)

    Gavrilov, I; Nacheva, M; Tzingilev, D

    2002-01-01

    To identify differences in clinical characteristics, histological features, hormone receptor status, and tumor marker expression between patients with sporadic and familial breast cancer. As in the previous Part I of this study, two groups of women with breast cancer were compared. The first group (group I) included 504 patients with a family history of breast cancer. The second (control) group (group II) consisted of 300 patients not reporting such a history in their relatives. The examined parameters in this report were stage and axillary lymph node involvement at the time of the initial diagnosis, treatment methods, hormone receptor status, and serum levels of the tumor markers CEA and CA 15.3. The data were processed and analysed using the SPSS statistical package. The statistical significance of differences between groups and subgroups was evaluated by x(2) Pearson's test and Student's paired t-test. Compared to sporadic cases, patients with familial breast cancer were more often diagnosed at an advanced III or IV stage; metastatic involvement of the regional lymph nodes was more frequent in group I patients. In the same group more radical surgical procedures combined with chemotherapy and local irradiation were performed. In group I the percentage of negative hormone receptors was higher (35.3% versus 22.6%; p result of their particular characteristics, these patients require more radical surgical techniques combined with pre- or postoperative local radiotherapy and systemic chemotherapy.

  4. Intraductal papillary mucinous neoplasm of the pancreas: cytologic features predict histologic grade

    National Research Council Canada - National Science Library

    Michaels, Paul J; Brachtel, Elena F; Bounds, Brenna C; Brugge, William R; Pitman, Martha Bishop

    2006-01-01

    Intraductal papillary mucinous neoplasm (IPMN) is an increasingly recognized cystic neoplasm of the pancreas, histologically classified by the degree of epithelial atypia and by the presence or absence of invasion of the cyst wall...

  5. The combination of SMAD4 expression and histological grade of dysplasia is a better predictor for the malignant transformation of oral leukoplakia.

    Science.gov (United States)

    Xia, Rong-Hui; Song, Xiao-Meng; Wang, Xiao-Jing; Li, Jiang; Mao, Li

    2013-01-01

    Oral leukoplakia (OL) is the most common premalignancy in the oral cavity and can progress to oral squamous cell carcinoma (OSCC). SMAD4 is a tumor suppressor implicated in multiple cancer types including OSCC. To assess the role of SMAD4 in oral leukoplakia malignant transformation, the authors investigated SMAD4 expression patterns in OL and OSCC using a highly specific antibody and correlated the patterns with the risk of malignant transformation oral leukoplakia. Immunohistochemistry and a quantitative imaging system were used to measure SMAD4 expression in OL from 88 OL patients, including 22 who later went through malignant transformation, and their OSCC counterpart. Forty-three (48.9%) of the 88 OL patients had strong SMAD4 expression. SMAD4 expression had no significant correlation with patients' clinicopathological parameters. Interestingly, 17 (39.5%) of the 43 OL lesions with strong SMAD4 expression went through malignant transformation whereas only 5 (11.1%) of the 45 OL lesions with weak SMAD4 expression did so (p = 0.002). The SMAD4 expression in OL was much higher than that in their OSCC counterpart. Kaplan-Meier analysis revealed that the combination of SMAD4 expression and histological grade of dysplasia (p = 0.007) is a better predictor for the malignant transformation of oral leukoplakia. In the multivariate analysis, both SMAD4 expression and grade of dysplasia were identified as independent factors for OL malignant transformation risk (p = 0.013 and 0.021, respectively). It was concluded that high SMAD4 expression may be indicative of an early carcinogenic process in OL and serve as an independent biomarker in assessing malignant transformation risk in patients with OL, and the combination of SMAD4 expression and histological grade of dysplasia is a better predictor for the malignant transformation of oral leukoplakia.

  6. Tumor Budding in Colorectal Carcinoma: Confirmation of Prognostic Significance and Histologic Cutoff in a Population-based Cohort.

    Science.gov (United States)

    Graham, Rondell P; Vierkant, Robert A; Tillmans, Lori S; Wang, Alice H; Laird, Peter W; Weisenberger, Daniel J; Lynch, Charles F; French, Amy J; Slager, Susan L; Raissian, Yassaman; Garcia, Joaquin J; Kerr, Sarah E; Lee, Hee Eun; Thibodeau, Stephen N; Cerhan, James R; Limburg, Paul J; Smyrk, Thomas C

    2015-10-01

    Tumor budding in colorectal carcinoma has been associated with poor outcome in multiple studies, but the absence of an established histologic cutoff for "high" tumor budding, heterogeneity in study populations, and varying methods for assessing tumor budding have hindered widespread incorporation of this parameter in clinical reports. We used an established scoring system in a population-based cohort to determine a histologic cutoff for "high" tumor budding and confirm its prognostic significance. We retrieved hematoxylin and eosin-stained sections from 553 incident colorectal carcinoma cases. Each case was previously characterized for select molecular alterations and survival data. Interobserver agreement was assessed between 2 gastrointestinal pathologists and a group of 4 general surgical pathologists. High budding (≥ 10 tumor buds in a ×20 objective field) was present in 32% of cases, low budding in 46%, and no budding in 22%. High tumor budding was associated with advanced pathologic stage (P 2 times risk of cancer-specific death (hazard ratio = 2.57 [1.27, 5.19]). After multivariate adjustment, by penalized smoothing splines, we found increasing tumor bud counts from 5 upward to be associated with an increasingly shortened cancer-specific survival. By this method, a tumor bud count of 10 corresponded to approximately 2.5 times risk of cancer-specific death. The interobserver agreement was good with weighted κ of 0.70 for 2 gastrointestinal pathologists over 121 random cases and 0.72 between all 6 pathologists for 20 random cases. Using an established method to assess budding on routine histologic stains, we have shown that a cutoff of 10 for high tumor budding is independently associated with a significantly worse prognosis. The reproducibility data provide support for the routine widespread implementation of tumor budding in clinical reports.

  7. HyMaP: A hybrid magnitude-phase approach to unsupervised segmentation of tumor areas in breast cancer histology images.

    Science.gov (United States)

    Khan, Adnan M; El-Daly, Hesham; Simmons, Emma; Rajpoot, Nasir M

    2013-01-01

    Segmentation of areas containing tumor cells in standard H&E histopathology images of breast (and several other tissues) is a key task for computer-assisted assessment and grading of histopathology slides. Good segmentation of tumor regions is also vital for automated scoring of immunohistochemical stained slides to restrict the scoring or analysis to areas containing tumor cells only and avoid potentially misleading results from analysis of stromal regions. Furthermore, detection of mitotic cells is critical for calculating key measures such as mitotic index; a key criteria for grading several types of cancers including breast cancer. We show that tumor segmentation can allow detection and quantification of mitotic cells from the standard H&E slides with a high degree of accuracy without need for special stains, in turn making the whole process more cost-effective. BASED ON THE TISSUE MORPHOLOGY, BREAST HISTOLOGY IMAGE CONTENTS CAN BE DIVIDED INTO FOUR REGIONS: Tumor, Hypocellular Stroma (HypoCS), Hypercellular Stroma (HyperCS), and tissue fat (Background). Background is removed during the preprocessing stage on the basis of color thresholding, while HypoCS and HyperCS regions are segmented by calculating features using magnitude and phase spectra in the frequency domain, respectively, and performing unsupervised segmentation on these features. All images in the database were hand segmented by two expert pathologists. The algorithms considered here are evaluated on three pixel-wise accuracy measures: precision, recall, and F1-Score. The segmentation results obtained by combining HypoCS and HyperCS yield high F1-Score of 0.86 and 0.89 with re-spect to the ground truth. In this paper, we show that segmentation of breast histopathology image into hypocellular stroma and hypercellular stroma can be achieved using magnitude and phase spectra in the frequency domain. The segmentation leads to demarcation of tumor margins leading to improved accuracy of mitotic cell

  8. HyMaP: A hybrid magnitude-phase approach to unsupervised segmentation of tumor areas in breast cancer histology images

    Directory of Open Access Journals (Sweden)

    Adnan M Khan

    2013-01-01

    Full Text Available Background: Segmentation of areas containing tumor cells in standard H&E histopathology images of breast (and several other tissues is a key task for computer-assisted assessment and grading of histopathology slides. Good segmentation of tumor regions is also vital for automated scoring of immunohistochemical stained slides to restrict the scoring or analysis to areas containing tumor cells only and avoid potentially misleading results from analysis of stromal regions. Furthermore, detection of mitotic cells is critical for calculating key measures such as mitotic index; a key criteria for grading several types of cancers including breast cancer. We show that tumor segmentation can allow detection and quantification of mitotic cells from the standard H&E slides with a high degree of accuracy without need for special stains, in turn making the whole process more cost-effective. Method: Based on the tissue morphology, breast histology image contents can be divided into four regions: Tumor, Hypocellular Stroma (HypoCS, Hypercellular Stroma (HyperCS, and tissue fat (Background. Background is removed during the preprocessing stage on the basis of color thresholding, while HypoCS and HyperCS regions are segmented by calculating features using magnitude and phase spectra in the frequency domain, respectively, and performing unsupervised segmentation on these features. Results: All images in the database were hand segmented by two expert pathologists. The algorithms considered here are evaluated on three pixel-wise accuracy measures: precision, recall, and F1-Score. The segmentation results obtained by combining HypoCS and HyperCS yield high F1-Score of 0.86 and 0.89 with re-spect to the ground truth. Conclusions: In this paper, we show that segmentation of breast histopathology image into hypocellular stroma and hypercellular stroma can be achieved using magnitude and phase spectra in the frequency domain. The segmentation leads to demarcation of tumor

  9. Pancreatic neuroendocrine neoplasms: Correlation between MR features and pathological tumor grades.

    Science.gov (United States)

    Jin, Feng; Wang, Kai; Qin, Ting-Ting; Li, Xin; Guo, Feng; Ma, Gui-Na; Hu, Xue-Han; Han, Ping

    2017-08-01

    This study investigated the accuracy of MRI features in differentiating the pathological grades of pancreatic neuroendocrine neoplasms (PNENs). A total of 31 PNENs patients were retrospectively evaluated, including 19 cases in grade 1, 5 in grade 2, and 7 in grade 3. Plain and contrastenhanced MRI was performed on all patients. MRI features including tumor size, margin, signal intensity, enhancement patterns, degenerative changes, duct dilatation and metastasis were analyzed. Chi square tests, Fisher's exact tests, one-way ANOVA and ROC analysis were conducted to assess the associations between MRI features and different tumor grades. It was found that patients with older age, tumors with higher TNM stage and without hormonal syndrome had higher grade of PNETs (all Pgrades (all Pgrade 3 from grade 1 and grade 2 tumors. Features of peripancreatic tissue or vascular invasion, and distant metastasis showed high specificity but relatively low sensitivity. In conclusion, larger size, poorlydefined margin, heterogeneous enhanced pattern during arterial phase, duct dilatation and the presence of metastases are common features of higher grade PNENs. Plain and contrast-enhanced MRI provides the ability to differentiate tumors with different pathological grades.

  10. Interlaboratory Variability in the Histologic Grading of Colorectal Adenocarcinomas in a Nationwide Cohort

    NARCIS (Netherlands)

    Kuijpers, Chantal C H J; Sluijter, Caro E.; von der Thüsen, Jan H.; Grünberg, Katrien; van Oijen, Martijn G H; van Diest, Paul J.; Jiwa, Mehdi; Nagtegaal, Iris D.; Overbeek, Lucy I H; Willems, Stefan M.

    Differentiation grade of colorectal adenocarcinoma (CRC) is a prognostic factor and important for therapy selection. In patients with stage II colon cancer, poor differentiation is an indication for adjuvant chemotherapy. The variability in daily practice in the grading of CRC was assessed in a

  11. Some growth factors in neoplastic tissues of brain tumors of different histological structure

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    O. I. Kit

    2016-01-01

    Full Text Available Introduction. Pathologic angiogenesis is typical for angiogenic diseases including tumor growth. Vascular endothelial growth factor (VEGF, fibroblast growth factor (FGF, transforming growth factor alpha and beta (which are also known as “triggers” of angiogenesis, and other factors (Gacche, Meshram, 2013; Nijaguna et al., 2015 play a special role in its development. Evaluation of the important mechanisms of angiogenesis in physiological and pathological conditions remains to be a subject of heightened interest for the past 30 years. It is known that VEGF A is the main trigger of growing blood vessels into the tumor tissue. This is specific mitogen signal for endothelial cells that triggers the mechanisms of cell division and migration. VEGF-induced tumor vasculature has a number of structural and functional features that provide growth and progression of tumors, including increased permeability of blood vessels and their chaotic arrangement.Objective: to study in comparative aspect the level of certain growth factors in the following tissues: glioblastomas, brain metastasis of the breast cancer, meningiomas as well as corresponding peritumoral areas.Materials and methods. Tissue samples were obtained from 56 patients admitted to the surgical treatment in Rostov Research Institute of Oncology: 24 patients had glioblastomas, 19 patients had brain metastasis of the breast cancer, 13 patients with meningiomas without peritumoral edema. Histological control was carried out in all cases. Age of patients ranged from 35 to 72 years. The level of growth factor was detected in the samples of tumor tissue and regions immediately adjacent to the tumor foci (peritumoral area by the method of immunoassay and using standard test systems. The following growth factor were detected: VEGF-A and its receptors VEGF-R1 (BenderMedSystem, Austria, VEGF-C and its receptor VEGF-R3 (BenderMedSystem, Austria, EGF (Biosource, USA, IFR-1 and IFR-2 (Mediagnost, USA, TGF

  12. Multi-Parametric MRI and Texture Analysis to Visualize Spatial Histologic Heterogeneity and Tumor Extent in Glioblastoma.

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    Leland S Hu

    Full Text Available Genetic profiling represents the future of neuro-oncology but suffers from inadequate biopsies in heterogeneous tumors like Glioblastoma (GBM. Contrast-enhanced MRI (CE-MRI targets enhancing core (ENH but yields adequate tumor in only ~60% of cases. Further, CE-MRI poorly localizes infiltrative tumor within surrounding non-enhancing parenchyma, or brain-around-tumor (BAT, despite the importance of characterizing this tumor segment, which universally recurs. In this study, we use multiple texture analysis and machine learning (ML algorithms to analyze multi-parametric MRI, and produce new images indicating tumor-rich targets in GBM.We recruited primary GBM patients undergoing image-guided biopsies and acquired pre-operative MRI: CE-MRI, Dynamic-Susceptibility-weighted-Contrast-enhanced-MRI, and Diffusion Tensor Imaging. Following image coregistration and region of interest placement at biopsy locations, we compared MRI metrics and regional texture with histologic diagnoses of high- vs low-tumor content (≥80% vs <80% tumor nuclei for corresponding samples. In a training set, we used three texture analysis algorithms and three ML methods to identify MRI-texture features that optimized model accuracy to distinguish tumor content. We confirmed model accuracy in a separate validation set.We collected 82 biopsies from 18 GBMs throughout ENH and BAT. The MRI-based model achieved 85% cross-validated accuracy to diagnose high- vs low-tumor in the training set (60 biopsies, 11 patients. The model achieved 81.8% accuracy in the validation set (22 biopsies, 7 patients.Multi-parametric MRI and texture analysis can help characterize and visualize GBM's spatial histologic heterogeneity to identify regional tumor-rich biopsy targets.

  13. {sup 18}F-FDG PET in the assessment of tumor grade and prediction of tumor recurrence in intracranial meningioma

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    Lee, Jeong Won [Seoul National University College of Medicine, Department of Nuclear Medicine, Jongno-gu, Seoul (Korea); Seoul National University, Cancer Research Institute, Seoul (Korea); Kang, Keon Wook; Chung, June-Key; Lee, Dong Soo [Seoul National University College of Medicine, Department of Nuclear Medicine, Jongno-gu, Seoul (Korea); Seoul National University, Cancer Research Institute, Seoul (Korea); Seoul National University College of Medicine, Institute of Radiation Medicine, Seoul (Korea); Park, Sung-Hye [Seoul National University College of Medicine, Department of Pathology, Seoul (Korea); Lee, Sang Mi; Paeng, Jin Chul [Seoul National University College of Medicine, Department of Nuclear Medicine, Jongno-gu, Seoul (Korea); Lee, Myung Chul [Seoul National University College of Medicine, Department of Nuclear Medicine, Jongno-gu, Seoul (Korea); Seoul National University College of Medicine, Institute of Radiation Medicine, Seoul (Korea)

    2009-10-15

    The purpose of this study was to investigate the role of {sup 18}F-fluorodeoxyglucose (FDG) PET in detecting high-grade meningioma and predicting the recurrence in patients with meningioma after surgical resection. Fifty-nine patients (27 men and 32 women) with intracranial meningioma who underwent preoperative FDG PET and subsequent surgical resection were enrolled. All patients underwent clinical follow-up for tumor recurrence with a mean duration of 34{+-}20 months. The tumor to gray matter ratio (TGR) of FDG uptake was calculated and a receiver-operating characteristic (ROC) curve of the TGR was drawn to determine the cutoff value of the TGR for detection of high-grade meningioma. Further, univariate analysis with the log-rank test was performed to assess the predictive factors of meningioma recurrence. The TGR in high-grade meningioma (WHO grade II and III) was significantly higher than that in low-grade ones (WHO grade I) (p=0.002) and significantly correlated with the MIB-1 labeling index (r=0.338, p=0.009) and mitotic count of the tumor (r=0.284, p=0.03). The ROC analysis revealed that the TGR of 1.0 was the best cutoff value for detecting high-grade meningioma with a sensitivity of 43%, specificity of 95%, and accuracy of 81%. Of 59 patients, 5 (9%) had a recurrent event. In the log-rank test, the TGR, MIB-1 labeling index, presence of brain invasion, and WHO grade were significantly associated with tumor recurrence. The cumulative recurrence-free survival rate of patients with a TGR of 1.0 or less was significantly higher than that of patients with a TGR of more than 1.0 (p=0.0003) FDG uptake in meningioma was the significant predictive factor of tumor recurrence and significantly correlated with the proliferative potential of the tumor. (orig.)

  14. Complete histologic response to chemotherapy in a patient with a mediastinal yolk sac tumor: a case report.

    Science.gov (United States)

    Akasbi, Yousra; Najib, Rajae; Arifi, Samia; Lakranbi, Marouane; Smahi, Mohammed; Mellas, Nawfel; ELMesbahi, Omar

    2014-11-17

    Malignant mediastinal germ cell tumors are a rare disease and represent only 1% to 4% of all mediastinal tumors. Gonadal germ cell tumors are generally the most common type and constitute 90% of germ cell tumors. The mediastinum is the second most frequently affected area ahead of other extragonadal areas, which include the retroperitoneum, the sacrococcygeal area, and the central nervous system. We report on the case of a mediastinal yolk sac tumor with a complete histological response to chemotherapy. A 26-year-old Moroccan man, without a medical or surgical history, presented with a four-month history of chest distress, dyspnea, and a frequent dry cough for the previous month. A computed tomographic scan of the chest revealed a bulky mediastinal mass, which was biopsied. Histologically, the tumoral mass proved to be a yolk sac tumor. The serum level of alpha-fetoprotein of this patient was elevated to 19052 ng/ml.After 4 courses of preoperative chemotherapy, the patient underwent a surgical resection of the tumor, with a complete pathologic response.At the time of writing, the patient is alive with complete remission without any evidence of recurrence. Primary mediastinal Yolk sac neoplasm represent a unique entity, and as such require specialized management. The diagnosis should be made not only by morphological studies but the patient's age and the elevation of serum alpha-fetoprotein should also be considered. The utilization of cisplatin-based chemotherapy is associated with the best chance of a cure for this disease. This should be followed by surgical resection of the residual tumor in the nonseminomatous germ cell tumor.

  15. No association between BRCA1 immunohistochemical expression and tumor grade, stage or overall survival in platinum-treated epithelial ovarian cancer patients.

    Science.gov (United States)

    Shawky, Abd El-Aty; El-Hafez, Amal Abd; El-Tantawy, Dina; Hamdy, Rasha

    2014-01-01

    The aim of this work is to assess the frequency of BRCA1 protein immunohistochemical (IHC) expression in epithelial ovarian cancer (EOC) and to evaluate the association of BRCA1 expression with clinical and pathological characteristics and the overall survival (OS) of patients treated with postoperative platinum- based chemotherapeutic agents. This retrospective study was conducted on 35 cases of epithelial ovarian cancer selected from the files of the Pathology Department, Faculty of Medicine, Mansoura University, Egypt. Immunohistochemistry (IHC) was performed for BRCA1 gene protein. BRCA1 expression was compared to patient's age, tumor histology, grade, stage and OS time. Statistical analysis was carried out with the SPSS version 16.0 to assess significant associations. BRCA1 nuclear expression was detected in 40% of EOC, in which a mild increase in the percentage of positive cases was observed with serous histology, stage IV, and grade 3 carcinomas. There was a significant statistical difference in BRCA1 expression with regard to histological subtypes of EOC (p=0.048), but not grade or stage. Mean OS and survival rate were slightly better for BRCA1 expressing group, but there was no statistically significant difference (p=0.528). No association between BRCA1 immunohistochemical expression and tumor grade, stage or overall survival was noted in platinum-treated epithelial ovarian cancer patients.

  16. Villous Tumor of the Urinary Bladder Resembling Low-grade Mucinous Neoplasm of the Appendix.

    Science.gov (United States)

    Ito, Ayako; Sakura, Yuma; Sugimoto, Mikio; Kakehi, Yoshiyuki; Kuroda, Naoto

    2016-05-01

    Mucinous neoplasms of the urinary tract are very rare. We present a 63-year-old-women who had a sessile papillary villous tumor in urinary bladder. Although transurethral resection of the bladder tumor (TURBT) was performed, the villous tumor repetitively recurred and gradually spread to the entire surface of bladder lumen. Histopathologic and immunohistochemical examination showed that the lesion was very similar to low-grade mucinous neoplasm arising in appendix vermiformis. There are no reports on appendiceal metaplasia of urinary bladder mucosa. In this case, we describe this unprecedented neoplasm as "villous tumor of the urinary bladder resembling low-grade mucinous neoplasm of the appendix."

  17. Spindle proteins are differentially expressed in the various histological subtypes of testicular germ cell tumors

    Science.gov (United States)

    Skotheim, Rolf I.; Schjølberg, Aasa R.; Røislien, Jo; Lothe, Ragnhild A.; Clausen, Ole Petter F.

    2010-01-01

    Background: Testicular germ cell tumors (TGCTs) are characterized by an aneuploid DNA content. Aberrant expression of spindle proteins such as the Aurora kinases and the spindle checkpoint proteins MAD2 and BUB1B, are thought to contribute to the development of chromosomal instability and DNA aneuploidy in cancer. The importance of these spindle proteins remains unknown in the development of TGCTs, thus we have explored the expression levels of these proteins in normal and malignant testicular tissues. Materials and Methods: Using tissue microarrays the expression levels of Aurora kinase A (AURKA), Aurora kinase B (AURKB), BUB1B and MAD2 were measured in normal, preneoplastic and malignant testicular tissues of different histological subtypes from 279 orchidectomy specimens by means of immunohistochemistry. Results: All the spindle proteins except for AURKB were expressed in normal testis. Sixty-eight and 36%, respectively, of the primary spermatocytes in the normal testis were positive for BUB1B and MAD2, while only 5% of the cells were positive for AURKA. There was a significantly lower expression of the spindle checkpoint proteins in carcinoma in situ compared to normal testis (P=0.008 and P=0.043 for BUB1B and MAD2, respectively), while the level of AURKA was increased, however, not significantly (P=0.18). The extent of spindle protein expression varied significantly within the different histological subtypes of TGCTs (P<0.001 for AURKB, BUB1B and MAD2, P=0.003 for AURKA). The expression of AURKA was significantly elevated in both non-seminomas (P=0.003) and seminomas (P=0.015). The level of BUB1B was significantly decreased in non-seminomas (P<0.001). A similar tendency was observed for MAD2 (P=0.11). Conclusions: In carcinoma in situ of TGCTs the spindle checkpoint proteins MAD2 and BUB1B are significantly less expressed compared to normal testis, while the expression of AURKA is increased. We suggest that these changes may be of importance in the transition

  18. Spindle proteins are differentially expressed in the various histological subtypes of testicular germ cell tumors

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    Burum-Auensen Espen

    2010-01-01

    Full Text Available Background: Testicular germ cell tumors (TGCTs are characterized by an aneuploid DNA content. Aberrant expression of spindle proteins such as the Aurora kinases and the spindle checkpoint proteins MAD2 and BUB1B, are thought to contribute to the development of chromosomal instability and DNA aneuploidy in cancer. The importance of these spindle proteins remains unknown in the development of TGCTs, thus we have explored the expression levels of these proteins in normal and malignant testicular tissues. Materials and Methods: Using tissue microarrays the expression levels of Aurora kinase A (AURKA, Aurora kinase B (AURKB, BUB1B and MAD2 were measured in normal, preneoplastic and malignant testicular tissues of different histological subtypes from 279 orchidectomy specimens by means of immunohistochemistry. Results: All the spindle proteins except for AURKB were expressed in normal testis. Sixty-eight and 36%, respectively, of the primary spermatocytes in the normal testis were positive for BUB1B and MAD2, while only 5% of the cells were positive for AURKA. There was a significantly lower expression of the spindle checkpoint proteins in carcinoma in situ compared to normal testis (P=0.008 and P=0.043 for BUB1B and MAD2, respectively, while the level of AURKA was increased, however, not significantly (P=0.18. The extent of spindle protein expression varied significantly within the different histological subtypes of TGCTs (P< 0.001 for AURKB, BUB1B and MAD2, P=0.003 for AURKA. The expression of AURKA was significantly elevated in both non-seminomas (P=0.003 and seminomas (P=0.015. The level of BUB1B was significantly decreased in non-seminomas (P< 0.001. A similar tendency was observed for MAD2 (P=0.11. Conclusions: In carcinoma in situ of TGCTs the spindle checkpoint proteins MAD2 and BUB1B are significantly less expressed compared to normal testis, while the expression of AURKA is increased. We suggest that these changes may be of importance in the

  19. The association of inherited variation in the CLOCK gene with breast cancer tumor grade

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    Neha Gupta

    2017-07-01

    Full Text Available Background: Sufficient sleep and maintenance of circadian rhythm are important to health. We have shown that short duration of sleep before diagnosis is associated with higher-grade tumors among breast cancer patients. Earlier studies suggest that genetic variation in the CLOCK gene is associated with risk of cancers, including breast cancer. Studies of the association of genetic variation, including in CLOCK, and tumor grade, a standard marker of tumor aggressiveness, are lacking. Methods: We investigated the relationship between single nucleotide polymorphisms (SNPs in the CLOCK gene and tumor grade and estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status in 293 breast cancer patients. Nine SNPs were determined by standard TaqMan assays. Tumor grade, receptor status, and other clinical variables were abstracted from medical records. Results: Two SNPs were excluded because of poor genotyping performance. None of the remaining seven variants had a statistically significant association with breast cancer tumor grade or with receptor status. Conclusion: As with all novel studies, further work is needed to examine the association of CLOCK and other genes in the circadian rhythm pathway with breast cancer tumor grade in other populations.

  20. Stromal response in different histological grades of oral squamous cell carcinoma: A histochemical study

    Directory of Open Access Journals (Sweden)

    Jiji George

    2012-01-01

    Clinical Relevance: The reactive changes in the tumor stroma may alter the biological aggressiveness of oral cancer, and by incorporating this concept into a prognostic system, we may help to reflect the biologic diversity of oral cancer and predict its clinical outcomes.

  1. Semi-Quantitative Calculations of Primary Tumor Metabolic Activity Using F-18 FDG PET/CT as a Predictor of Survival in 92 Patients With High-Grade Bone or Soft Tissue Sarcoma

    DEFF Research Database (Denmark)

    Andersen, Kim Francis; Fuglo, Hanna Maria; Rasmussen, Sine Hvid

    2015-01-01

    To assess the prognostic value of primary tumor metabolic activity in patients with high-grade bone sarcomas (BS) or soft tissue sarcomas (STS) using F-18 FDG PET/CT. A single-site, retrospective study including 92 patients with high-grade BS or STS. Pretreatment F-18 FDG PET/CT scan was performe...... metabolic activity with pretherapeutic SUVmax using F-18 FDG PET/CT demonstrates independent properties beyond histologic grading for prediction of survival in patients with high-grade STS, but not with high-grade BS.......To assess the prognostic value of primary tumor metabolic activity in patients with high-grade bone sarcomas (BS) or soft tissue sarcomas (STS) using F-18 FDG PET/CT. A single-site, retrospective study including 92 patients with high-grade BS or STS. Pretreatment F-18 FDG PET/CT scan was performed...

  2. Evaluation of the WHO 2010 grading and AJCC/UICC staging systems in prognostic behavior of intestinal neuroendocrine tumors.

    Directory of Open Access Journals (Sweden)

    Paula B Araujo

    Full Text Available BACKGROUND: The increasing incidence and heterogeneous behavior of intestinal neuroendocrine tumors (iNETs pose a clinicopathological challenge. Our goal was to decribe the prognostic value of the new WHO 2010 grading and the AJCC/UICC TNM staging systems for iNETs. Moreover, outcomes of patients treated with somatostatin analogs were assessed. METHODS: We collected epidemiological and clinicopathological data from 93 patients with histologically proven iNETs including progression and survival outcomes. The WHO 2010 grading and the AJCC/UICC TNM staging systems were applied for all cases. RECIST criteria were used to define progression. Kaplan-Meier analyses for progression free survival (PFS and overall survival (OS were performed. RESULTS: Mean follow-up was 58.6 months (4-213 months. WHO 2010 grading yielded PFS and disease-specific OS of 125.0 and 165.8 months for grade 1 (G1, 100.0 and 144.2 months for G2 and 15.0 and 15.8 months for G3 tumors (p = 0.004 and p = 0.001. Using AJCC staging, patients with stage I and II tumors had no progression and no deaths. Stage III and IV patients demonstrated PFS of 138.4 and 84.7 months (p = 0.003 and disease-specific OS of 210.0 and 112.8 months (p = 0.017. AJCC staging also provided informative PFS (91.2 vs. 50.0 months, p = 0.004 and OS (112.3 vs. 80.0 months, p = 0.005 measures with somatostatin analog use in stage IV patients. CONCLUSION: Our findings underscore the complementarity of WHO 2010 and AJCC classifications in providing better estimates of iNETS disease outcomes and extend the evidence for somatostatin analog benefit in patients with metastatic disease.

  3. Analyzing the gene expression profile of anaplastic histology Wilms' tumor with real-time polymerase chain reaction arrays.

    Science.gov (United States)

    Lu, Jun; Tao, Yan-Fang; Li, Zhi-Heng; Cao, Lan; Hu, Shao-Yan; Wang, Na-Na; Du, Xiao-Juan; Sun, Li-Chao; Zhao, Wen-Li; Xiao, Pei-Fang; Fang, Fang; Xu, Li-Xiao; Li, Yan-Hong; Li, Gang; Zhao, He; Ni, Jian; Wang, Jian; Feng, Xing; Pan, Jian

    2015-01-01

    Wilms' tumor (WT) is one of the most common malignant neoplasms of the urinary tract in children. Anaplastic histology (unfavorable histology) accounts for about 10% of whole WTs, and it is the single most important histologic predictor of treatment response and survival in patients with WT; however, until now the molecular basis of this phenotype is not very clearly. A real-time polymerase chain reaction (PCR) array was designed and tested. Next, the gene expression profile of pediatric anaplastic histology WT and normal adjacent tissues were analyzed. These expression data were anlyzed with Multi Experiment View (MEV) cluster software further. Datasets representing genes with altered expression profiles derived from cluster analyses were imported into the Ingenuity Pathway Analysis Tool (IPA). 88 real-time PCR primer pairs for quantitative gene expression analysis of key genes involved in pediatric anaplastic histology WT were designed and tested. The gene expression profile of pediatric anaplastic histology WT is significantly different from adjacent normal controls; we identified 15 genes that are up-regulated and 16 genes that are down-regulated in the former. To investigate biological interactions of these differently regulated genes, datasets representing genes with altered expression profiles were imported into the IPA for further analysis, which revealed three significant networks: Cancer, Hematological Disease, and Gene Expression, which included 27 focus molecules and a significance score of 43. The IPA analysis also grouped the differentially expressed genes into biological mechanisms related to Cell Death and Survival 1.15E(-12), Cellular Development 2.84E(-11), Cellular Growth and Proliferation 2.84E(-11), Gene Expression 4.43E(-10), and DNA Replication, Recombination, and Repair 1.39E(-07). The important upstream regulators of pediatric anaplastic histology WT were TP53 and TGFβ1 signaling (P = 1.15E(-14) and 3.79E(-13), respectively). Our study

  4. Facilitating tumor functional assessment by spatially relating 3D tumor histology and in vivo MRI: Image registration approach

    NARCIS (Netherlands)

    Alić, L.; Haeck, J.C.; Bol, K.; Klein, S.; Tiel, S.T. van; Wielopolski, P.A.; Bijster, M.; Bernsen, M.; Jong, M. de; Niessen, W.J.; Veenland, J.F.

    2011-01-01

    Background: Magnetic resonance imaging (MRI), together with histology, is widely used to diagnose and to monitor treatment in oncology. Spatial correspondence between these modalities provides information about the ability of MRI to characterize cancerous tissue. However, registration is complicated

  5. Peritoneal Involvement Is More Common Than Nodal Involvement in Patients With High-Grade Appendix Tumors Who Are Undergoing Prophylactic Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

    Science.gov (United States)

    Mehta, Akash; Mittal, Rohin; Chandrakumaran, Kandiah; Carr, Norman; Dayal, Sanjeev; Mohamed, Faheez; Moran, Brendan; Cecil, Tom

    2017-11-01

    Right hemicolectomy is routinely recommended in patients with histologic findings of high-grade appendix tumors after appendicectomy. Undetected peritoneal disease may be encountered at surgery. In high-grade appendix tumors with disease detected radiologically, complete cytoreduction may not be possible and outcomes poor. For these reasons, we adopted a policy of prophylactic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. The purpose of this study was to quantify the rates of peritoneal and nodal metastatic disease in patients with high-grade appendix tumors without obvious metastatic disease and to report the long-term outcomes of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in these patients. Data regarding peritoneal and nodal metastatic disease were extracted from surgical and histologic records. The study was conducted at a high-volume tertiary referral center for peritoneal malignancy. Patients referred with histologically high-grade appendix tumors at appendicectomy, without detectable metastatic spread, between January 1994 and September 2016 were included MAIN OUTCOME MEASURES:: A total of 62 patients with high-grade pathology at appendicectomy, without clinical or radiological peritoneal disease, underwent complete cytoreduction with hyperthermic intraperitoneal chemotherapy. Thirty-five (57%) of 62 patients had peritoneal disease (median peritoneal cancer index 5 (range, 1-28)). Eleven (31%) of 35 had microscopic peritoneal disease. Overall, 23 (37%) of 62 had peritoneal disease beyond the confines of a standard right hemicolectomy. Nine (15%) of 62 had nodal involvement. Mean overall and disease-free survival were 110.9 (95% CI, 94.8-127.0 mo) and 102.1 months (95% CI, 84.3-119.9 mo), with 5-year overall and disease-free survival of 83.2% and 76.0%. The retrospective nature limits the interpretation of these results. Complete cytoreduction was achieved in all of the patients, with excellent long

  6. Oncocytoma-like renal tumor with transformation toward high-grade oncocytic carcinoma: a unique case with morphologic, immunohistochemical, and genomic characterization.

    Science.gov (United States)

    Sirintrapun, Sahussapont J; Geisinger, Kim R; Cimic, Adela; Snow, Anthony; Hagenkord, Jill; Monzon, Federico; Legendre, Benjamin L; Ghazalpour, Anatole; Bender, Ryan P; Gatalica, Zoran

    2014-10-01

    Renal oncocytoma is a benign tumor with characteristic histologic findings. We describe an oncocytoma-like renal tumor with progression to high-grade oncocytic carcinoma and metastasis. A 74-year-old man with no family history of cancer presented with hematuria. Computed tomography showed an 11 cm heterogeneous multilobulated mass in the right kidney lower pole, enlarged aortocaval lymph nodes, and multiple lung nodules. In the nephrectomy specimen, approximately one third of the renal tumor histologically showed regions classic for benign oncocytoma transitioning to regions of high-grade carcinoma without sharp demarcation. With extensive genomic investigation using single nucleotide polymorphism-based array virtual karyotyping, multiregion sequencing, and expression array analysis, we were able to show a common lineage between the benign oncocytoma and high-grade oncocytic carcinoma regions in the tumor. We were also able to show karyotypic differences underlying this progression. The benign oncocytoma showed no chromosomal aberrations, whereas the high-grade oncocytic carcinoma showed loss of the 17p region housing FLCN (folliculin [Birt-Hogg-Dubé protein]), loss of 8p, and gain of 8q. Gene expression patterns supported dysregulation and activation of phosphoinositide 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homolog (Akt), mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK), and mechanistic target of rapamycin (serine/threonine kinase) (mTOR) pathways in the high-grade oncocytic carcinoma regions. This was partly attributable to FLCN underexpression but further accentuated by overexpression of numerous genes on 8q. In the high-grade oncocytic carcinoma region, vascular endothelial growth factor A along with metalloproteinases matrix metallopeptidase 9 and matrix metallopeptidase 12 were overexpressed, facilitating angiogenesis and invasiveness. Genetic molecular testing provided evidence for the development of an

  7. Virtual microscopy: an evaluation of its validity and diagnostic performance in routine histologic diagnosis of skin tumors.

    Science.gov (United States)

    Nielsen, Patricia Switten; Lindebjerg, Jan; Rasmussen, Jan; Starklint, Henrik; Waldstrøm, Marianne; Nielsen, Bjarne

    2010-12-01

    Digitization of histologic slides is associated with many advantages, and its use in routine diagnosis holds great promise. Nevertheless, few articles evaluate virtual microscopy in routine settings. This study is an evaluation of the validity and diagnostic performance of virtual microscopy in routine histologic diagnosis of skin tumors. Our aim is to investigate whether conventional microscopy of skin tumors can be replaced by virtual microscopy. Ninety-six skin tumors and skin-tumor-like changes were consecutively gathered over a 1-week period. Specimens were routinely processed, and digital slides were captured on Mirax Scan (Carl Zeiss MicroImaging, Göttingen, Germany). Four pathologists evaluated the 96 virtual slides and the associated 96 conventional slides twice with intermediate time intervals of at least 3 weeks. Virtual slides that caused difficulties were reevaluated to identify possible reasons for this. The accuracy was 89.2% for virtual microscopy and 92.7% for conventional microscopy. All κ coefficients expressed very good intra- and interobserver agreement. The sensitivities were 85.7% (78.0%-91.0%) and 92.0% (85.5%-95.7%) for virtual and conventional microscopy, respectively. The difference between the sensitivities was 6.3% (0.8%-12.6%). The subsequent reevaluation showed that virtual slides were as useful as conventional slides when rendering a diagnosis. Differences seen are presumed to be due to the pathologists' lack of experience using the virtual microscope. We conclude that it is feasible to make histologic diagnosis on the skin tumor types represented in this study using virtual microscopy after pathologists have completed a period of training. Larger studies should be conducted to verify whether virtual microscopy can replace conventional microscopy in routine practice. Copyright © 2010 Elsevier Inc. All rights reserved.

  8. Villous Tumor of the Urinary Bladder Resembling Low-grade Mucinous Neoplasm of the Appendix

    OpenAIRE

    Ito, Ayako; Sakura, Yuma; Sugimoto, Mikio; Kakehi, Yoshiyuki; Kuroda, Naoto

    2016-01-01

    Mucinous neoplasms of the urinary tract are very rare. We present a 63-year-old-women who had a sessile papillary villous tumor in urinary bladder. Although transurethral resection of the bladder tumor (TURBT) was performed, the villous tumor repetitively recurred and gradually spread to the entire surface of bladder lumen. Histopathologic and immunohistochemical examination showed that the lesion was very similar to low-grade mucinous neoplasm arising in appendix vermiformis. There are no re...

  9. Genetic variation in mitotic regulatory pathway genes is associated with breast tumor grade

    DEFF Research Database (Denmark)

    Purrington, Kristen S; Slettedahl, Seth; Bolla, Manjeet K

    2014-01-01

    Mitotic index is an important component of histologic grade and has an etiologic role in breast tumorigenesis. Several small candidate gene studies have reported associations between variation in mitotic genes and breast cancer risk. We measured associations between 2156 single nucleotide polymor...

  10. Markers of fibrosis and epithelial to mesenchymal transition demonstrate field cancerization in histologically normal tissue adjacent to breast tumors

    Science.gov (United States)

    Trujillo, Kristina A.; Heaphy, Christopher M.; Mai, Minh; Vargas, Keith M.; Jones, Anna C.; Vo, Phung; Butler, Kimberly S.; Joste, Nancy E.; Bisoffi, Marco; Griffith, Jeffrey K

    2011-01-01

    Previous studies have shown that a field of genetically altered but histologically normal tissue extends 1 cm or more from the margins of human breast tumors. The extent, composition and biological significance of this field are only partially understood, but the molecular alterations in affected cells could provide mechanisms for limitless replicative capacity, genomic instability and a microenvironment that supports tumor initiation and progression. We demonstrate by microarray, qRT-PCR and immunohistochemistry a signature of differential gene expression that discriminates between patient-matched, tumor-adjacent histologically normal breast tissues located 1 cm and 5 cm from the margins of breast adenocarcinomas (TAHN-1 and TAHN-5, respectively). The signature includes genes involved in extracellular matrix remodeling, wound healing, fibrosis and epithelial to mesenchymal transition (EMT). Myofibroblasts, which are mediators of wound healing and fibrosis, and intra-lobular fibroblasts expressing MMP2, SPARC, TGF-β3, which are inducers of EMT, were both prevalent in TAHN-1 tissues, sparse in TAHN-5 tissues, and absent in normal tissues from reduction mammoplasty. Accordingly, EMT markers S100A4 and vimentin were elevated in both luminal and myoepithelial cells, and EMT markers α-smooth muscle actin and SNAIL were elevated in luminal epithelial cells of TAHN-1 tissues. These results identify cellular processes that are differentially activated between TAHN-1 and TAHN-5 breast tissues, implicate myofibroblasts as likely mediators of these processes, provide evidence that EMT is occurring in histologically normal tissues within the affected field and identify candidate biomarkers to investigate whether or how field cancerization contributes to the development of primary or recurrent breast tumors. PMID:21105047

  11. Cross platform analysis of methylation, miRNA and stem cell gene expression data in germ cell tumors highlights characteristic differences by tumor histology.

    Science.gov (United States)

    Poynter, Jenny N; Bestrashniy, Jessica R B M; Silverstein, Kevin A T; Hooten, Anthony J; Lees, Christopher; Ross, Julie A; Tolar, Jakub

    2015-10-23

    Alterations in methylation patterns, miRNA expression, and stem cell protein expression occur in germ cell tumors (GCTs). Our goal is to integrate molecular data across platforms to identify molecular signatures in the three main histologic subtypes of Type I and Type II GCTs (yolk sac tumor (YST), germinoma, and teratoma). We included 39 GCTs and 7 paired adjacent tissue samples in the current analysis. Molecular data available for analysis include DNA methylation data (Illumina GoldenGate Cancer Methylation Panel I), miRNA expression (NanoString nCounter miRNA platform), and stem cell factor expression (SABiosciences Human Embryonic Stem Cell Array). We evaluated the cross platform correlations of the data features using the Maximum Information Coefficient (MIC). In analyses of individual datasets, differences were observed by tumor histology. Germinomas had higher expression of transcription factors maintaining stemness, while YSTs had higher expression of cytokines, endoderm and endothelial markers. We also observed differences in miRNA expression, with miR-371-5p, miR-122, miR-302a, miR-302d, and miR-373 showing elevated expression in one or more histologic subtypes. Using the MIC, we identified correlations across the data features, including six major hubs with higher expression in YST (LEFTY1, LEFTY2, miR302b, miR302a, miR 126, and miR 122) compared with other GCT. While prognosis for GCTs is overall favorable, many patients experience resistance to chemotherapy, relapse and/or long term adverse health effects following treatment. Targeted therapies, based on integrated analyses of molecular tumor data such as that presented here, may provide a way to secure high cure rates while reducing unintended health consequences.

  12. Noninvasive Tumor Grading of Glioblastomas Before Surgery Using Arterial Spin Labeling. A Cohort Study.

    Science.gov (United States)

    Gao, Fei; Guo, Rui; Hu, Xiao-Jing; Li, Chun-Jing; Li, Meng

    2015-12-01

    To assess the clinical value of using arterial spin labeling (ASL) technique preoperatively for non-invasive tumor grading in glioblastoma (GBM) patients. Forty-nine patients with GBMs were selected, including 21 patients with high-grade gliomas and 28 patients with low-grade gliomas. ASL perfusion imaging was performed with GE Signa Excite HD 3.0 T MR scanning system (GE Healthcare). Relative cerebral blood flow (rCBF) and relative tumor blood flow (rTBF) were quantified in all patients. Statistical analysis was performed with STATA version 12.0 software. Further, relevant human cohort studies published in Chinese and English languages were identified by database searches and screened. Data was extracted and meta-analysis was performed using Comprehensive Meta-analysis version 2.0 software. The ratios of rTBF to rCBF in the contralateral white matter, contralateral gray matter, and contralateral hemisphere of high-grade gliomas were higher than low-grade gliomas (all p 0.05) when 2 and 5 cm distances from tumor margin were compared. Importantly, rCBF values showed statistical differences when the 2 cm distance was compared with the 5 cm distance from tumor margin (all p < 0.05). Finally, meta-analysis results supported the conclusion that rCBF and rTBF values were significantly higher in high-grade GBM as compared to low-grade GBM. We present convincing data that ASL is highly effective in differentiating between high-grade and low-grade gliomas, and thus is a useful tool for preoperative evaluation of GBM.

  13. Induction of a menopausal state alters the growth and histology of ovarian tumors in a mouse model of ovarian cancer.

    Science.gov (United States)

    Laviolette, Laura A; Ethier, Jean-François; Senterman, Mary K; Devine, Patrick J; Vanderhyden, Barbara C

    2011-05-01

    Ovarian cancer is often diagnosed in women after menopause when the levels of the serum gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are increased because of the depletion of growing follicles within the ovary. The ability of FSH and LH to modulate the disease has not been well studied owing to a lack of physiologically relevant models of ovarian cancer. In this study, 4-vinylcyclohexene diepoxide (VCD) was used to deplete ovarian follicles and increase the levels of circulating FSH and LH in the tgCAG-LS-TAg mouse model of ovarian cancer. VCD-induced follicle depletion was performed either before or after induction of the oncogene SV40 large and small T-antigens in the ovarian surface epithelial cells of tgCAG-LS-TAg mice, which was mediated by the intrabursal delivery of an adenovirus expressing Cre recombinase (AdCre). tgCAG-LS-TAg mice injected with AdCre developed undifferentiated ovarian tumors with mixed epithelial and stromal components and some features of sex cord stromal tumors. Treatment with VCD before or after AdCre injection yielded tumors of similar histology, but with the unique appearance of Sertoli cell nests. In mice treated with VCD before the induction of tumorigenesis, the ovarian tumors tended to grow more slowly. The human ovarian cancer cell lines SKOV3 and OVCAR3 responded similarly to increased levels of gonadotropins in a second model of menopause, growing more slowly in ovariectomized mice compared with cycling controls. These results suggest that follicle depletion and increased gonadotropin levels can alter the histology and the rate of growth of ovarian tumors.

  14. Grading and outcome prediction of pediatric diffuse astrocytic tumors with diffusion and arterial spin labeling perfusion MRI in comparison with 18F-DOPA PET.

    Science.gov (United States)

    Morana, Giovanni; Piccardo, Arnoldo; Tortora, Domenico; Puntoni, Matteo; Severino, Mariasavina; Nozza, Paolo; Ravegnani, Marcello; Consales, Alessandro; Mascelli, Samantha; Raso, Alessandro; Cabria, Manlio; Verrico, Antonio; Milanaccio, Claudia; Rossi, Andrea

    2017-11-01

    The aim of this study was to investigate MRI-derived diffusion weighted imaging (DWI) and arterial spin labeling (ASL) perfusion imaging in comparison with (18)F-dihydroxyphenylalanine (DOPA) PET with respect to diagnostic performance in tumor grading and outcome prediction in pediatric patients with diffuse astrocytic tumors (DAT). We retrospectively analyzed 26 children with histologically proven treatment naïve low and high grade DAT who underwent ASL and DWI performed within 2 weeks of (18)F-DOPA PET. Relative ASL-derived cerebral blood flow max (rCBF max) and DWI-derived minimum apparent diffusion coefficient (rADC min) were compared with (18)F-DOPA uptake tumor/normal tissue (T/N) and tumor/striatum (T/S) ratios, and correlated with World Health Organization (WHO) tumor grade and progression-free survival (PFS). Statistics included Pearson's chi-square and Mann-Whitney U tests, Spearman's rank correlation, receiver operating characteristic (ROC) analysis, discriminant function analysis (DFA), Kaplan-Meier survival curve, and Cox analysis. A significant correlation was demonstrated between rCBF max, rADC min, and (18)F-DOPA PET data (p PET data increased the predictive power for prognosticating tumor progression (AUC 0.97, p PET provide useful complementary information for pediatric DAT grading. (18)F-DOPA uptake better correlates with PFS prediction. Combining MRI and PET data provides the highest predictive power for prognosticating tumor progression suggesting a synergistic role of these diagnostic tools.

  15. The reliability of histological grade in breast cancer core needle biopsies depends on biopsy size: a comparative study with subsequent surgical excisions.

    Science.gov (United States)

    Focke, Cornelia M; Decker, Thomas; van Diest, Paul J

    2016-12-01

    In breast cancer patients undergoing neoadjuvant chemotherapy, histological grading needs to be performed on core needle biopsies (CNBs) that may not be representative of the whole tumour when they are small. Our aim was to study the influence of biopsy size on agreement rates for histological grade between CNBs and subsequent surgical excision biopsies (SEBs). We calculated agreement and Cohen's κ between CNBs and SEBs of 300 early-stage breast cancers. The number of cores, total core length, total tumour length and tumour/tissue ratio were assessed for each CNB set. Agreement rates for grade were calculated for different classes of core number and tumour/tissue ratio, and for total core lengths and tumour lengths per CNB set in 5-15-mm intervals. Agreement on grade between CNBs and SEBs was 73% (κ = 0.59), with underestimation of grade in CNBs in 26% of cases and overestimation in 1% of cases. There was significantly higher concordance between CNBs and SEBs at a total core length of ≥50 mm than at a total core length of cores than at fewer than three cores (75% versus 58% agreement, P = 0.048). The tumour/tissue ratio, pathological tumour size and radiological tumour size were not statistically different between concordant and discordant cases. Agreement rates for histological grade in CNBs versus SEBs improve with increasing biopsy sample size. © 2016 John Wiley & Sons Ltd.

  16. Usefulness of Permeability Map by Perfusion MRI of Brain Tumor the Grade Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Sung Jin [Dept. of Radiology, Dongsan Hospital, Keimyung University, Daegu (Korea, Republic of); Lee, Joo Young [GE Healthcare, Seoul (Korea, Republic of); Chang, Hyuk Won [Dept. of Radiology, Keimyung University College of Medicine, Daegu (Korea, Republic of)

    2009-09-15

    This study was conducted to assess how effective the permeability ratio and relative cerebral blood volume ratio are to tumor through perfusion MRI by measuring and reflecting the grade assessment and differential diagnosis and the permeability and relative cerebral blood volume of contrast media plunged from blood vessel into organ due to breakdown of blood-brain barrier in cerebral. Subject and Method : Subject of study was 29 patients whose diagnosis were confirmed by biopsy after surgery and 550 (11 slice x 50 image) perfusion MRI were used to make image of relative cerebral blood volume with the program furnished on instrument. The other method was to transmit to private computer and the image analysis was made additionally by making image of relative cerebral blood volume-reformulated singular value decomposition, rCBV-rSVD and permeability using IDL.6.2. In addition, Kruskal-wallis test tonggyein non numerical average by a comparative analysis of brain tumors Results : The rCBV ratio (Functool PF; GE Medical Systems and IDL 6.2 program by analysis) and permeability ratio of tumors were as follows; high grade glioma(n=4), (14.75, 19.25) 13.13. low grade astrocytoma(n=5) (14.80, 15.90) 11.60, glioblastoma(n=5) (10.90, 18.60), 22.00, metastasis(n=6) (11.00, 15.08). 22.33. meningioma(n=6) (18.58, 7.67), 5.58. oliogodendroglioma(n=3) (23.33, 16.33, 15.67. Conclusion : It was not easy to classify the grade with the relative cerebral blood volume ratio measured by using the relative cerebral blood image by type of tumors, however, permeability ratio measured by permeability image revealed that the higher the grade of tumor, the higher the measured permeability ratio, showing the assessment of tumor grade is more effective to differential diagnosis.

  17. Preoperative Monocyte-to-Lymphocyte Ratio in Peripheral Blood Predicts Stages, Metastasis, and Histological Grades in Patients with Ovarian Cancer.

    Science.gov (United States)

    Xiang, Jiangdong; Zhou, Lina; Li, Xing; Bao, Wei; Chen, Taizhong; Xi, Xiaowei; He, Yinyan; Wan, Xiaoping

    2017-02-01

    The monocyte-to-lymphocyte ratio (MLR) has been shown to be associated with the prognosis of various solid tumors. This study sought to evaluate the important value of the MLR in ovarian cancer patients. A total of 133 ovarian cancer patients and 43 normal controls were retrospectively reviewed. The patients' demographics were analyzed along with clinical and pathologic data. The counts of peripheral neutrophils, lymphocytes, monocytes, and platelets were collected and used to calculate the MLR, neutrophil-to-lymphocyte ratio (NLR). and platelet-to-lymphocyte ratio (PLR). The optimal cutoff value of the MLR was determined by using receiver operating characteristic curve analysis. We compared the MLR, NLR, and PLR between ovarian cancer and normal control patients and among patients with different stages and different grades, as well as between patients with lymph node metastasis and non-lymph node metastasis. We then investigated the value of the MLR in predicting the stage, grade, and lymph node positivity by using logistic regression. The impact of the MLR on overall survival (OS) was calculated by Kaplan-Meier method and compared by log-rank test. Statistically significant differences in the MLR were observed between ovarian cancer patients and normal controls. However, no difference was found for the NLR and PLR. Highly significant differences in the MLR were found among patients with different stages (stage I-II and stage III-IV), grades (G1 and >G1), and lymph node metastasis status. The MLR was a significant and independent risk factor for lymph node metastasis, as determined by logistic regression. The optimal cutoff value of the MLR was 0.23. We also classified the data according to tumor markers (CA125, CA199, HE4, AFP, and CEA) and conventional coagulation parameters (International Normalized Ratio [INR] and fibrinogen). Highly significant differences in CA125, CA199, HE4, INR, fibrinogen levels, and lactate dehydrogenase were found between the low

  18. Mechanic effect of pulsed focused ultrasound in tumor and muscle tissue evaluated by MRI, histology, and microarray analysis

    Energy Technology Data Exchange (ETDEWEB)

    Hundt, Walter, E-mail: walter.hundt@web.de [Lucas MRS Research Center, Department of Radiology, Stanford University School of Medicine, Stanford, CA, 94305-5488 (United States); Department of Radiology, Philipps University Marburg (Germany); Yuh, Esther L. [Lucas MRS Research Center, Department of Radiology, Stanford University School of Medicine, Stanford, CA, 94305-5488 (United States); Steinbach, Silke [Department of Otolaryngology Head and Neck Surgery, Technical University of Dresden (Germany); Bednarski, Mark D.; Guccione, Samira [Lucas MRS Research Center, Department of Radiology, Stanford University School of Medicine, Stanford, CA, 94305-5488 (United States)

    2010-11-15

    The purpose of this study was to investigate the effect of pulsed high-intensity focused ultrasound (HIFU) to tumor and muscle tissue. Pulsed HIFU was applied to tumor and muscle tissue in C3H/Km mice. Three hours after HIFU treatment pre- and post-contrast T1-wt, T2-wt images and a diffusion-wt STEAM-sequence were obtained. After MR imaging, the animals were euthenized and the treated tumor and muscle was taken out for histology and functional genomic analysis. In the tumor tissue a slight increase of the diffusion coefficient could be found. In the muscle tissue T2 images showed increased signal intensity and post-contrast T1 showed a decreased contrast uptake in the center and a severe contrast uptake in the surrounding muscle tissue. A significant increase of the diffusion coefficient was found. Gene expression analysis revealed profound changes in the expression levels of 29 genes being up-regulated and 3 genes being down-regulated in the muscle tissue and 31 genes being up-regulated and 15 genes being down-regulated in the SCCVII tumor tissue. Seven genes were up-regulated in both tissue types. The highest up-regulated gene in the tumor and muscle tissue encoded for Mouse histone H2A.1 gene (FC = 13.2 {+-} 20.6) and Apolipoprotein E (FC = 12.8 {+-} 27.4) respectively MHC class III (FC = 83.7 {+-} 67.4) and hsp70 (FC = 75.3 {+-} 85.0). Immunoblot confirmed the presence of HSP70 protein in the muscle tissue. Pulsed HIFU treatment on tumor and muscle tissue results in dramatic changes in gene expression, indicating that the effect of pulsed HIFU is in some regard dependent and also independent of the tissue type.

  19. MRI of high-grade astrocytic tumors: early appearance and evolution

    Energy Technology Data Exchange (ETDEWEB)

    Okamoto, K.; Takahashi, N.; Ishikawa, K.; Furusawa, T.; Sakai, K. [Department of Radiology, Niigata University Faculty of Medicine (Japan); Ito, J.; Tokiguchi, S. [Department of Radiology, Niigata University Faculty of Dentistry (Japan)

    2002-05-01

    The clinical management and prognosis of patients with diffusely infiltrating astrocytomas are dependent on neuropathological grading of the tumors. The characteristics of MR images of high-grade astrocytic tumors are well known, but the early MRI appearance and the MRI evolution of high-grade astrocytic tumors have rarely been examined. We retrospectively reviewed MR images obtained from 4 months to 3 years and 3 months before admission, as well as MR images on admission, for five patients with pathologically proven high-grade astrocytic tumors (two glioblastomas and three anaplastic astrocytomas). In two patients, neoplastic lesions were not detectable on initial MRI, even retrospectively. In the remaining three patients, however, hyperintense areas with little or no mass effect were demonstrated on T2-weighted imaging. These lesions were misinterpreted as non-neoplastic processes, such as ischemic lesion or infarction, or demyelinating processes. All tumors showed gadolinium enhancement on admission, that emerged from the previously existing hyperintense areas on T2-weighted images without gadolinium enhancement, except for one de novo glioblastoma. Development of a small central cyst without gadolinium enhancement was demonstrated in one case before the emergence of an enhancing area. (orig.)

  20. Barrett's oesophagus patients with low-grade dysplasia can be accurately risk-stratified after histological review by an expert pathology panel

    NARCIS (Netherlands)

    Duits, Lucas C.; Phoa, K. Nadine; Curvers, Wouter L.; Ten Kate, Fiebo J W; Meijer, Gerrit A.; Seldenrijk, Cees A.; Offerhaus, G. Johan; Visser, Mike; Meijer, Sybren L.; Krishnadath, Kausilia K.; Tijssen, Jan G P; Mallant-Hent, Rosalie C.; Bergman, Jacques J G H M

    Objective Reported malignant progression rates for low-grade dysplasia (LGD) in Barrett's oesophagus (BO) vary widely. Expert histological review of LGD is advised, but limited data are available on its clinical value. This retrospective cohort study aimed to determine the value of an expert

  1. P-gp and MRP1 Expression in Parathyroid Tumors Related to Histology, Weight and Tc-99m-Sestamibi Imaging Results

    NARCIS (Netherlands)

    Jorna, F. H.; Hollema, H.; Hendrikse, H. N.; Bart, J.; Brouwers, A. H.; Plukker, J. T. M.

    Objective: P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) are membrane efflux pumps that may have a role in the kinetics of Tc-99m-sestamibi (MIBI) in parathyroid tumors. P-gp and MRP1 expression in parathyroid tumors was studied and related to histology, weight and pre- and

  2. Immunohistochemical profiling of benign, low malignant potential and low grade serous epithelial ovarian tumors

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    Rancourt Claudine

    2008-11-01

    Full Text Available Abstract Background Serous epithelial ovarian tumors can be subdivided into benign (BOV, low malignant potential (LMP or borderline and invasive (TOV tumors. Although the molecular characteristics of serous BOV, LMP and low grade (LG TOV tumors has been initiated, definitive immunohistochemical markers to distinguish between these tumor types have not been defined. Methods In the present study, we used a tissue array composed of 27 BOVs, 78 LMPs and 23 LG TOVs to evaluate the protein expression of a subset of selected candidates identified in our previous studies (Ape1, Set, Ran, Ccne1 and Trail or known to be implicated in epithelial ovarian cancer disease (p21, Ccnb1, Ckd1. Results Statistically significant difference in protein expression was observed for Ccnb1 when BOV tumors were compared to LMP tumors (p = 0.003. When BOV were compared to LG TOV tumors, Trail was significantly expressed at a higher level in malignant tumors (p = 0.01. Expression of p21 was significantly lower in LG tumors when compared with either BOVs (p = 0.03 or LMPs (p = 0.001. We also observed that expression of p21 was higher in LMP tumors with no (p = 0.02 or non-invasive (p = 0.01 implants compared to the LMP associated with invasive implants. Conclusion This study represents an extensive analyse of the benign and highly differentiated ovarian disease from an immunohistochemical perspective.

  3. Anthropometric measures and the risk of endometrial cancer, overall and by tumor microsatellite status and histological subtype.

    Science.gov (United States)

    Amankwah, Ernest K; Friedenreich, Christine M; Magliocco, Anthony M; Brant, Rollin; Courneya, Kerry S; Speidel, Thomas; Rahman, Wahida; Langley, Annie R; Cook, Linda S

    2013-06-15

    Obesity is an established risk factor for endometrial cancer, but this association is not well understood for subtypes of endometrial cancer. We evaluated the association of recent and adult-life obesity with subtypes of endometrial cancer based on microsatellite status (microsatellite-stable (MSS) vs. microsatellite-instable (MSI)) and histology (type I vs. type II). Analyses were based on a population-based case-control study (524 cases and 1,032 controls) conducted in Alberta, Canada (2002-2006) and included the following groupings of subtypes: MSS = 337 and MSI = 130; type I = 458 and type II = 66. Logistic and polytomous logistic regression were used to estimate odds ratios and 95% confidence intervals for overall endometrial cancer and subtypes of endometrial cancer, respectively. The risks of all subtypes of endometrial cancer, except type II, increased with an increase in all of the anthropometric characteristics examined. The risks for MSI tumors were suggestively stronger than those for MSS tumors; the risk with high (≥30) body mass index (weight (kg)/height (m)(2)) was significantly stronger for MSI tumors (odds ratio = 4.96, 95% confidence interval: 2.76, 8.91) than for MSS tumors (odds ratio = 2.33, 95% confidence interval: 1.66, 3.28) (P-heterogeneity = 0.02). Obesity is associated with most subtypes of endometrial cancer, and further studies are warranted to elucidate the biological mechanisms underlying the stronger risk for the MSI subtype with a high body mass index.

  4. Continuous representation of tumor microvessel density and detection of angiogenic hotspots in histological whole-slide images

    Science.gov (United States)

    Kather, Jakob Nikolas; Marx, Alexander; Reyes-Aldasoro, Constantino Carlos; Schad, Lothar R.; Zöllner, Frank Gerrit; Weis, Cleo-Aron

    2015-01-01

    Blood vessels in solid tumors are not randomly distributed, but are clustered in angiogenic hotspots. Tumor microvessel density (MVD) within these hotspots correlates with patient survival and is widely used both in diagnostic routine and in clinical trials. Still, these hotspots are usually subjectively defined. There is no unbiased, continuous and explicit representation of tumor vessel distribution in histological whole slide images. This shortcoming distorts angiogenesis measurements and may account for ambiguous results in the literature. In the present study, we describe and evaluate a new method that eliminates this bias and makes angiogenesis quantification more objective and more efficient. Our approach involves automatic slide scanning, automatic image analysis and spatial statistical analysis. By comparing a continuous MVD function of the actual sample to random point patterns, we introduce an objective criterion for hotspot detection: An angiogenic hotspot is defined as a clustering of blood vessels that is very unlikely to occur randomly. We evaluate the proposed method in N=11 images of human colorectal carcinoma samples and compare the results to a blinded human observer. For the first time, we demonstrate the existence of statistically significant hotspots in tumor images and provide a tool to accurately detect these hotspots. PMID:26061817

  5. High grade neuroendocrine lung tumors: pathological characteristics, surgical management and prognostic implications.

    Science.gov (United States)

    Grand, Bertrand; Cazes, Aurélie; Mordant, Pierre; Foucault, Christophe; Dujon, Antoine; Guillevin, Elizabeth Fabre; Barthes, Françoise Le Pimpec; Riquet, Marc

    2013-09-01

    Among non-small cell lung cancers (NSCLC), large cell carcinoma (LCC) is credited of significant adverse prognosis. Its neuroendocrine subtype has even a poorer diagnosis, with long-term survival similar to small cell lung cancer (SCLC). Our purpose was to review the surgical characteristics of those tumors. The clinical records of patients who underwent surgery for lung cancer in two French centers from 1980 to 2009 were retrospectively reviewed. We more particularly focused on patients with LCC or with high grade neuroendocrine lung tumors. High grade neuroendocrine tumors were classified as pure large cell neuroendocrine carcinoma (pure LCNEC), NSCLC combined with LCNEC (combined LCNEC), and SCLC combined with LCNEC (combined SCLC). There were 470 LCC and 155 high grade neuroendocrine lung tumors, with no difference concerning gender, mean age, smoking habits. There were significantly more exploratory thoracotomies in LCC, and more frequent postoperative complications in high grade neuroendocrine lung tumors. Pathologic TNM and 5-year survival rates were similar, with 5-year ranging from 34.3% to 37.6% for high grade neuroendocrine lung tumors and LCC, respectively. Induction and adjuvant therapy were not associated with an improved prognosis. The subgroups of LCNEC (pure NE, combined NE) and combined SCLC behaved similarly, except visceral pleura invasion, which proved more frequent in combined NE and less frequent in combined SCLC. Survival analysis showed a trend toward a lower 5-year survival in case of combined SCLC. Therefore, LCC, LCNEC and combined SCLC share the same poor prognosis, but surgical resection is associated with long-term survival in about one third of patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. Association of SOX4 regulated by tumor suppressor miR-30a with poor prognosis in low-grade chondrosarcoma.

    Science.gov (United States)

    Lu, Ning; Lin, Tao; Wang, Lin; Qi, Mei; Liu, Zhiyan; Dong, Hongyan; Zhang, Xiying; Zhai, Chunyan; Wang, Yan; Liu, Long; Xiang, Lei; Qi, Lei; Han, Bo; Li, Jinsong

    2015-05-01

    The sex-determining region Y-box 4 (SOX4), a transcription factor, is involved in various developmental processes. It has been reported in multiple human cancers. However, the prognostic value and its exact role in chondrosarcoma remain poorly understood. In the current study, SOX4 was overexpressed in 28 of 92 (30.4 %) interpretable chondrosarcoma patients compared with 3 of 43 (6.9 %) interpretable chondroma cases (P = 0.003). Its overexpression in chondrosarcoma was significantly associated with histological grade (P chondrosarcoma patients with low histological grade. Functionally, SOX4 silencing significantly suppressed the proliferation, migratory, and invasive capacity of SW1353 cells, suggesting an oncogenic role of SOX4 in chondrosarcoma in vitro. In an attempt of characterizing SOX4 overexpression mechanism, we identified miR-30a as a tumor suppressor that directly targets SOX4 in chondrosarcoma cells. Clinically, miR-30a expression was negatively correlated with SOX4 expression in chondrosarcoma cases. In all, we identified that SOX4 was oncogenic in chondrosarcoma and negatively regulated by miR-30a in vitro. Importantly, SOX4 overexpression may serve as a prognostic marker for patients with low-histological-grade chondrosarcoma.

  7. Pre-operative neutrophil count and neutrophil-lymphocyte count ratio (NLCR) in predicting the histological grade of paediatric brain tumours: a preliminary study.

    Science.gov (United States)

    Wilson, J R F; Saeed, F; Tyagi, A K; Goodden, J R; Sivakumar, G; Crimmins, D; Elliott, M; Picton, S; Chumas, P D

    2017-11-29

    The neutrophil-lymphocyte count ratio (NLCR) is an established prognostic marker for renal, lung and colorectal carcinomas and has been suggested to be predictive of histological grade and outcome in adult intracranial tumours. The purpose of this study was to determine whether a correlation of the pre-operative neutrophil count (NC) and NLCR with the final histological grade exists in paediatric intracranial tumours. A retrospective analysis was undertaken at a single centre. Patients less than 18 years old at the time of surgery who underwent tumour-related procedures from 2006 to 2015 were included. Patients with recurrent tumours, previous bone marrow transplant and metastases were excluded. Pre-operative full blood counts (FBC), collected before the diagnosis of intracranial pathology and before administration of steroids, were matched with histological diagnosis for each patient. Post-operative FBC was also recorded, together with survival data where applicable. A total of 116 patients (74 male, 42 female; mean age, 8 ± 0.9 years) with a diagnosis of primary intracranial tumours had pre-operative FBC that could be matched to final histological grade. Pre-operative NC and NLCR were higher with increasing grade of tumour: grade 1 (NC 4.29 109/l, NLCR 2.26), grade 2 (NC 4.59 109/l, NLCR 2.38), grade 3 (NC 5.67 109/l, NLCR 2.72) and grade 4 (NC 6.59 109/l, NLCR 3.31). Patients with WHO grade 1 and 2 tumours pooled together had a lower NC (4.37 95% CI ± 0.67 109/l) compared to WHO grade 3 and 4 patients (6.41 95% CI ± 0.99 109/l, p = 0.0013). The NLCR was lower in grade 1 and 2 tumours (2.29 ± 0.59) (compared to grade 3 and 4 tumours; 3.20 ± 0.76) but this did not reach significance (p = 0.069). The subgroup of patients with pilocytic astrocytoma had a significantly lower NC when compared to patients with high-grade tumours (p = 0.005). Medulloblastoma and supratentorial PNET subgroups had significantly higher NC compared to the low-grade

  8. Papillary Ependymoma WHO Grade II of the Aqueduct Treated by Endoscopic Tumor Resection

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    Andreas M. Stark

    2009-01-01

    Full Text Available Papillary ependymoma is a rare tumor that may be located along the ventricular walls or within the spinal cord. We report the case of a 54-year-old patient with a papillary ependymoma WHO grade II arising at the entrance of the aqueduct. The tumor caused hydrocephalus. The tumor was completely removed via a right-sided endoscopic approach with restoration of the aqueduct. The free cerebrospinal fluid passage through the aqueduct was not only visualized by endoscopy but also controlled by intraoperative high-field magnetic resonance imaging. Therefore, an additional endoscopic third ventriculostomy was unneccessary.

  9. Neuronal transcription factor Brn-3a(l is over expressed in high-grade ovarian carcinomas and tumor cells from ascites of patients with advanced-stage ovarian cancer

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    Ahmed Nuzhat

    2010-07-01

    Full Text Available Abstract Objectives In view of the recent association of Brn-3 transcription factors with neuroblastomas, cervical, breast, and prostate cancers we examined the expression of Brn-3a(l in normal ovaries and in different histological grades of ovarian tumors. The expression of Brn-3a(l was also evaluated in normal ovarian and cancer cell lines and tumor cells isolated from the ascites of advanced-stage ovarian cancer patients. Methods Normal ovaries, benign, borderline, grades 1, 2 and 3 ovarian tumors were analyzed by immunohistochemistry for Brn-3a(l expression. A total of 46 ovarian specimens were included in the study. Immunofluorescence was used to investigate the expression of Brn-3a in normal ovarian and cancer cell lines. Brn-3a(l expression was also evaluated by Western blot in tumor cells isolated from ascites of advanced-stage ovarian cancer patients and also in ovarian cancer cell lines. Results Nearly 12% of normal and benign ovarian tissues and 57% of borderline ovarian tumors were positive for epithelial Brn-3a(l expression. Stromal staining was higher and it constituted 40% of normal non-cancerous ovaries compared to 50 and 86% in benign and borderline tumors. On the other hand, 85-100% of grades 1, 2 & 3 ovarian tumors demonstrated nuclear and cytoplasmic Brn-3a(l staining in the epithelium. Stromal staining in grades1, 2 and 3 tumors constituted 71-88% of total staining. Overall, immunoreactive Brn-3a was present in all grades of ovarian tumors. The extent of epithelial and stromal Brn-3a staining was significantly different between the normal and histological grades of tumors (epithelial-χ2 = 41.01, df = 20, P = 0.004, stromal-χ2 = 24.66. df = 15, P = 0.05. The extent of epithelial staining was significantly higher in grades 1 and 2 ovarian tumors compared to normal ovaries and benign ovarian tumors (p Conclusion These data suggest that like other cancers, Brn-3a(l expression is enhanced in ovarian tumors and its expression is

  10. Crossed cerebellar diaschisis and brain tumor biochemistry studied with positron emission tomography, [F-18] fluorodeoxyglucose and [C-11]methionine

    NARCIS (Netherlands)

    Otte, A; Roelcke, U; von Ammon, K; Hausmann, O; Maguire, RP; Missimer, J; Muller-Brand, J; Radu, EW; Leenders, KL

    1998-01-01

    Cerebral gliomas may cause a reduction of glucose metabolism in the cerebellum contralateral to the tumor side (crossed cerebellar diaschisis, CCD). We investigated whether CCD is related to tumor localization, histological grade, size and tumor biochemistry. Cerebellar glucose metabolism was

  11. Peritumoral Brain Edema in Meningiomas Depends on Aquaporin-4 Expression and Not on Tumor Grade, Tumor Volume, Cell Count, or Ki-67 Labeling Index.

    Science.gov (United States)

    Gawlitza, Matthias; Fiedler, Eckhard; Schob, Stefan; Hoffmann, Karl-Titus; Surov, Alexey

    2017-04-01

    The aim of this study was to investigate to which degree the peritumoral brain edema in patients with meningiomas depends on aquaporin-4 (AQP4) expression, tumor grade, tumor volume, Ki-67 expression, and cell count. Thirty-three patients (25 women, 8 men; mean age 56.6 ± 16.0 years) with an intracranial meningioma underwent a standardized magnetic resonance (MR) examination prior to surgical resection. Edema indices (EIs) and tumor volumes were measured on the MR images. Tumor grade was classified according to the World Health Organization, and the proliferation index was estimated on Ki-67 antigen-stained specimens. Tumor cell count was evaluated. Eighteen specimens were stained for AQP4 expressioon. Significant intergroup differences between AQP4 expression grades and EIs were observed (P = 0.03), and a positive correlation was detected between EIs and AQP4 expression grades (r = 0.54; P tumor grading, tumor volume, Ki-67 expression, or cell count. Moreover, we observed no significant positive or negative correlations between the EI and tumor grading (P = 0.7), tumor volume (P = 0.19), Ki-67 index (P = 0.9), and cell count (P = 0.34). Peritumoral brain edema in patients with meningiomas may depend on AQP4 expression grades and not on tumor grade, tumor volume, Ki-67 expression, and cell count. The amount of edema predicted AQP4 expressions with moderate-to-good sensitivity and specificity.

  12. Flotillin-1 protein is upregulated in human endometrial cancer and localization shifts from epithelial to stromal with increasing tumor grade.

    Science.gov (United States)

    Winship, Amy Louise; Rainczuk, Kate; Dimitriadis, Evdokia

    2016-01-01

    Endometrial cancer is the most common invasive gynecological malignancy. Flotillin-1 is an integral membrane protein and estrogen responsive gene. Flotillin-1 expression and localization in human endometrial cancers grades 1-3 was investigated using real-time RT-PCR and immunohistochemistry. Flotillin-1 mRNA levels were unchanged in endometrial cancer versus benign endometrium. Flotillin-1 protein was significantly reduced in the epithelial compartment with increasing tumor grade, although levels increased in the tumor stroma across grades. We have identified a novel factor in human endometrial cancer and observed a shift in epithelial to stromal localization with increasing tumor grade in women.

  13. Bilateral synchronous occurrence of three different histological types of renal tumor: a case report

    Directory of Open Access Journals (Sweden)

    Radopoulos Demetrios

    2009-04-01

    Full Text Available Abstract Introduction Renal cell carcinomas account for 85% of all renal neoplasms. With the introduction of modern imaging modalities, there has been an increased diagnosis of renal tumors. Recent studies have shown that partial nephrectomy can be as safe as radical nephrectomy for smaller renal tumors. Renal cell carcinomas are usually unilateral, however, they can be bilateral in 2% to 4% of sporadic cases and considerably more common in familial cases. Case presentation In this case report, we describe an unusual case of two bilateral synchronous chromophobe renal cell carcinomas accompanied by an oncocytoma and an angiomyolipoma, that were all treated by open partial nephrectomy. Conclusions To the best of our knowledge, this is the first case report on the synchronous occurrence of bilateral chromophobe renal cell carcinomas associated with an oncocytoma and an angiomyolipoma.

  14. Accuracy of high-field intraoperative MRI in the detectability of residual tumor in glioma grade IV resections

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    Hesselmann, Volker; Mager, Ann-Kathrin [Asklepios-Klinik Nord, Hamburg (Germany). Radiology/Neurologie; Goetz, Claudia; Kremer, Paul [Asklepios-Klinik Nord, Hamburg (Germany). Dept. of Neurosurgery; Detsch, Oliver [Asklepios-Klinik Nord, Hamburg (Germany). Dept. of Anaesthesiology and Intensive Care Medicine; Theisgen, Hannah-Katharina [Universitaetsklinikum Schleswig-Holstein, Kiel (Germany). Dept. of Neurosurgery; Friese, Michael; Gottschalk, Joachim [Asklepios-Klinik Nord, Hamburg (Germany). Dept. of Pathology and Neuropathology; Schwindt, Wolfram [Univ. Hospital Muenster (Germany). Dept. of Clinical Radiology

    2017-06-15

    To assess the sensitivity/specificity of tumor detection by T1 contrast enhancement in intraoperative MRI (ioMRI) in comparison to histopathological assessment as the gold standard in patients receiving surgical resection of grade IV glioblastoma. 68 patients with a primary or a recurrent glioblastoma scheduled for surgery including fluorescence guidance and neuronavigation were included (mean age: 59 years, 26 female, 42 male patients). The ioMRI after the first resection included transverse FLAIR, DWI, T2-FFE and T1 - 3 d FFE ± GD-DPTA. The second resection was performed whenever residual contrast-enhancing tissue was detected on ioMRI. Resected tissue samples were histopathologically evaluated (gold standard). Additionally, we evaluated the early postoperative MRI scan acquired within 48 h post-OP for remaining enhancing tissue and compared them with the ioMRI scan. In 43 patients ioMRI indicated residual tumorous tissue, which could be confirmed in the histological specimens of the second resection. In 16 (4 with recurrent, 12 with primary glioblastoma) cases, ioMRI revealed truly negative results without residual tumor and follow-up MRI confirmed complete resection. In 7 cases (3 with recurrent, 4 with primary glioblastoma) ioMRI revealed a suspicious result without tumorous tissue in the histopathological workup. In 2 (1 for each group) patients, residual tumorous tissue was detected in spite of negative ioMRI. IoMRI had a sensitivity of 95 % (94 % recurrent and 96 % for primary glioblastoma) and a specificity of 69.5 % (57 % and 75 %, respectively). The positive predictive value was 86 % (84 % for recurrent and 87 % for primary glioblastoma), and the negative predictive value was 88 % (80 % and 92 %, respectively). ioMRI is effective for detecting remaining tumorous tissue after glioma resection. However, scars and leakage of contrast agent can be misleading and limit specificity. Intraoperative MRI (ioMRI) presents with a high sensitivity for residual

  15. High-Grade Tumor Budding Stratifies Early-Stage Cervical Cancer with Recurrence Risk.

    Science.gov (United States)

    Huang, Bangxing; Cai, Jing; Xu, Xia; Guo, Shuang; Wang, Zehua

    2016-01-01

    This study investigated prognostic significance of tumor budding in early-stage cervical cancer (ESCC) following radical surgery and its contribution to improve the stratification of patients with recurrence risk. The archival medical records and H&E-stained slides of 643 patients with IA2-IIA stage cervical cancer who underwent radical surgery were retrospectively reviewed. Clinicopathological parameters were noted, and tumor buds were counted using immunohistochemistry for each case. The prognostic significance of tumor budding was analyzed. Prediction models that comprised tumor budding were established, and the performance was compared between the novel models and classic criteria via log-rank test and receiver operating characteristic analysis. Tumors with high-grade tumor budding (HTB) exhibited a substantially increased risk of recurrence (hazard ratio = 4.287, P tumor size ≥ 4 cm, deep stromal invasion of outer 1/3, and lymphovascular space invasion to stratify patients with an intermediate risk was most predictive of recurrence compared with the classic criteria. Tumor budding is an independent, unfavorable, prognostic factor for ESCC patients following radical surgery and holds promise for improved recurrence risk stratification.

  16. Histological Grading of Hepatocellular Carcinomas with Intravoxel Incoherent Motion Diffusion-weighted Imaging: Inconsistent Results Depending on the Fitting Method.

    Science.gov (United States)

    Ichikawa, Shintaro; Motosugi, Utaroh; Hernando, Diego; Morisaka, Hiroyuki; Enomoto, Nobuyuki; Matsuda, Masanori; Onishi, Hiroshi

    2017-08-16

    To compare the abilities of three intravoxel incoherent motion (IVIM) imaging approximation methods to discriminate the histological grade of hepatocellular carcinomas (HCCs). Fifty-eight patients (60 HCCs) underwent IVIM imaging with 11 b-values (0-1000 s/mm2). Slow (D) and fast diffusion coefficients (D*) and the perfusion fraction (f) were calculated for the HCCs using the mean signal intensities in regions of interest drawn by two radiologists. Three approximation methods were used. First, all three parameters were obtained simultaneously using non-linear fitting (method A). Second, D was obtained using linear fitting (b = 500 and 1000), followed by non-linear fitting for D* and f (method B). Third, D was obtained by linear fitting, f was obtained using the regression line intersection and signals at b = 0, and non-linear fitting was used for D* (method C). A receiver operating characteristic analysis was performed to reveal the abilities of these methods to distinguish poorly-differentiated from well-to-moderately-differentiated HCCs. Inter-reader agreements were assessed using intraclass correlation coefficients (ICCs). The measurements of D, D*, and f in methods B and C (Az-value, 0.658-0.881) had better discrimination abilities than did those in method A (Az-value, 0.527-0.607). The ICCs of D and f were good to excellent (0.639-0.835) with all methods. The ICCs of D* were moderate with methods B (0.580) and C (0.463) and good with method A (0.705). The IVIM parameters may vary depending on the fitting methods, and therefore, further technical refinement may be needed.

  17. Histological diagnosis of gastric submucosal tumors: A pilot study of endoscopic ultrasonography-guided fine-needle aspiration biopsy vs mucosal cutting biopsy.

    Science.gov (United States)

    Ikehara, Hisatomo; Li, Zhaoliang; Watari, Jiro; Taki, Masato; Ogawa, Tomohiro; Yamasaki, Takahisa; Kondo, Takashi; Toyoshima, Fumihiko; Kono, Tomoaki; Tozawa, Katsuyuki; Ohda, Yoshio; Tomita, Toshihiko; Oshima, Tadayuki; Fukui, Hirokazu; Matsuda, Ikuo; Hirota, Seiichi; Miwa, Hiroto

    2015-10-10

    To compare the usefulness of endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNAB) without cytology and mucosal cutting biopsy (MCB) in the histological diagnosis of gastric submucosal tumor (SMT). We prospectively compared the diagnostic yield, feasibility, and safety of EUS-FNAB and those of MCB based on endoscopic submucosal dissection. The cases of 20 consecutive patients with gastric SMT ≥ 1 cm in diameter. who underwent both EUS-FNAB and MCB were investigated. The histological diagnoses were gastrointestinal stromal tumors (n = 7), leiomyoma (n = 6), schwannoma (n = 2), aberrant pancreas (n = 2), and one case each of glomus tumor, metastatic hepatocellular carcinoma, and no-diagnosis. The tumors' mean size was 23.6 mm. Histological diagnosis was made in 65.0% of the EUS-FNABs and 60.0% of the MCBs, a nonsignificant difference. There were no significant differences in the diagnostic yield concerning the tumor location or tumor size between the two methods. However, diagnostic specimens were significantly more frequently obtained in lesions with intraluminal growth than in those with extraluminal growth by the MCB method (P = 0.01). All four SMTs with extraluminal growth were diagnosed only by EUS-FNAB (P = 0.03). No complications were found in either method. MCB may be chosen as an alternative diagnostic modality in tumors showing the intraluminal growth pattern regardless of tumor size, whereas EUS-FNAB should be performed for SMTs with extraluminal growth.

  18. MAL2 and tumor protein D52 (TPD52 are frequently overexpressed in ovarian carcinoma, but differentially associated with histological subtype and patient outcome

    Directory of Open Access Journals (Sweden)

    Fanayan Susan

    2010-09-01

    Full Text Available Abstract Background The four-transmembrane MAL2 protein is frequently overexpressed in breast carcinoma, and MAL2 overexpression is associated with gain of the corresponding locus at chromosome 8q24.12. Independent expression microarray studies predict MAL2 overexpression in ovarian carcinoma, but these had remained unconfirmed. MAL2 binds tumor protein D52 (TPD52, which is frequently overexpressed in ovarian carcinoma, but the clinical significance of MAL2 and TPD52 overexpression was unknown. Methods Immunohistochemical analyses of MAL2 and TPD52 expression were performed using tissue microarray sections including benign, borderline and malignant epithelial ovarian tumours. Inmmunohistochemical staining intensity and distribution was assessed both visually and digitally. Results MAL2 and TPD52 were significantly overexpressed in high-grade serous carcinomas compared with serous borderline tumours. MAL2 expression was highest in serous carcinomas relative to other histological subtypes, whereas TPD52 expression was highest in clear cell carcinomas. MAL2 expression was not related to patient survival, however high-level TPD52 staining was significantly associated with improved overall survival in patients with stage III serous ovarian carcinoma (log-rank test, p Conclusions MAL2 is frequently overexpressed in ovarian carcinoma, and TPD52 overexpression is a favourable independent prognostic marker of potential value in the management of ovarian carcinoma patients.

  19. Validation of a Proposed Tumor Regression Grading Scheme for Pancreatic Ductal Adenocarcinoma After Neoadjuvant Therapy as a Prognostic Indicator for Survival.

    Science.gov (United States)

    Lee, Sun Mi; Katz, Matthew H G; Liu, Li; Sundar, Manonmani; Wang, Hua; Varadhachary, Gauri R; Wolff, Robert A; Lee, Jeffrey E; Maitra, Anirban; Fleming, Jason B; Rashid, Asif; Wang, Huamin

    2016-12-01

    Neoadjuvant therapy has been increasingly used to treat patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC). Although the College of American Pathologists (CAP) grading scheme for tumor response in posttherapy specimens has been used, its clinical significance has not been validated. Previously, we proposed a 3-tier histologic tumor regression grading (HTRG) scheme (HTRG 0, no viable tumor; HTRG 1, scheme correlated with prognosis. In this study, we sought to validate our proposed HTRG scheme in a new cohort of 167 consecutive PDAC patients who completed neoadjuvant therapy and pancreaticoduodenectomy. We found that patients with HTRG 0 or 1 were associated with a lower frequency of lymph node metastasis (P=0.004) and recurrence (P=0.01), lower ypT (P0.05). In multivariate analysis, HTRG grade 0 or 1 was an independent prognostic factor for better DFS (P=0.03), but not OS. Therefore we validated the proposed HTRG scheme from our previous study. The proposed HTRG scheme is simple and easy to apply in practice by pathologists and might be used as a successful surrogate for longer DFS in patients with potentially resectable PDAC who completed neoadjuvant therapy and surgery.

  20. A Pilot Comparative Study of Quantitative Ultrasound, Conventional Ultrasound, and MRI for Predicting Histology-Determined Steatosis Grade in Adult Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Paige, Jeremy S; Bernstein, Gregory S; Heba, Elhamy; Costa, Eduardo A C; Fereirra, Marilia; Wolfson, Tanya; Gamst, Anthony C; Valasek, Mark A; Lin, Grace Y; Han, Aiguo; Erdman, John W; O'Brien, William D; Andre, Michael P; Loomba, Rohit; Sirlin, Claude B

    2017-05-01

    The purpose of this study is to explore the diagnostic performance of two investigational quantitative ultrasound (QUS) parameters, attenuation coefficient and backscatter coefficient, in comparison with conventional ultrasound (CUS) and MRI-estimated proton density fat fraction (PDFF) for predicting histology-confirmed steatosis grade in adults with nonalcoholic fatty liver disease (NAFLD). In this prospectively designed pilot study, 61 adults with histology-confirmed NAFLD were enrolled from September 2012 to February 2014. Subjects underwent QUS, CUS, and MRI examinations within 100 days of clinical-care liver biopsy. QUS parameters (attenuation coefficient and backscatter coefficient) were estimated using a reference phantom technique by two analysts independently. Three-point ordinal CUS scores intended to predict steatosis grade (1, 2, or 3) were generated independently by two radiologists on the basis of QUS features. PDFF was estimated using an advanced chemical shift-based MRI technique. Using histologic examination as the reference standard, ROC analysis was performed. Optimal attenuation coefficient, backscatter coefficient, and PDFF cutoff thresholds were identified, and the accuracy of attenuation coefficient, backscatter coefficient, PDFF, and CUS to predict steatosis grade was determined. Interobserver agreement for attenuation coefficient, backscatter coefficient, and CUS was analyzed. CUS had 51.7% grading accuracy. The raw and cross-validated steatosis grading accuracies were 61.7% and 55.0%, respectively, for attenuation coefficient, 68.3% and 68.3% for backscatter coefficient, and 76.7% and 71.3% for MRI-estimated PDFF. Interobserver agreements were 53.3% for CUS (κ = 0.61), 90.0% for attenuation coefficient (κ = 0.87), and 71.7% for backscatter coefficient (κ = 0.82) (p predicting hepatic steatosis grade in patients with NAFLD.

  1. Translationally Controlled Tumor Protein in Prostatic Adenocarcinoma: Correlation with Tumor Grading and Treatment-Related Changes

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    Bruno Jim Rocca

    2015-01-01

    Full Text Available Prostate cancer is the second leading cause of cancer-related death. The androgen deprivation therapy is the standard treatment for advanced stages. Unfortunately, virtually all tumors become resistant to androgen withdrawal. The progression to castration-resistance is not fully understood, although a recent paper has suggested translationally controlled tumor protein to be implicated in the process. The present study was designed to investigate the role of this protein in prostate cancer, focusing on the correlation between its expression level with tumor differentiation and response to treatment. We retrieved 292 prostatic cancer specimens; of these 153 had been treated only by radical prostatectomy and 139 had undergone radical prostatectomy after neoadjuvant treatment with combined androgen blockade therapy. Non-neoplastic controls were represented by 102 prostatic peripheral zone specimens. In untreated patients, the expression of the protein, evaluated by RT-qPCR and immunohistochemistry, was significantly higher in tumor specimens than in non-neoplastic control, increasing as Gleason pattern and score progressed. In treated prostates, the staining was correlated with the response to treatment. An association between protein expression and the main clinicopathological factors involved in prostate cancer aggressiveness was identified. These findings suggest that the protein may be a promising prognostic factor and a target for therapy.

  2. Histological and Demographic Characteristics of the Distribution of Brain and Central Nervous System Tumors' Sizes: Results from SEER Registries Using Statistical Methods.

    Science.gov (United States)

    Pokhrel, Keshav P; Vovoras, Dimitrios; Tsokos, Chris P

    2012-09-01

    The examination of brain tumor growth and its variability among cancer patients is an important aspect of epidemiologic and medical data. Several studies for tumors of brain interpreted descriptive data, in this study we perform inference in the extent possible, suggesting possible explanations for the differentiation in the survival rates apparent in the epidemiologic data. Population based information from nine registries in the USA are classified with respect to age, gender, race and tumor histology to study tumor size variation. The Weibull and Dagum distributions are fitted to the highly skewed tumor sizes distributions, the parametric analysis of the tumor sizes showed significant differentiation between sexes, increased skewness for both the male and female populations, as well as decreased kurtosis for the black female population. The effect of population characteristics on the distribution of tumor sizes is estimated by quantile regression model and then compared with the ordinary least squares results. The higher quantiles of the distribution of tumor sizes for whites are significantly higher than those of other races. Our model predicted that the effect of age in the lower quantiles of the tumor sizes distribution is negative given the variables race and sex. We apply probability and regression models to explore the effects of demographic and histology types and observe significant racial and gender differences in the form of the distributions. Efforts are made to link tumor size data with available survival rates in relation to other prognostic variables.

  3. Quantified analysis of histological components and architectural patterns of gleason grades in apparent diffusion coefficient restricted areas upon diffusion weighted MRI for peripheral or transition zone cancer locations.

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    Helfrich, Olivier; Puech, Philippe; Betrouni, Nacim; Pinçon, Claire; Ouzzane, Adil; Rizk, Jérome; Marcq, Gauthier; Randazzo, Marco; Durand, Matthieu; Lakroum, Said; Leroy, Xavier; Villers, Arnauld

    2017-12-01

    To quantify and compare the histological components and architectural patterns of Gleason grades in cancerous areas with restriction on apparent diffusion coefficient (ADC) maps. Twelve consecutive cases with 14 separate ADC restriction areas, positive for cancer in the peripheral zone (PZ) and transition zone (TZ) were included. All had 3 Tesla MRI and radical prostatectomy. Ten regions of interest (ROIs) within and outside the 14 ADC restriction areas positive for cancer were selected. For each ROI, we performed quantitative analysis of (a) prostate benign and malignant histological component surface ratios, including stroma, glands, epithelium, lumen, cellular nuclei; (b) percent of Gleason grades and measures of ADC values. Means of histological components according to ADC restriction for cancerous area were compared with analyses of variance with repeated measures. Independent predictors of the probability of cancer were median epithelium/ROI ratio (P = 0.001) and nuclei/ROI ratio (P = 0.03). Independent predictors of the probability of ADC restriction were malignant glands/ROI and luminal space/ROI (P histological components for the comparison of true positive and false negative (P Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1786-1796. © 2017 International Society for Magnetic Resonance in Medicine.

  4. Noninvasive Grading of Glioma Tumor Using Magnetic Resonance Imaging with Convolutional Neural Networks

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    Saed Khawaldeh

    2017-12-01

    Full Text Available In recent years, Convolutional Neural Networks (ConvNets have rapidly emerged as a widespread machine learning technique in a number of applications especially in the area of medical image classification and segmentation. In this paper, we propose a novel approach that uses ConvNet for classifying brain medical images into healthy and unhealthy brain images. The unhealthy images of brain tumors are categorized also into low grades and high grades. In particular, we use the modified version of the Alex Krizhevsky network (AlexNet deep learning architecture on magnetic resonance images as a potential tumor classification technique. The classification is performed on the whole image where the labels in the training set are at the image level rather than the pixel level. The results showed a reasonable performance in characterizing the brain medical images with an accuracy of 91.16%.

  5. Short sleep duration as a contributor to racial disparities in breast cancer tumor grade

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    Kevin Allan

    2017-07-01

    Full Text Available Although African Americans (AAs are less likely to get breast cancer than European Americans (EAs, they get more aggressive forms. We previously showed that short sleep is associated with higher tumor grade. It is well documented that AAs get less sleep, on average, than EAs. We studied the contribution of short sleep to racial disparities in breast cancer aggressiveness among 809 invasive breast cancer patients who responded to a survey on their lifestyle. Multivariable regressions and mediation analyses were performed to assess the effect of sleep duration on the association of race with tumor grade. AAs reported shorter average sleep (mean [standard deviation] 6.57 [1.47] h than EAs (mean [standard deviation] 7.11 [1.16] h; P<0.0001 and were almost twice as likely to report less than 6 h of sleep per night (48.0% vs. 25.3%, P<0.0001. AA patients were more likely to have high-grade tumors (52.6% vs. 28.7% in EAs, P=0.0002. In multivariate analysis, race was associated with tumor grade (P<0.0001. On adjustment for sleep duration, the effect of race was reduced by 7.1%, but remained statistically significant (P=0.0006. However, the Sobel test did not indicate statistical significance (z=1.69, P=0.091. In other models accounting for these and additional confounders, we found similar results. Because of the conservative nature of the mediation analysis and smaller sample size, replication of our results in larger studies with more AA patients is warranted.

  6. Meta-analysis of the concordance of histological grade of breast cancer between core needle biopsy and surgical excision specimen

    NARCIS (Netherlands)

    Knuttel, F. M.; Menezes, G. L G; Van Diest, P. J.; Witkamp, A. J.; Van Den Bosch, M. A A J; Verkooijen, H. M.

    2016-01-01

    Background With the increasing use of neoadjuvant chemotherapy and minimally invasive ablative therapy in breast cancer, pretreatment assessment of tumour grade on core needle biopsy (CNB) is increasingly needed. However, grading on CNB is possibly less accurate than grading based on the surgical

  7. Diagnostic Value of Preoperative Needle Biopsy for Tumor Grading Assessment in Hepatocellular Carcinoma.

    Science.gov (United States)

    Wang, Lijun; Wang, Jianguo; Zhang, Xuanyu; Li, Jie; Wei, Xuyong; Cheng, Jun; Ling, Qi; Xie, Haiyang; Zhou, Lin; Xu, Xiao; Zheng, Shusen

    2015-01-01

    Needle core biopsy (NCB) is one of the most widely used and accepted methods for the diagnosis of focal hepatic lesions. Although many studies have assessed the diagnostic accuracy of NCB in predicting the tumor grade, it is still under debate. To identify the influence of number of biopsies on NCB diagnostic accuracy. 153 patients with HCC were selected from patients who received preoperative NCB under the guidance of ultrasonography in our hospital. The diagnostic reference standard was the surgical pathologic diagnosis. Using a 3-tier grading scheme (well, moderate and poor), the accuracy of NCB has no significant differences among different number of passes in HCC ≤5 cm. For HCC >5≤8 cm, the increasing number of passes could increase the diagnostic accuracy (63.3%, 81.8%, and 84.8% for passes one, two, and three, respectively). While in HCC>8 cm, the diagnostic accuracy of passes one, two, and three were 62.1%, 69%, and 75.8%, respectively. The accuracy of NCB in assessing tumor grading associated with tumor size and number of passes. Meanwhile, a minimum of two passes should be performed to get better accuracy in patients with HCC >5 cm.

  8. Diagnostic Value of Preoperative Needle Biopsy for Tumor Grading Assessment in Hepatocellular Carcinoma.

    Directory of Open Access Journals (Sweden)

    Lijun Wang

    Full Text Available Needle core biopsy (NCB is one of the most widely used and accepted methods for the diagnosis of focal hepatic lesions. Although many studies have assessed the diagnostic accuracy of NCB in predicting the tumor grade, it is still under debate.To identify the influence of number of biopsies on NCB diagnostic accuracy.153 patients with HCC were selected from patients who received preoperative NCB under the guidance of ultrasonography in our hospital. The diagnostic reference standard was the surgical pathologic diagnosis.Using a 3-tier grading scheme (well, moderate and poor, the accuracy of NCB has no significant differences among different number of passes in HCC ≤5 cm. For HCC >5≤8 cm, the increasing number of passes could increase the diagnostic accuracy (63.3%, 81.8%, and 84.8% for passes one, two, and three, respectively. While in HCC>8 cm, the diagnostic accuracy of passes one, two, and three were 62.1%, 69%, and 75.8%, respectively.The accuracy of NCB in assessing tumor grading associated with tumor size and number of passes. Meanwhile, a minimum of two passes should be performed to get better accuracy in patients with HCC >5 cm.

  9. Tumor size, depth of invasion, and grading of the invasive tumor front are the main prognostic factors in early squamous cell cervical carcinoma.

    Science.gov (United States)

    Kristensen, G B; Abeler, V M; Risberg, B; Trop, C; Bryne, M

    1999-08-01

    The objective of this study was to evaluate the prognostic significance of clinical and histopathologic factors, including a new grading system focusing on the invasive tumor front. A retrospective analysis of 125 surgically treated patients with squamous cell cervical carcinoma FIGO stage IB was conducted. For each tumor, the degree of keratinization, nuclear polymorphism, pattern of invasion, and degree of lymphoid infiltration at the invasive tumor front were graded and given scores between 1 and 4. Clinical tumor size, depth of invasion, and grading of the invasive front had prognostic significance in multivariate analysis, while lymph vascular space involvement, lymph node status, and grade of differentiation did not. Based on clinical tumor size, depth of invasion, and grading of the invasive tumor front, patients could be separated into three groups: One group with minimal risk of recurrence (5-year disease-free survival (DFS) of 100%) consisting of 24% of the patients, an intermediate group with a fairly low risk of recurrence (5-year DFS of about 92%), and a high risk group with a 5-year DFS of 45%. This latter group contained 26% of the patients with 78% of all relapses occurring in the total group of patients. The invasive tumor front grading was reliably reproducible, with inter- and intraobserver agreement of 79 to 87% and kappa values of 0.47 to 0.66. Clinical tumor size, depth of invasion, and grading of the invasive tumor front were the main predictors of prognosis in patients with stage IB squamous cell cancer of the cervix. Copyright 1999 Academic Press.

  10. Ganglioglioma: comparison with other low-grade brain tumors Ganglioglioma: estudo comparativo com outros tumores cerebrais primarios de baixo grau

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    Paulo Thadeu Brainer-Lima

    2006-09-01

    Full Text Available METHOD: Forty-two patients with low-grade brain tumor and refractory epilepsy were studied. The mean age was 22.3 years. They were divided into two groups: Group A, patients with ganglioglioma (n=19 and group B, patients with other low-grade tumors (n=23 (14 astrocytoma, 6 oligodendroglioma, 2 dysembryoplastic neuroepithelial tumor, and 1 xanthoastrocytoma. RESULTS: Age at seizure’s onset was 7 years or less in 73% of the patients in group A and in 30.4% of the patients in group B (p=0.045. Complex partial occurred frequently in group A and B (94.7% versus 82%, respectively. Seizure’s frequency was higher in group B (p=0.002.Computerized tomography (CT was normal in 36.8% of group A patients and abnormal in all group B patients. Magnetic resonance imaging (MRI was abnormal in all patients. Surgical removal was complete in 89.5% of the patients in group A and in 78.2% of the patients in group B. CONCLUSION: The association of refractory epilepsy and complex partial seizures, at a relatively low frequency, in young patients potentially normal CT and a MRI hypointense temporal lobe lesion in T1-weighed slices were habitual image findings in ganglioglioma, rather than other low-grade tumor.MÉTODO: Foram estudados 42 pacientes com tumor cerebral primário de baixo grau e epilepsia refratária. A idade média foi 22,3 anos. Eles foram divididos em dois grupos: no grupo A os pacientes com ganglioglioma (n=19 e no grupo B os pacientes com outros tumores primários de crescimento lento (n=23 (14 astrocitomas, 6 oligodendrogliomas, 2 tumores desembrioblástico neuroepitelial e um xantoastrocitoma. RESULTADOS: A idade de início das crises convulsivas foi 7 anos ou menos em 73% dos pacientes no grupo A e 30,4% dos pacientes no grupo B (p=0,045. A crise convulsiva do tipo parcial complexa foi a mais identificada nos grupos A e B (94,7% versus 82%, respectivamente. A freqüência de crise foi mais alta no grupo B (p=0,002. A tomografia computadorizada

  11. Assessing the performance of four different categories of histological criteria in brain tumours grading by means of a computer-aided diagnosis image analysis system.

    Science.gov (United States)

    Kostopoulos, S; Konstandinou, C; Sidiropoulos, K; Ravazoula, P; Kalatzis, I; Asvestas, P; Cavouras, D; Glotsos, D

    2015-10-01

    Brain tumours are considered one of the most lethal and difficult to treat forms of cancer, with unknown aetiology and lack of any realistic screening. In this study, we examine, whether the combination of descriptive criteria, used by expert histopathologists in assessing histologic tissue samples, and quantitative image analysis features may improve the diagnostic accuracy of brain tumour grading. Data comprised 61 cases of brain cancers (astrocytomas, oligodendrogliomas, meningiomas) collected from the archives of the University Hospital of Patras, Greece. Incorporating physician's descriptive criteria and image analysis's quantitative features into a discriminant function, a computer-aided diagnosis system was designed for discriminating low-grade from high-grade brain tumours. Physician's descriptive features, when solely used in the system, proved of high discrimination accuracy (93.4%). When verbal descriptive features were combined with quantitative image analysis features in the system, discrimination accuracy improved to 98.4%. The generalization of the proposed system to unseen data converged to an overall prediction accuracy of 86.7% ± 5.4%. Considering that histological grading affects treatment selection and diagnostic errors may be notable in clinical practice, the utilization of the proposed system may safeguard against diagnostic misinterpretations in every day clinical practice. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

  12. Susceptibility Imaging in Glial Tumor Grading; Using 3 Tesla Magnetic Resonance (MR) System and 32 Channel Head Coil.

    Science.gov (United States)

    Aydin, Omer; Buyukkaya, Ramazan; Hakyemez, Bahattin

    2017-01-01

    Susceptibility weighted imaging (SWI) is a velocity compensated, high-resolution three-dimensional (3D) spoiled gradient-echo sequence that uses magnitude and filtered-phase data. SWI seems to be a valuable tool for non-invasive evaluation of central nervous system gliomas. Relative cerebral blood volume (rCBV) ratio is one of the best noninvasive methods for glioma grading. Degree of intratumoral susceptibility signal (ITSS) on SWI correlates with rCBV ratio and histopathological grade. This study investigated the effectiveness of ITSS grading and rCBV ratio in preoperative assessment. Thirty-one patients (17 males and 14 females) with histopathogical diagnosis of glial tumor undergoing routine cranial MRI, SWI, and perfusion MRI examinations between October 2011 and July 2013 were retrospectively enrolled. All examinations were performed using 3T apparatus with 32-channel head coil. We used ITSS number for SWI grading. Correlations between SWI grade, rCBV ratio, and pathological grading were evaluated. ROC analysis was performed to determine the optimal rCBV ratio to distinguish between high-grade and low-grade glial tumors. There was a strong positive correlation between both pathological and SWI grading. We determined the optimal rCBV ratio to discriminate between high-grade and low-grade tumors to be 2.21. In conclusion, perfusion MRI and SWI using 3T MR and 32-channel head coil may provide useful information for preoperative glial tumor grading. SWI can be used as an accessory to perfusion MR technique in preoperative tumor grading.

  13. IDH mutant and 1p/19q co-deleted oligodendrogliomas: tumor grade stratification using diffusion-, susceptibility-, and perfusion-weighted MRI

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    Lin, Yu; Xing, Zhen; She, Dejun; Yang, Xiefeng; Zheng, Yingyan; Xiao, Zebin; Cao, Dairong [First Affiliated Hospital of Fujian Medical University, Department of Radiology, Fuzhou, Fujian (China); Wang, Xingfu [First Affiliated Hospital of Fujian Medical University, Department of Pathology, Fuzhou (China)

    2017-06-15

    Currently, isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion are proven diagnostic biomarkers for both grade II and III oligodendrogliomas (ODs). Non-invasive diffusion-weighted imaging (DWI), susceptibility-weighted imaging (SWI), and dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) are widely used to provide physiological information (cellularity, hemorrhage, calcifications, and angiogenesis) of neoplastic histology and tumor grade. However, it is unclear whether DWI, SWI, and DSC-PWI are able to stratify grades of IDH-mutant and 1p/19q co-deleted ODs. We retrospectively reviewed the conventional MRI (cMRI), DWI, SWI, and DSC-PWI obtained on 33 patients with IDH-mutated and 1p/19q co-deleted ODs. Features of cMRI, normalized ADC (nADC), intratumoral susceptibility signals (ITSSs), normalized maxim CBV (nCBV), and normalized maximum CBF (nCBF) were compared between low-grade ODs (LGOs) and high-grade ODs (HGOs). Receiver operating characteristic curve and logistic regression were applied to determine diagnostic performances. HGOs tended to present with prominent edema and enhancement. nADC, ITSSs, nCBV, and nCBF were significantly different between groups (all P < 0.05). The combination of SWI and DSC-PWI for grading resulted in sensitivity and specificity of 100.00 and 93.33%, respectively. IDH-mutant and 1p/19q co-deleted ODs can be stratified by grades using cMRI and advanced magnetic resonance imaging techniques including DWI, SWI, and DSC-PWI. Combined ITSSs with nCBV appear to be a promising option for grading molecularly defined ODs in clinical practice. (orig.)

  14. Anti-tumor necrosis factor treatment in cherubism--clinical, radiological and histological findings in two children.

    Science.gov (United States)

    Hero, M; Suomalainen, A; Hagström, J; Stoor, P; Kontio, R; Alapulli, H; Arte, S; Toiviainen-Salo, S; Lahdenne, P; Mäkitie, O

    2013-01-01

    Cherubism is a rare and disfiguring genetic disorder with excessive bone resorption and multilocular lesions in the mandible and/or maxilla. The disease-causing gain-of-function mutations in the SH3-binding protein 2 (SH3BP2) gene result in increased myeloid cell responses to macrophage colony stimulating factor and RANK ligand, formation of hyperactive osteoclasts (giant cells), and hyper-reactive macrophages that produce excessive amounts of the inflammatory cytokine tumor necrosis factor α (TNF-α). Recent findings in the cherubism mouse model suggest that TNF-α plays a major role in disease pathogenesis and that removal of TNF-α prevents development of the bone phenotype. We treated two children with cherubism with the TNF-α antagonist adalimumab for approximately 2.5 years and collected extensive clinical, radiological and histological follow-up data during the treatment. Histologically the treatment resulted in a significant reduction in the number of multinucleated giant cells and TNF-α staining positivity in both patients. As evaluated by computed tomography and magnetic resonance imaging, the lesions in Patient 1 showed either moderate enlargement (mandibular symphysis) or remained stable (mandibular rami and body, the maxilla). In Patient 2, the lesions in mandibular symphysis showed enlargement during the first 8 months of treatment, and thereafter the lesions remained unchanged. Bone formation and resorption markers remained unaffected. The treatment was well tolerated. Based on our findings, TNF-α antagonist may decrease the formation of pathogenic giant cells, but does not result in lesion regression or prevent lesion expansion in active cherubism. TNF-α modulator treatment thus does not appear to provide sufficient amelioration for patients suffering from cherubism. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Tumor budding in colorectal carcinomas.

    Science.gov (United States)

    Sert Bektaş, Sevda; Inan Mamak, Gülsün; Cırış, Ibrahim Metin; Bozkurt, Kemal Kürşat; Kapucuoğlu, Nilgün

    2012-01-01

    In colorectal carcinomas, tumor budding has been defined as the presence of isolated single tumor cells or small cell clusters in the stroma at the invasive tumor margin. In this study, the relationship between tumor budding density at the invasive tumor margin and pathological parameters is investigated. Haematoxylin and eosin stained slides of 73 cases with colorectal carcinoma were retrospectively evaluated for the presence and intensity of tumor budding by 2 observers. After the specimens were assessed, the highest density of tumor budding area was counted in a microscopic field of x200. Cases were separated into 2 groups according to tumor budding density as low grade ( tumor invasion, histological grade, vascular invasion and lymph node involvement was investigated. Of the 73 colorectal carcinoma cases, 33 (45.2%) had low and 40 (54.8%) had high grade tumor budding density, respectively. There was a statistically significant relationship between high grade tumor budding density and histological grade (p=0.042), lymph node involvement (p=0.0001) and vascular invasion (p=0.0034). High grade tumor budding density is associated with aggressive phenotypical features in colorectal carcinoma.

  16. Tumor Necrosis Adds Prognostically Significant Information to Grade in Clear Cell Renal Cell Carcinoma: A Study of 842 Consecutive Cases From a Single Institution.

    Science.gov (United States)

    Khor, Li-Yan; Dhakal, Hari P; Jia, Xuefei; Reynolds, Jordan P; McKenney, Jesse K; Rini, Brian I; Magi-Galluzzi, Cristina; Przybycin, Christopher G

    2016-09-01

    Tumor necrosis has been shown to be an independent predictor of adverse outcome in renal cell carcinoma. A modification of the International Society of Urological Pathology (ISUP) grading system for renal cell carcinomas has recently been proposed, which incorporates the presence of tumor necrosis into grade. The investigators proposing this system found that necrosis added significant prognostic information to ISUP grade. We attempted to describe our experience with the effect of tumor necrosis in relationship to nuclear grade by reviewing the slides from a large consecutive series of localized clear cell renal cell carcinomas from our institution and obtaining long-term clinical follow-up information (overall survival). Of the 842 clear cell renal cell carcinomas reviewed, 265 (31.5%) were ISUP grade 1 or 2, 437 (51.9%) were ISUP grade 3, and 140 (16.6%) were ISUP grade 4. Tumor necrosis was present in 177 (21%) cases. Five hundred and forty-seven (64.9%) cases were stage pT1, 83 (9.9%) were stage pT2, 193 (22.9%) were stage pT3a, and 19 (2.3%) were pT3b or higher. Median follow-up was 73.2 months (range 0.12 to 273.6), and 310 (36.8%) patients died. On univariable analysis, there was no significant difference in outcome for tumors of ISUP grades 1 to 3. After adjustment for age, tumor stage, and tumor size, ISUP grade 4 and necrosis were significant predictors of overall survival on multivariable analysis. When the recently proposed modified grading system incorporating tumor necrosis was applied to our data, there was no significant difference in overall survival between patients with modified grade 1 tumors and those with modified grade 2 tumors (P=0.31); however, there was a statistically significant difference between patients with modified grade 1 or 2 tumors and those with modified grade 3 tumors (P=0.04),and a substantial difference in outcome between those with modified grade 3 and modified grade 4 tumors (Pnecrosis and could be divided into 3

  17. Enhanced Sentinel Lymphoscintigraphic Mapping in Breast Tumor Using the Graded Shield Technique

    Directory of Open Access Journals (Sweden)

    Yu-Wen Chen

    2003-07-01

    Full Text Available The graded shield technique was developed to increase the sentinel node detection rate by improving lymphoscintigraphic image contrast. In a 6-month period, 50 women with clinical suspicion of early stage breast cancer (T1 and T2 tumors were enrolled in this study. The patients had a mean age of 47.2 ± 10.3 years. A composite graded shield was constructed using three concentric layers of leaded plastic measuring 3 cm, 5 cm, and 7 cm each in diameter. The graded shield was designed with a movable Velcro backing for accurate positioning over the injection site. Images were acquired with a vertical angle dual-head gamma camera using an established injection procedure developed at our institution. The rate of detection of sentinel lymph nodes using lymphoscintigraphic mapping improved from 74% (37/50 patients to 96% (48/50 using the graded shield (p < 0.05. In addition to the increased detection rate, our technique also increased the number of nodes detected and improved visualization of the adjacent lymphatic basin. By enhancing nodal contrast, we have demonstrated that the graded shield technique is an effective method for improving the rate of sentinel node detection.

  18. Analysis of EZH2: micro-RNA network in low and high grade astrocytic tumors.

    Science.gov (United States)

    Sharma, Vikas; Purkait, Suvendu; Takkar, Sonam; Malgulwar, Prit Benny; Kumar, Anupam; Pathak, Pankaj; Suri, Vaishali; Sharma, Mehar C; Suri, Ashish; Kale, Shashank Sharad; Kulshreshtha, Ritu; Sarkar, Chitra

    2016-04-01

    Enhancer of Zeste homologue2 (EZH2) is an epigenetic regulator that functions as oncogene in astrocytic tumors, however, EZH2 regulation remains little studied. In this study, we measured EZH2 levels in low (Gr-II,DA) and high grade (Gr-IV,GBM) astrocytic tumors and found significant increased EZH2 transcript level with grade(median DA-8.5, GBM-28.9).However, a different trend was reflected in protein levels, with GBMs showing high EZH2 LI(median-26.5) compared to DA (median 0.3). This difference in correlation of EZH2 protein and RNA levels suggested post-transcriptional regulation of EZH2, likely mediated by miRNAs. We selected eleven miRNAs that strongly predicted to target EZH2 and measured their expression. Three miRNAs (miR-26a-5p,miR27a-3p and miR-498) showed significant correlation with EZH2 protein, suggesting them as regulators of EZH2, however miR-26a-5p levels decreased with grade. ChIP analyses revealed H3K27me3 modifications in miR-26a promoter suggesting feedback loop between EZH2 and miR26a. We further measured six downstream miRNA targets of EZH2 and found significant downregulation of four (miR-181a/b and 200b/c) in GBM. Interestingly, EZH2 associated miRNAs were predicted to target 25 genes in glioma-pathway, suggesting their role in tumor formation or progression. Collectively, our work suggests EZH2 and its miRNA interactors may serve as promising biomarkers for progression of astrocytic tumors and may offer novel therapeutic strategies.

  19. Tumor thickness and histological features as predictors of invasive foci within preoperatively diagnosed ductal carcinoma in situ.

    Science.gov (United States)

    Mori, Kiyoshi; Takeda, Masashi; Kodama, Yoshinori; Kiyokawa, Hiroki; Yasojima, Hiroyuki; Mizutani, Makiko; Otani, Yoko; Morikawa, Nozomi; Masuda, Norikazu; Mano, Masayuki

    2017-06-01

    Small invasion into ductal carcinoma in situ (DCIS) can easily be overlooked in resected breast specimens. To disclose useful markers predictive of invasive foci within preoperatively diagnosed DCIS lesions, a retrospective histopathological comparison was made between postoperatively diagnosed invasive ductal carcinoma with a predominant intraductal component (IDCPIC) (n=43) and pure DCIS (n=82). Through a multivariate logistic regression analysis model, 5 variables (DCIS grade, "tumor thickness," extent of retraction cleft, presence of lymph node metastasis, and HER2 score) were found to be significantly associated with the presence of invasive foci within DCIS; with a cutoff point of 0.315, sensitivity, specificity, positive predictive value, and negative predictive value were 0.93, 0.77, 0.68, and 0.95, respectively. No statistically significant difference was observed in recurrence-free survival between IDCPIC and pure DCIS, whereas the IDCPIC curve showed a slightly earlier decline than the DCIS one. In general, preoperative detection of lymph node metastasis in DCIS patients is elusive because of the extremely tiny metastatic size in most cases; thus, a 4-variable model, without lymph node metastasis, would be the actual working model. Furthermore, tumor "thickness" was found to be the most significant parameter predictive of invasive foci within DCIS. Although IDCPIC and pure DCIS showed similar recurrence-free survival curves, prediction of invasive foci within DCIS necessitates postoperative pathological analysis of surgically resected lesions. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Expression of merlin, NDRG2, ERBB2, and c-MYC in meningiomas: relationship with tumor grade and recurrence.

    Science.gov (United States)

    Ongaratti, B R; Silva, C B O; Trott, G; Haag, T; Leães, C G S; Ferreira, N P; Oliveira, M C; Pereira-Lima, J F S

    2016-01-01

    Meningiomas are common, usually benign tumors of the central nervous system that have a high rate of post-surgical recurrence or regrowth. We determined expression of the proteins merlin, NDRG2, ERBB2, and c-MYC in meningiomas using immunohistochemistry and assessed relationships between protein expression and gender, age, tumor grade, and recurrence or regrowth. The study sample comprised 60 patients, (44 women and 16 men) with a mean age of 53.2 ± 12.7 years. Tumors were classified as grade I (n=48) or grades II and III (n=12). Expression of merlin, NDRG2, ERBB2, and c-MYC was not significantly different statistically with relation to gender, age, or meningioma recurrence or regrowth. Merlin was expressed in 100% of the cases. No statistically significant difference between tumor grade and recurrence or regrowth was identified. Statistically significant differences were identified between the mean age of patients with grade I (54.83 ± 11.60) and grades II and III (46.58 ± 15.08) meningiomas (P=0.043), between strong c-MYC expression and grades II and III (Pmerlin on tumorigenesis, the association of c-MYC with aggressive meningiomas, and that partial surgical resection is associated with tumor recurrence or regrowth.

  1. Histological grading of papillary urothelial carcinoma of the bladder: prognostic value of the 1998 WHO/ISUP classification system and comparison with conventional grading systems

    NARCIS (Netherlands)

    Oosterhuis, J. W. A.; Schapers, R. F. M.; Janssen-Heijnen, M. L. G.; Pauwels, R. P. E.; Newling, D. W.; ten Kate, F.

    2002-01-01

    AIM: To test the prognostic value of the 1998 WHO/ISUP (World Health Organisation/International Society of Urologic Pathology) consensus classification system in Ta papillary urothelial neoplasms of the bladder. METHODS: The histological slides of 322 patients with a primary Ta tumour were

  2. Comparable outcome between endometrioid and non-endometrioid tumors in patients with early-stage high-grade endometrial cancer

    NARCIS (Netherlands)

    Reynaers, E. A. E. M.; Ezendam, N. P. M.; Pijnenborg, J. M. A.

    2015-01-01

    Background Approximately 25% of endometrial cancer patients present with high-grade tumors. Unlike the clearly defined work-up for non-endometrioid endometrial cancer, no consensus exists for surgical staging and adjuvant therapy in high-grade endometrioid endometrial cancer. We compared the

  3. Comparable outcome between endometrioid and non-endometrioid tumors in patients with early-stage high-grade endometrial cancer

    NARCIS (Netherlands)

    Reynaers, E.A.; Ezendam, N.P.; Pijnenborg, J.M.A.

    2015-01-01

    BACKGROUND: Approximately 25% of endometrial cancer patients present with high-grade tumors. Unlike the clearly defined work-up for non-endometrioid endometrial cancer, no consensus exists for surgical staging and adjuvant therapy in high-grade endometrioid endometrial cancer. We compared the

  4. Clinical outcome of patients with previously untreated soft tissue sarcomas in relation to tumor grade, DNA ploidy and karyotype

    NARCIS (Netherlands)

    Plaat, B E; Muntinghe, F L; Molenaar, W M; Hoekstra, H J; Bosveld, H E; Dam, A; Dijkhuizen, T; van den Berg, E

    1997-01-01

    The most important prognostic factor in soft tissue sarcomas (STS) is tumor grade. Since most grading methods are subject to the interpretation of the individual pathologist, there is a need for objective criteria such as DNA ploidy and karyotype, which are of prognostic value in several types of

  5. IDH mutant and 1p/19q co-deleted oligodendrogliomas: tumor grade stratification using diffusion-, susceptibility-, and perfusion-weighted MRI.

    Science.gov (United States)

    Lin, Yu; Xing, Zhen; She, Dejun; Yang, Xiefeng; Zheng, Yingyan; Xiao, Zebin; Wang, Xingfu; Cao, Dairong

    2017-06-01

    Currently, isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion are proven diagnostic biomarkers for both grade II and III oligodendrogliomas (ODs). Non-invasive diffusion-weighted imaging (DWI), susceptibility-weighted imaging (SWI), and dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) are widely used to provide physiological information (cellularity, hemorrhage, calcifications, and angiogenesis) of neoplastic histology and tumor grade. However, it is unclear whether DWI, SWI, and DSC-PWI are able to stratify grades of IDH-mutant and 1p/19q co-deleted ODs. We retrospectively reviewed the conventional MRI (cMRI), DWI, SWI, and DSC-PWI obtained on 33 patients with IDH-mutated and 1p/19q co-deleted ODs. Features of cMRI, normalized ADC (nADC), intratumoral susceptibility signals (ITSSs), normalized maxim CBV (nCBV), and normalized maximum CBF (nCBF) were compared between low-grade ODs (LGOs) and high-grade ODs (HGOs). Receiver operating characteristic curve and logistic regression were applied to determine diagnostic performances. HGOs tended to present with prominent edema and enhancement. nADC, ITSSs, nCBV, and nCBF were significantly different between groups (all P IDH-mutant and 1p/19q co-deleted ODs can be stratified by grades using cMRI and advanced magnetic resonance imaging techniques including DWI, SWI, and DSC-PWI. Combined ITSSs with nCBV appear to be a promising option for grading molecularly defined ODs in clinical practice.

  6. Number of Polyploid Giant Cancer Cells and Expression of EZH2 Are Associated with VM Formation and Tumor Grade in Human Ovarian Tumor

    Directory of Open Access Journals (Sweden)

    Li Zhang

    2014-01-01

    Full Text Available To investigate the associations among the number of polyploid giant cancer cells (PGCCs and vasculogenic mimicry (VM, EZH2 expression, and serous ovarian tumor grade, a total of 80 paraffin-embedded serous ovarian tumor samples including 21 cases of primary carcinoma and their metastatic tumors, 26 cases of primary carcinoma without metastasis, and 12 cases of serous borderline cystadenoma were analyzed. PGCCs and VM were detected in human serous ovarian tumor. The metastatic foci of ovarian carcinoma had the highest number of PGCCs and VM. The number of PGCCs and VM increased with the grade of ovarian carcinomas. PGCCs generated erythrocytes via budding and together they formed VM. Tumor cells and cancer-associated fibroblasts were positive for EZH2 immunohistochemical staining. The tumor cells and cancer associated fibroblasts in the metastatic foci had the highest staining index of EZH2 staining. Both tumor cells and cancer-associated fibroblasts express EZH2 which then contributes to the malignant grade of serous ovarian tumor.

  7. Risk of Local Recurrence of Benign and Borderline Phyllodes Tumors

    DEFF Research Database (Denmark)

    Borhani-Khomani, Kaveh; Talman, Maj-Lis Møller; Kroman, Niels

    2016-01-01

    PURPOSE: To determine the recurrence rate of benign and borderline phyllodes tumors (PTs) of the breast, the association between the size of resection margin and risk of recurrence and the risk of progression of histological grading at recurrence. METHODS: Nationwide retrospective study on Danish...... in histological grading was found. The results do not justify wide excision margins of nonmalignant phyllodes tumors of the breast....... women aged 18 years or older, operated from 1999 to 2014, with resected benign or borderline PTs. Information on age, size of primary tumor and recurrence, histological grade, surgical treatment, margin size, and local recurrence were collected from the national Danish Pathology Register. RESULTS...

  8. Clinical outcomes and histological findings of patients with advanced metastatic germ cell tumors undergoing post-chemotherapy resection of retroperitoneal lymph nodes and residual extraretroperitoneal masses.

    Science.gov (United States)

    Nakamura, Terukazu; Oishi, Masakatsu; Ueda, Takashi; Fujihara, Atsuko; Nakanishi, Hiroyuki; Kamoi, Kazumi; Naya, Yoshio; Hongo, Fumiya; Okihara, Koji; Miki, Tsuneharu

    2015-07-01

    To assess clinical outcomes of patients with advanced germ cell tumor undergoing post-chemotherapy retroperitoneal lymph node dissection with or without extraretroperitoneal mass resection. Between 1998 and 2013, 175 retroperitoneal lymph node dissections for advanced metastatic germ cell tumors were carried out at Kyoto Prefectural University of Medicine, Kyoto, Japan. Of patients receiving retroperitoneal lymph node dissections, 156 underwent post-chemotherapy retroperitoneal lymph node dissection with or without extraretroperitoneal mass resection as first surgery after completion of chemotherapy. Of these 156 patients, 47 underwent both post-chemotherapy retroperitoneal lymph node dissection and extraretroperitoneal mass resection. The histological findings were necrosis in 59.6%, teratoma in 31.4% and viable cancer in 9.0% at retroperitoneal lymph node. At extraretroperitoneal mass resection, necrosis was present in 59.6%, teratoma in 31.9% and viable cancer in 8.5%. Overall histological discordance between retroperitoneal lymph node and extraretroperitoneal mass was found in 31.9%. Five-year disease-free survival stratified by retroperitoneal lymph node histology in 156 patients was 91.3% for necrosis, 78.7% for teratoma and 63.5% for viable cancer (log-rank, P = 0.009). Antegrade ejaculation was preserved in 80.9%. In the worst histology of post-chemotherapy retroperitoneal lymph node dissection or extraretroperitoneal mass resection in 156 patients, 5-year disease-free survival was 93.2% for necrosis, 79.0% for teratoma and 63.4% for viable cancer (log-rank, P retroperitoneal lymph node histology and salvage chemotherapy. The presence of viable cancer at the retroperitoneal lymph node is an independent predictor of disease recurrence. In approximately one-third of cases, there is a histological discordance between retroperitoneal lymph node and extraretroperitoneal mass. Resection of residual retroperitoneal lymph node and extraretroperitoneal masses

  9. Small RNAs and the competing endogenous RNA network in high grade serous ovarian cancer tumor spread.

    Science.gov (United States)

    Bachmayr-Heyda, Anna; Auer, Katharina; Sukhbaatar, Nyamdelger; Aust, Stefanie; Deycmar, Simon; Reiner, Agnes T; Polterauer, Stephan; Dekan, Sabine; Pils, Dietmar

    2016-06-28

    High grade serous ovarian cancer (HGSOC) is among the most deadly malignancies in women, frequently involving peritoneal tumor spread. Understanding molecular mechanisms of peritoneal metastasis is essential to develop urgently needed targeted therapies. We described two peritoneal tumor spread types in HGSOC apparent during surgery: miliary (numerous millet-sized implants) and non-miliary (few big, bulky implants). The former one is defined by a more epithelial-like tumor cell characteristic with less immune cell reactivity and with significant worse prognosis, even if corrected for typical clinicopathologic factors.23 HGSOC patients were enrolled in this study. Isolated tumor cells from fresh tumor tissues of ovarian and peritoneal origin and from ascites were used for ribosomal RNA depleted RNA and small RNA sequencing. RT-qPCR was used to validate results and an independent cohort of 32 patients to validate the impact on survival. Large and small RNA sequencing data were integrated and a new gene-miRNA set analysis method was developed.Thousands of new small RNAs (miRNAs and piwi-interacting RNAs) were predicted and a 13 small RNA signature was developed to predict spread type from formalin-fixed paraffin-embedded tissues. Furthermore, integrative analyses of RNA sequencing and small RNA sequencing data revealed a global upregulation of the competing endogenous RNA network in tumor tissues of non-miliary compared to miliary spread, i.e. higher expression of circular RNAs and long non-coding RNAs compared to coding RNAs but unchanged abundance of small RNAs. This global deregulated expression pattern could be co-responsible for the spread characteristic, miliary or non-miliary, in ovarian cancer.

  10. Histological grading in the deep invasive front of T1 and T2 glottic squamous cell carcinomas has high prognostic value.

    Science.gov (United States)

    Bryne, M; Jenssen, N; Boysen, M

    1995-01-01

    The characteristics of the deep invasive front area of squamous cell carcinomas may reflect tumour prognosis better than other parts of the tumour. Consequently, the authors have recently developed a simple malignancy grading system based solely on the characteristics of the deep invasive front area of oral squamous cell carcinomas, which has great prognostic value. Our previous materials were somewhat heterogeneous, and the prognostic value of our system needed to be confirmed in homogeneous patient material. In the present study of 95 T1-2/N0 glottic carcinomas all treated by radiation, the high prognostic value for invasive front grading of biopsy specimens is confirmed. The grading significantly predicted local recurrence, i.e. treatment failure (P = 0.001). Histological characteristics of the deep invasive front proved to be a better indicator of prognosis than the T-category (size of tumour), and our findings may be of value in the selection of treatment. Of the individual variables in the grading system (pattern of invasion, degree of keratinization, nuclear polymorphism and host response), pattern of invasion and degree of keratinization were the strongest prognosticators in the multivariate analyses. Invasive front characteristics may also prove to be of prognostic value in other cancers.

  11. Evaluation of renal cell carcinoma histological subtype and fuhrman grade using {sup 18}F-fluorodeoxyglucose-positron emission tomography/computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, Reiko; Nozaki, Sayumi; Abe, Koichiro; Sakai, Shuji [Tokyo Women' s Medical University, Department of Diagnostic Imaging and Nuclear Medicine, Tokyo (Japan); Kondo, Tsunenori [Tokyo Women' s Medical University, Department of Urology, Tokyo (Japan); Nagashima, Yoji [Tokyo Women' s Medical University, Department of Surgical Pathology, Tokyo (Japan)

    2017-11-15

    We evaluated {sup 18}F-fluorodeoxyglucose (FDG) uptake by renal cell carcinomas (RCCs) to determine whether different histological subtypes and Fuhrman grades can be distinguished. We retrospectively reviewed the records and maximum standardised uptake value (SUVmax) of 147 patients with 154 RCCs who underwent FDG-positron emission tomography (PET)/computed tomography (CT) prior to tumour resection. The SUVmax was significantly lower in chromophobe RCC (chRCC) tumours than in clear cell RCC (ccRCC; p = 0.003) and papillary RCC (pRCC; p = 0.034) tumours. The mean tumour SUVmax was 4.58 ± 4.1 (range, 1.29-30.4) for ccRCC, 3.98 ± 1.9 (range, 0.49-6.72) for pRCC, and 1.93 ± 0.9 (range, 0.89-3.41) for chRCC. The SUVmax was not significantly different between the ccRCC and pRCC groups. In ccRCC and pRCC tumours, high-grade tumours had a significantly greater SUVmax (p < 0.001 and p < 0.05) than low-grade tumours by analysis of variance (ANOVA) and the Mann-Whitney U test. In ccRCC, multivariate regression analysis indicated that the SUVmax was a significant indicator of Fuhrman grade. No significant differences in uptake were observed between high- and low-grade chRCC tumours. The SUVmax obtained using FDG-PET/CT may be an important indicator for predicting tumour grade in ccRCC and pRCC. (orig.)

  12. Association of des-γ-carboxy prothrombin production and Sonazoid-enhanced ultrasound findings in hepatocellular carcinomas of different histologic grades.

    Science.gov (United States)

    Murata, Kazumoto; Saito, Akiko; Katagiri, Satoshi; Ariizumi, Shunichi; Nakano, Masayuki; Yamamoto, Masakazu

    2017-08-21

    We previously reported that hepatocellular carcinoma (HCC) changes to a phenotype producing des-γ-carboxy prothrombin (DCP) during epithelial mesenchymal transition (EMT) in vitro. To confirm this change in vivo, we evaluated the association between DCP production and HCC hemodynamics in patients undergoing resection as EMT and hemodynamic changes are closely associated with each other. We evaluated HCC hemodynamics by employing Sonazoid-enhanced ultrasound (SEUS) before surgical resection, and sought associations with histological grade and immunohistochemical staining of DCP in 19 areas from 11 patients. In 10 HCC areas showing early washout (3 min ≥) using SEUS, three areas corresponded to poorly differentiated HCC and the remaining seven areas corresponded to moderately differentiated HCC, and positive DCP staining was observed in only two of the seven moderately differentiated HCC areas, whereas no staining was observed in poorly differentiated HCC areas. Six HCC areas showing intermediate washout (3-10 min) using SEUS were moderately differentiated, of which five demonstrated positive DCP staining (83.3%, 5/6). However, all HCC areas without enhancement in the arterial phase were well-differentiated and did not show DCP staining. Our preliminary findings suggest that HCC hemodynamics evaluated by SEUS are associated with histological grade and/or DCP production.

  13. Advances in Tumor Screening, Imaging, and Avatar Technologies for High-Grade Serous Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Anders eOhman

    2014-11-01

    Full Text Available The majority of high-grade serous ovarian carcinoma cases are detected in advanced stages when treatment options are limited. Surgery is less effective at eradicating the disease when it is widespread, resulting in high rates of disease relapse and chemoresistance. Current screening techniques are ineffective for early tumor detection and consequently, BRCA mutations carriers, with an increased risk for developing high-grade serous ovarian cancer, elect to undergo risk-reducing surgery. While prophylactic surgery is associated with a significant reduction in the risk of cancer development, it also results in surgical menopause and significant adverse side effects. The development of efficient early-stage screening protocols and imaging technologies is critical to improving the outcome and quality of life for current patients and women at increased risk. In addition, more accurate animal models are necessary in order to provide relevant in vivo testing systems and advance our understanding of the disease origin and progression. Moreover, both genetically engineered and tumor xenograft animal models enable the preclinical testing of novel imaging techniques and molecularly targeted therapies as they become available. Recent advances in xenograft technologies have made possible the creation of avatar mice, personalized tumorgrafts, which can be used as therapy testing surrogates for individual patients prior to or during treatment. High-grade serous ovarian cancer may be an ideal candidate for use with avatar models based on key characteristics of the tumorgraft platform. This review explores multiple strategies, including novel imaging and screening technologies in both patients and animal models, aimed at detecting cancer in the early stages and improving the disease prognosis.

  14. Mechanical phenotyping of cells and extracellular matrix as grade and stage markers of lung tumor tissues.

    Science.gov (United States)

    Panzetta, Valeria; Musella, Ida; Rapa, Ida; Volante, Marco; Netti, Paolo A; Fusco, Sabato

    2017-07-15

    The mechanical cross-talk between cells and the extra-cellular matrix (ECM) regulates the properties, functions and healthiness of the tissues. When this is disturbed it changes the mechanical state of the tissue components, singularly or together, and cancer, along with other diseases, may start and progress. However, the bi-univocal mechanical interplay between cells and the ECM is still not properly understood. In this study we show how a microrheology technique gives us the opportunity to evaluate the mechanics of cells and the ECM at the same time. The mechanical phenotyping was performed on the surgically removed tissues of 10 patients affected by adenocarcinoma of the lung. A correlation between the mechanics and the grade and stage of the tumor was reported and compared to the mechanical characteristics of the healthy tissue. Our findings suggest a sort of asymmetric modification of the mechanical properties of the cells and the extra-cellular matrix in the tumor, being the more compliant cell even though it resides in a stiffer matrix. Overall, the simultaneous mechanical characterization of the tissues constituents (cells and ECM) provided new support for diagnosis and offered alternative points of analysis for cancer mechanobiology. When the integrity of the mechanical cross-talk between cells and the extra-cellular matrix is disturbed cancer, along with other diseases, may initiate and progress. Here, we show how a new technique gives the opportunity to evaluate the mechanics of cells and the ECM at the same time. It was applied on surgically removed tissues of 10 patients affected by adenocarcinoma of the lung and a correlation between the mechanics and the grade and stage of the tumor was reported and compared to the mechanical characteristics of the healthy tissue. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  15. Molecular grading of tumors of the upper urothelial tract using FGFR3 mutation status identifies patients with favorable prognosis

    Directory of Open Access Journals (Sweden)

    Lyle SR

    2012-12-01

    Full Text Available Stephen R Lyle,1 Chung-Cheng Hsieh,1 Cecilia A Fernandez,2 Anthony P Shuber21University of Massachusetts, Worcester, MA, 2Predictive Biosciences Inc., Lexington, MA, USABackground: Mutations in FGFR3 have been shown to occur in tumors of the upper urothelial tract and may be indicative of a good prognosis. In bladder tumors, the combination of FGFR3 mutation status and Ki-67 level has been used to define a tumor's molecular grade and predict survival. Pathological evaluation of upper urothelial tumors is currently the best predictor of prognosis, but suffers from variability in pathological assessments. This study investigated the association with prognosis of FGFR3 mutations alone and in combination with Ki-67 in this patient population.Methods: Genomic DNA was isolated from tumor samples of 80 patients with upper urothelial cancer. The presence of mutation in FGFR3 was evaluated using real-time polymerase chain reaction. Ki-67 protein expression was determined by immunohistochemistry. Kaplan–Meier survival analysis evaluated the relationship of FGFR3 mutations and Ki-67 levels with survival.Results: FGFR3 mutations were identified in 40% of tumors and were predominantly associated with noninvasive tumors. Overall survival was higher in patients with FGFR3 mutant tumors (P = 0.02 and in molecular grade 1 tumors as determined by FGFR3 and Ki-67 (P = 0.02.Conclusion: In this study, we confirm the occurrence of FGFR3 mutations in tumors of the upper urothelial tract and its association with a good prognosis. Both FGFR3 and molecular grading are predictors of overall survival. Molecular grading can help to assess the prognosis of patients with upper urinary tract cancer and may represent a new tool for managing this population of patients.Keywords: upper tract, urothelial carcinoma, ureter, renal pelvis, Ki-67, survival

  16. Does Clinical Staging and Histological Grading Show Parallelism In Oral Submucous Fibrosis? A Retrospective Study from an Indian City

    Directory of Open Access Journals (Sweden)

    Manish Narayan

    2014-06-01

    Conclusions: There was no correlation between clinical staging and histopathological grading of oral submucous fibrosis. The test results were statistically not significant. (p=0.635 This may be due to difference in severity and extent of fibrosis in different parts of the oral mucosa. [J Interdiscipl Histopathol 2014; 2(3.000: 145-149

  17. Comparative genomic and proteomic analysis of high grade glioma primary cultures and matched tumor in situ.

    LENUS (Irish Health Repository)

    Howley, R

    2012-10-15

    Developing targeted therapies for high grade gliomas (HGG), the most common primary brain tumor in adults, relies largely on glioma cultures. However, it is unclear if HGG tumorigenic signaling pathways are retained under in-vitro conditions. Using array comparative genomic hybridization and immunohistochemical profiling, we contrasted the epidermal and platelet-derived growth factor receptor (EGFR\\/PDGFR) in-vitro pathway status of twenty-six primary HGG cultures with the pathway status of their original HGG biopsies. Genomic gains or amplifications were lost during culturing while genomic losses were more likely to be retained. Loss of EGFR amplification was further verified immunohistochemically when EGFR over expression was decreased in the majority of cultures. Conversely, PDGFRα and PDGFRβ were more abundantly expressed in primary cultures than in the original tumor (p<0.05). Despite these genomic and proteomic differences, primary HGG cultures retained key aspects of dysregulated tumorigenic signaling. Both in-vivo and in-vitro the presence of EGFR resulted in downstream activation of P70s6K while reduced downstream activation was associated with the presence of PDGFR and the tumor suppressor, PTEN. The preserved pathway dysregulation make this glioma model suitable for further studies of glioma tumorigenesis, however individual culture related differences must be taken into consideration when testing responsiveness to chemotherapeutic agents.

  18. High bone sialoprotein (BSP expression correlates with increased tumor grade and predicts a poorer prognosis of high-grade glioma patients.

    Directory of Open Access Journals (Sweden)

    Tao Xu

    Full Text Available OBJECTIVES: To investigate the expression and prognostic value of bone sialoprotein (BSP in glioma patients. METHODS: We determined the expression of BSP using real-time RT-PCR and immunohistochemistry in tissue microarrays containing 15 normal brain and 270 glioma samples. Cumulative survival was calculated by the Kaplan-Meier method and analyzed by the log-rank test. Univariate and multivariate analyses were performed by the stepwise forward Cox regression model. RESULTS: Both BSP mRNA and protein levels were significantly elevated in high-grade glioma tissues compared with those of normal brain and low-grade glioma tissues, and BSP expression positively correlated with tumor grade (P<0.001. Univariate and multivariate analysis showed high BSP expression was an independent prognostic factor for a shorter progression-free survival (PFS and overall survival (OS in both grade III and grade IV glioma patients [hazard ratio (HR = 2.549 and 3.154 for grade III glioma, and HR = 1.637 and 1.574 for grade IV glioma, respectively]. Patients with low BSP expression had a significantly longer median OS and PFS than those with high BSP expression. Small extent of resection and lineage of astrocyte served as independent risk factors of both shorter PFS and OS in grade III glioma patients; GBM patients without O(6-methylguanine (O(6-meG DNA methyltransferase (MGMT methylation and Karnofsky performance score (KPS less than 70 points were related to poor prognosis. Lack of radiotherapy related to shorter OS but not affect PFS in both grade III and grade IV glioma patients. CONCLUSION: High BSP expression occurs in a significant subset of high-grade glioma patients and predicts a poorer outcome. The study identifies a potentially useful molecular marker for the categorization and targeted therapy of gliomas.

  19. The prognostic value of a histologic grading system, DNA profile, and MIB-1 expression in early stages of cervical squamous cell carcinomas.

    Science.gov (United States)

    Graflund, Marianne; Sorbe, B; Bryne, M; Karlsson, M

    2002-01-01

    This study evaluated the prognostic importance of a new grading system focusing on the invasive tumor front, DNA profile, and the proliferation marker MIB-1. A complete geographic series of 172 women treated with radical hysterectomy (Wertheim-Meigs) for FIGO stage I-II cervical carcinomas was the target population. The analyses were performed on 141 (82%) squamous cell carcinomas of the complete series. During the period of observation (mean 222 months), 17 recurrences (12.1%) were encountered. Prognostic factors for disease-free survival were lymph node status (P < 0.000001), radical surgical margins (P = 0.00004), and tumor size (P = 0.002). The complete score of the invasive front grading system (IFG), and the individual scores of two variables-pattern of invasion and host response-were all significantly (P = 0.002, P = 0.007, P = 0.0001) associated with pelvic lymph node metastases. Host response was the single most important factor in the IFG system, and it was superior to the complete score in predicting lymph node metastases. The total IFG score was also a significant (P = 0.003) prognostic factor for disease-free survival. DNA ploidy, S-phase fraction, and MIB-1 expression were nonsignificant factors in predicting pelvic lymph node metastases and disease-free survival of the patient. The IFG in the original or modified versions could predict low- and high-risk groups of tumors and therefore be of value in treatment planning for these patients.

  20. Polymorphous Low-Grade Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Shubhangi Mhaske

    2010-01-01

    Full Text Available Polymorphous low-grade adenocarcinoma (PLGA is a rare, malignant salivary gland tumor commonly affecting the minor salivary glands, histologically showing morphological diversity and a low metastatic potential. Hereby reporting a case of PLGA in a 58-year-old male patient showing involvement of antral floor.

  1. Loss of the urothelial differentiation marker FOXA1 is associated with high grade, late stage bladder cancer and increased tumor proliferation.

    Directory of Open Access Journals (Sweden)

    David J DeGraff

    Full Text Available Approximately 50% of patients with muscle-invasive bladder cancer (MIBC develop metastatic disease, which is almost invariably lethal. However, our understanding of pathways that drive aggressive behavior of MIBC is incomplete. Members of the FOXA subfamily of transcription factors are implicated in normal urogenital development and urologic malignancies. FOXA proteins are implicated in normal urothelial differentiation, but their role in bladder cancer is unknown. We examined FOXA expression in commonly used in vitro models of bladder cancer and in human bladder cancer specimens, and used a novel in vivo tissue recombination system to determine the functional significance of FOXA1 expression in bladder cancer. Logistic regression analysis showed decreased FOXA1 expression is associated with increasing tumor stage (p<0.001, and loss of FOXA1 is associated with high histologic grade (p<0.001. Also, we found that bladder urothelium that has undergone keratinizing squamous metaplasia, a precursor to the development of squamous cell carcinoma (SCC exhibited loss of FOXA1 expression. Furthermore, 81% of cases of SCC of the bladder were negative for FOXA1 staining compared to only 40% of urothelial cell carcinomas. In addition, we showed that a subpopulation of FOXA1 negative urothelial tumor cells are highly proliferative. Knockdown of FOXA1 in RT4 bladder cancer cells resulted in increased expression of UPK1B, UPK2, UPK3A, and UPK3B, decreased E-cadherin expression and significantly increased cell proliferation, while overexpression of FOXA1 in T24 cells increased E-cadherin expression and significantly decreased cell growth and invasion. In vivo recombination of bladder cancer cells engineered to exhibit reduced FOXA1 expression with embryonic rat bladder mesenchyme and subsequent renal capsule engraftment resulted in enhanced tumor proliferation. These findings provide the first evidence linking loss of FOXA1 expression with histological subtypes

  2. Histology far away from Flatland: 3D roller-coasting into grade-dependent angiogenetic patterns in oligodendrogliomas.

    Science.gov (United States)

    Cassoni, P; Gaetano, L; Senetta, R; Bussolati, B; Molinaro, L; Bussolati, G

    2008-04-01

    Angiogenesis plays a key role in tumour progression, and undergoes structural changes associated to tumour biology itself. Although vessel density can be easily evaluated in brain tumours using a traditional immuno-histochemical approach, other parameters of conceptual/biological interest, such as the complex patterns of vascular growth, cannot be fully understood using a traditional bi-dimensional evaluation. We use here surgical specimens derived from oligodendrogliomas as a model for a novel elucidative 3D reconstruction of the grade-dependent vascular arborisation in brain tumours.

  3. Effect of continuous high intensity focused ultrasound in a squamous cell carcinoma tumor model compared to muscle tissue evaluated by MRI, histology, and gene expression.

    Science.gov (United States)

    Hundt, Walter; Yuh, Esther L; Steinbach, Silke; Bednarski, Mark D

    2009-04-01

    The purpose of this study was to investigate the effect of the continuous mode of high intensity focused ultrasound (HIFU) in a mouse head and neck cancer model (SCCVII) compared to muscle tissue. HIFU was applied to SCCVII tumors and to muscle tissue in C3H/Km mice using a dual ultrasound system (imaging 6 MHz/therapeutic 1 MHz). A continuous HIFU mode (total time 20 sec, intensity 6730.6 W/cm(2)) was applied. Three hours after HIFU treatment pre- and post-contrast T1-wt, T2-wt images, and a diffusion-wt STEAM sequence were obtained. After MR imaging, the animals were euthenized and the treated tumor and muscle tissue was taken out for histology and functional genomic analysis. T2 images showed increased signal intensity, post-contrast T1 showed a decreased contrast uptake in the central parts in the tumor tissue as well as in the muscle tissue. In addition a significant higher diffusion coefficient was found in both tissue types. Histological evaluation (H&E, Immunohistochemistry) of the tumors and the muscle tissue revealed areas of significant necrosis. In the tumor tissue 23 genes were up-regulated (> 2 fold change) and 4 genes were down-regulated (muscle tissue 29 genes were up-regulated and 17 genes down-regulated. Thirteen genes were up-regulated in both tissue types, 8 genes only in the SCCVII tissue, and 11 genes only in the muscle tissue. The use of HIFU treatment on tumor and muscle tissue results in dramatic changes in gene expression. The expression of some genes are tissue specific, the expression of other genes are independent of the tissue type.

  4. FOXP3+regulatory T cells in normal prostate tissue, postatrophic hyperplasia, prostatic intraepithelial neoplasia, and tumor histological lesions in men with and without prostate cancer.

    Science.gov (United States)

    Davidsson, Sabina; Andren, Ove; Ohlson, Anna-Lena; Carlsson, Jessica; Andersson, Swen-Olof; Giunchi, Francesca; Rider, Jennifer R; Fiorentino, Michelangelo

    2018-01-01

    The tumor promoting or counteracting effects of the immune response to cancer development are thought to be mediated to some extent by the infiltration of regulatory T cells (T regs ). In the present study we evaluated the prevalence of T reg populations in stromal and epithelial compartments of normal, post atrophic hyperplasia (PAH), prostatic intraepithelial neoplasia (PIN), and tumor lesions in men with and without prostate cancer. Study subjects were 102 men consecutively diagnosed with localized prostate cancer undergoing radical prostatectomy and 38 men diagnosed with bladder cancer undergoing cystoprostatectomy without prostate cancer at the pathological examination. Whole mount sections from all patients were evaluated for the epithelial and stromal expression of CD4 + T regs and CD8 + T regs in normal, PAH, PIN, and tumor lesions. A Friedmańs test was used to investigate differences in the mean number of T regs across histological lesions. Logistic regression was used to estimate crude and adjusted odds ratios (OR) for prostate cancer for each histological area. In men with prostate cancer, similarly high numbers of stromal CD4 + T regs were identified in PAH and tumor, but CD4 + T regs were less common in PIN. Greater numbers of epithelial CD4+ T regs in normal prostatic tissue were positively associated with both Gleason score and pT-stage. We observed a fourfold increased risk of prostate cancer in men with epithelial CD4 + T regs in the normal prostatic tissue counterpart. Our results may suggest a possible pathway through which PAH develops directly into prostate cancer in the presence of CD4 + T regs and indicate that transformation of the anti-tumor immune response may be initiated even before the primary tumor is established. © 2017 The Authors. The Prostate Published by Wiley Periodicals Inc.

  5. Accuracy of Grading Gleason Score 7 Prostatic Adenocarcinoma on Needle Biopsy: Influence of Percent Pattern 4 and Other Histological Factors.

    Science.gov (United States)

    Meliti, Abdelrazak; Sadimin, Evita; Diolombi, Mario; Khani, Francesca; Epstein, Jonathan I

    2017-05-01

    Recognition of Gleason pattern 4 in prostatic needle biopsies is crucial for both prognosis and therapy. Recently, it has been recommended to record percent pattern 4 when Gleason score 7 cancer is the highest grade in a case. Four hundred and five prostate needle core biopsies received for a second opinion at our institution from February-June, 2015 were prospectively diagnosed with prostatic adenocarcinoma Gleason score 7 as the highest score on review by a consultant urological pathologist. Percentage of core involvement by cancer, percentage of Gleason pattern 4 per core, distribution of Gleason pattern 4 (clustered, scattered), morphology of pattern 4 (cribriform, non-cribriform), and whether the cancer was continuous or discontinuous were recorded. Better agreement was noted between the consultant and referring pathologists when pattern 4 was clustered as opposed to dispersed in biopsies (P = 0.009). The percentage of core involvement by cancer, morphology of pattern 4, and continuity of cancer did not affect the agreement between the consultant and referring pathologists. There was a trend (P = 0.06) for better agreement based on the percent of pattern 4. When pattern 4 is scattered amongst pattern 3 as opposed to being discrete foci, there is less interobserver reproducibility in grading Gleason score 7 cancer, and in this setting pathologists should consider obtaining second opinions either internally within their group or externally. Prostate 77: 681-685, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  6. Nonlinear ghost waves accelerate the progression of high-grade brain tumors

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    Pardo, Rosa; Martínez-González, Alicia; Pérez-García, Víctor M.

    2016-10-01

    We study a reduced continuous model describing the evolution of high grade gliomas in response to hypoxic events through the interplay of different cellular phenotypes. We show that hypoxic events, even when sporadic and/or limited in space, may have a crucial role on the acceleration of high grade gliomas growth. Our modeling approach is based on two cellular phenotypes. One of them is more migratory and a second one is more proliferative. Transitions between both phenotypes are driven by the local oxygen values, assumed in this simple model to be uniform. Surprisingly, even very localized in time hypoxia events leading to transient migratory populations have the potential to accelerate the tumor's invasion speed up to speeds close to those of the migratory phenotype. The high invasion speed persists for times much longer than the lifetime of the hypoxic event. Moreover, the phenomenon is observed both when the migratory cells form a persistent wave of cells located on the invasion front and when they form a evanescent "ghost" wave disappearing after a short time by decay to the more proliferative phenotype. Our findings are obtained through numerical simulations of the model equations both in 1D and higher dimensional scenarios. We also provide a deeper mathematical analysis of some aspects of the problem such as the conditions for the existence of persistent waves of cells with a more migratory phenotype.

  7. Description of the prevalence, histologic characteristics, concomitant abnormalities, and outcomes of mammary gland tumors in companion rats (Rattus norvegicus): 100 cases (1990-2015).

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    Vergneau-Grosset, Claire; Keel, M Kevin; Goldsmith, Dayna; Kass, Philip H; Paul-Murphy, Joanne; Hawkins, Michelle G

    2016-11-15

    OBJECTIVE To describe the prevalence, histologic characteristics, concomitant abnormalities, and outcomes for various types of mammary gland tumors in companion rats (Rattus norvegicus). DESIGN Retrospective case series. ANIMALS 100 client-owned rats. PROCEDURES Medical records of companion rats that had an SC mass and were examined at a veterinary teaching hospital between 1990 and 2015 were reviewed. Information regarding the signalment, age at mass detection, reproductive sterilization status, histologic diagnosis of the SC mass, location of the initial and all subsequent SC masses, treatments administered, and clinical outcomes was extracted from each record and summarized. RESULTS 105 SC masses were initially detected in 100 rats. The most prevalent SC mass identified was mammary gland fibroadenoma (56/105 [53%]), followed by mammary gland carcinoma (13/105 [12%]). Overall, 26 of 105 (25%) masses were malignant. Sexually intact males were more likely to have nonmammary SC tumors than sexually intact females. In rats receiving no adjunctive treatment after excision of a mammary gland fibroadenoma (n = 16), a second fibroadenoma was detected 1 to 8 months after initial excision, at a median of 4.5 months after surgery. A concomitant pituitary gland tumor was identified in most rats with mammary gland fibroadenoma (21/28 [75%]) and other types of mammary gland tumors (10/17 [59%]). Fourteen of 35 (40%) rats with mammary gland fibroadenoma had concomitant reproductive tract abnormalities. CONCLUSION AND CLINICAL RELEVANCE Results suggested that, like other species, companion rats with SC masses should undergo a thorough diagnostic workup that includes histologic examination of the excised mass.

  8. Malignant phyllodes tumor of the breast with heterologous high-grade angiosarcoma

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    Ghassan Tranesh

    2017-03-01

    Full Text Available Phyllodes tumors (PTs account for <3% of fibroepithelial breast lesions and for 0.3% to 1.0% of primary breast tumors. They occur predominantly in middle-aged women (mean age range, 40–50 years. PTs can be categorized into benign, borderline, and malignant; the first 2 categories are distinguished only by degree of cellular atypia and mitotic activity. Malignant PTs are more frequent among persons of Hispanic ethnicity, especially those born in Central America or South America. Heterologous sarcomatous elements may be present in malignant PTs, predominantly liposarcoma and rarely fibrosarcoma, rhabdomyosarcoma, leiomyosarcoma, osteosarcoma, and chondrosarcoma. Breast angiosarcoma (BA is a rare heterologous, sarcomatous element that may arise secondary to malignant PT. We report a 47-year-old woman with no history of previous surgery or radiation therapy who presented to the emergency department with a painful right breast mass. She admittedly noticed the right breast mass for many years; however, recently it increased in size. Mammography and ultrasonography identified a partially cystic mass. Core needle biopsy showed dense hyalinized fibrous tissue with old blood clots, suggestive of infarcted fibroadenoma. The patient received antibiotics and analgesics; however, she reported intractable pain and a worsening skin rash of her right breast. Chest computed tomography and magnetic resonance imaging showed a doubling in mass size, with pectoralis major muscle involvement. Incisional biopsy showed malignant PT with heterologous high-grade angiosarcoma. The diagnosis of angiosarcoma was confirmed through immunoreactivity for CD31, FLI1, and ERG immunostains.

  9. [Malignant cartilage tumors].

    Science.gov (United States)

    Geirnaerdt, M J; Hogendoorn, P C; Taminiau, A H; Bloem, J L

    1998-06-01

    Malignant cartilaginous tumors (chondrosarcomas) are, with a relative frequency of 20%, the second most common malignant tumors of bone after osteosarcoma. The diagnosis of chondrosarcoma can usually be made confidently based on combination of clinical information, radiographs, Gd-enhanced MR imaging, and histologic examination of a biopsy sample. The combination of these parameters is important because accuracy of histologic diagnosis is adversely affected by unrepresentative sampling of these usually large tumors. The prognosis of patients with chondrosarcoma becomes poorer with more axial location, higher histologic grade, larger tumor size and inadequate resection. By careful analysis of radiographs and Gd-enhanced MR imaging the radiologist has the ability to improve the management of patients with chondrosarcoma.

  10. Significance of HER2 and C-MYC oncogene amplifications in breast cancer in atomic bomb survivors: associations with radiation exposure and histologic grade.

    Science.gov (United States)

    Miura, Shiro; Nakashima, Masahiro; Ito, Masahiro; Kondo, Hisayoshi; Meirmanov, Serik; Hayashi, Tomayoshi; Soda, Midori; Matsuo, Takeshi; Sekine, Ichiro

    2008-05-15

    It has been postulated that radiation induces breast cancers in atomic bomb (A-bomb) survivors. Oncogene amplification is an important mechanism during breast carcinogenesis and also serves as an indicator of genomic instability (GIN). The objective of this study was to clarify the association of oncogene amplification in breast cancer in A-bomb survivors with radiation exposure. In total, 593 breast cancers were identified in A-bomb survivors from 1968 to 1999, and the association between breast cancer incidence and A-bomb radiation exposure was evaluated. Invasive ductal cancers from 67 survivors and 30 nonsurvivors were analyzed for amplification of the HER2 and C-MYC genes by fluorescence in situ hybridization, and expression levels of hormone receptors were analyzed by immunostaining. The incidence rate increased significantly as exposure distance decreased from the hypocenter (hazard ratio per 1-km decrement, 1.47; 95% confidence interval [95% CI], 1.30-1.66). The incidence of HER2 and C-MYC amplification was increased significantly in the order of the control group, the distal group (P = .0238), and the proximal group (P = .0128). Multivariate analyses revealed that distance was a risk factor for the coamplification of C-MYC and HER2 in breast cancer in survivors (odds ratio per 1-km increment, 0.17; 95% CI, 0.01-0.63). The histologic grade of breast cancers became significantly higher in the order of the control group, the distal group, and the proximal group and was associated with oncogene amplifications. The current results suggested that A-bomb radiation may affect the development of oncogene amplification by inducing GIN and may be associated with a higher histologic grade in breast cancer among A-bomb survivors. (c) 2008 American Cancer Society.

  11. SOX10-positive salivary gland tumors: a growing list, including mammary analogue secretory carcinoma of the salivary gland, sialoblastoma, low-grade salivary duct carcinoma, basal cell adenoma/adenocarcinoma, and a subgroup of mucoepidermoid carcinoma.

    Science.gov (United States)

    Hsieh, Min-Shu; Lee, Yi-Hsuan; Chang, Yih-Leong

    2016-10-01

    Transcription factor SRY-related HMG-box 10 (SOX10) is an important marker for melanocytic, schwannian, myoepithelial, and some salivary gland tumors. The aim of this study was to investigate SOX10 expression more thoroughly in the salivary gland neoplasms, including mammary analogue secretory carcinoma and hyalinizing clear cell carcinoma harboring specific genetic rearrangements. A new rabbit monoclonal anti-SOX10 antibody (clone EP268) was used to examine SOX10 expression in 14 different types of salivary gland tumors. We found that acinic cell carcinoma (AciCC), adenoid cystic carcinoma, mammary analogue secretory carcinoma (MASC), epithelial-myoepithelial carcinoma, low-grade salivary duct carcinoma, sialoblastoma, basal cell adenocarcinoma, basal cell adenoma, and pleomorphic adenoma were SOX10 positive. Salivary duct carcinoma, lymphoepithelial carcinoma, hyalinizing clear cell carcinoma, and oncocytoma were SOX10 negative. Earlier, mucoepidermoid carcinoma (MEC) was considered a SOX10-negative tumor. This study identified a subgroup of SOX10-positive MEC cases with characteristic polygonal epithelial cells, pale-to-eosinophilic cytoplasm, and colloid-like dense eosinophilic material. Our data show SOX10 expression can be observed in salivary gland tumors with either one of the 4 cell types: acinic cells, cuboidal ductal cells with low-grade cytologic features, basaloid cells, and myoepithelial cells. In this article we thoroughly evaluated SOX10 expression in salivary gland tumors. SOX10 is useful in the differential diagnosis between myoepithelial carcinoma with clear cell features and hyalinizing clear cell carcinoma. It can also be used to discriminate low-grade salivary duct carcinoma from high-grade ones. Pathologists should be cautious with the interpretation of SOX10 positivity in salivary gland tumors, and correlation with histologic feature is mandatory. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. New malignancy grading is a better prognostic indicator than Broders' grading in oral squamous cell carcinomas.

    Science.gov (United States)

    Bryne, M; Koppang, H S; Lilleng, R; Stene, T; Bang, G; Dabelsteen, E

    1989-09-01

    The prognostic value of histopathologic grading of oral squamous cell carcinomas (SCC) has varied from not any to highly significant. We have retrospectively studied all (130) SCCs registered in Norway 1963-72 in the buccal and maxillary alveolar mucosa. From 68 of these cases biopsy specimens of acceptable quality were obtained. Broders' method of grading was compared with a modification of a recent malignancy grading system recommended by Anneroth et al. which was performed only within the histologically most invasive areas of the tumors. Cox's multivariate survival analyses showed that this grading in the invasive sites had highly significant prognostic value. Broders grade had no prognostic value. The stage of tumor had also prognostic value. These highly significant results indicate that the histologically invasive areas may be primarily responsible for the clinical behavior of the tumor, and this may be of importance for the choice of therapy for oral SCC.

  13. Mini-pillar array for hydrogel-supported 3D culture and high-content histologic analysis of human tumor spheroids.

    Science.gov (United States)

    Kang, Jihoon; Lee, Dong Woo; Hwang, Hyun Ju; Yeon, Sang-Eun; Lee, Moo-Yeal; Kuh, Hyo-Jeong

    2016-06-21

    Three-dimensional (3D) cancer cell culture models mimic the complex 3D organization and microenvironment of human solid tumor tissue and are thus considered as highly predictive models representing avascular tumor regions. Confocal laser scanning microscopy is useful for monitoring drug penetration and therapeutic responses in 3D tumor models; however, photonic attenuation at increasing imaging depths and limited penetration of common fluorescence tracers are significant technical challenges to imaging. Immunohistological staining would be a good alternative, but the preparation of tissue sections from rather fragile spheroids through fixing and embedding procedures is challenging. Here we introduce a novel 3 × 3 mini-pillar array chip that can be utilized for 3D cell culturing and sectioning for high-content histologic analysis. The mini-pillar array chip facilitated the generation of 3D spheroids of human cancer cells within hydrogels such as alginate, collagen, and Matrigel. As expected, visualization of the 3D distribution of calcein AM and doxorubicin by optical sectioning was limited by photonic attenuation and dye penetration. The integrity of the 3D microtissue section was confirmed by immunostaining on paraffin sections and cryo-sections. The applicability of the mini-pillar array for drug activity evaluation was tested by measuring viability changes in spheroids exposed to anti-cancer agents, 5-fluorouracil and tirapazamine. Thus, our novel mini-pillar array platform can potentially promote high-content histologic analysis of 3D cultures and can be further optimized for field-specific needs.

  14. 2000 Volvo Award winner in basic science studies: Exogenous tumor necrosis factor-alpha mimics nucleus pulposus-induced neuropathology. Molecular, histologic, and behavioral comparisons in rats.

    Science.gov (United States)

    Igarashi, T; Kikuchi, S; Shubayev, V; Myers, R R

    2000-12-01

    This study tested the hypothesis that the 17-kDa form of tumor necrosis factor-alpha is the pathophysiologic agent expressed by herniated nucleus pulposus in vivo that is primarily responsible for the histologic and behavioral manifestations of experimental sciatica associated with herniated lumbar discs. The authors determined the molecular weight and concentration of active tumor necrosis factor-alpha in rat herniated disc and used exogenous tumor necrosis factor-alpha at the same molecular weight to study its neuropathologic effect on rat nerve root and dorsal root ganglion preparations in vivo. Expressed by herniated nucleus pulposus in culture, tumor necrosis factor-alpha causes neuropathologic injury in nerve roots and neuropathic pain states in which mechanical allodynia is seen in response to peripheral stimuli. Western blotting was used to identify the molecular weight of the operative tumor necrosis factor-alpha protein form, and measures of optical density were used for semiquantitative determination of concentration. Plastic-embedded nerve roots and dorsal root ganglion were used for neuropathologic evaluation, and von Frey stimulation was used to quantify mechanical allodynia. The 17-kDa form of tumor necrosis factor-alpha is expressed by herniated nucleus pulposus at a concentration of approximately 0.48 ng per herniated rat lumbar disc. Exogenous tumor necrosis factor-alpha applied in vivo to rat nerve roots produced neuropathologic changes and behavior deficits that mimicked experimental studies with herniated nucleus pulposus applied to nerve roots. The data reinforce other evidence that tumor necrosis factor-alpha is involved in mechanisms of neuropathic pain.

  15. ANK1 Methylation regulates expression of MicroRNA-486-5p and discriminates lung tumors by histology and smoking status.

    Science.gov (United States)

    Tessema, Mathewos; Yingling, Christin M; Picchi, Maria A; Wu, Guodong; Ryba, Tyrone; Lin, Yong; Bungum, Aaron O; Edell, Eric S; Spira, Avrum; Belinsky, Steven A

    2017-12-01

    The intragenic tumor-suppressor microRNA miR-486-5p is often down-regulated in non-small cell lung cancer (NSCLC) but the mechanism is unclear. This study investigated epigenetic co-regulation of miR-486-5p and its host gene ANK1. MiR-486-5p expression in lung tumors and cell lines was significantly reduced compared to normal lung (p < 0.001) and is strongly correlated with ANK1 expression. In vitro, siRNA-mediated ANK1 knockdown in NSCLC cells also reduced miR-486-5p while the DNA methylation inhibitor 5-aza-2'-deoxycytidine induced expression of both. ANK1 promoter CpG island was unmethylated in normal lung but methylated in 45% (118/262) lung tumors and 55% (17/31) NSCLC cell lines. After adjustment for tumor histology and smoking, methylation was significantly more prevalent in adenocarcinoma (101/200, 51%) compared to squamous cell carcinoma (17/62, 27%), p < 0.001; HR = 3.513 (CI: 1.818-6.788); and in smokers (73/128, 57%) than never-smokers (28/72, 39%), p = 0.014; HR = 2.086 (CI: 1.157-3.759). These results were independently validated using quantitative methylation data for 809 NSCLC cases from The Cancer Genome Atlas project. Together, our data indicate that aberrant ANK1 methylation is highly prevalent in lung cancer, discriminate tumors by histology and patients' smoking history, and contributes to miR-486-5p repression. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. DNA copy number changes in high-grade malignant peripheral nerve sheath tumors by array CGH

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    Bjerkehagen Bodil

    2008-06-01

    Full Text Available Abstract Background Malignant peripheral nerve sheath tumors (MPNSTs are rare and highly aggressive soft tissue tumors showing complex chromosomal aberrations. In order to identify recurrent chromosomal regions of gain and loss, and thereby novel gene targets of potential importance for MPNST development and/or progression, we have analyzed DNA copy number changes in seven high-grade MPNSTs using microarray-based comparative genomic hybridization (array CGH. Results Considerable more gains than losses were observed, and the most frequent minimal recurrent regions of gain included 1q24.1-q24.2, 1q24.3-q25.1, 8p23.1-p12, 9q34.11-q34.13 and 17q23.2-q25.3, all gained in five of seven samples. The 17q23.2-q25.3 region was gained in all five patients with poor outcome and not in the two patients with disease-free survival. cDNA microarray analysis and quantitative real-time reverse transcription PCR were used to investigate expression of genes located within these regions. The gene lysyl oxidase-like 2 (LOXL2 was identified as a candidate target for the 8p23.1-p12 gain. Within 17q, the genes topoisomerase II-α (TOP2A, ets variant gene 4 (E1A enhancer binding protein, E1AF (ETV4 and baculoviral IAP repeat-containing 5 (survivin (BIRC5 showed increased expression in all samples compared to two benign tumors. Increased expression of these genes has previously been associated with poor survival in other malignancies, and for TOP2A, in MPNSTs as well. In addition, we have analyzed the expression of five micro RNAs located within the 17q23.2-q25.3 region, but none of them showed high expression levels compared to the benign tumors. Conclusion Our study shows the potential of using DNA copy number changes obtained by array CGH to predict the prognosis of MPNST patients. Although no clear correlations between the expression level and patient outcome were observed, the genes TOP2A, ETV4 and BIRC5 are interesting candidate targets for the 17q gain associated

  17. Histological evaluation of high-intensity focused ultrasound with lower-intensity focused ultrasound pre-exposure on the treatment of rabbit VX2 liver tumors

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    Zou Hairong; Zou Jianzhong; Wang Yan; Ou Xia [State Key Laboratory of Ultrasound Engineering in Medicine Co-founded by Chongqing and the Ministry of Science and Technology, Chongqing Key laboratory of Ultrasound in Medicine and Engineering, Department of Biomedical Engineering, Chongqing Medical (China)

    2012-10-03

    This study was to evaluate the effect of pre-exposure lower-intensity focused ultrasound(US), or LIFU, in high-intensity focused ultrasound(HIFU) ablation of rabbit VX2 liver tumors . Liver VX2 tumor models were established in 30 rabbits, which were divided randomly into two groups. The liver tumors of rabbits in Group A underwent single HIFU ablation; those in Group B were given LIFU exposure before HIFU treatment. Five rabbits from each of the two groups were sacrificed at 0 hours, 3 days, and 7 days after HIFU ablation. Tissue samples that included targeted and short-range sounding (s-RS, within 5 mm of the targeted) and far-range sounding (f-RS, more than 5 mm of the targeted) tissues were observed using light microscope and transmission electron microscopy. The histological examination indicated that not only the targeted tumor cells became irreversible damage, but also the short-range sounding tumors were severely damaged by the HIFU with LIFU pre-exposure in group B. It is concluded that LIFU pre-exposure can enhance the effects of HIFU ablation on the destruction of cell ultrastructures and can enlarge the region of HIFU ablation.

  18. Histologic assessment of tumor budding in preoperative biopsies to predict nodal metastasis in squamous cell carcinoma of the tongue and floor of the mouth.

    Science.gov (United States)

    Seki, Mai; Sano, Takaaki; Yokoo, Satoshi; Oyama, Tetsunari

    2016-04-01

    In squamous cell carcinoma (SCC) of the tongue and the floor of the mouth (FOM), it is important to predict lymph node metastasis, including occult metastasis, before operating. The purpose of this study was for us to determine practical histopathologic parameters as predictive factors for lymph node metastasis in preoperative SCC biopsy specimens. We examined 91 cases of SCC for conventional histopathologic assessment and a new factor, tumor budding, and their relationship with lymph node metastasis. Significant factors via univariate analysis (p budding (score ≥3) and tumor depth (≥3 mm) and these were associated with lymph node metastasis. Moreover, both budding and tumor depth significantly correlated with relapse-free survival; however, evaluating biopsy specimens often proved inaccurate for predicting true tumor depth of cancer invasion. Tumor budding using immunohistochemistry for cytokeratin should be added to routine histologic assessments as a new criterion factoring into the decision as to whether neck dissection is indicated. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1582-E1590, 2016. © 2015 Wiley Periodicals, Inc.

  19. TARGET Researchers Identify Mutations in SIX1/2 and microRNA Processing Genes in Favorable Histology Wilms Tumor | Office of Cancer Genomics

    Science.gov (United States)

    TARGET researchers molecularly characterized favorable histology Wilms tumor (FHWT), a pediatric renal cancer. Comprehensive genome and transcript analyses revealed single-nucleotide substitution/deletion mutations in microRNA processing genes (15% of FHWT patients) and Sine Oculis Homeobox Homolog 1/2 (SIX1/2) genes (7% of FHWT patients). SIX1/2 genes play a critical role in renal development and were not previously associated with FHWT, thus presenting a novel role for SIX1/2 pathway aberrations in this disease.

  20. Intrinsic subtypes and tumor grades in breast cancer are associated with distinct 3-D power Doppler sonographic vascular features

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    Chang, Yeun-Chung [Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10041, Taiwan, ROC (China); Huang, Yao-Sian [Department of Computer Science and Information Engineering, National Taiwan University, Taipei 10617, Taiwan, ROC (China); Huang, Chiun-Sheng [Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10041, Taiwan, ROC (China); Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, Taiwan, ROC (China); Chen, Jeon-Hor [Center for Functional Onco-Imaging and Department of Radiological Science, University of California Irvine, California, CA 92868 (United States); Department of Radiology, E-Da Hospital and I-Shou University, Kaohsiung 82445, Taiwan, ROC (China); Chang, Ruey-Feng, E-mail: rfchang@csie.ntu.edu.tw [Department of Computer Science and Information Engineering, National Taiwan University, Taipei 10617, Taiwan, ROC (China); Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, Taiwan, ROC (China)

    2014-08-15

    Purpose: This study aimed to investigate the three-dimensional (3-D) power Doppler ultrasonographic (PDUS) vascular features of breast carcinoma according to intrinsic subtypes, nodal stage, and tumor grade. Materials and methods: Total 115 receiving mastectomy breast carcinomas (mean size, 2.5 cm; range, 0.7–6.5 cm), including 102 invasive ductal carcinomas (IDC), 10 ductal carcinomas in situ (DCIS), and 3 invasive lobular carcinomas (ILC) diagnosed after mastectomy, were used in this retrospective study. Sixty IDC had nodal status and histopathologic tumor grades available for analysis. Vascular features, including number of vascular trees (NV), longest path length (LPL), total vessel length (TVL), number of bifurcations (NB), distance metric (DM), inflection count metric (ICM), vessel diameter (VD), and vessel-to-volume ratio (VVR) were extracted using 3-D thinning method. The Mann–Whitney U test, Student's t-test, one-way ANOVA, and Kruskal–Wallis test were performed as appropriate. Results: There was no significant difference of vascular features among IDC, DCIS and ILC. Except VD, vascular features in luminal type were significantly lower compared to HER2-enriched or triple negative types (p < 0.05). Compared to ER+ (estrogen receptor positive) tumors, all features in ER− (estrogen receptor negative) tumors were significantly higher (p < 0.01). Despite some significantly higher vascular features in high grade IDC compared to low and intermediate grade, there was no significant correlation between vascular features and nodal stages. Conclusion: Differences in 3-D PDUS vascular features among intrinsic types of IDC are attributed to their ER status. Vascular features extracted by 3-D PDUS correlate with tumor grades but not nodal stage in IDC.

  1. Diffusion kurtosis imaging of gliomas grades II and III - a study of perilesional tumor infiltration, tumor grades and subtypes at clinical presentation

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    Delgado Anna F.

    2017-05-01

    Full Text Available Diffusion kurtosis imaging (DKI allows for assessment of diffusion influenced by microcellular structures. We analyzed DKI in suspected low-grade gliomas prior to histopathological diagnosis. The aim was to investigate if diffusion parameters in the perilesional normal-appearing white matter (NAWM differed from contralesional white matter, and to investigate differences between glioma malignancy grades II and III and glioma subtypes (astrocytomas and oligodendrogliomas.

  2. Gliomas: application of cumulative histogram analysis of normalized cerebral blood volume on 3 T MRI to tumor grading.

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    Hyungjin Kim

    Full Text Available BACKGROUND: Glioma grading assumes significant importance in that low- and high-grade gliomas display different prognoses and are treated with dissimilar therapeutic strategies. The objective of our study was to retrospectively assess the usefulness of a cumulative normalized cerebral blood volume (nCBV histogram for glioma grading based on 3 T MRI. METHODS: From February 2010 to April 2012, 63 patients with astrocytic tumors underwent 3 T MRI with dynamic susceptibility contrast perfusion-weighted imaging. Regions of interest containing the entire tumor volume were drawn on every section of the co-registered relative CBV (rCBV maps and T2-weighted images. The percentile values from the cumulative nCBV histograms and the other histogram parameters were correlated with tumor grades. Cochran's Q test and the McNemar test were used to compare the diagnostic accuracies of the histogram parameters after the receiver operating characteristic curve analysis. Using the parameter offering the highest diagnostic accuracy, a validation process was performed with an independent test set of nine patients. RESULTS: The 99th percentile of the cumulative nCBV histogram (nCBV C99, mean and peak height differed significantly between low- and high-grade gliomas (P = <0.001, 0.014 and <0.001, respectively and between grade III and IV gliomas (P = <0.001, 0.001 and <0.001, respectively. The diagnostic accuracy of nCBV C99 was significantly higher than that of the mean nCBV (P = 0.016 in distinguishing high- from low-grade gliomas and was comparable to that of the peak height (P = 1.000. Validation using the two cutoff values of nCBV C99 achieved a diagnostic accuracy of 66.7% (6/9 for the separation of all three glioma grades. CONCLUSION: Cumulative histogram analysis of nCBV using 3 T MRI can be a useful method for preoperative glioma grading. The nCBV C99 value is helpful in distinguishing high- from low-grade gliomas and grade IV from III gliomas.

  3. Histological assessment of the efficacy of drug-eluting beads in portal tumor thrombosis of hepatocellular carcinoma

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    Yusuke Imai, MD

    2017-03-01

    Full Text Available A 58-year-old man was diagnosed with advanced hepatocellular carcinoma with portal vein tumor thrombosis (PVTT. The tumors were multiple and existed in both lobes. Drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE was performed for the tumors in the left lobe. Embosphere and Hepasphere were selected for embolization of the arterioportal shunt, followed by loaded epirubicin infusion into the left hepatic artery. Computed tomography showed reduction of PVTT. However, liver failure progressed, and the patient died 67 days after DEB-TACE. Autopsy showed that the beads reached the tumor thrombosis in the portal vein. The prognosis of hepatocellular carcinoma with PVTT is poor. Although there are no established treatments for unresectable PVTT, DEB-TACE might be a useful option for such cases.

  4. Associations of three-dimensional T1 rho MR mapping and three-dimensional T2 mapping with macroscopic and histologic grading as a biomarker for early articular degeneration of knee cartilage.

    Science.gov (United States)

    Sasho, T; Katsuragi, J; Yamaguchi, S; Haneishi, H; Aizimu, T; Tanaka, T; Watanabe, A; Sato, Y; Akagi, R; Matsumoto, K; Uno, T; Motoori, K

    2017-04-29

    T1 rho and T2 mapping are magnetic resonance imaging (MRI) techniques to detect early degenerative changes in cartilage. Recent advancements have enabled 3D acquisition for both techniques. The objective of the present study was to examine the correlation of 3D T1 rho and 3D T2 mapping with macroscopic and histological characteristics of knee cartilage. Twenty-one patients who underwent total knee arthroplasty due to osteoarthritis with involvement of the medial compartment but with minimum involvement of the lateral compartment were enrolled. Prior to surgery, five series of MRI were acquired with a 3-T scanner. 3D T1 rho/T2 analyses were performed following determination of regions to be assessed using in-house software that incorporated three series of MRI acquisitions data (3D-MERGE, 3D-SPGR, and 3D-CUBE). During surgery, the cartilage of the lateral compartment was macroscopically assessed with the International Cartilage Research Society (ICRS) articular classification system. The extracted specimens were histologically assessed using the OARSI histology score. Three regions of interest (ROI) were assessed for each slice (two slices per knee): the central lateral femoral condyle (cLFC), the posterior portion of the lateral femoral condyle (pLFC), and the lateral tibia plateau (LTP). For each ROI, the mean T1 rho and T2 relaxation time, the ICRS grade, and the OARSI score were compared. Neither the T1 rho nor the T2 reflected the macroscopic grading. The T1 rho could discriminate between histological grades 1 and 2. However, the T2 could not. The T1 rho relaxation time was higher in the pLFC than in the cLFC even in the same grade. Compared to T2 mapping, T1 rho mapping may have an advantage in differentiating grades I and II cartilage degeneration on OARSI histological grading system.

  5. Evaluation of vacuum-assisted biopsy as a new method for histological diagnosis of soft-tissue tumors

    OpenAIRE

    Klein, Torsten

    2010-01-01

    Background: The exact pre-operative diagnosis of a low invasive and complication-poor biopsy-method is often problematic. Often, the taken tissue-specimen is not sufficient impeded in order to investigate the exact histopathology of soft-tissue-tumors, which complicates an adequate operative therapy. Vacuum-assisted-biopsy is a new method whose valence histopathology diagnosis for the praeoperative of soft-tissue-tumors, has not yet examined scientifically. The feasibility and the exact pre-o...

  6. Management Options for Advanced Low or Intermediate Grade Gastroenteropancreatic Neuroendocrine Tumors: Review of Recent Literature

    Directory of Open Access Journals (Sweden)

    Vladimir Neychev

    2017-01-01

    Full Text Available Our understanding of the biology, genetics, and natural history of neuroendocrine tumors (NETs of the gastrointestinal tract and pancreas has improved considerably in the last several decades and the spectrum of available therapeutic options is rapidly expanding. The management of patients with metastatic low or intermediate grade NETs has been revolutionized by the development of new treatment strategies such as molecular targeting therapies with everolimus and sunitinib, somatostatin analogs, tryptophan hydroxylase inhibitors, and peptide receptor radionuclide therapy that can be used alone or as a multimodal approach with or without surgery. To further define and clarify the utility, appropriateness, and the sequence of the growing list of available therapies for this patient population will require more high level evidence; however, data from well-designed randomized phase III clinical trials is rapidly accumulating that will further stimulate development of new management strategies. It is therefore important to thoroughly review emerging evidence and report major findings in frequent updates, which will expand our knowledge and contribute to a better understanding, characterization, and management of advanced NETs.

  7. A Novel Method to Generate and Expand Clinical-Grade, Genetically Modified, Tumor-Infiltrating Lymphocytes

    Directory of Open Access Journals (Sweden)

    Marie-Andrée Forget

    2017-08-01

    Full Text Available Following the clinical success achieved with the first generation of adoptive cell therapy (ACT utilizing in vitro expanded tumor-infiltrating lymphocytes (TILs, the second and third generations of TIL ACT are evolving toward the use of genetically modified TIL. TIL therapy generally involves the transfer of a high number of TIL, ranging from 109 to 1011 cells. One of the technical difficulties in genetically modifying TIL, using a retroviral vector, is the ability to achieve large expansion of transduced TIL, while keeping the technique suitable to a Good Manufacturing Practices (GMP environment. Consequently, we developed and optimized a novel method for the efficient production of large numbers of GMP-grade, gene-modified TIL for the treatment of patients with ACT. The chemokine receptor CXCR2 was used as the gene of interest for methodology development. The optimized procedure is currently used in the production of gene-modified TIL for two clinical trials for the treatment of metastatic melanoma at MD Anderson Cancer Center.

  8. Extended diffusion weighted magnetic resonance imaging with two-compartment and anomalous diffusion models for differentiation of low-grade and high-grade brain tumors in pediatric patients

    Energy Technology Data Exchange (ETDEWEB)

    Burrowes, Delilah; Deng, Jie [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, Chicago, IL (United States); Northwestern University, Feinberg School of Medicine, Department of Radiology, Chicago, IL (United States); Fangusaro, Jason R. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Hematology/Oncology, Chicago, IL (United States); Northwestern University, Feinberg School of Medicine, Department of Pediatrics-Hematology, Oncology, and Stem Cell Transplantation, Chicago, IL (United States); Nelson, Paige C.; Rozenfeld, Michael J. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, Chicago, IL (United States); Zhang, Bin [Cincinnati Children' s Hospital Medical Center, Department of Biostatistics and Epidemiology, Cincinnati, OH (United States); Wadhwani, Nitin R. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Pathology and Laboratory Medicine, Chicago, IL (United States); Northwestern University, Feinberg School of Medicine, Department of Pathology, Chicago, IL (United States)

    2017-08-15

    The purpose of this study was to examine advanced diffusion-weighted magnetic resonance imaging (DW-MRI) models for differentiation of low- and high-grade tumors in the diagnosis of pediatric brain neoplasms. Sixty-two pediatric patients with various types and grades of brain tumors were evaluated in a retrospective study. Tumor type and grade were classified using the World Health Organization classification (WHO I-IV) and confirmed by pathological analysis. Patients underwent DW-MRI before treatment. Diffusion-weighted images with 16 b-values (0-3500 s/mm{sup 2}) were acquired. Averaged signal intensity decay within solid tumor regions was fitted using two-compartment and anomalous diffusion models. Intracellular and extracellular diffusion coefficients (D{sub slow} and D{sub fast}), fractional volumes (V{sub slow} and V{sub fast}), generalized diffusion coefficient (D), spatial constant (μ), heterogeneity index (β), and a diffusion index (index{sub d}iff = μ x V{sub slow}/β) were calculated. Multivariate logistic regression models with stepwise model selection algorithm and receiver operating characteristic (ROC) analyses were performed to evaluate the ability of each diffusion parameter to distinguish tumor grade. Among all parameter combinations, D and index{sub d}iff jointly provided the best predictor for tumor grades, where lower D (p = 0.03) and higher index{sub d}iff (p = 0.009) were significantly associated with higher tumor grades. In ROC analyses of differentiating low-grade (I-II) and high-grade (III-IV) tumors, index{sub d}iff provided the highest specificity of 0.97 and D provided the highest sensitivity of 0.96. Multi-parametric diffusion measurements using two-compartment and anomalous diffusion models were found to be significant discriminants of tumor grading in pediatric brain neoplasms. (orig.)

  9. Tumorer

    DEFF Research Database (Denmark)

    Prause, J.U.; Heegaard, S.

    2005-01-01

    oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer......oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer...

  10. Expression of protein tyrosine phosphatase alpha (RPTPalpha) in human breast cancer correlates with low tumor grade, and inhibits tumor cell growth in vitro and in vivo

    DEFF Research Database (Denmark)

    Ardini, E; Agresti, R; Tagliabue, E

    2000-01-01

    of Src family kinases, and regulation of integrin signaling, cell adhesion, and growth factor responsiveness. To explore its potential contribution to human neoplasia, we surveyed RPTPalpha protein levels in primary human breast cancer. We found RPTPalpha levels to vary widely among tumors, with 29......% of cases manifesting significant overexpression. High RPTPalpha protein levels correlated significantly with low tumor grade and positive estrogen receptor status. Expression of RPTPalpha in breast carcinoma cells led to growth inhibition, associated with increased accumulation in G0 and G1, and delayed...... tumor growth and metastasis. To our knowledge, this is the first example of a study correlating expression level of a specific bona fide PTP with neoplastic disease status in humans....

  11. Enhanced apoptotic reaction correlates with suppressed tumor glucose utilization after cytotoxic chemotherapy: use of 99mTc-Annexin V, 18F-FDG, and histologic evaluation.

    Science.gov (United States)

    Takei, Toshiki; Kuge, Yuji; Zhao, Songji; Sato, Masayuki; Strauss, H William; Blankenberg, Francis G; Tait, Jonathan F; Tamaki, Nagara

    2005-05-01

    Cancer chemotherapy enhances the apoptosis, whereas apoptosis is a suicidal mechanism requiring energy. We determined the relationship between apoptosis and glucose utilization during cancer chemotherapy using (99m)Tc-annexin V ((99m)Tc-annexin A5) and (18)F-FDG and compared their uptake with histologic findings in a rat tumor model. Allogenic hepatoma cells (KDH-8) were inoculated into the left calf muscle of male Wistar rats (WKA). Eleven days after the inoculation, the rats were randomly divided into 3 groups: The first group (n = 7) received a single dose of gemcitabine (90 mg/kg, intravenously), the second group (n = 8) received cyclophosphamide (150 mg/kg, intraperitoneally), and the third group (n = 7) was untreated and served as the control group. We injected (99m)Tc-annexin V 48 h after the chemotherapy and then injected (18)F-FDG to all rats 1 h before sacrifice. Six hours after (99m)Tc-annexin V injection, the rats were sacrificed and the organs, including the tumor, were removed and radioactivity was counted. The radioactivities of (18)F and (99m)Tc in the organs were determined using normalization by tissue weight. Histologic evaluation by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) method and the immunostaining of glucose transporter-1 (GLUT-1) were also performed to obtain the indices of apoptosis and glucose utilization, respectively. The rate of positively stained cells was calculated and analyzed statistically. After chemotherapy using gemcitabine and cyclophosphamide, the (99m)Tc-annexin V uptake (percentage injected dose per gram x kg [(%ID/g) x kg]; mean +/- SD) in tumor increased significantly (0.062 +/- 0.012 (%ID/g) x kg in the gemcitabine-treated group and 0.050 +/- 0.012 (%ID/g) x kg in the cyclophosphamide group vs. 0.031 +/- 0.005 (%ID/g) x kg in the control group; P chemotherapy as determined using radiotracers and histologic evaluation. The increase in (99m)Tc-annexin V and the

  12. Serum anti-Helicobacter pylori immunoglobulin G titer correlates with grade of histological gastritis, mucosal bacterial density, and levels of serum biomarkers.

    Science.gov (United States)

    Tu, Huakang; Sun, Liping; Dong, Xiao; Gong, Yuehua; Xu, Qian; Jing, Jingjing; Yuan, Yuan

    2014-03-01

    OBJECTIVE. Clinical implications of serum anti-Helicobacter pylori immunoglobulin G (IgG) titer were unclear. This study investigated the associations of serum anti-H. pylori IgG titer with grade of histological gastritis, mucosal bacterial density and levels of serum biomarkers, including pepsinogen (PG) I, PGII, PGI/II ratio and gastrin-17. MATERIAL AND METHODS. Study participants were from a screening program in northern China. Serum anti-H. pylori IgG measurements were available for 5922 patients with superficial gastritis. Serum anti-H. pylori IgG titer and serum biomarkers were measured using ELISA, and gastric biopsies were evaluated using standardized criteria. RESULTS. In patients with mild, moderate or severe superficial gastritis, the mean serum anti-H. pylori IgG titers were 17.3, 33.4 and 54.4 EIU (p for trend gastritis, mucosal bacterial density and concentrations of serum PGI, PGII and gastrin-17, and negatively with PGI/II ratio.

  13. Cisplatin-induced renal toxicity via tumor necrosis factor-α, interleukin 6, tumor suppressor P53, DNA damage, xanthine oxidase, histological changes, oxidative stress and nitric oxide in rats: protective effect of ginseng.

    Science.gov (United States)

    Yousef, Mokhtar I; Hussien, Hend M

    2015-04-01

    Cisplatin is an effective chemotherapeutic agent successfully used in the treatment of a wide range of solid tumors, while its usage is limited due to its nephrotoxicity. The present study was undertaken to examine the effectiveness of ginseng to ameliorate the renal nephrotoxicity, damage in kidney genomic DNA, tumor necrosis factor-α, interleukin 6, tumor suppressor P53, histological changes and oxidative stress induced by cisplatin in rats. Cisplatin caused renal damage, including DNA fragmentation, upregulates gene expression of tumor suppressor protein p53 and tumor necrosis factor-α and IL-6. Cisplatin increased the levels of kidney TBARS, xanthine oxidase, nitric oxide, serum urea and creatinine. Cisplatin decreased the activities of antioxidant enzymes (GST, GPX, CAT and SOD), ATPase and the levels of GSH. A microscopic examination showed that cisplatin caused kidney damage including vacuolization, severe necrosis and degenerative changes. Ginseng co-treatment with cisplatin reduced its renal damage, oxidative stress, DNA fragmentation and induced DNA repair processes. Also, ginseng diminished p53 activation and improved renal cell apoptosis and nephrotoxicity. It can be concluded that, the protective effects of ginseng against cisplatin induced-renal damage was associated with the attenuation of oxidative stress and the preservation of antioxidant enzymes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Microscopic and nuclear morphometric findings of chromophobe renal cell carcinoma, renal oncocytoma, and tumor with overlapping histology.

    Science.gov (United States)

    Kim, Sung Sun; Choi, Yoo Duk; Shim, Min Keun; Kim, Jin; Cho, Yong Mee; Jang, Ja June; Park, Ryung Jin; Juhng, Sang Woo; Choi, Chan

    2012-12-01

    We compared the microscopic and nuclear morphometric characteristics of classical chromophobe renal cell carcinoma (C-ChRC) and renal oncocytoma (RO) and applied meaningful characteristics to differentiate eosinophilic chromophobe renal cell carcinoma (E-ChRC) from RO that has overlapping histology (RO-OH) with E-ChRC to know the usefulness of nuclear morphometry. Microscopic and morphometric characteristics were evaluated in 24 C-ChRCs, 6 E-ChRCs, 5 RO-OHs, and 25 classical ROs (C-ROs). The microscopic findings favoring C-ChRC were rasinoid nuclei, perinuclear halo, and distinct cytoplasmic membrane. Characteristic for C-RO was either stromal edema or hyalinization. The morphometric values of nearest nuclear distance, shortest nuclear diameter, and nuclear diameter ratio were significantly different between C-ChRC and C-RO. However, it was impossible to distinguish E-ChRC from RO-OH by histology and nuclear morphometry. The results of our study show that nuclear morphometry and histomorphology can distinguish between C-ChRC and C-RO but not between E-ChRC and RO-OH. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. [A comparative microspectrophotometric study of the concentration of DNA in the cells of laryngeal tumors in histologic and cytologic preparations].

    Science.gov (United States)

    Avtandilov, G G; Krasnova, V G; Nikitina, N I

    1975-01-01

    A microspectrophotometric study of DNA content in nuclei of cells of the normal larynx mucosa, papiloma, epithelial layer of fibromas, areas of atypical hyperplasia of the epithelium of papillomas, intraepithelial cancer, squamous-cell carcinoma of the larynx, matastases in the regional lymph nodes, was carried out on the basis of bioptic and operation materials. A total of 82 histological sections and 50 cytological preparations (impressions) obtained from the same specimens of the tissue were investigated. The microspectrophotometric investigation revealed the growth of DNA "accumulation indices" from stratified squamous epithelium (2.5) through atypical proliferation (3.9) to squamous-cell carcinoma of the larynx (8.2) and its metastases (12.4). The DNA content in intrapithelial cancer was higher than that in invasive squamous-cell carcinoma. Determination of the type of distribution of nuclei of cells of a tumour in cytological and histological preparations (in growth zones) according to ploidity and of characteristic features of the tissue with the help of the generalized "accumulation index" of DNA may be helpful as objective tests in morphological diagnosis of precancer and cancer processes in the larynx and in taking decisions concerning their prognosis.

  16. KI-67 heterogeneity in well differentiated gastro-entero-pancreatic neuroendocrine tumors: when is biopsy reliable for grade assessment?

    Science.gov (United States)

    Grillo, Federica; Valle, Luca; Ferone, Diego; Albertelli, Manuela; Brisigotti, Maria Pia; Cittadini, Giuseppe; Vanoli, Alessandro; Fiocca, Roberto; Mastracci, Luca

    2017-09-01

    Ki-67 heterogeneity can impact on gastroenteropancreatic neuroendocrine tumor grade assignment, especially when tissue is scarce. This work is aimed at devising adequacy criteria for grade assessment in biopsy specimens. To analyze the impact of biopsy size on reliability, 360 virtual biopsies of different thickness and lengths were constructed. Furthermore, to estimate the mean amount of non-neoplastic tissue component present in biopsies, 28 real biopsies were collected, the non-neoplastic components (fibrosis and inflammation) quantified and the effective area of neoplastic tissue calculated for each biopsy. Heterogeneity of Ki-67 distribution, G2 tumors and biopsy size all play an important role in reducing the reliability of biopsy samples in Ki-67-based grade assignment. In particular in G2 cases, 59.9% of virtual biopsies downgraded the tumor and the smaller the biopsy, the more frequent downgrading occurs. In real biopsies the presence of non-neoplastic tissue reduced the available total area by a mean of 20%. By coupling the results from these two different approaches we show that both biopsy size and non-neoplastic component must be taken into account for biopsy adequacy. In particular, we can speculate that if the minimum biopsy area, necessary to confidently (80% concordance) grade gastro-entero-pancreatic neuroendocrine tumors on virtual biopsies ranges between 15 and 30 mm2, and if real biopsies are on average composed of only 80% of neoplastic tissue, then biopsies with a surface area not <12 mm2 should be performed; using 18G needles, this corresponds to a minimum total length of 15 mm.

  17. Semiautomatic segmentation and follow-up of multicomponent low-grade tumors in longitudinal brain MRI studies

    Energy Technology Data Exchange (ETDEWEB)

    Weizman, Lior, E-mail: weizmanl@gmail.com [School of Engineering and Computer Science, The Hebrew University of Jerusalem, Jerusalem 91904 (Israel); Sira, Liat Ben [Department of Radiology, Tel Aviv Medical Center, Tel Aviv University, Tel Aviv 64239 (Israel); Joskowicz, Leo [School of Engineering and Computer Science and The Edmond and Lily Safra Center for Brain Sciences (ELSC), The Hebrew University of Jerusalem, Jerusalem 91904 (Israel); Rubin, Daniel L.; Yeom, Kristen W. [Department of Radiology, Stanford University, Stanford, California 94305 (United States); Constantini, Shlomi; Shofty, Ben [Tel Aviv Medical Center, Dana Children' s Hospital, Tel Aviv University, Tel Aviv 64239 (Israel); Bashat, Dafna Ben [Tel Aviv Medical Center, Functional Brain Center, Tel Aviv University, Tel Aviv 64239 (Israel)

    2014-05-15

    Purpose: Tracking the progression of low grade tumors (LGTs) is a challenging task, due to their slow growth rate and associated complex internal tumor components, such as heterogeneous enhancement, hemorrhage, and cysts. In this paper, the authors show a semiautomatic method to reliably track the volume of LGTs and the evolution of their internal components in longitudinal MRI scans. Methods: The authors' method utilizes a spatiotemporal evolution modeling of the tumor and its internal components. Tumor components gray level parameters are estimated from the follow-up scan itself, obviating temporal normalization of gray levels. The tumor delineation procedure effectively incorporates internal classification of the baseline scan in the time-series as prior data to segment and classify a series of follow-up scans. The authors applied their method to 40 MRI scans of ten patients, acquired at two different institutions. Two types of LGTs were included: Optic pathway gliomas and thalamic astrocytomas. For each scan, a “gold standard” was obtained manually by experienced radiologists. The method is evaluated versus the gold standard with three measures: gross total volume error, total surface distance, and reliability of tracking tumor components evolution. Results: Compared to the gold standard the authors' method exhibits a mean Dice similarity volumetric measure of 86.58% and a mean surface distance error of 0.25 mm. In terms of its reliability in tracking the evolution of the internal components, the method exhibits strong positive correlation with the gold standard. Conclusions: The authors' method provides accurate and repeatable delineation of the tumor and its internal components, which is essential for therapy assessment of LGTs. Reliable tracking of internal tumor components over time is novel and potentially will be useful to streamline and improve follow-up of brain tumors, with indolent growth and behavior.

  18. RASSF1A promoter methylation in high-grade serous ovarian cancer: A direct comparison study in primary tumors, adjacent morphologically tumor cell-free tissues and paired circulating tumor DNA.

    Science.gov (United States)

    Giannopoulou, Lydia; Chebouti, Issam; Pavlakis, Kitty; Kasimir-Bauer, Sabine; Lianidou, Evi S

    2017-03-28

    The RASSF1A promoter is frequently methylated in high-grade serous ovarian cancer (HGSC). We examined RASSF1A promoter methylation in primary tumors, adjacent morphologically tumor cell-free tissues and corresponding circulating tumor DNA (ctDNA) samples of patients with HGSC, using a real-time methylation specific PCR (real-time MSP) and a methylation-sensitive high-resolution melting analysis (MS-HRMA) assay for the detection and semi-quantitative estimation of methylation, respectively. Two groups of primary HGSC tumor FFPE samples were recruited (Group A n=67 and Group B n=61), along with matched adjacent morphologically tumor cell-free tissues (n=58) and corresponding plasma samples (n=59) for group B. Using both assays, RASSF1A promoter was found highly methylated in primary tumors of both groups, and at lower percentages in the adjacent morphologically tumor cell-free tissues. Interestingly, RASSF1A promoter methylation was also observed in ctDNA by real-time MSP. Overall survival (OS) was significantly associated with RASSF1A promoter methylation in primary tumor samples using MS-HRMA (P=0.023). Our results clearly indicate that RASSF1A promoter is methylated in adjacent tissue surrounding the tumor in HGSC patients. We report for the first time that RASSF1A promoter methylation provides significant prognostic information in HGSC patients.

  19. BMP and TGFbeta pathways in human central chondrosarcoma: enhanced endoglin and Smad 1 signaling in high grade tumors

    Science.gov (United States)

    2012-01-01

    Background As major regulators of normal chondrogenesis, the bone morphogenic protein (BMP) and transforming growth factor β (TGFB) signaling pathways may be involved in the development and progression of central chondrosarcoma. In order to uncover their possible implication, the aim of this study was to perform a systematic quantitative study of the expression of BMPs, TGFBs and their receptors and to assess activity of the corresponding pathways in central chondrosarcoma. Methods Gene expression analysis was performed by quantitative RT-PCR in 26 central chondrosarcoma and 6 healthy articular cartilage samples. Expression of endoglin and nuclear localization of phosphorylated Smad1/5/8 and Smad2 was assessed by immunohistochemical analysis. Results The expression of TGFB3 and of the activin receptor-like kinase ALK2 was found to be significantly higher in grade III compared to grade I chondrosarcoma. Nuclear phosphorylated Smad1/5/8 and Smad2 were found in all tumors analyzed and the activity of both signaling pathways was confirmed by functional reporter assays in 2 chondrosarcoma cell lines. Immunohistochemical analysis furthermore revealed that phosphorylated Smad1/5/8 and endoglin expression were significantly higher in high-grade compared to low-grade chondrosarcoma and correlated to each other. Conclusions The BMP and TGFβ signaling pathways were found to be active in central chondrosarcoma cells. The correlation of Smad1/5/8 activity to endoglin expression suggests that, as described in other cell types, endoglin could enhance Smad1/5/8 signaling in high-grade chondrosarcoma cells. Endoglin expression coupled to Smad1/5/8 activation could thus represent a functionally important signaling axis for the progression of chondrosarcoma and a regulator of the undifferentiated phenotype of high-grade tumor cells. PMID:23088614

  20. Frequency of argyrophilic nucleolar organizer regions in fine-needle aspirates and biopsy specimens from mast cell tumors in dogs.

    Science.gov (United States)

    Kravis, L D; Vail, D M; Kisseberth, W C; Ogilvie, G K; Volk, L M

    1996-10-15

    To determine for mast cell tumors in dogs whether frequency of argyrophilic nucleolar organizer regions (AgNOR) determined by examining fine-needle aspirates (FNA) correlated with frequencies determined by examining biopsy specimens or with histologic grade. Case series. 25 dogs with 32 histologically confirmed tumors. Biopsy specimens and FNA were collected from each tumor. Histologic grade and AgNOR frequency were determined. Frequency of AgNOR in FNA was significantly correlated with frequency in biopsy specimens and was significantly associated with histologic grade of the tumor. Determining AgNOR frequency in FNA of mast cell tumors in dogs is a rapid, minimally invasive means of obtaining information that potentially could be used to help predict biological behavior of the tumor and to guide clinicians and owners in making decisions about further diagnostic tests and treatment.

  1. Progressive Deregulation of the Cell Cycle With Higher Tumor Grade in the Stroma of Breast Phyllodes Tumors

    NARCIS (Netherlands)

    Kuijper, Arno; Vos, R.A.I. de; Lagendijk, J.H.; Wall, E. van der; Diest, P.J. van

    2005-01-01

    We studied cell cycle–regulating proteins in phyllodes tumor pathogenesis by immunohistochemical analysis for Ki-67, cyclin A, cyclin D1, retinoblastoma protein (pRb), p53, p16INK4A, bcl-2, and p21waf1 in the epithelium and stroma of 40 primary (benign, 21; borderline, 8; malignant, 11) and 7

  2. Time trends in incidence rates and survival of newly diagnosed stage IV breast cancer by tumor histology: a population-based analysis.

    Science.gov (United States)

    Di Meglio, Antonio; Freedman, Rachel A; Lin, Nancy U; Barry, William T; Metzger-Filho, Otto; Keating, Nancy L; King, Tari A; Sertoli, Mario Roberto; Boccardo, Francesco; Winer, Eric P; Vaz-Luis, Ines

    2016-06-01

    Few contemporary data are available that compare incidence and survival of metastatic breast cancer between ductal and lobular carcinomas. Using the Surveillance, Epidemiology, and End Results-9 registries, we identified 10,639 patients with de novo metastatic breast cancer diagnosed from 1990 to 2011. Annual age-adjusted incidence rates and annual percent changes (APCs) were analyzed. Multivariable Cox regression models were used to investigate the impact of year of diagnosis and histology on overall survival. 9250 (86.9 %) patients had ductal and 1389 (13.1 %) had lobular carcinomas. Metastatic breast cancer incidence increased slightly over time for ductal (APC = +1.7, 95 % confidence interval (CI) = +1.0 to +2.4) and lobular carcinomas (APC = +3.0, 95 % CI = +1.8 to +4.3). Median overall survival was 22 months among the whole cohort. More recent year of diagnosis was associated with better overall survival only for patients with ductal carcinomas (interaction p value = 0.006), with an adjusted hazard ratio of death for every five-year increment in the date of diagnosis of 0.93 (95 % CI =  0.91-0.95) among ductal carcinomas, compared with 1.05 (95 % CI = 0.95-1.10) among lobular carcinomas. Overall survival was longer for lobular versus ductal carcinomas (28 versus 21 months, respectively; adjusted hazard ratio of death = 0.93, 95 % CI = 0.87-0.99), but the magnitude of this effect was attenuated among the cohort restricted to hormone receptor-positive tumors. In this population-based analysis, incidence rates of metastatic breast cancer at presentation increased slightly over time for both histologies, and particularly for lobular tumors. A modest improvement in metastatic breast cancer median overall survival was observed, but was apparently limited to ductal carcinomas.

  3. Multimodal Imaging of Patients With Gliomas Confirms 11C-MET PET as a Complementary Marker to MRI for Noninvasive Tumor Grading and Intraindividual Follow-Up After Therapy

    Directory of Open Access Journals (Sweden)

    Kai R. Laukamp MD

    2017-01-01

    Full Text Available The value of combined L-(methyl-[11C] methionine positron-emitting tomography (MET-PET and magnetic resonance imaging (MRI with regard to tumor extent, entity prediction, and therapy effects in clinical routine in patients with suspicion of a brain tumor was investigated. In n = 65 patients with histologically verified brain lesions n = 70 MET-PET and MRI (T1-weighted gadolinium-enhanced [T1w-Gd] and fluid-attenuated inversion recovery or T2-weighted [FLAIR/T2w] examinations were performed. The computer software “visualization and analysis framework volume rendering engine (Voreen” was used for analysis of extent and intersection of tumor compartments. Binary logistic regression models were developed to differentiate between World Health Organization (WHO tumor types/grades. Tumor sizes as defined by thresholding based on tumor-to-background ratios were significantly different as determined by MET-PET (21.6 ± 36.8 cm3, T1w-Gd-MRI (3.9 ± 7.8 cm3, and FLAIR/T2-MRI (64.8 ± 60.4 cm3; P < .001. The MET-PET visualized tumor activity where MRI parameters were negative: PET positive tumor volume without Gd enhancement was 19.8 ± 35.0 cm3 and without changes in FLAIR/T2 10.3 ± 25.7 cm3. FLAIR/T2-MRI visualized greatest tumor extent with differences to MET-PET being greater in posttherapy (64.6 ± 62.7 cm3 than in newly diagnosed patients (20.5 ± 52.6 cm3. The binary logistic regression model differentiated between WHO tumor types (fibrillary astrocytoma II n = 10 from other gliomas n = 16 with an accuracy of 80.8% in patients at primary diagnosis. Combined PET and MRI improve the evaluation of tumor activity, extent, type/grade prediction, and therapy-induced changes in patients with glioma and serve information highly relevant for diagnosis and management.

  4. Multimodal Imaging of Patients With Gliomas Confirms (11)C-MET PET as a Complementary Marker to MRI for Noninvasive Tumor Grading and Intraindividual Follow-Up After Therapy.

    Science.gov (United States)

    Laukamp, Kai R; Lindemann, Florian; Weckesser, Matthias; Hesselmann, Volker; Ligges, Sandra; Wölfer, Johannes; Jeibmann, Astrid; Zinnhardt, Bastian; Viel, Thomas; Schäfers, Michael; Paulus, Werner; Stummer, Walter; Schober, Otmar; Jacobs, Andreas H

    2017-01-01

    The value of combined L-( methyl-[(11)C]) methionine positron-emitting tomography (MET-PET) and magnetic resonance imaging (MRI) with regard to tumor extent, entity prediction, and therapy effects in clinical routine in patients with suspicion of a brain tumor was investigated. In n = 65 patients with histologically verified brain lesions n = 70 MET-PET and MRI (T1-weighted gadolinium-enhanced [T1w-Gd] and fluid-attenuated inversion recovery or T2-weighted [FLAIR/T2w]) examinations were performed. The computer software "visualization and analysis framework volume rendering engine (Voreen)" was used for analysis of extent and intersection of tumor compartments. Binary logistic regression models were developed to differentiate between World Health Organization (WHO) tumor types/grades. Tumor sizes as defined by thresholding based on tumor-to-background ratios were significantly different as determined by MET-PET (21.6 ± 36.8 cm(3)), T1w-Gd-MRI (3.9 ± 7.8 cm(3)), and FLAIR/T2-MRI (64.8 ± 60.4 cm(3); P PET visualized tumor activity where MRI parameters were negative: PET positive tumor volume without Gd enhancement was 19.8 ± 35.0 cm(3) and without changes in FLAIR/T2 10.3 ± 25.7 cm(3). FLAIR/T2-MRI visualized greatest tumor extent with differences to MET-PET being greater in posttherapy (64.6 ± 62.7 cm(3)) than in newly diagnosed patients (20.5 ± 52.6 cm(3)). The binary logistic regression model differentiated between WHO tumor types (fibrillary astrocytoma II n = 10 from other gliomas n = 16) with an accuracy of 80.8% in patients at primary diagnosis. Combined PET and MRI improve the evaluation of tumor activity, extent, type/grade prediction, and therapy-induced changes in patients with glioma and serve information highly relevant for diagnosis and management.

  5. Tipifarnib in Treating Young Patients With Recurrent or Progressive High-Grade Glioma, Medulloblastoma, Primitive Neuroectodermal Tumor, or Brain Stem Glioma

    Science.gov (United States)

    2013-10-07

    Childhood High-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  6. Long-term Behavior of Serous Borderline Tumors Subdivided Into Atypical Proliferative Tumors and Noninvasive Low-grade Carcinomas

    DEFF Research Database (Denmark)

    Vang, Russell; Hannibal, Charlotte G; Junge, Jette

    2017-01-01

    Ovarian serous borderline tumors (SBTs) have been the subject of considerable controversy, particularly with regard to terminology and behavior. It has been proposed that they constitute a heterogenous group of tumors composed, for the most part, of typical SBTs that are benign and designated...... to 36 years (median, 15 y). All the microscopic slides from the contributing hospitals were rereviewed by a panel of 2 pathologists (R.V. and R.J.K.) who were blinded to the follow-up. After excluding those that were not SBTs by the pathology panel, as well as cases with a prior or concurrent cancer......, all-cause mortality was not statistically significantly different between APST and niLGSC. Of all women with advanced stage disease, 114 (86%) had noninvasive implants, whereas 19 (14%) were invasive. Noninvasive implants were significantly associated with subsequent development of carcinoma (HR=7...

  7. Low-grade osteosarcoma of the maxillary sinus

    Energy Technology Data Exchange (ETDEWEB)

    Park, Yong-Koo [Department of Pathology, College of Medicine, Kyung Hee University, Seoul (Korea); Department of Pathology, Kyung Hee University Hospital, Hoeki-dong, Dongdaemoon-ku, Seoul (Korea); Ryu, Kyung Nam [Department of Diagnostic Radiology, College of Medicine, Kyung Hee University, Seoul (Korea); Park, Hye-Rim; Kim, Duck-Whan [Department of Pathology, College of Medicine, Hallym University, Seoul (Korea); 4

    2003-03-01

    Low-grade osteosarcomas of the paranasal sinus are extremely rare. Most reported cases of maxillary sinus osteosarcoma are high-grade. We present a 51-year-old man with a low-grade osteosarcoma which was histologically difficult to diagnose in isolation since it had bland features. The presence of an aggressive destructive lesion on imaging influenced the final pathological diagnosis as often appears to be the case with this rare tumor. We briefly discuss paranasal sinus osteosarcomas. (orig.)

  8. Pattern of Tumor Shrinkage during Neoadjuvant Chemotherapy Is Associated with Prognosis in Low-Grade Luminal Early Breast Cancer.

    Science.gov (United States)

    Fukada, Ippei; Araki, Kazuhiro; Kobayashi, Kokoro; Shibayama, Tomoko; Takahashi, Shunji; Gomi, Naoya; Kokubu, Yumi; Oikado, Katsunori; Horii, Rie; Akiyama, Futoshi; Iwase, Takuji; Ohno, Shinji; Hatake, Kiyohiko; Sata, Naohiro; Ito, Yoshinori

    2018-01-01

    Purpose To evaluate the association between tumor shrinkage patterns shown with magnetic resonance (MR) imaging during neoadjuvant chemotherapy (NAC) and prognosis in patients with low-grade luminal breast cancer. Materials and Methods This retrospective study was approved by the institutional review board and informed consent was obtained from all subjects. The low-grade luminal breast cancer was defined as hormone receptor-positive and human epidermal growth factor receptor 2-negative with nuclear grades 1 or 2. The patterns of tumor shrinkage as revealed at MR imaging were categorized into two types: concentric shrinkage (CS) and non-CS. Among 854 patients who had received NAC in a single institution from January 2000 to December 2009, 183 patients with low-grade luminal breast cancer were retrospectively evaluated for the development set. Another data set from 292 patients who had received NAC in the same institution between January 2010 and December 2012 was used for the validation set. Among these 292 patients, 121 patients with low-grade luminal breast cancer were retrospectively evaluated. Results In the development set, the median observation period was 67.9 months. Recurrence was observed in 31 patients, and 16 deaths were related to breast cancer. There were statistically significant differences in both the disease-free survival (DFS) and overall survival (OS) rates between patterns of tumor shrinkage (P breast cancer. DFS rate was significantly longer in patients with the CS pattern (72.8 months; 95% confidence interval [CI]: 69.9, 75.6 months) than in those with the non-CS pattern (56.0 months; 95% CI: 49.1, 62.9 months; P ≤ .001). The CS pattern was associated with an excellent prognosis (median OS, 80.6 months; 95% CI: 79.3, 81.8 months vs 65.0 months; 95% CI: 60.1, 69.8 months; P = .004). Multivariate analysis demonstrated that the CS pattern had the only significant independent association with DFS (P = .007) and OS (P = .037) rates. Conclusion

  9. Morphologic evaluation of the effect of denosumab on giant cell tumors of bone and a new grading scheme

    Directory of Open Access Journals (Sweden)

    Kivilcim Eren Erdogan

    2017-02-01

    Full Text Available Giant cell tumor (GCT is a rare, usually benign but locally aggressive neoplasm. Recent studies suggest new approaches in light of the elucidation of molecular pathways in bone. The osteolytic nature of GCT is caused by the receptor for activating nuclear factor-kB ligand (RANKL associated osteoclasts. Denosumab is a monoclonal antibody that affects GCT through RANKL and it prevents normal and neoplastic osteolysis. The aim of this study is to evaluate the histopathologic alterations due to denosumab treatment and the efficiency of this drug in GCT therapy. Ten patients had been treated with denosumab and were included in the study. Pretreatment biopsies were interpreted as conventional GCTs and posttreatment biopsies of the ten patients’ GCTs were classified in accordance with the grading system. Only one patient had tumor remaining after treatment. There is limited data on histopathologic alterations that follow denosumab treatment. The bone pathologist should keep these changes in mind because they mimic different types of bone tumors. Furthermore, there is no widely accepted grading system to evaluate the effect of denosumab in GCT. Our study suggested a scheme that would be helpful to evaluate the efficiency of denosumab treatment in GCT.

  10. MFH Mimic in Breast: A High-Grade Malignant Phyllodes Tumor

    OpenAIRE

    Hemalatha, A. L.; Sindhuram, V. Sumana; Asha, U.

    2012-01-01

    Malignant phyllodes tumor is usually diagnosed by the presence of benign duct-like epithelium and malignant mesenchymal tissue. In addition to the usual fibrosarcomatous features, the mesenchymal component may show areas resembling osteogenic sarcoma, chondrosarcoma, liposarcoma, leiomyosarcoma, rhabdomyosarcoma, malignant mesenchymoma, and, very rarely, malignant fibrous histiocytoma. We present one such rare case of malignant phyllodes tumor with malignant fibrous histiocytoma-like stromal ...

  11. Occurrence of thymosin ß4 in human breast cancer cells and in other cell types of the tumor microenvironment

    DEFF Research Database (Denmark)

    Larsson, Lars-Inge; Holck, Susanne

    2007-01-01

    to thymosin ß4, whereas myofibroblasts were negative. There was no correlation between the intensity of tumor cell staining and histological grade, whereas there was a tendency toward a correlation between endothelial cell staining and grade. These results demonstrate that multiple cell types within the tumor...

  12. Long-term Behavior of Serous Borderline Tumors Subdivided Into Atypical Proliferative Tumors and Noninvasive Low-grade Carcinomas: A Population-based Clinicopathologic Study of 942 Cases.

    Science.gov (United States)

    Vang, Russell; Hannibal, Charlotte G; Junge, Jette; Frederiksen, Kirsten; Kjaer, Susanne K; Kurman, Robert J

    2017-06-01

    Ovarian serous borderline tumors (SBTs) have been the subject of considerable controversy, particularly with regard to terminology and behavior. It has been proposed that they constitute a heterogenous group of tumors composed, for the most part, of typical SBTs that are benign and designated "atypical proliferative serous tumor (APST)" and a small subset of SBTs with micropapillary architecture that have a poor outcome and are designated "noninvasive low-grade serous carcinoma (niLGSC)". It also has been argued that the difference in behavior between the 2 groups is not due to the subtype of the primary tumor but rather the presence of extraovarian disease, specifically invasive implants. According to the terminology of the 2014 WHO Classification, typical SBTs are equivalent to APSTs and SBTs displaying micropapillary architecture are synonymous with niLGSC. In addition, "invasive implants" were renamed "low-grade serous carcinoma" (LGSC). The argument as to whether it is the appearance of the primary tumor or the presence of extraovarian LGSC that determines outcome remains unsettled. The current study was initiated in 2004 and was designed to determine what factors were predictive of outcome, with special attention to the appearance of the primary tumor (APST vs. niLGSC) and that of the extraovarian disease (noninvasive vs. invasive implants). Our study is population based, involving the entire female population of Denmark. None of the women in the study were lost to follow-up, which ranged up to 36 years (median, 15 y). All the microscopic slides from the contributing hospitals were rereviewed by a panel of 2 pathologists (R.V. and R.J.K.) who were blinded to the follow-up. After excluding those that were not SBTs by the pathology panel, as well as cases with a prior or concurrent cancer or undefined stage, 942 women remained, of which 867 were APSTs and 75 were niLGSCs. The median patient age was 50 years (range, 16 to 97 y). Eight hundred nine women (86

  13. Stochastic modelling of slow-progressing tumors: Analysis and applications to the cell interplay and control of low grade gliomas

    Science.gov (United States)

    Rodríguez, Clara Rojas; Fernández Calvo, Gabriel; Ramis-Conde, Ignacio; Belmonte-Beitia, Juan

    2017-08-01

    Tumor-normal cell interplay defines the course of a neoplastic malignancy. The outcome of this dual relation is the ultimate prevailing of one of the cells and the death or retreat of the other. In this paper we study the mathematical principles that underlay one important scenario: that of slow-progressing cancers. For this, we develop, within a stochastic framework, a mathematical model to account for tumor-normal cell interaction in such a clinically relevant situation and derive a number of deterministic approximations from the stochastic model. We consider in detail the existence and uniqueness of the solutions of the deterministic model and study the stability analysis. We then focus our model to the specific case of low grade gliomas, where we introduce an optimal control problem for different objective functionals under the administration of chemotherapy. We derive the conditions for which singular and bang-bang control exist and calculate the optimal control and states.

  14. Accuracy of preoperative tumor grade and intraoperative gross examination of myometrial invasion in patients with endometrial cancer

    DEFF Research Database (Denmark)

    Traen, Koen; Hølund, Berit; Mogensen, Ole

    2007-01-01

    BACKGROUND AND AIMS: Preoperative prediction of metastases to the regional lymph nodes in women with endometrioid endometrial cancer is a challenge. According to the Danish Gynaecological Cancer Society guidelines, a pelvic lymphadenectomy is warranted in all poorly differentiated tumors and all...... registered in 72 women with stage I endometrioid endometrial cancer, operated between 1 September 2004 and 18 April 2006. The pre- and intraoperative findings were compared with the final pathology report. RESULTS: The preoperative prediction of grade (well, moderate or poorly differentiated) was correct...

  15. Impact of histology and surgical approach on survival among women with early-stage, high-grade uterine cancer: An NRG Oncology/Gynecologic Oncology Group ancillary analysis ✩

    Science.gov (United States)

    Fader, Amanda N.; Java, James; Tenney, Meaghan; Ricci, Stephanie; Gunderson, Camille C.; Temkin, Sarah M.; Spirtos, Nick; Kushnir, Christina L.; Pearl, Michael L.; Zivanovic, Oliver; Tewari, Krishnansu S.; O'Malley, David; Hartenbach, Ellen M.; Hamilton, Chad A.; Gould, Natalie S.; Mannel, Robert S.; Rodgers, William; Walker, Joan L.

    2016-01-01

    Objectives We sought to analyze the clinicopathologic features, recurrence patterns and survival outcomes of women with high-grade uterine cancer (UC) enrolled on The Gynecologic Oncology Group (GOG) LAP2 trial. Methods This is a post-hoc analysis of LAP-2 patients with grade 3 endometrioid adenocarcinoma (ENDO), uterine serous (USC), clear cell (CC) and carcinosarcoma (CS). Demographics, clinicopathologic features, and recurrence patterns, were compared by histology and surgical approach. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results Of the 2600 patients enrolled in LAP-2, 753 patients had high-grade UC: 350 had ENDO, 289 had USC, 42 had CC and 72 had CS. Compared with the ENDO cohort, those with other high-grade subtypes were older (p cytology (p < 0.001), positive lymph nodes (p = 0.05) and higher disease stage on final pathology (p < 0.001). With a median follow-up time of 60 months, compared to patients with ENDO, those with USC, CCC and CS subtypes had higher recurrence rates (p < 0.001), extra-pelvic recurrences (p < 0.001) and poorer PFS (p < 0.001) and OS (p < 0.001). Those diagnosed with USC and CS experienced the worst survival outcomes (p = 0.003). Patterns of recurrence and survival were not different in those staged with LSC vs LAP. On multivariable analysis, age, stage, pelvic washings and Type II histology were independently and adversely associated with survival. Conclusions Women with apparent early-stage, USC and CS histologies have poorer outcomes than women with grade 3 endometrioid adenocarcinoma. Patterns of recurrence and survival were not impacted by surgical approach. PMID:27743738

  16. CA 15–3 cell lines and tissue expression in canine mammary cancer and the correlation between serum levels and tumour histological grade

    Directory of Open Access Journals (Sweden)

    Manuali Elisabetta

    2012-06-01

    Full Text Available Abstract Background Mammary tumours are the most common malignancy diagnosed in female dogs and a significant cause of mortality and morbidity in this species. Carbohydrate antigen (CA 15–3 is a mucinous glycoprotein aberrantly over-expressed in human mammary neoplasms and one of the most widely used serum tumour markers in women with breast cancer. The aim of this study was to investigate the antigenic analogies of human and canine CA 15–3 and to assess its expression in canine mammary cancer tissues and cell lines. Immunohistochemical expression of CA 15–3 was evaluated in 7 canine mammary cancer cell lines and 50 malignant mammary tumours. As a positive control, the human breast carcinoma cell line MCF7 and tissue were used. To assess CA 15–3 staining, a semi-quantitative method was applied. To confirm the specificity and cross-reactivity of an anti-human CA 15–3 antibody to canine tissues, an immunoblot analysis was performed. We also investigated serum CA 15–3 activity to establish whether its expression could be assigned to several tumour characteristics to evaluate its potential use as a serum tumour marker in the canine mammary oncology field. Results Immunocytochemical analysis revealed CA 15–3 expression in all examined canine mammary cancer cell lines, whereas its expression was confirmed by immunoblot only in the most invasive cells (CMT-W1, CMT-W1M, CMT-W2 and CMT-W2M. In the tissue, an immunohistochemical staining pattern was observed in 34 (68% of the malignant tumours. A high statistical correlation (p = 0.0019 between serum CA 15–3 levels and the degree of tumour proliferation and differentiation was shown, which indicates that the values of this serum marker increase as the tumour stage progresses. Conclusions The results of this study reveal that CA 15–3 is expressed in both canine mammary tumour cell lines and tissues and that serum levels significantly correlate with the histological grade of the

  17. Perfusion MRI derived indices of microvascular shunting and flow control correlate with tumor grade and outcome in patients with cerebral glioma

    DEFF Research Database (Denmark)

    Tietze, Anna; Mouridsen, Kim; Lassen-Ramshad, Yasmin

    2015-01-01

    Objectives: Deficient microvascular blood flow control is thought to cause tumor hypoxia and increase resistance to therapy. In glioma patients, we tested whether perfusion-weighted MRI (PWI) based indices of microvascular flow control provide more information on tumor grade and patient outcome...... than does the established PWI angiogenesis marker, cerebral blood volume (CBV). Material and Methods: Seventy-two glioma patients (sixty high-grade, twelve low-grade gliomas) were included. Capillary transit time heterogeneity (CTH) and COV, its ratio to blood mean transit time, provide indices...

  18. MFH Mimic in Breast: A High-Grade Malignant Phyllodes Tumor

    Directory of Open Access Journals (Sweden)

    A. L. Hemalatha

    2012-01-01

    Full Text Available Malignant phyllodes tumor is usually diagnosed by the presence of benign duct-like epithelium and malignant mesenchymal tissue. In addition to the usual fibrosarcomatous features, the mesenchymal component may show areas resembling osteogenic sarcoma, chondrosarcoma, liposarcoma, leiomyosarcoma, rhabdomyosarcoma, malignant mesenchymoma, and, very rarely, malignant fibrous histiocytoma. We present one such rare case of malignant phyllodes tumor with malignant fibrous histiocytoma-like stromal differentiation.

  19. A comparative study of histological grade and expression of Ki67 protein in oral squamous cell carcinoma in young and old patients

    Directory of Open Access Journals (Sweden)

    Parviz Deyhimi

    2013-01-01

    Conclusion: Histological and immunohistochemical evidence of this study show that oral SCC of young patients and oral SCC lesions of old patients didn′t show any differences in histopathological differention and proliferative activity.

  20. Perfusion MRI derived indices of microvascular shunting and flow control correlate with tumor grade and outcome in patients with cerebral glioma.

    Directory of Open Access Journals (Sweden)

    Anna Tietze

    Full Text Available Deficient microvascular blood flow control is thought to cause tumor hypoxia and increase resistance to therapy. In glioma patients, we tested whether perfusion-weighted MRI (PWI based indices of microvascular flow control provide more information on tumor grade and patient outcome than does the established PWI angiogenesis marker, cerebral blood volume (CBV.Seventy-two glioma patients (sixty high-grade, twelve low-grade gliomas were included. Capillary transit time heterogeneity (CTH and the coefficient of variation (COV, its ratio to blood mean transit time, provide indices of microvascular flow control and the extent to which oxygen can be extracted by tumor tissue. The ability of these parameters and CBV to differentiate tumor grade were assessed by receiver operating characteristic curves and logistic regression. Their ability to predict time to progression and overall survival was examined by the Cox proportional-hazards regression model, and by survival curves using log-rank tests.The best prediction of grade (AUC = 0.876; p < 0.05 was achieved by combining knowledge of CBV and CTH in the enhancing tumor and peri-focal edema, and patients with glioblastoma multiforme were identified best by CTH (AUC = 0.763; p<0.001. CTH outperformed CBV and COV in predicting time to progression and survival in all gliomas and in a subgroup consisting of only high-grade gliomas.Our study confirms the importance of microvascular flow control in tumor growth by demonstrating that determining CTH improves tumor grading and outcome prediction in glioma patients compared to CBV alone.

  1. Abundant immunohistochemical expression of dopamine D{sub 2} receptor and p53 protein in meningiomas: follow-up, relation to gender, age, tumor grade, and recurrence

    Energy Technology Data Exchange (ETDEWEB)

    Trott, G.; Pereira-Lima, J.F.S.; Leães, C.G.S. [Programa de Graduação em Patologia, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Centro de Neuroendocrinologia, Complexo Hospitalar Santa Casa de Porto Alegre, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Ferreira, N.P. [Centro de Neuroendocrinologia, Complexo Hospitalar Santa Casa de Porto Alegre, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Barbosa-Coutinho, L.M. [Programa de Graduação em Patologia, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Oliveira, M.C. [Programa de Graduação em Patologia, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Centro de Neuroendocrinologia, Complexo Hospitalar Santa Casa de Porto Alegre, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil)

    2015-03-03

    Meningiomas are common, usually benign tumors, with a high postoperative recurrence rate. However, the genesis and development of these tumors remain controversial. We aimed to investigate the presence and implications of a mutated p53 protein and dopamine D{sub 2} receptor in a representative series of meningiomas and to correlate these findings with age, gender, tumor grade, and recurrence. Tumor tissue samples of 157 patients diagnosed with meningioma (37 males and 120 females, mean age 53.6±14.3 years) who underwent surgical resection between 2003 and 2012 at our institution were immunohistochemically evaluated for the presence of p53 protein and dopamine D{sub 2} receptor and were followed-up to analyze tumor recurrence or regrowth. Tumors were classified as grades I (n=141, 89.8%), II (n=13, 8.3%), or grade III (n=3, 1.9%). Dopamine D{sub 2} receptor and p53 protein expression were positive in 93.6% and 49.7% of the cases, respectively. Neither of the markers showed significant expression differences among different tumor grades or recurrence or regrowth statuses. Our findings highlight the potential role of p53 protein in meningioma development and/or progression. The high positivity of dopamine D{sub 2} receptor observed in this study warrants further investigation of the therapeutic potential of dopamine agonists in the evolution of meningiomas.

  2. Abundant immunohistochemical expression of dopamine D2 receptor and p53 protein in meningiomas: follow-up, relation to gender, age, tumor grade, and recurrence

    Directory of Open Access Journals (Sweden)

    G. Trott

    2015-05-01

    Full Text Available Meningiomas are common, usually benign tumors, with a high postoperative recurrence rate. However, the genesis and development of these tumors remain controversial. We aimed to investigate the presence and implications of a mutated p53 protein and dopamine D2 receptor in a representative series of meningiomas and to correlate these findings with age, gender, tumor grade, and recurrence. Tumor tissue samples of 157 patients diagnosed with meningioma (37 males and 120 females, mean age 53.6±14.3 years who underwent surgical resection between 2003 and 2012 at our institution were immunohistochemically evaluated for the presence of p53 protein and dopamine D2 receptor and were followed-up to analyze tumor recurrence or regrowth. Tumors were classified as grades I (n=141, 89.8%, II (n=13, 8.3%, or grade III (n=3, 1.9%. Dopamine D2 receptor and p53 protein expression were positive in 93.6% and 49.7% of the cases, respectively. Neither of the markers showed significant expression differences among different tumor grades or recurrence or regrowth statuses. Our findings highlight the potential role of p53 protein in meningioma development and/or progression. The high positivity of dopamine D2 receptor observed in this study warrants further investigation of the therapeutic potential of dopamine agonists in the evolution of meningiomas.

  3. Food-grade titanium dioxide exposure exacerbates tumor formation in colitis associated cancer model.

    Science.gov (United States)

    Urrutia-Ortega, Ismael M; Garduño-Balderas, Luis G; Delgado-Buenrostro, Norma L; Freyre-Fonseca, Verónica; Flores-Flores, José O; González-Robles, Arturo; Pedraza-Chaverri, José; Hernández-Pando, Rogelio; Rodríguez-Sosa, Miriam; León-Cabrera, Sonia; Terrazas, Luis I; van Loveren, Henk; Chirino, Yolanda I

    2016-07-01

    Colorectal cancer is the fourth worldwide cause of death and even if some dietary habits are consider risk factors, the contribution of food additives including foodgrade titanium dioxide (TiO2), designated as E171, has been poorly investigated. We hypothesized that oral E171 intake could have impact on the enhancement of colorectal tumor formation and we aimed to investigate if E171 administration could enhance tumor formation in a colitis associated cancer (CAC) model. BALB/c male mice were grouped as follows: a) control, b) E171, c) CAC and d) CAC + E171 group (n = 6). E171 used in this study formed agglomerates of 300 nm in water. E171 intragastric administration (5 mg/kg body weight/5 days/10 weeks) was unable to induce tumor formation but dysplastic alterations were observed in the distal colon but enhanced the tumor formation in distal colon (CAC + E171 group) measured by tumor progression markers. Some E171 particles were internalized in colonic cells of the E171 and CAC + E171 groups and both groups showed a decrease in goblet cells in the distal colon. However the CAC + E171 group showed a higher decrease of these cells that act as protection barrier in colon. These results suggest that E171 could worsen pre-existent intestinal diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Tumor Delineation and Quantitative Assessment of Glucose Metabolic Rate within Histologic Subtypes of Non-Small Cell Lung Cancer by Using Dynamic18F Fluorodeoxyglucose PET.

    Science.gov (United States)

    Meijer, Tineke W H; de Geus-Oei, Lioe-Fee; Visser, Eric P; Oyen, Wim J G; Looijen-Salamon, Monika G; Visvikis, Dimitris; Verhagen, Ad F T M; Bussink, Johan; Vriens, Dennis

    2017-05-01

    Purpose To assess whether dynamic fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) positron emission tomography (PET) has added value over static 18 F-FDG PET for tumor delineation in non-small cell lung cancer (NSCLC) radiation therapy planning by using pathology volumes as the reference standard and to compare pharmacokinetic rate constants of 18 F-FDG metabolism, including regional variation, between NSCLC histologic subtypes. Materials and Methods The study was approved by the institutional review board. Patients gave written informed consent. In this prospective observational study, 1-hour dynamic 18 F-FDG PET/computed tomographic examinations were performed in 35 patients (36 resectable NSCLCs) between 2009 and 2014. Static and parametric images of glucose metabolic rate were obtained to determine lesion volumes by using three delineation strategies. Pathology volume was calculated from three orthogonal dimensions (n = 32). Whole tumor and regional rate constants and blood volume fraction (V B ) were computed by using compartment modeling. Results Pathology volumes were larger than PET volumes (median difference, 8.7-25.2 cm 3 ; Wilcoxon signed rank test, P metabolic rate and 18 F-FDG phosphorylation rate were higher in squamous cell carcinoma (SCC) than in adenocarcinoma (AC), whereas V B was lower (Mann-Whitney U test or t test, P = .003, P = .036, and P = .019, respectively). Glucose metabolic rate, 18 F-FDG phosphorylation rate, and V B were less heterogeneous in AC than in SCC (Friedman analysis of variance). Conclusion Parametric images are not superior to static images for NSCLC delineation. FLAB-based segmentation on static 18 F-FDG PET images is in best agreement with pathology volume and could be useful for NSCLC autocontouring. Differences in glycolytic rate and V B between SCC and AC are relevant for research in targeting agents and radiation therapy dose escalation. © RSNA, 2016 Online supplemental material is available for this article.

  5. Management of borderline ovarian tumors.

    Science.gov (United States)

    Tîrnovanu, Mihaela-Camelia; Amancei, Simona; Dumitrescu, A; Onofriescu, M; Dumitraşcu, Irina

    2012-01-01

    Borderline ovarian tumors are an intermediate stage between benign cystadenomas and adenocarcinomas. The paper evaluates the management of borderline ovarian tumors (BOTs) in the patients admitted and treated in our clinic in the interval January 2003 - June 2011. The observation sheets and pathology results of 264 patients with malignant ovarian tumors were analyzed. Of the 264 malignant ovarian tumors 74 (28.03%) were low malignant potential. Patients with BOT were aged 18-72 years (mean 46 +/- 6.2 years) and those with invasive tumors 14-83 years (mean 53 +/- 9.8 years). 92.18% were in stage 1. Sixty tumors were graded G1. 53.52 % of the tumors were over 10 cm (maximum 30 cm) in size. The histological types were: serous - 35 cases, mucinous - 19 cases, mixed (serous and mucinous) - 8 cases, and endometrioid - 2 cases. Fifteen patients presented intraepithelial carcinoma and 11 noninvasive implants into the peritoneal cavity. Five women had recurrences. Ovarian borderline tumors with histological characteristics of carcinoma, but with good behavior are now with better defined histological features. The biggest challenge in the management of women with these tumors is to identify the subset that will behave in a malignant fashion and to develop effective treatment for them.

  6. Identifying Grade/Stage-Related Active Modules in Human Co-regulatory Networks: A Case Study for Breast Cancer

    OpenAIRE

    Feng, Chenchen; Chen, Lina; Li, Wan; Wang, Hong; Zhang, Liangcai; Jia, Xu; Miao, Zhengqiang; Qu, Xiaoli; Li, Weiguo; He, Weiming

    2012-01-01

    The histological grade/stage of tumor is widely acknowledged as an important clinical prognostic factor for cancer progression. Recent experimental studies have explored the following two topics at the molecular level: (1) whether or not gene expression levels vary by different degrees among different tumor grades/stages, and (2) whether some well-defined modules could distinguish one grade/stage from another. In this article, using breast cancer as an example, we investigated this topic and ...

  7. Invasive Front Grading and Epithelial-Mesenchymal Transition in Canine Oral and Cutaneous Squamous Cell Carcinomas.

    Science.gov (United States)

    Nagamine, E; Hirayama, K; Matsuda, K; Okamoto, M; Ohmachi, T; Uchida, K; Kadosawa, T; Taniyama, H

    2017-09-01

    Oral and cutaneous tissues are the most frequent origin in canine squamous cell carcinoma (SSC). In SCC, changes in adhesion molecule expression and transition from epithelial to mesenchymal phenotype are thought to be important in development of invasive behavior of neoplastic cells at the leading front of the tumor. We therefore investigated histological invasive front grading and epithelial-mesenchymal transition (EMT) in both oral SCCs and cutaneous SCCs. EMT was assessed by evaluating immunohistochemical expression of E-cadherin, β-catenin, desmoglein, vimentin, and N-cadherin. Regardless of the anatomic location, invasive front grading resulted in higher histological grades than grading of the surface. Most oral SCCs were of significantly higher histologic grade than cutaneous SCCs ( P front grading and loss of E-cadherin, β-catenin, and desmoglein ( P front grading with assessment of immunohistochemical expression of E-cadherin, β-catenin, and desmoglein may allow more accurate prediction of biological behavior of canine SCCs.

  8. An elevated serum alkaline phosphatase level in hepatic metastases of grade 1 and 2 gastrointestinal neuroendocrine tumors is unusual and of prognostic value.

    Science.gov (United States)

    Andriantsoa, Maeva; Hoibian, Solene; Autret, Aurelie; Gilabert, Marine; Sarran, Anthony; Niccoli, Patricia; Raoul, Jean-Luc

    2017-01-01

    In our clinical practice we have observed that despite a high hepatic metastatic tumor burden, serum alkaline phosphatase (AP) levels are frequently normal in cases of metastatic neuroendocrine tumor (NET). We retrospectively reviewed the records of patients with grade 1 and 2 NETs with liver metastases but without bone metastases seen at our institution in 2013. In total, 49 patients were included (22 female), with a median age of 60 years (range: 28 to 84 years). The primary tumors were located in the duodenum/pancreas (n = 29), small bowel (n = 17) or colon/rectum (n = 3); 10 cases were grade 1 and 39 grade 2. Hepatic involvement was bulky, with more than 10 lesions in 23 patients and a tumor burden above 10% of the liver volume in 26 patients. Serum AP levels were elevated (≥ upper limit of normal (ULN)) in 16 patients. In multiparametric analysis, elevated serum AP levels were not associated with the primary site, grade, or number or volume of metastases. In multiparametric analysis, progression-free survival was only correlated with grade (p = 0.010) and AP level (p = 0.017). Serum AP levels are frequently normal in liver metastases from NET, even in the event of a major tumor burden, and the serum AP level can be of prognostic value.

  9. Patterns of lymph node sampling and the impact of lymph node density in favorable histology Wilms tumor: An analysis of the national cancer database.

    Science.gov (United States)

    Saltzman, A F; Carrasco, A; Amini, A; Aldrink, J H; Dasgupta, R; Gow, K W; Glick, R D; Ehrlich, P F; Cost, N G

    2017-10-31

    There is controversy about the role of lymph node (LN) sampling or dissection in the management of favorable histology (FH) Wilms tumor (WT), specifically how it performed and how it may impact survival. The objective of this study was to analyze factors affecting LN sampling patterns and the impact of LN yield and density (number of positive LNs/LNs examined) on overall survival (OS) in patients with advanced-stage favorable histology Wilms tumor (FHWT). The National Cancer Database (NCDB) was queried for patients with FHWT during 2004-2013. Demographic, clinical and OS data were abstracted for those who underwent surgical resection. Poisson regression was performed to analyze how factors influenced LN yield. Patients with positive LNs had LN density calculated and were further analyzed. A total of 2340 patients met criteria, with a median age at diagnosis of 3 years (range 0-78 years). The median number of LNs examined was three (range 0-87). Lymph node yield was affected by age, race, insurance, tumor size, laterality, advanced stage, LN positivity, and institutional volume. A total of 390 (16.6%) patients had LN-positive disease. Median LN density for these LN-positive patients was 0.38 (range 0.02-1) (Summary Figure). Estimated 5-year OS was significantly improved for those with LN density ≤0.38 vs. >0.38 (94% vs. 84.6%, P = 0.012). In this population, on multivariate analysis, age and LN density were significant predictors of OS. It is difficult to compile large numbers of cases in rare diseases like WT, and fortunately a large administrative database such as the NCDB can serve as a great resource. However, administrative data come with inherent limitations such as missing data and inability to account for a variety of factors that may influence LN yield and/or OS (specimen designation, pathologist experience, surgeon experience/volume, institutional Children's Oncology Group (COG) association, etc.). In this specific disease, the American Joint Committee

  10. Methylation status as a predictor of intravesical Bacillus Calmette-Guérin (BCG) immunotherapy response of high grade non-muscle invasive bladder tumor.

    Science.gov (United States)

    Husek, Petr; Pacovsky, Jaroslav; Chmelarova, Marcela; Podhola, Miroslav; Brodak, Milos

    2017-06-01

    Genetic and epigenetic alterations play an important role in urothelial cancer pathogenesis. Deeper understanding of these processes could help us achieve better diagnosis and management of this life-threatening disease. The aim of this research was to evaluate the methylation status of selected tumor suppressor genes for predicting BCG response in patients with high grade non-muscle-invasive bladder tumor (NMIBC). We retrospectively evaluated 82 patients with high grade non-muscle-invasive bladder tumor (stage Ta, T1, CIS) who had undergone BCG instillation therapy. We compared epigenetic methylation status in BCG-responsive and BCG-failure groups. We used the MS-MLPA (Methylation-Specific Multiplex Ligation-Dependent Probe Amplification probe sets ME001 and ME004. The control group was 13 specimens of normal urotel (bladder tissue)). Newly identified methylations in high grade NMIBC were found in MUS81a, NTRK1 and PCCA. The methylation status of CDKN2B (P=0.00312 ** ) and MUS81a (P=0.0191 * ) is associated with clinical outcomes of BCG instillation therapy response. CDKN2B and MUS81a unmethylation was found in BCG failure patients. The results show that the methylation status of selected tumor suppressor genes (TSGs) has the potential for predicting BCG response in patients with NMIBC high grade tumors. Tumor suppressor genes such as CDKN2b, MUS81a, PFM-1, MSH6 and THBS1 are very promising for future research.

  11. Retrospective analysis of a Computer-Aided Detection (CAD) system in full-field digital mammography in correlation to tumor histology; Retrospektive Analyse eines computerassistierten Detektions-Systems (CAD) in der digitalen Vollfeldmammographie in Abhaengigkeit von der Histologie

    Energy Technology Data Exchange (ETDEWEB)

    Obenauer, S.; Sohns, C.; Grabbe, E. [Abt. Diagnostische Radiologie, Georg-August-Univ. Goettingen (Germany); Werner, C. [Abt. fuer Medizinische Statistik, Georg-August-Univ. Goettingen (Germany)

    2005-08-01

    Purpose: to evaluate the usefulness of a computer-aided detection (CAD) system in full-field digital mammography in correlation to tumor histology. Material and methods: a total of 476 patients (226 patients with histologically proven malignant tumors, 250 healthy women) took part in this study. The mammograms were studied retrospectively, using the CAD system Image Checker. For 226 patients digital mammograms in MLO-projection were available. For 186 of these patients the CC-projection was also available. CAD markers that correlated with histologically proven carcinomas were considered to be true-positive markers. All other CAD markers were considered to be false-positive. Histologically proven carcinomas without markers were false-negative results. The dependence of the CAD markers placement upon the different carcinoma histologies was studied using the Chi-square test. Results: no significant difference could be proven for the detectability of malignant breast lesions of different histologic types. For the detectability of ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), lobular carcinoma in situ (LCIS), tubular carcinoma and ductulo-lobular carcinoma, the true positives were 71.1%, 75%, 70.7%, 70%, 60% and 80%, respectively, in the MLO projection and 83.9%, 75.9%, 81.8%, 77.8%, 87.5% and 33.3%, respectively, in the CC projection. There was an average of 0.5 false-positive markers per mammographic image. Conclusion: The histologic type of carcinoma seems to have no influence on detectability when using the CAD system. The high rate of false-positive markers shows, however, the limited specificity of the CAD system and that improvements are necessary. (orig.)

  12. PET/CT imaging of the diapeutic alkylphosphocholine analog 124I-CLR1404 in high and low-grade brain tumors.

    Science.gov (United States)

    Hall, Lance T; Titz, Benjamin; Robins, H Ian; Bednarz, Bryan P; Perlman, Scott B; Weichert, Jamey P; Kuo, John S

    2017-01-01

    CLR1404 is a cancer-selective alkyl phosphocholine (APC) analog that can be radiolabeled with 124I for PET imaging, 131I for targeted radiotherapy and/or SPECT imaging, or 125I for targeted radiotherapy. Studies have demonstrated avid CLR1404 uptake and prolonged retention in a broad spectrum of preclinical tumor models. The purpose of this pilot trial was to demonstrate avidity of 124I-CLR1404 in human brain tumors and develop a framework to evaluate this uptake for use in larger studies. 12 patients (8 men and 4 women; mean age of 43.9 ± 15.1 y; range 23-66 y) with 13 tumors were enrolled. Eleven patients had suspected tumor recurrence and 1 patient had a new diagnosis of high grade tumor. Patients were injected with 185 MBq ± 10% of 124I-CLR1404 followed by PET/CT imaging at 6-, 24-, and 48-hour. 124I-CLR1404 PET uptake was assessed qualitatively and compared with MRI. After PET image segmentation SUV values and tumor to background ratios were calculated. There was no significant uptake of 124I-CLR1404 in normal brain. In tumors, uptake tended to increase to 48 hours. Positive uptake was detected in 9 of 13 lesions: 5/5 high grade tumors, 1/2 low grade tumors, 1/1 meningioma, and 2/4 patients with treatment related changes. 124I-CLR1404 uptake was not detected in 1/2 low grade tumors, 2/4 lesions from treatment related changes, and 1/1 indeterminate lesion. For 6 malignant tumors, the average tumor to background ratios (TBR) were 9.32 ± 4.33 (range 3.46 to 15.42) at 24 hours and 10.04 ± 3.15 (range 5.17 to 13.17) at 48 hours. For 2 lesions from treatment related change, the average TBR were 5.05 ± 0.4 (range 4.76 to 5.33) at 24 hours and 4.88 ± 1.19 (range 4.04 to 5.72) at 48 hours. PET uptake had areas of both concordance and discordance compared with MRI. 124I-CLR1404 PET demonstrated avid tumor uptake in a variety of brain tumors with high tumor-to-background ratios. There were regions of concordance and discordance compared with MRI, which has

  13. Anti-tumor necrosis factor α prevents bowel fibrosis assessed by messenger RNA, histology, and magnetization transfer MRI in rats with Crohn's disease.

    Science.gov (United States)

    Adler, Jeremy; Rahal, Kinan; Swanson, Scott D; Schmiedlin-Ren, Phyllissa; Rittershaus, Ahren C; Reingold, Laura J; Brudi, Josh S; Shealy, David; Cai, Ann; McKenna, Barbara J; Zimmermann, Ellen M

    2013-01-01

    Treatment of Crohn's disease (CD) with anti-tumor necrosis factor α (TNFα) decreases intestinal inflammation, but the effect on fibrosis remains unclear. We hypothesized that treatment with rat-specific anti-TNFα will decrease the development of intestinal fibrosis in a rat model of CD. We further hypothesized that magnetization transfer magnetic resonance imaging (MT-MRI) will be sensitive in detecting these differences in collagen content. Rats were injected in the distal ileum and cecum with peptidoglycan-polysaccharide (PG-PS) or human serum albumin (control) at laparotomy and then received intraperitoneal injections of rat-specific anti-TNFα or vehicle daily for 21 days after laparotomy. Rats underwent MT-MRI abdominal imaging on day 19 or 20. MT ratio was calculated in the cecal wall. Cecal tissue histologic inflammation was scored. Cecal tissue procollagen, cytokine, and growth factor messenger RNAs were measured by quantitative real-time PCR. PG-PS-injected rats treated with anti-TNFα had less histologic inflammation, and cecal tissue expressed lower levels of proinflammatory cytokine messenger RNAs than vehicle-treated PG-PS-injected rats (IL-1β: 5.59 ± 1.53 versus 10.41 ± 1.78, P = 0.02; IL-6: 23.23 ± 9.33 versus 45.89 ± 11.79, P = 0.07). PG-PS-injected rats treated with anti-TNFα developed less intestinal fibrosis than vehicle-treated PG-PS-injected rats by tissue procollagen I (2.87 ± 0.66 versus 9.28 ± 1.11; P = 0.00002), procollagen III (2.25 ± 0.35 versus 7.28 ± 0.76; P = 0.0000009), and MT-MRI (MT ratio: 17.79 ± 1.61 versus 27.95 ± 1.75; P = 0.0001). Insulin-like growth factor I (2.52 ± 0.44 versus 5.14 ± 0.60; P = 0.0007) and transforming growth factor β1 (2.34 ± 0.29 versus 3.45 ± 0.29; P = 0.006) were also decreased in anti-TNFα-treated PG-PS-injected rats. Anti-TNFα prevents the development of bowel wall inflammation and fibrosis in the PG-PS rat model of CD. MT-MRI measurably demonstrates this decrease in intestinal

  14. Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Gondi, Vinai [Department of Human Oncology, University of Wisconsin, Madison, WI (United States); Hermann, Bruce P. [Department of Neurology, University of Wisconsin, Madison, WI (United States); Mehta, Minesh P. [Department of Radiation Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL (United States); Tome, Wolfgang A., E-mail: tome@humonc.wisc.edu [Department of Human Oncology, University of Wisconsin, Madison, WI (United States); Department of Medical Physics, University of Wisconsin, Madison, WI (United States); Department of Biomedical Engineering, University of Wisconsin, Madison, WI (United States)

    2013-02-01

    Purpose: To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult brain tumors treated with fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Adult patients with benign or low-grade adult brain tumors were treated with FSRT per institutional practice. No attempt was made to spare the hippocampus. NCF testing was conducted at baseline and 18 months follow-up, on a prospective clinical trial. Regression-based standardized z scores were calculated by using similar healthy control individuals evaluated at the same test-retest interval. NCF impairment was defined as a z score {<=}-1.5. After delineation of the bilateral hippocampi according to the Radiation Therapy Oncology Group contouring atlas, dose-volume histograms were generated for the left and right hippocampi and for the composite pair. Biologically equivalent doses in 2-Gy fractions (EQD{sub 2}) assuming an {alpha}/{beta} ratio of 2 Gy were computed. Fisher's exact test and binary logistic regression were used for univariate and multivariate analyses, respectively. Dose-response data were fit to a nonlinear model. Results: Of 29 patients enrolled in this trial, 18 completed both baseline and 18-month NCF testing. An EQD{sub 2} to 40% of the bilateral hippocampi >7.3 Gy was associated with impairment in Wechsler Memory Scale-III Word List (WMS-WL) delayed recall (odds ratio [OR] 19.3; p = 0.043). The association between WMS-WL delayed recall and EQD{sub 2} to 100% of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068). Conclusion: EQD{sub 2} to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy techniques can reduce the dose to the bilateral hippocampi below this dosimetric threshold

  15. Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Gondi, Vinai [Department of Human Oncology, University of Wisconsin, Madison, WI (United States); Hermann, Bruce P. [Department of Neurology, University of Wisconsin, Madison, WI (United States); Mehta, Minesh P. [Department of Radiation Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL (United States); Tome, Wolfgang A., E-mail: tome@humonc.wisc.edu [Department of Human Oncology, University of Wisconsin, Madison, WI (United States); Department of Medical Physics, University of Wisconsin, Madison, WI (United States); Department of Biomedical Engineering, University of Wisconsin, Madison, WI (United States)

    2012-07-15

    Purpose: To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult brain tumors treated with fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Adult patients with benign or low-grade adult brain tumors were treated with FSRT per institutional practice. No attempt was made to spare the hippocampus. NCF testing was conducted at baseline and 18 months follow-up, on a prospective clinical trial. Regression-based standardized z scores were calculated by using similar healthy control individuals evaluated at the same test-retest interval. NCF impairment was defined as a z score {<=}-1.5. After delineation of the bilateral hippocampi according to the Radiation Therapy Oncology Group contouring atlas, dose-volume histograms were generated for the left and right hippocampi and for the composite pair. Biologically equivalent doses in 2-Gy fractions (EQD{sub 2}) assuming an {alpha}/{beta} ratio of 2 Gy were computed. Fisher's exact test and binary logistic regression were used for univariate and multivariate analyses, respectively. Dose-response data were fit to a nonlinear model. Results: Of 29 patients enrolled in this trial, 18 completed both baseline and 18-month NCF testing. An EQD{sub 2} to 40% of the bilateral hippocampi >7.3 Gy was associated with impairment in Wechsler Memory Scale-III Word List (WMS-WL) delayed recall (odds ratio [OR] 19.3; p = 0.043). The association between WMS-WL delayed recall and EQD{sub 2} to 100% of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068). Conclusion: EQD{sub 2} to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy techniques can reduce the dose to the bilateral hippocampi below this dosimetric threshold

  16. The CIN4 chromosomal instability qPCR classifier defines tumor aneuploidy and stratifies outcome in grade 2 breast cancer

    DEFF Research Database (Denmark)

    Szász, Attila Marcell; Li, Qiyuan; Eklund, Aron Charles

    2013-01-01

    and aneuploidy. The CIN4 score stratified grade 2 carcinomas into good and poor prognostic cohorts (mean RFS: 83.864.9 and 69.468.2 months, respectively, p = 0.016) and its predictive power was confirmed by multivariate analysis outperforming MI and Ki67 expression. Conclusions: The first clinically applicable q......Purpose: Quantifying chromosomal instability (CIN) has both prognostic and predictive clinical utility in breast cancer. In order to establish a robust and clinically applicable gene expression-based measure of CIN, we assessed the ability of four qPCR quantified genes selected from the 70-gene...... investigated whether the categorical CIN4 score derived from the CIN4 signature was correlated with recurrence-free survival (RFS) and ploidy status in this cohort. Results: We observed a significant association of tumor proliferation, defined by Ki67 and mitotic index (MI), with both CIN4 expression...

  17. High-Grade Salivary-Gland Involvement, Assessed by Histology or Ultrasonography, Is Associated with a Poor Response to a Single Rituximab Course in Primary Sjögren’s Syndrome: Data from the TEARS Randomized Trial

    Science.gov (United States)

    Cornec, Divi; Jousse-Joulin, Sandrine; Costa, Sebastian; Marhadour, Thierry; Marcorelles, Pascale; Berthelot, Jean-Marie; Hachulla, Eric; Hatron, Pierre-Yves; Goeb, Vincent; Vittecoq, Olivier; Nowak, Emmanuel; Pers, Jacques-Olivier; Devauchelle-Pensec, Valérie; Saraux, Alain

    2016-01-01

    Purpose To determine whether the severity of salivary-gland involvement, assessed using salivary gland ultrasonography [SGUS], histological focus score, or the unstimulated whole salivary flow [UWSF], was associated with the response to rituximab in patients with primary Sjögren’s syndrome [pSS]. Materials and Methods Among the 120 patients with pSS enrolled in the randomised TEARS trial of rituximab versus placebo, 35 underwent either centralised minor salivary-gland biopsy or SGUS at inclusion. The echostructure of each parotid and submandibular gland was graded on a scale of 0 to 4. Histologic minor salivary gland involvement was assessed by the focus score. Among rituximab-treated patients with available data (n = 14), half met the Sjögren’s Syndrome Responder Index [SSRI]-30 definition of a response at week 24. Results The SGUS score correlated positively to the focus score [r = 0.61] and negatively to the UWSF [r = -0.68]. The focus score was not correlated to the UWSF. The median total SGUS grade at inclusion was 9 [6-11] in responders versus 16 [11-16] in non-responders [p = 0.04]. The proportion of SSRI-30 responders was 0% among patients with SGUS grade 4 and 88% among those with SGUS grade ≤3. Low baseline SGUS scores were associated with sicca-related outcomes improvement, but not with fatigue or biological improvement. Median baseline focus score was 0.3 [0.0–1.3] in the responders versus 4.0 [2.7–5.3] in the non-responders [p = 0.02]. Baseline UWSF was not associated with the response rate. Conclusion In patients with pSS, the highest SGUS grade or a high histological focus score is associated with absence of a response to a single rituximab course after 6 months. Further studies, including more patients and different treatment strategies, are required to confirm the clinical utility of these potential biomarkers in pSS. PMID:27662653

  18. High-Grade Salivary-Gland Involvement, Assessed by Histology or Ultrasonography, Is Associated with a Poor Response to a Single Rituximab Course in Primary Sjögren's Syndrome: Data from the TEARS Randomized Trial.

    Directory of Open Access Journals (Sweden)

    Divi Cornec

    Full Text Available To determine whether the severity of salivary-gland involvement, assessed using salivary gland ultrasonography [SGUS], histological focus score, or the unstimulated whole salivary flow [UWSF], was associated with the response to rituximab in patients with primary Sjögren's syndrome [pSS].Among the 120 patients with pSS enrolled in the randomised TEARS trial of rituximab versus placebo, 35 underwent either centralised minor salivary-gland biopsy or SGUS at inclusion. The echostructure of each parotid and submandibular gland was graded on a scale of 0 to 4. Histologic minor salivary gland involvement was assessed by the focus score. Among rituximab-treated patients with available data (n = 14, half met the Sjögren's Syndrome Responder Index [SSRI]-30 definition of a response at week 24.The SGUS score correlated positively to the focus score [r = 0.61] and negatively to the UWSF [r = -0.68]. The focus score was not correlated to the UWSF. The median total SGUS grade at inclusion was 9 [6-11] in responders versus 16 [11-16] in non-responders [p = 0.04]. The proportion of SSRI-30 responders was 0% among patients with SGUS grade 4 and 88% among those with SGUS grade ≤3. Low baseline SGUS scores were associated with sicca-related outcomes improvement, but not with fatigue or biological improvement. Median baseline focus score was 0.3 [0.0-1.3] in the responders versus 4.0 [2.7-5.3] in the non-responders [p = 0.02]. Baseline UWSF was not associated with the response rate.In patients with pSS, the highest SGUS grade or a high histological focus score is associated with absence of a response to a single rituximab course after 6 months. Further studies, including more patients and different treatment strategies, are required to confirm the clinical utility of these potential biomarkers in pSS.

  19. Low-grade fibromyxoid sarcoma, a deceptively benign tumor in a 5-year-old child.

    Science.gov (United States)

    Menon, Seema; Krivanek, Michael; Cohen, Ralph

    2012-02-01

    Low-grade fibromyxoid sarcoma (LGFMS) is very uncommon in the pediatric population with only 20% of reported cases under the age of 18. The youngest reported case to date has been in a 4-year-old child. Lesions are usually slow growing and asymptomatic, and locations described in children have included paravertebral, thigh and intrathoracic. Although benign in appearance, these lesions can behave aggressively, with local recurrence and distant metastases primarily to lungs. These lesions can be resistant to the usual chemotherapy and radiotherapy with surgical resection being the treatment of choice. We report a case of a 5-year-old boy who presented with a mass in the left buttock.

  20. Histologic Evaluation of Metastases in Renal Cell Carcinoma With Sarcomatoid Transformation and Its Implications for Systemic Therapy

    Science.gov (United States)

    Shuch, Brian; Said, Jonathan; LaRochelle, Jeffrey C.; Zhou, Ying; Li, Gang; Klatte, Tobias; Pouliot, Frederic; Kabbinavar, Fairooz F.; Belldegrun, Arie S.; Pantuck, Allan J.

    2011-01-01

    BACKGROUND Sarcomatoid features in renal cell carcinoma may represent an aggressive subclone arising from the primary tumor. The patterns of metastases for these tumors were evaluated to determine if sarcomatoid features were retained at metastasis and whether the percentage of sarcomatoid features in the primary tumor influenced spread. METHODS All patients with sarcomatoid features found at nephrectomy with synchronous or metachronous resection of metastases were evaluated. The histology, grade, and percentage of sarcomatoid features in the primary and metastatic site were recorded. The association between percentage of sarcomatoid features, grade, histology, and pattern of metastases was evaluated. RESULTS Thirty-two patients were identified with sarcomatoid features and resected metastases. Fifty-two metastatic sites were evaluated. A single histologic appearance (sarcomatoid or carcinomatoid) was present in 50 of 52 sites (96%). Thirty sites (58%) demonstrated only a sarcomatoid pattern, whereas 20 (38%) contained only a carcinoma pattern. Histology and carcinoma grade did not influence metastatic pattern; however, greater percentage of sarcomatoid features was associated with the presence of distant sarcomatoid histology. A cutoff of 30% sarcomatoid features in the primary tumor was useful in predicting systemic sarcomatoid histology. CONCLUSIONS Sarcomatoid elements are frequently observed in the metastases of primary tumors with sarcomatoid features, and these metastases generally contain a solitary pattern supporting the subclone hypothesis. However, both components can metastasize in the same patient. The percentage of sarcomatoid features influences the pattern of spread, and patients with >30% sarcomatoid features in the primary tumor frequently have distant sarcomatoid histology. This cutpoint may be helpful for inclusion criteria for future clinical trials. PMID:19998348

  1. Histology-specific long-term trends in the incidence of ovarian cancer and borderline tumor in Japanese females: a population-based study from 1983 to 2007 in Niigata.

    Science.gov (United States)

    Yahata, Tetsuro; Banzai, Chiaki; Tanaka, Kenichi

    2012-04-01

    The histology-specific long-term trends in the incidence of ovarian cancer and borderline tumors in Japanese women were examined, based on data from the population-based cancer registry in Niigata, Japan. Data were obtained from the Niigata Gynecological Cancer Registry, which covered the entire female population in Niigata prefecture, Japan, during the period from 1983 to 2007. A total of 3134 females with epithelial ovarian cancer, including borderline tumor cases, were diagnosed between 1983 and 2007. The age-standardized rates (ASRs) of both ovarian cancer and borderline tumors have steadily increased, with significant changes in ovarian cancer in all age groups, and borderline ovarian tumors in subjects aged ovarian cancer and borderline tumors in Japanese females. The incidence of ovarian cancer has steadily increased, with significant increases in the incidence of clear cell and mucinous adenocarcinomas in the total population during the past two decades. Because of the poor response rate of these histological subtypes to platinum-based regimens, novel treatment approaches should be adopted to improve the prognostic outcome in patients with ovarian cancer in Japan. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

  2. In vivo tumor grading of prostate cancer using quantitative 111In-capromab pendetide SPECT/CT.

    Science.gov (United States)

    Seo, Youngho; Aparici, Carina Mari; Cooperberg, Matthew R; Konety, Badrinath R; Hawkins, Randall A

    2010-01-01

    We have developed an in vivo method to quantify antibody uptake using (111)In-capromab pendetide SPECT combined with CT (SPECT/CT). Our goal was to evaluate this method for potential grading of prostate tumors. Our phantom experiments focused on the robustness of an advanced iterative reconstruction algorithm that involves corrections for photon attenuation, scatter, and geometric blurring caused by radionuclide collimators. The conversion factors between image values and tracer concentrations (in Bq/mL) were calculated from a uniform phantom filled with an aqueous solution of (111)InCl(3) using the same acquisition protocol and reconstruction parameters as for patient studies. In addition, the spatial resolution of the reconstructed images was measured from a point source phantom. The measured spatial resolution was modeled into a point-spread function, and the point-spread function was implemented in a deconvolution-based partial-volume-error correction algorithm. The recovery capability to correctly estimate true tracer concentrations was tested using prostatelike and bladderlike lesion phantoms fitted in the modified National Electrical Manufacturers Association/International Electrotechnical Commission body phantom. Patients with biopsy-proven prostate cancer (n = 10) who underwent prostatectomy were prospectively enrolled in the preoperative SPECT/CT studies at the San Francisco Veterans Affairs Medical Center. The CT portion of SPECT/CT was used to generate CT-based attenuation maps and as an anatomic localization tool for clinical interpretation. Pathologic Gleason grades were compared with in vivo antibody uptake value (AUV) normalized by injected dose, effective half-life, and injection-scan time difference. AUVs were calculated in each lobe of the prostate gland with cylindric volumes of interest having dimensions of 1.5 cm in both diameter and height. Reconstructed SPECT images further corrected by the deconvolution-based partial-volume-error correction

  3. Histological reclassification, histochemical characterization and c-kit immunoexpression in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    P R Rekha

    2008-01-01

    Full Text Available Objectives: Renal cell carcinoma is the most lethal of all urologic malignancies. Several parameters such as histological subtype, nuclear grade and TNM staging help in determining the prognosis and treatment options. A newer therapeutic modality has been suggested based on expression of c-kit antigen by the tumor cells. This study was designed to evaluate various histological parameters and correlate them with c-kit expression. Materials and Methods: The study was done on 40 consecutive cases of renal epithelial tumors. Histological sections were reviewed and reclassified according to WHO (2004 classification and nuclear grade assessed. Hale′s colloidal iron stain was done to identify the chromophobe variant. Immunostaining with c-kit was done and its expression was studied. The results were correlated and statistical significance was assessed. Results: The age range was 31-81 years, with a male to female ratio of 2:1. Seventy per cent of the cases were clear cell RCC (ClRCC, 17.5% were chromophobe type, 7.5% were papillary RCCs and 5% cases were oncocytomas. Fuhrman nuclear grading revealed 60.5% cases to be of low grade and 39.5% high grade. Hale′s colloidal iron staining was positive in chromophobe RCC and oncocytomas, while it was negative in ClRCC. Immunostaining with c-kit was positive only in oncocytomas. Conclusions: Clear cell RCC was the most common histological subtype of RCC. Clear cell RCC known to have a poor prognosis, showed a statistically significant higher nuclear grade than chromophobe and papillary RCCs which have a better prognosis. Hale′s colloidal iron staining was extremely useful in distinguishing chromophobe RCC and oncocytoma from the granular cell variant of clear RCC. Our study revealed c-kit negativity in all RCC. As Imatinib could be ineffective in such tumors, its clinical activity has to be carefully assessed in such tumors through further studies.

  4. Prognostic value of WHO grade in pancreatic neuro-endocrine tumors in Multiple Endocrine Neoplasia type 1 : Results from the DutchMEN1 Study Group

    NARCIS (Netherlands)

    Conemans, Elfi B.; Brosens, Lodewijk A. A.; Raicu-Ionita, Gabriela M.; Pieterman, Carolina R. C.; de Herder, Wouter W.; Dekkers, Olaf M.; Hermus, Ad R.; van der Horst-Schrivers, Anouk N.; Bisschop, Peter H.; Havekes, Bas; Drent, Madeleine L.; Timmers, H. Th Marc; Offerhaus, G. Johan; Valk, Gerlof D.; Vriens, Menno R.

    2017-01-01

    Background: The prognostic value of WHO grade in pancreatic neuroendocrine tumors (PanNETs) in patients with Multiple Endocrine Neoplasia Type 1 (MEN1) is unknown. Methods: We performed a cohort study using the Dutch National MEN1 database, which includes >90% of the Dutch MEN1 population with data

  5. Treatment Regimen, Surgical Outcome, and T-cell Differentiation Influence Prognostic Benefit of Tumor-Infiltrating Lymphocytes in High-Grade Serous Ovarian Cancer

    NARCIS (Netherlands)

    Wouters, Maartje C. A.; Komdeur, Fenne L.; Workel, Hagma H.; Klip, Harry G.; Plat, Annechien; Kooi, Neeltje M.; Wisman, G. Bea A.; Mourits, Marian J. E.; Arts, Henriette J. G.; Oonk, Maaike H. M.; Yigit, Refika; de Jong, Steven; Melief, Cornelis J. M.; Hollema, Harry; Duiker, Evelien W.; Daemen, Toos; de Bruyn, Marco; Nijman, Hans W.

    2016-01-01

    Purpose: Tumor-infiltrating lymphocytes (TIL) are associated with a better prognosis in high-grade serous ovarian cancer (HGSC). However, it is largely unknown how this prognostic benefit of TIL relates to current standard treatment of surgical resection and (neo-)adjuvant chemotherapy. To address

  6. Finding of IDH1 R132H mutation in histologically non-neoplastic glial tissue changes surgical strategies, a case report

    DEFF Research Database (Denmark)

    Søndergaard, Christian Baastrup; Scheie, David; Sehested, Astrid Marie

    2017-01-01

    INTRODUCTION: In 2016, the WHO classification of diffuse astrocytoma began to include isocitrate dehydrogenase (IDH) mutation in addition to histology. RESULTS: We here demonstrate a case where a 14-year-old boy presented with a parietal tumor with no histological evidence of neoplasia but with a......INTRODUCTION: In 2016, the WHO classification of diffuse astrocytoma began to include isocitrate dehydrogenase (IDH) mutation in addition to histology. RESULTS: We here demonstrate a case where a 14-year-old boy presented with a parietal tumor with no histological evidence of neoplasia...... but with an IDH1 mutation. Due to the IDH1 R132H mutation, the patient was diagnosed with diffuse astrocytoma WHO grade II and underwent successful gross total resection of this near-eloquently located tumor. CONCLUSION: This case exemplifies how inclusion of immunohistochemistry in tumor classification alters...

  7. Cervical cytology of atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H): characteristics and histologic outcomes.

    Science.gov (United States)

    Sherman, Mark E; Castle, Philip E; Solomon, Diane

    2006-10-25

    The 2001 Bethesda System category of atypical squamous cells (ASC) denotes changes suggestive, but inconclusive for, a squamous intraepithelial lesion (SIL). ASC is subcategorized as: 1) "undetermined significance (ASC-US)," when changes suggest low-grade or indeterminate-grade SIL and 2) "cannot exclude high-grade squamous intraepithelial lesion (ASC-H)," when a cancer precursor is suspected. To better define the characteristics of ASC-H, the authors analyzed and compared human papillomavirus (HPV) testing data and outcomes after 2 years for participants in the Atypical Squamous Cells of Undetermined Significance Low-Grade SIL Triage Study (ALTS), a randomized trial of 5060 women. Among women with thin-layer cytology findings of ASC-H, 84% tested positive for HPV, 50% (95% confidence interval [95% CI], 41%-60%) were diagnosed with cervical intraepithelial neoplasia (CIN) type 2+, and 30% (95% CI, 22-39%) were diagnosed with CIN3+. Positive HPV tests and diagnoses of CIN2+ and CIN3+ were found to be more common among women with ASCH compared with those with ASC-US, but the highest frequencies were found to be associated with high-grade SIL. For women age /=35 years tested positive for HPV (P = 0.009). A finding of ASC-H seems to confer a substantially higher risk for CIN2+ and CIN3+ than ASC-US. Immediate colposcopy may be the appropriate management for young women with ASC-H, but the utility of HPV testing for managing older women with ASC-H requires additional study. (c) 2006 American Cancer Society.

  8. The Potential Value of EGFR and P53 Immunostaining in Tumors of ...

    African Journals Online (AJOL)

    The expression of EGFR and p53 has not been adequately studied as a prognostic tool in urinary bladder tumors. We analyzed 74 bladder cancer samples from Egypt for EGFR and p53 expression using immunohistochemistry. The tumors were of different histological types, grades and clinical stages, and with established ...

  9. Tissue thioredoxin reductase-1 expression in astrocytomas of different grades.

    Science.gov (United States)

    Esen, Hasan; Erdi, Fatih; Kaya, Bulent; Feyzioglu, Bahadır; Keskin, Fatih; Demir, Lutfi Saltuk

    2015-02-01

    Thioredoxin (Trx) is a redox active protein that regulates several physiological and biochemical functions, such as growth, apoptosis and cellular defense. The function of Trx itself is regulated by thioredoxin reductase (TrxR). Studies performed in a variety of human primary tumors have shown that thioredoxin reductase 1 (TrxR1) is overexpressed in tumoral tissues compared with corresponding normal tissues. This study was designed to determine the expression of TrxR1 in astrocytoma tissues of different World Health Organization (WHO) grades (grade I-IV). The proliferative (Ki-67) and apoptotic indices of the specimens were also investigated for correlation analysis. Astrocytoma tissues were extracted from the histopathological specimens of 40 patients. These samples included seven histologically normal brain tissues that served as a control group and ten tumoral samples for each grade of astrocytoma (grade I-IV). The histologically normal brain tissues were obtained from the non-tumoral portions of the pathological specimens of grade I (2 cases), grade II (2 cases), grade III (2 cases) and grade IV (1 case) astrocytomas. TrxR1 expression was evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunostaining. The proliferative and apoptotic indices of the specimens were investigated by Ki-67 immunostaining and TUNEL assay, respectively. TrxR1 expression, as assessed by qRT-PCR, increased significantly with astrocytoma grade (p = 0.01). The immunostaining intensity of TrxR1 in grade IV astrocytomas was significantly greater than that in the control tissue and all other astrocytoma grades (p grade III astrocytomas was significantly greater than that in the control group and grade I astrocytomas (p grades, but the differences between grade I and the control, grade II and the control, grades II and I, grades III and II were not statistically significant (p > 0.05). Ki-67 index values increased significant in accordance with grade

  10. High-grade ureteroscopic biopsy is associated with advanced pathology of upper-tract urothelial carcinoma tumors at definitive surgical resection.

    Science.gov (United States)

    Clements, Thomas; Messer, Jamie C; Terrell, John D; Herman, Michael P; Ng, Casey K; Scherr, Douglas S; Scoll, Benjamin; Boorjian, Stephen A; Uzzo, Robert G; Wille, Mark; Eggener, Scott E; Lucas, Steven M; Lotan, Yair; Shariat, Shahrokh F; Raman, Jay D

    2012-04-01

    Accurate assessment of upper-tract urothelial carcinoma (UTUC) pathology may guide use of endoscopic vs extirpative therapy. We present a multi-institutional cohort of patients with UTUC who underwent surgical resection to characterize the association of ureteroscopic (URS) biopsy features with final pathology results. URS biopsy data were available in 238 patients who underwent surgical resection of UTUC. Biopsies were performed using a brush biopsy kit, mechanical biopsy device, or basket. Stage was classified as a positive brush, nonmuscle-invasive (biopsy, 88/238 (37%) patients had a positive brush, 140 (59%) had a diagnosis of non-MI, and 10 (4%) had MI disease. Biopsy results showed low-grade cancer in 140 (59%) and high-grade cancer in 98 (41%). Pathologic evaluation at surgical resection demonstrated non-MI tumors in 140 (59%) patients, MI in 98 (41%), and high-grade disease in 150 (63%). On univariate analysis, high URS biopsy grade was associated with high-grade (positive predictive value [PPV] 92%, Pbiopsy stage, however, was associated with surgical pathology grade (P=0.005), but not MI (P=0.16) disease. On multivariate analysis, high URS grade, but not biopsy stage, was associated with high final pathology grade (hazard ratio [HR] 16.6, 95% confidence interval [CI] 7.0-39.5, Pbiopsy grade, but not stage, is associated with adverse tumor pathology. This information may play a valuable role for risk stratification and in the appropriate selection of endoscopic management vs surgical extirpation for UTUC.

  11. Preoperative Diagnosis of Gastric Tumors by Three-dimensional Multidetector Row CT and Double Contrast Barium Meal Study: Correlation with Surgical and Histologic Results

    Directory of Open Access Journals (Sweden)

    Bang-Bin Chen

    2007-11-01

    Conclusion: MDCT has a similar high accuracy in the preoperative diagnosis of different gastric tumors compared with DCBM and provides additional information including tumor depth, lymph node and hepatic metastasis. Therefore, MDCT may be used as a primary tool for preoperative tumor diagnosis and staging.

  12. Intracranial solitary fibrous tumors/hemangiopericytomas: first report of malignant progression.

    Science.gov (United States)

    Apra, Caroline; Mokhtari, Karima; Cornu, Philippe; Peyre, Matthieu; Kalamarides, Michel

    2017-06-23

    OBJECTIVE Meningeal solitary fibrous tumors/hemangiopericytomas (MSFTs/HPCs) are rare intracranial tumors resembling meningiomas. Their classification was redefined in 2016 by the World Health Organization (WHO) as benign Grade I fibrohyaline type, intermediate Grade II hypercellular type, and malignant highly mitotic Grade III. This grouping is based on common histological features and identification of a common NAB2-STAT6 fusion. METHODS The authors retrospectively identified 49 cases of MSFT/HPC. Clinical data were obtained from the medical records, and all cases were analyzed according to this new 2016 WHO grading classification in order to identify malignant transformations. RESULTS Recurrent surgery was performed in 18 (37%) of 49 patients. Malignant progression was identified in 5 (28%) of these 18 cases, with 3 Grade I and 2 Grade II tumors progressing to Grade III, 3-13 years after the initial surgery. Of 31 Grade III tumors treated in this case series, 16% (5/31) were proved to be malignant progressions from lower-grade tumors. CONCLUSIONS Low-grade MSFTs/HPCs can transform into higher grades as shown in this first report of such progression. This is a decisive argument in favor of a common identity for MSFT and meningeal HPC. High-grade MSFTs/HPCs tend to recur more often and be associated with reduced overall survival. Malignant progression could be one mechanism explaining some recurrences or metastases, and justifying long-term follow-up, even for patients with Grade I tumors.

  13. Characterization of fusion genes in common and rare epithelial ovarian cancer histologic subtypes.

    Science.gov (United States)

    Earp, Madalene A; Raghavan, Rama; Li, Qian; Dai, Junqiang; Winham, Stacey J; Cunningham, Julie M; Natanzon, Yanina; Kalli, Kimberly R; Hou, Xiaonan; Weroha, S John; Haluska, Paul; Lawrenson, Kate; Gayther, Simon A; Wang, Chen; Goode, Ellen L; Fridley, Brooke L

    2017-07-18

    Gene fusions play a critical role in some cancers and can serve as important clinical targets. In epithelial ovarian cancer (EOC), the contribution of fusions, especially by histological type, is unclear. We therefore screened for recurrent fusions in a histologically diverse panel of 220 EOCs using RNA sequencing. The Pipeline for RNA-Sequencing Data Analysis (PRADA) was used to identify fusions and allow for comparison with The Cancer Genome Atlas (TCGA) tumors. Associations between fusions and clinical prognosis were evaluated using Cox proportional hazards regression models. Nine recurrent fusions, defined as occurring in two or more tumors, were observed. CRHR1-KANSL1 was the most frequently identified fusion, identified in 6 tumors (2.7% of all tumors). This fusion was not associated with survival; other recurrent fusions were too rare to warrant survival analyses. One recurrent in-frame fusion, UBAP1-TGM7, was unique to clear cell (CC) EOC tumors (in 10%, or 2 of 20 CC tumors). We found some evidence that CC tumors harbor more fusions on average than any other EOC histological type, including high-grade serous (HGS) tumors. CC tumors harbored a mean of 7.4 fusions (standard deviation [sd] = 7.4, N = 20), compared to HGS EOC tumors mean of 2.0 fusions (sd = 3.3, N = 141). Few fusion genes were detected in endometrioid tumors (mean = 0.24, sd = 0.74, N = 55) or mucinous tumors (mean = 0.25, sd = 0.5, N = 4) tumors. To conclude, we identify one fusion at 10% frequency in the CC EOC subtype, but find little evidence for common (> 5% frequency) recurrent fusion genes in EOC overall, or in HGS subtype-specific EOC tumors.

  14. Does Type of Tumor Histology Impact Survival among Patients with Stage IIIB/IV Non-Small Cell Lung Cancer Treated with First-Line Doublet Chemotherapy?

    Science.gov (United States)

    Clements, Karen M.; Peltz, Gerson; Faries, Douglas E.; Lang, Kathleen; Nyambose, Joshua; Earle, Craig C.; Sugarman, Katherine P.; Taylor, Douglas C. A.; Thompson, David; Marciniak, Martin D.

    2010-01-01

    Chemotherapy regimens may have differential efficacy by histology in nonsmall cell lung cancer (NSCLC). We examined the impact of histology on survival of patients (N = 2,644) with stage IIIB/IV NSCLC who received first-line cisplatin/carboplatin plus gemcitabine (C/C+G) and cisplatin/carboplatin plus a taxane (C/C+T) identified retrospectively in the SEER cancer registry (1997–2002). Patients with squamous and nonsquamous cell carcinoma survived 8.5 months and 8.1 months, respectively (P = .018). No statistically significant difference was observed in survival between C/C+G and C/C+T in both histologies. Adjusting for clinical and demographic characteristics, the effect of treatment regimen on survival did not differ by histology (P for interaction = .257). There was no statistically significant difference in hazard of death by histology in both groups. These results contrast the predictive role of histology and improved survival outcomes observed for cisplatin-pemetrexed regimens in advanced nonsquamous NSCLC. PMID:22482053

  15. Does Type of Tumor Histology Impact Survival among Patients with Stage IIIB/IV Non-Small Cell Lung Cancer Treated with First-Line Doublet Chemotherapy?

    Directory of Open Access Journals (Sweden)

    Karen M. Clements

    2010-01-01

    Full Text Available Chemotherapy regimens may have differential efficacy by histology in nonsmall cell lung cancer (NSCLC. We examined the impact of histology on survival of patients (N=2,644 with stage IIIB/IV NSCLC who received first-line cisplatin/carboplatin plus gemcitabine (C/C+G and cisplatin/carboplatin plus a taxane (C/C+T identified retrospectively in the SEER cancer registry (1997–2002. Patients with squamous and nonsquamous cell carcinoma survived 8.5 months and 8.1 months, respectively (P=.018. No statistically significant difference was observed in survival between C/C+G and C/C+T in both histologies. Adjusting for clinical and demographic characteristics, the effect of treatment regimen on survival did not differ by histology (P for interaction =.257. There was no statistically significant difference in hazard of death by histology in both groups. These results contrast the predictive role of histology and improved survival outcomes observed for cisplatin-pemetrexed regimens in advanced nonsquamous NSCLC.

  16. BAFF, APRIL, TWEAK, BCMA, TACI and Fn14 proteins are related to human glioma tumor grade: immunohistochemistry and public microarray data meta-analysis.

    Directory of Open Access Journals (Sweden)

    Vassiliki Pelekanou

    Full Text Available Gliomas are common and lethal tumors of the central nervous system (CNS. Genetic alterations, inflammatory and angiogenic processes have been identified throughout tumor progression; however, treatment still remains palliative for most cases. Biological research on parameters influencing cell survival, invasion and tumor heterogeneity identified several cytokines interfering in CNS inflammation, oxidative stress and malignant transformation, including TNF-superfamily (TNFSF members. In this report we performed a meta-analysis of public gene-array data on the expression of a group of TNFSF ligands (BAFF, APRIL, TWEAK and their receptors (BAFF-R, TACI, BCMA, Fn14 in gliomas. In addition, we investigated by immunohistochemistry (IHC the tumor cells' expression of these ligands and receptors in a series of 56 gliomas of different grade. We show that in IHC, BAFF and APRIL as well as their cognate receptors (BCMA, TACI and Fn14 expression correlate with tumor grade. This result was not evidenced in micro-arrays meta-analysis. Finally, we detected for the first time Fn14, BAFF, BCMA and TACI in glioma-related vascular endothelium. Our data, combined with our previous report in glioma cell lines, suggest a role for these receptors and ligands in glioma biology and advance these molecules as potential markers for the classification of these tumors to the proliferative, angiogenic or stem-like molecular subtype.

  17. Influence of the Presence of Muscularis Propria on Recurrence and the Quality of Transurethral Resection in Low-Grade, Stage pTa Bladder Tumors

    Directory of Open Access Journals (Sweden)

    Hakan Türk

    2016-03-01

    Full Text Available Objective Transurethral resection (TUR of the bladder and intravesical chemotherapy is the standard treatment option for non-muscle-invasive bladder tumors. Inadequate tumor resection results in early recurrence and staging inaccuracies, which all will change the course of the disease. High-quality TUR treatment is therefore an important factor in the treatment of non-muscle-invasive bladder tumors. In this study, we investigated the significance of detecting the presence of muscularis propria (MP in pathology specimens of low-grade, stage pTa tumors in patients who were treated with TUR due to primary bladder tumors, with regard to recurrence, time to recurrence and progression. Materials and Methods Initially, 841 patients who were treated with TUR due to primary bladder tumors were enrolled in the study. A total of 597 patients were excluded from the study because they failed to meet the study criteria. Group 1 consisted of patients with MP detected in the pathology specimens; whereas group 2 consisted of patients whose TUR specimens did not include MP. The patients were evaluated with regard to gender, tumor number, presence or absence of MP, and recurrence status. Results MP was observed in only 14 (15.2% of 92 patients with recurrence, but not in the remaining 78 (84.8% (p=0.004. Progression occurred in 4 (14.2% patients of group 1 and 28 (29% patients of group 2 (p=0.159. In univariate analysis, tumor multiplicity (p=0.003 and the absence of MP (p=0.004 were found to have effects on recurrence. In multivariate analysis, these two parameters were also found to be have effects on recurrence (p=0.004. Conclusion In this study, it was pointed out that MP presence in the pathology specimens of low-grade stage pTa tumors is an indicator of a high quality TUR and, a well-done TUR is important for the prevention of recurrence.

  18. What are the Functional Results, Complications, and Outcomes of Using a Custom Unipolar Wrist Hemiarthroplasty for Treatment of Grade III Giant Cell Tumors of the Distal Radius?

    Science.gov (United States)

    Wang, Baichuan; Wu, Qiang; Liu, Jianxiang; Chen, Songfeng; Zhang, Zhicai; Shao, Zengwu

    2016-12-01

    A giant cell tumor (GCT) of bone presenting in the distal radius is rare, however, when they occur, Campanacci Grade III tumors can present formidable reconstructive challenges. They are associated with a high local recurrence rate with intralesional treatment, therefore approaches to reconstruct the wrist after en bloc resection warrant study. We asked: (1) What are the functional outcomes after en bloc resection and reconstruction of the wrist with a unipolar prosthesis in patients with Grade III GCT of the distal radius? (2) What complications occur with use of a unipolar prosthesis in these patients? (3) What are the oncologic outcomes with using en bloc resection and reconstruction with a custom unipolar wrist hemiarthroplasty for Grade III GCTs of the distal radius? We retrospectively analyzed 10 patients with Campanacci Grade III GCTs of the distal radius treated by a unipolar prosthesis after wide resection of the tumor between January 2008 and October 2013. During that period, all patients at our medical group who presented with a Grade III GCT of the distal radius were treated with wide resection and reconstruction using a custom unipolar implant. Pre- and postoperative pain at rest were assessed according to a 10-cm VAS score. The functional outcomes of the wrist were assessed using the modified Mayo wrist score, and the degenerative changes were evaluated radiographically by a new rating system based on the Knirk and Jupiter scale. We also analyzed tumor recurrence, metastases, and complications associated with the reconstruction procedure. All patients were available for followup at a mean of 52 months (range, 24-90 months). Although the complication rate associated with prosthetic arthroplasty was relatively high (six of 10), none of our patients experienced severe complications. Two patients reported having occasional pain of the involved wrist at the time of final followup (VAS, preoperative versus postoperative: 0 versus 3; 5 versus 2, respectively

  19. Pancreatic neuroendocrine tumors containing areas of iso- or hypoattenuation in dynamic contrast-enhanced computed tomography: Spectrum of imaging findings and pathological grading.

    Science.gov (United States)

    Hyodo, Ryota; Suzuki, Kojiro; Ogawa, Hiroshi; Komada, Tomohiro; Naganawa, Shinji

    2015-11-01

    To evaluate dynamic contrast-enhanced computed tomography (CT) features of pancreatic neuroendocrine tumors (PNETs) containing areas of iso- or hypoattenuation and the relationship with pathological grading. Between June 2006 and March 2014, 61 PNETs in 58 consecutive patients (29 male, 29 female; median-age 55 years), which were surgically diagnosed, underwent preoperative dynamic contrast-enhanced CT. PNETs were classified based on contrast enhancement patterns in the pancreatic phase: iso/hypo-PNETs were defined as tumors containing areas of iso- or hypoattenuation except for cystic components, and hyper-PNETs were tumors showing hyperattenuation over the whole area. CT findings and contrast-enhancement patterns of the tumors were evaluated retrospectively by two radiologists and compared with the pathological grading. Iso/hypo-PNETs comprised 26 tumors, and hyper-PNETs comprised 35 tumors. Not only hyper-PNETs but also most iso/hypo-PNETs showed peak enhancement in the pancreatic phase and a washout from the portal venous phase to the delayed phase. Iso/hypo-PNETs showed larger tumor size than the hyper-PNETs (mean, 3.7 cm vs. 1.6 cm; PIso/hypo-PNETs also showed significantly higher pathological grading (WHO 2010 classification; iso/hypo, G1=14, G2=11, G3=1; hyper, G1=34, G2=1; Piso/hypo-areas showed a rapid enhancement pattern as well as hyper-PNETs, various radiological features and higher malignant potential. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. KRAS mutation testing in borderline ovarian tumors and low-grade ovarian carcinomas with a rapid, fully integrated molecular diagnostic system.

    Science.gov (United States)

    Sadlecki, Pawel; Antosik, Paulina; Grzanka, Dariusz; Grabiec, Marek; Walentowicz-Sadlecka, Malgorzata

    2017-10-01

    Epithelial ovarian neoplasms are a heterogeneous group of tumors, including various malignancies with distinct clinicopathologic and molecular features. Mutations in BRAF and KRAS genes are the most frequent genetic aberrations found in low-grade serous ovarian carcinomas and serous and mucinous borderline tumors. Implementation of targeted therapeutic strategies requires access to highly specific and highly sensitive diagnostic tests for rapid determination of mutation status. One candidate for such test is fully integrated, real-time polymerase chain reaction-based Idylla™ system for quick and simple detection of KRAS mutations in formaldehyde fixed-paraffin embedded tumor samples. The primary aim of this study was to verify whether fully integrated real-time polymerase chain reaction-based Idylla system may be useful in determination of KRAS mutation status in patients with borderline ovarian tumors and low-grade ovarian carcinomas. The study included tissue specimens from 37 patients with histopathologically verified ovarian masses, operated on at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz (Poland) between January 2009 and June 2012. Based on histopathological examination of surgical specimens, 30 lesions were classified as low-grade ovarian carcinomas and 7 as borderline ovarian tumors. Seven patients examined with Idylla KRAS Mutation Test tested positive for KRAS mutation. No statistically significant association was found between the incidence of KRAS mutations and histopathological type of ovarian tumors. Mean survival of the study subjects was 48.51 months (range 3-60 months). Presence of KRAS mutation did not exert a significant effect on the duration of survival in our series. Our findings suggest that Idylla KRAS Mutation Test may be a useful tool for rapid detection of KRAS mutations in ovarian tumor tissue.

  1. Expression of Progestrone Receptor and Proliferative Marker ki 67, in Various Grades of Meningioma

    Directory of Open Access Journals (Sweden)

    Nasrin Shayanfar

    2010-05-01

    Full Text Available Meningiomas are slow-growing neoplasms which recur locally, their morphologic grading is simple but do not always correlate with patient outcome. The aim of present study is to evaluate the status of progesterone receptor (PR and proliferation marker Ki67 in various grades of meningioma in a group of Iranian patients. 78 cases of meningioma were selected from the file of a hospital university. All archival H&E stained sections were reviewed and regraded according to WHO criteria. Immunohistochemical analysis for PR and Ki67 was performed on formalin- fixed, paraffin- embedded samples. PR status considered positive if > 10% of tumor cell's nuclei were strongly immunoreactive, or if > 50% of nuclei were stained with medium intensity. The Ki67 labeling index (LI is defined as the percentage area with strongest immunostaining. PR were positive in 61/63(96.8% of grade I tumors,2/10(20% of grade II,and 0/5(0% of grade III tumors.Ki67 LI was %2.98±2.27 in grade I tumors, %9.30±5.79 in grade II tumors and %34.00±5.47 in grade III tumors. For both markers, differences between grade I,II and III tumors were significant(P<0.001.There was a reverse relationship between mean of Ki67 LI and PR status,with increasing grade of tumor. Evaluation of PR status and Ki67 LI together with conventional histologic evaluation can help in providing more information about the biologic behaviour of meningiomas,especially for those that histological grading is not straightforward.

  2. Tumor blood flow from arterial spin labeling perfusion MRI: a key parameter in distinguishing high-grade gliomas from primary cerebral lymphomas, and in predicting genetic biomarkers in high-grade gliomas.

    Science.gov (United States)

    Yoo, Roh-Eul; Choi, Seung Hong; Cho, Hye Rim; Kim, Tae Min; Lee, Se-Hoon; Park, Chul-Kee; Park, Sung-Hye; Kim, Il Han; Yun, Tae Jin; Kim, Ji-Hoon; Sohn, Chul-Ho; Han, Moon Hee; Chang, Kee Hyun

    2013-10-01

    To evaluate the usefulness of pseudo-continuous arterial spin labeling (pCASL) imaging in differentiating high-grade gliomas from lymphomas and in noninvasively predicting genetic biomarkers in high-grade gliomas. Twelve glioblastoma multiforme (GBM), 3 anaplastic astrocytoma (AA), 5 recurred GBM, and 9 lymphoma patients underwent conventional MR and pCASL imaging. On pCASL perfusion map, mean absolute tumor blood flow (mTBF) was calculated from five regions of interest (ROIs) within the enhancing portion of the tumor. Relative TBF (rTBF = mTBF/mBFgm × 100) was also calculated. mTBF and rTBF of high-grade gliomas and lymphomas were compared using unpaired Student's t-test and receiver operating characteristic (ROC) analysis. Additionally, the association of TBF and six immunohistochemically confirmed genetic biomarkers was analyzed by Pearson correlation analysis in the group of high-grade gliomas. Both mTBF and rTBF of the high-grade gliomas were significantly higher than those of the lymphomas: 92.1 ± 34.7 versus 53.6 ± 30.5 mL/min/100 mg (P = 0.008) and 182.3 ± 69.5 versus 92.5 ± 44.9 (P = 0.002), respectively. Only epidermal growth factor receptor (EGFR) expression status showed a significant positive correlation with mTBF(P = 0.015) and rTBF(P = 0.007). pCASL imaging may facilitate differentiation of high-grade gliomas from lymphomas and prediction of EGFR expression status in high-grade gliomas. Copyright © 2013 Wiley Periodicals, Inc.

  3. Iodine-123-MIBG scintigraphy in neuroblastoma. Relationship between the intensity of uptake and tumor characteristics

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    Okuyama, Chio; Ushijima, Yo; Watanabe, Kaori; Sugihara, Hiroki; Nishimura, Tsunehiko [Kyoto Prefectural Univ. of Medicine (Japan)

    1999-10-01

    Iodine-123-MlBG ({sup 123}I-MIBG) scintigraphy were performed for 23 patients with neuroblastoma at diagnosis. The intensity of MIBG activity in the primary tumor was evaluated visually (grade 3; intense uptake-grade 0; no definite uptake), and its relationship to the size, degree of tumor spread, urinary catecholamine metabolites (VMA, HVA), and histological types were investigated. The results of {sup 123}I-MIBG uptake grade were as follows: grade 3; 44% (10/23), grade 2; 30% (7/23), grade 1; 17% (4/23), grade 0; 9% (2/23). The grade was not associated with the tumor size, or the degree of tumor extension to the distant lesion, either. The more catecholamine metabolites were excreted in the urine, the tumor tended to have more intense uptake. The tumors of neuroblastoma rosette fibrillary type, and ganglioneuroblastoma poorly differentiated type had more intense uptake than neuroblastoma round cell type and ganglioneuroblastoma well differentiated type. The case of ganglioneuroma did not have definite MIBG uptake. The intensity of MIBG uptake is not relevant to the pathological grade of neuroblastoma, but considering the electromicroscopical features of neuroblastoma reported previously, it is thought to reflect the histological type. (author)

  4. Tumor

    Science.gov (United States)

    ... peanut plants (aflatoxins) Excessive sunlight exposure Genetic problems Obesity Radiation exposure Viruses Types of tumors known to be caused by or linked with viruses are: Cervical cancer (human papillomavirus) Most anal cancers (human papillomavirus) Some ...

  5. Prognostic role of histological necrosis for nonmetastatic clear cell renal cell carcinoma: correlation with pathological features and molecular markers.

    Science.gov (United States)

    Minervini, Andrea; Di Cristofano, Claudio; Gacci, Mauro; Serni, Sergio; Menicagli, Michele; Lanciotti, Michele; Salinitri, Giuseppe; Rocca, Carlo Della; Lapini, Alberto; Nesi, Gabriella; Bevilacqua, Generoso; Minervini, Riccardo; Carini, Marco

    2008-10-01

    We defined the prognostic role of tumor necrosis and its extent in nonmetastatic clear cell renal cell carcinoma. Also, we further investigated its pathogenesis by correlating this tumor feature with other pathological characteristics and molecular markers related to the von Hippel Lindau-hypoxia inducible factor pathway and to tumor proliferation. A total of 213 patients with nonmetastatic clear cell renal cell carcinoma were evaluated. Mean followup was 66 months. The presence and extent of histological necrosis were correlated with clinicopathological factors, Ki-67 antigen expression calculated by the MIB-1 (Ki-67 antibody) index, pVHL, HIF-1alpha, the tumor infiltrating lymphocyte subset and cancer specific survival. Histological necrosis was present in 63.8% of clear cell renal cell carcinoma cases. Necrosis was significantly associated with grade and the degree of tumor infiltrating lymphocytes, while its extent correlated significantly with grade, the degree of tumor infiltrating lymphocytes and stage. Tumor necrosis was a significant prognostic factor, which was confirmed even when limiting analysis to patients with intracapsular renal cell carcinoma. On multivariate analysis histological necrosis was not an independent predictor of cancer specific survival. The extent of tumor necrosis was not a significant prognostic factor. The presence and extent of histological necrosis was not associated with high Ki-67 expression and it did not correlate with pVHL expression or with nuclear and cytoplasmic HIF-1alpha expression. Based on our results we cannot support histological necrosis and its extent as prognostic factors for clear cell renal cell carcinoma. Efforts should be made to develop nomograms that use routinely available and objective predictor variables. The precise mechanism that causes tumor necrosis remains unknown but the host immune response might significantly contribute to its development.

  6. Deletion and low expression of NFKBIA are associated with poor prognosis in lower-grade glioma patients

    OpenAIRE

    Gabriela Sarti Kinker; Andrew Maltez Thomas; Vinicius Jardim Carvalho; Felipe Prata Lima; André Fujita

    2016-01-01

    Lower-grade gliomas (LGGs), which are uniformly fatal in young adults, are classified as grades II-III tumors according to their histological features. The NF?B transcription factor, a crucial player in cancer initiation and progression, is inactivated in the cytoplasm by inhibitory proteins (I?Bs) that have been shown to exert tumor-suppressor activity. Therefore, using The Cancer Genome Atlas copy number alteration and RNA-Seq data from 398 patients, we evaluated the association between the...

  7. Histopathologic findings of small renal tumor biopsies performed immediately after cryoablation therapy: a retrospective study of 50 cases.

    Science.gov (United States)

    Tayal, Shalini; Kim, Fernando J; Sehrt, David; Miano, Roberto; Pompeo, Alexandre; Molina, Wilson

    2014-01-01

    To evaluate the histopathology of small renal tumor biopsies following cryoablation. We retrospectively evaluated small renal tumor biopsy specimens after cryoablation treatment for renal cell carcinoma and determined the ability to differentiate tumor types, effect on nuclear grading, immunohistochemical staining, and if the number of freeze cycles affected interpretation. Of the biopsy specimens, 66% were diagnostic of tumor and 34% showed normal renal parenchyma. Tumor subtype was determined in 91% of diagnostic cases. Nuclear grading was affected due to freeze effect, complicating the assessment of chromatin pattern and nucleolar details at low magnification. In particular, the distinction between Fuhrman nuclear grades I and II was compromised; these were designated as low nuclear grade. Immunohistochemical staining was retained similar to untreated tumors. Tumor subtyping was not affected after one or two freeze cycles. Biopsies performed immediately after cryoablation can be used to render an optimal histologic diagnosis.

  8. In vivo assessment of tumor heterogeneity in WHO 2016 glioma grades using diffusion kurtosis imaging: Diagnostic performance and improvement of feasibility in routine clinical practice.

    Science.gov (United States)

    Hempel, J-M; Schittenhelm, J; Bisdas, S; Brendle, C; Bender, B; Bier, G; Skardelly, M; Tabatabai, G; Castaneda Vega, S; Ernemann, U; Klose, U

    2017-09-01

    To assess the diagnostic performance of normalized and non-normalized diffusion kurtosis imaging (DKI) metrics extracted from different tumor volume data for grading glioma according to the integrated approach of the revised 2016 WHO classification. Sixty patients with histopathologically confirmed glioma, who provided written informed consent, were retrospectively assessed between 01/2013 and 08/2016 from a prospective trial approved by the local institutional review board. Mean kurtosis (MK) and mean diffusivity (MD) metrics from DKI were assessed by two blinded physicians from four different volumes of interest (VOI): whole solid tumor including (VOItu-ed) and excluding perifocal edema (VOItu), infiltrative zone (VOIed), and single slice of solid tumor core (VOIslice). Intra-class correlation coefficient (ICC) was calculated to assess inter-rater agreement. One-way ANOVA was used to compare MK between 2016 CNS WHO tumor grades. Friedman's test compared MK and MD of each VOI. Spearman's correlation coefficient was used to correlate MK with 2016 CNS WHO tumor grades. ROC analysis was performed on MK for significant results. The MK assessment showed excellent inter-rater agreement for each VOI (ICC, 0.906-0.955). MK was significantly lower in IDHmutant astrocytoma (0.40±0.07), than in 1p/19q-confirmed oligodendroglioma (0.54±0.10, P=0.001) or IDHwild-type glioblastoma (0.68±0.13, Pgrades were strongly and positively correlated (VOItu-ed, r=0.684; VOItu, r=0.734; VOIed, r=0.625; VOIslice, r=0.698; P<0.001). Non-normalized MK values obtained from VOItu and VOIslice showed the best reproducibility and highest diagnostic performance for stratifying glioma according to the integrated approach of the recent 2016 WHO classification. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Percutaneous computed tomography-guided core needle biopsy of soft tissue tumors: results and correlation with surgical specimen analysis

    Energy Technology Data Exchange (ETDEWEB)

    Chojniak, Rubens; Grigio, Henrique Ramos; Bitencourt, Almir Galvao Vieira; Pinto, Paula Nicole Vieira; Tyng, Chiang J.; Cunha, Isabela Werneck da; Aguiar Junior, Samuel; Lopes, Ademar, E-mail: chojniak@uol.com.br [Hospital A.C. Camargo, Sao Paulo, SP (Brazil)

    2012-09-15

    Objective: To evaluate the efficacy of percutaneous computed tomography (CT)-guided core needle biopsy of soft tissue tumors in obtaining appropriate samples for histological analysis, and compare its diagnosis with the results of the surgical pathology as available. Materials and Methods: The authors reviewed medical records, imaging and histological reports of 262 patients with soft-tissue tumors submitted to CT-guided core needle biopsy in an oncologic reference center between 2003 and 2009. Results: Appropriate samples were obtained in 215 (82.1%) out of the 262 patients. The most prevalent tumors were sarcomas (38.6%), metastatic carcinomas (28.8%), benign mesenchymal tumors (20.5%) and lymphomas (9.3%). Histological grading was feasible in 92.8% of sarcoma patients, with the majority of them (77.9%) being classified as high grade tumors. Out of the total sample, 116 patients (44.3%) underwent surgical excision and diagnosis confirmation. Core biopsy demonstrated 94.6% accuracy in the identification of sarcomas, with 96.4% sensitivity and 89.5% specificity. A significant intermethod agreement about histological grading was observed between core biopsy and surgical resection (p < 0.001; kappa = 0.75). Conclusion: CT-guided core needle biopsy demonstrated a high diagnostic accuracy in the evaluation of soft tissue tumors as well as in the histological grading of sarcomas, allowing an appropriate therapeutic planning (author)

  10. A Novel Grading System Based on Tumor Budding and Cell Nest Size Is a Strong Predictor of Patient Outcome in Esophageal Squamous Cell Carcinoma.

    Science.gov (United States)

    Jesinghaus, Moritz; Boxberg, Melanie; Konukiewitz, Björn; Slotta-Huspenina, Julia; Schlitter, Anna M; Steiger, Katja; Specht, Katja; Wieczorek, Kathrin; Warth, Arne; Schmidt, Thomas; Hartmann, Arndt; Demir, Ihsan E; Feith, Markus; Ott, Katja; Weichert, Wilko

    2017-08-01

    The determination of prognosis in patients with esophageal squamous cell carcinoma (ESCC) is primarily based on staging according to the TNM-classification, whereas conventional grading is of minor clinical importance because of its deficiencies in prognostic patient stratification. Recently, a novel, highly prognostic grading scheme based on budding activity and cell nest size has been proposed for squamous cell carcinoma (SCC) of both pulmonary as well as oral origin. In order to investigate the utility and transferability of this approach to ESCC, we evaluated budding activity and cell nest size, as well as other histomorphologic characteristics, in a cohort of 135 primarily resected tumors and correlated the results with clinicopathologic and outcome parameters. High budding activity and small cell nest size showed a strong association with reduced overall, disease-specific, and disease-free survival (Ptumor budding and cell nest size as excellent outcome predictors in ESCC and validate the utility of a previously established grading scheme proposed for oral and pulmonary SCC in this tumor entity. Ultimately, these combined efforts may result in a universal grading system for SCC regardless of the site of origin.

  11. Combined analysis of smoking, TP53, and FGFR3 mutations in Tunisian patients with invasive and superficial high-grade bladder tumors.

    Science.gov (United States)

    Ouerhani, Slah; Rouissi, Kamel; Kourda, Nadia; Marrakchi, Raja; Bougatef, Karim; Riadh Ben Slama, Mohamed; Sfaxi, Mohamed; Chebil, Mohamed; Ben Jilani, Sarra; Benammar Elgaaied, Amel

    2009-12-01

    In our cohort, FGFR3 mutations were detected in 31.1% of bladder tumors and are associated with lower stage and grade. Concerning TP53, 62 mutations were found in tumors from 44 cases (48.88%) and are associated with advanced forms. The combined analysis of FGFR3 and TP53 mutations in our cohort showed an independent distribution. In addition, we have reported that FGFR3 mutations spectrum depends on the intensity of tobacco use (pack years: PY). Finally, we have found that the FGFR3wt/TP53mut genotype, which was associated with advanced bladder tumors; was overrepresented in light smokers (PY < 40) compared to nonsmoker patients (p =.01).

  12. Adult Pilomyxoid Astrocytoma Mimicking a Cortical Brain Tumor: MR Imaging Findings

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Jong Chang; Weon, Young Cheol; Suh, Jae Hee; Kim, Young; Hwang, Jae Cheol [Ulsan University Hospital, Ulsan (Korea, Republic of)

    2010-08-15

    A pilomyxoid astrocytoma (PMA) is a recently identified low-grade neoplasm that was previously classified as a pilocytic astrocytoma (PA), yet demonstrates unique histological features and more aggressive behavior. Although a PMA is generally a tumor of early childhood and typically occurs in the hypothalamic/chiasmatic region, it can mimic cortical tumors, especially in adults. We report the MR findings of a PMA presenting as a cortical brain tumor in an adult with neurofibromatosis 1 (NF1)

  13. Production of basement membrane laminin and type IV collagen by tumors of striated muscle: an immunohistochemical study of rhabdomyosarcomas of different histologic types and a benign vaginal rhabdomyoma.

    Science.gov (United States)

    Autio-Harmainen, H; Apaja-Sarkkinen, M; Martikainen, J; Taipale, A; Rapola, J

    1986-12-01

    Immunohistochemical methods were used to demonstrate the distribution of basement membrane laminin and type IV collagen in eight tumors derived from striated muscle (three botryoid, two alveolar, and two adult-type rhabdomyosarcomas; one benign vaginal rhabdomyoma). All of the tumors produced significant amounts of both basement membrane components. Stainings clearly revealed the alveolar nature of the rhabdomyosarcomas, with the alveolar spaces surrounded by distinct basement membranes. Different stages of cellular development were identified in the botryoid sarcomas, with the most immature cells of the cambium layer devoid of external basement membrane around the tumor cells, although the stroma contained finely dispersed basement membrane material and some cells contained intracytoplasmic laminin or type IV collagen, indicative of the synthesis of these proteins. The more mature cells, which had abundant granular cytoplasm, were enveloped by distinct basement membranes and seemed to have coalesced, forming structures resembling myotubes. The adult-type rhabdomyosarcomas were composed of large pleomorphic cells that were surrounded by basement membranes, either individually or in small groups. Some giant cells contained intracytoplasmic laminin. The vaginal rhabdomyoma was composed of round rhabdoblastic cells or elongated strap cells with cross-striations. Cells of both of these types were surrounded by thin but distinct basement membranes. The results suggest that demonstration of basement membranes would be helpful in the diagnosis of tumors derived from striated muscle. The findings concerning different stages of maturation of tumor cells are in accordance with previous in vitro observations of myoblastic cells.

  14. Krüppel-like factor 8 (KLF8 is expressed in gliomas of different WHO grades and is essential for tumor cell proliferation.

    Directory of Open Access Journals (Sweden)

    Oliver Schnell

    Full Text Available Krüppel-like factor 8 (KLF8 has only recently been identified to be involved in tumor cell proliferation and invasion of several different tumor entities like renal cell carcinoma, hepatocellular carcinoma and breast cancer. In the present study, we show for the first time the expression of KLF8 in gliomas of different WHO grades and its functional impact on glioma cell proliferation. In order to get information about KLF8-mRNA regulation qPCR was performed and did not reveal any significant difference in samples (n = 10 each of non-neoplastic brain (NNB, low-grade gliomas (LGG, WHO°II and glioblastomas (GBM, WHO°IV. Immunohistochemistry of tissue samples (n = 7 LGG, 11 AA and 12 GBM did not show any significant difference in the fraction of KLF8-immunopositive cells of all analyzed cells in LGG (87%, AA (80% or GBM (89%. Tissue samples from cerebral breast cancer metastasis, meningiomas but also non-neoplastic brain demonstrated comparable relative cell counts as well. Moreover, there was no correlation between KLF8 expression and the expression pattern of the assumed proliferation marker Ki67, which showed high variability between different tumor grade (9% (LGG, 6% (AA and 15% (GBM of Ki67-immunopositive cells. Densitometric analysis of Western blotting revealed that the relative amount of KLF8-protein did also not differ between the highly aggressive and proliferative GBM (1.05 compared to LGG (0.93; p<0.05, studens t-test. As demonstrated for some other non-glial cancer entities, KLF8-knockdown by shRNA in U87-MG cells confirmed its functional relevance, leading to an almost complete loss of tumor cell proliferation. Selective blocking of KLF8 might represent a novel anti-proliferative treatment strategy for malignant gliomas. Yet, its simultaneous expression in non-proliferating tissues could hamper this approach.

  15. Associations between 18F-FDG-PET, DWI, and DCE Parameters in Patients with Head and Neck Squamous Cell Carcinoma Depend on Tumor Grading

    Directory of Open Access Journals (Sweden)

    Leonard Leifels

    2017-01-01

    Full Text Available Our purpose was to analyze associations between positron emission tomography (PET, diffusion weighted imaging (DWI, and dynamic contrast-enhanced (DCE imaging in patients with head and neck squamous cell carcinoma (HNSCC. The study involved 34 patients (9 women, 25 men, mean age: 56.7±10.2 years. In all patients a simultaneous 18F-FDG-PET/MR was performed. DWI was obtained by using of an axial EPI sequence. Minimal ADC values (ADCmin, mean ADC values (ADCmean, and maximal ADC values (ADCmax were estimated. DCE MRI was performed by using dynamic T1w DCE sequence. The following parameters were estimated: Ktrans, Ve, and Kep. Spearman’s correlation coefficient was used to analyze associations between investigated parameters. In overall sample, ADCmean correlated significantly with Ve and Ktrans, ADCmin correlated with Ve, and ADCmax correlated with Ktrans and Ve. SUVmean tended to correlate slightly with Ktrans. In G1/2 tumors, only Ktrans correlated well with ADCmax and SUVmean. In G3 tumors, Ktrans correlated well with Kep and Ve. Ve showed significant correlations with ADCmean and ADCmax. Ktrans correlated with ADCmax. Kep was higher in cancers with N2/3 stages. Tumor metabolism, water diffusion, and tumor perfusion have complex relationships in HNSCC. Furthermore, these associations depend on tumor grading. Kep may predict lymphonodal metastasizing.

  16. High-grade primary pulmonary leiomyosarcoma

    Directory of Open Access Journals (Sweden)

    Rodrigo Afonso da Silva Sardenberg

    2011-12-01

    Full Text Available Primary sarcomas of the lung are rare and account for 0.5% of all primary lung tumors. There were approximately 300 cases described in the literature as of 2006. All histologic types of sarcoma were described, and the most common intrathoracic types reported were angiosarcoma, leiomyosarcoma, fibrosarcoma, hemangiopericytoma, and rhabdomyosarcoma. The biological behavior of these tumors is not well-known due to their low frequency. Leiomyosarcomas represent one of the most common subtypes encountered in the lungs, and usually occur during the sixth decade, with male predominance. Although the frequency of metastatic disease is not related to tumor size, prognosis was reported to be poorer in high-grade tumors. In comparison with other sarcomas, survival after complete resection of pulmonary leiomyosarcoma was reported as longer. We report on a patient with primary leiomyosarcoma originating from the bronchus with complete resection and long-term follow-up.

  17. ICAM-2 expression mediates a membrane-actin link, confers a nonmetastatic phenotype and reflects favorable tumor stage or histology in neuroblastoma.

    Directory of Open Access Journals (Sweden)

    Karina Jin Yoon

    Full Text Available The actin cytoskeleton is a primary determinant of tumor cell motility and metastatic potential. Motility and metastasis are thought to be regulated, in large part, by the interaction of membrane proteins with cytoplasmic linker proteins and of these linker proteins, in turn, with actin. However, complete membrane-to-actin linkages have been difficult to identify. We used co-immunoprecipitation and competitive peptide assays to show that intercellular adhesion molecule-2 (ICAM-2/alpha-actinin/actin may comprise such a linkage in neuroblastoma cells. ICAM-2 expression limited the motility of these cells and redistributed actin fibers in vitro, and suppressed development of disseminated tumors in an in vivo model of metastatic neuroblastoma. Consistent with these observations, immunohistochemical analysis demonstrated ICAM-2 expression in primary neuroblastoma tumors exhibiting features that are associated with limited metastatic disease and more favorable clinical outcome. In neuroblastoma cell lines, ICAM-2 expression did not affect AKT activation, tumorigenic potential or chemosensitivity, as has been reported for some types of transfected cells. The observed ICAM-2-mediated suppression of metastatic phenotype is a novel function for this protein, and the interaction of ICAM-2/alpha-actinin/actin represents the first complete membrane-linker protein-actin linkage to impact tumor cell motility in vitro and metastatic potential in an in vivo model. Current work focuses on identifying specific protein domains critical to the regulation of neuroblastoma cell motility and metastasis and on determining if these domains represent exploitable therapeutic targets.

  18. Tumor Delineation and Quantitative Assessment of Glucose Metabolic Rate within Histologic Subtypes of Non-Small Cell Lung Cancer by Using Dynamic 18F Fluorodeoxyglucose PET

    NARCIS (Netherlands)

    Meijer, T.W.H.; Geus-Oei, L.F. de; Visser, E.P.; Oyen, W.J.G.; Looijen-Salamon, M.G.; Visvikis, D.; Verhagen, A.F.T.M.; Bussink, J.; Vriens, D.

    2017-01-01

    Purpose To assess whether dynamic fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) has added value over static 18F-FDG PET for tumor delineation in non-small cell lung cancer (NSCLC) radiation therapy planning by using pathology volumes as the reference standard and to

  19. Radiogenomic analysis of lower grade glioma: a pilot multi-institutional study shows an association between quantitative image features and tumor genomics

    Science.gov (United States)

    Mazurowski, Maciej A.; Clark, Kal; Czarnek, Nicholas M.; Shamsesfandabadi, Parisa; Peters, Katherine B.; Saha, Ashirbani

    2017-03-01

    Recent studies showed that genomic analysis of lower grade gliomas can be very effective for stratification of patients into groups with different prognosis and proposed specific genomic classifications. In this study, we explore the association of one of those genomic classifications with imaging parameters to determine whether imaging could serve a similar role to genomics in cancer patient treatment. Specifically, we analyzed imaging and genomics data for 110 patients from 5 institutions from The Cancer Genome Atlas and The Cancer Imaging Archive datasets. The analyzed imaging data contained preoperative FLAIR sequence for each patient. The images were analyzed using the in-house algorithms which quantify 2D and 3D aspects of the tumor shape. Genomic data consisted of a cluster of clusters classification proposed in a very recent and leading publication in the field of lower grade glioma genomics. Our statistical analysis showed that there is a strong association between the tumor cluster-of-clusters subtype and two imaging features: bounding ellipsoid volume ratio and angular standard deviation. This result shows high promise for the potential use of imaging as a surrogate measure for genomics in the decision process regarding treatment of lower grade glioma patients.

  20. Loss of Raf-1 kinase inhibitor protein (RKIP) is strongly associated with high-grade tumor budding and correlates with an aggressive phenotype in pancreatic ductal adenocarcinoma (PDAC)

    Science.gov (United States)

    2013-01-01

    Background Raf-1 kinase inhibitor protein (RKIP) has emerged as a significant metastatic suppressor in a variety of human cancers and is known to inhibit Ras/Raf/MEK/ERK signaling. By suppressing the activation of the NFkB/SNAIL circuit, RKIP can regulate the induction of epithelial-mesenchymal transition (EMT). The aim of this study was to evaluate RKIP expression and to determine its association with clinicopathological features, including EMT in form of tumor budding in pancreatic ductal adenocarcinoma (PDAC). Methods Staining for RKIP was performed on a multipunch Tissue Microarray (TMA) of 114 well-characterized PDACs with clinico-pathological, follow-up and adjuvant therapy information. RKIP-expression was assessed separately in the main tumor body and in the tumor buds. Another 3 TMAs containing normal pancreatic tissue, precursor lesions (Pancreatic Intraepithelial Neoplasia, PanINs) and matched lymph node metastases were stained in parallel. Cut-off values were calculated by receiver operating characteristic (ROC) curve analysis. Results We found a significant progressive loss of RKIP expression between normal pancreatic ductal epithelia (average: 74%), precursor lesions (PanINs; average: 37%), PDAC (average 20%) and lymph node metastases (average 8%, p tumor buds (average: 6%) compared to the main tumor body (average 20%; p tumor body was marginally associated with advanced T-stage (p = 0.0599) as well as high-grade peritumoral (p = 0.0048) and intratumoral budding (p = 0.0373). RKIP loss in the buds showed a clear association with advanced T stage (p = 0.0089). Conclusions The progressive loss of RKIP seems to play a major role in the neoplastic transformation of pancreas, correlates with aggressive features in PDAC and is associated with the presence of EMT in form of tumor budding. PMID:24330423

  1. Distinct Patterns of Stromal and Tumor Expression of ROR1 and ROR2 in Histological Subtypes of Epithelial Ovarian Cancer 1

    OpenAIRE

    Henry, CE; Emmanuel, C.; Lambie, N; C. Loo; Kan, B; Kennedy, CJ; de Fazio, A; Hacker, NF; Ford, CE

    2017-01-01

    OBJECTIVE: The ROR1 and ROR2 receptor tyrosine kinases have both been implicated in ovarian cancer progression and have been shown to drive migration and invasion. There is an increasing importance of the role of stroma in ovarian cancer metastasis; however, neither ROR1 nor ROR2 expression in tumor or stromal cells has been analyzed in the same clinical cohort. AIM: To determine ROR1 and ROR2 expression in ovarian cancer and surrounding microenvironment and examine associations with clinicop...

  2. Fuzzy logic selection as a new reliable tool to identify molecular grade signatures in breast cancer--the INNODIAG study.

    Science.gov (United States)

    Kempowsky-Hamon, Tatiana; Valle, Carine; Lacroix-Triki, Magali; Hedjazi, Lyamine; Trouilh, Lidwine; Lamarre, Sophie; Labourdette, Delphine; Roger, Laurence; Mhamdi, Loubna; Dalenc, Florence; Filleron, Thomas; Favre, Gilles; François, Jean-Marie; Le Lann, Marie-Véronique; Anton-Leberre, Véronique

    2015-02-07

    Personalized medicine has become a priority in breast cancer patient management. In addition to the routinely used clinicopathological characteristics, clinicians will have to face an increasing amount of data derived from tumor molecular profiling. The aims of this study were to develop a new gene selection method based on a fuzzy logic selection and classification algorithm, and to validate the gene signatures obtained on breast cancer patient cohorts. We analyzed data from four published gene expression datasets for breast carcinomas. We identified the best discriminating genes by comparing molecular expression profiles between histologic grade 1 and 3 tumors for each of the training datasets. The most pertinent probes were selected and used to define fuzzy molecular grade 1-like (good prognosis) and fuzzy molecular grade 3-like (poor prognosis) profiles. To evaluate the prognostic performance of the fuzzy grade signatures in breast cancer tumors, a Kaplan-Meier analysis was conducted to compare the relapse-free survival deduced from histologic grade and fuzzy molecular grade classification. We applied the fuzzy logic selection on breast cancer databases and obtained four new gene signatures. Analysis in the training public sets showed good performance of these gene signatures for grade (sensitivity from 90% to 95%, specificity 67% to 93%). To validate these gene signatures, we designed probes on custom microarrays and tested them on 150 invasive breast carcinomas. Good performance was obtained with an error rate of less than 10%. For one gene signature, among 74 histologic grade 3 and 18 grade 1 tumors, 88 cases (96%) were correctly assigned. Interestingly histologic grade 2 tumors (n = 58) were split in these two molecular grade categories. We confirmed the use of fuzzy logic selection as a new tool to identify gene signatures with good reliability and increased classification power. This method based on artificial intelligence algorithms was successfully

  3. Head and neck tumours: combined MRI assessment based on IVIM and TIC analyses for the differentiation of tumors of different histological types

    Energy Technology Data Exchange (ETDEWEB)

    Sumi, Misa; Nakamura, Takashi [Nagasaki University School of Dentistry, Department of Radiology and Cancer Biology, Nagasaki (Japan)

    2014-01-15

    We evaluated the combined use of intravoxel incoherent motion (IVIM) and time-signal intensity curve (TIC) analyses to diagnose head and neck tumours. We compared perfusion-related parameters (PP) and molecular diffusion values (D) determined from IVIM theory and TIC profiles among 92 tumours with different histologies. IVIM parameters (f and D values) and TIC profiles in combination were distinct among the different types of head and neck tumours, including squamous cell carcinomas (SCCs), lymphomas, malignant salivary gland tumours, Warthin's tumours, pleomorphic adenomas and schwannomas. A multiparametric approach using both IVIM parameters and TIC profiles differentiated between benign and malignant tumours with 97 % accuracy and diagnosed different tumour types with 89 % accuracy. Combined use of IVIM parameters and TIC profiles has high efficacy in diagnosing head and neck tumours. (orig.)

  4. Overexpression and ratio disruption of ΔNp63 and TAp63 isoform equilibrium in endometrial adenocarcinoma: correlation with obesity, menopause, and grade I/II tumors.

    Science.gov (United States)

    Vakonaki, Eleni; Soulitzis, Nikolaos; Sifakis, Stavros; Papadogianni, Danae; Koutroulakis, Dimitrios; Spandidos, Demetrios A

    2012-08-01

    p63 plays an important role in several intracellular processes such as transcription activation and apoptosis. p63 has two N-terminal isoforms, TAp63 and ΔNp63. TAp63 isoform has p53-like functions, while ΔNp63 acts as a dominant negative inhibitor of the p53 family and is considered oncogenic. Although p63 and its isoforms are overexpressed in a wide variety of human malignancies such as cervical, head and neck, and lung cancer, their role in endometrial carcinoma has not been investigated. We measured by quantitative real-time polymerase chain reaction the mRNA expression of TAp63 and ΔNp63 in a series of 20 endometrioid adenocarcinomas paired with adjacent normal tissue. TAp63 isoform exhibited 1.8-fold overexpression in malignant samples, while ΔNp63 was 4.3-fold overexpressed in cancer specimens. Further analysis revealed that the ΔN/TA isoform ratio shifted from 0.5 in normal samples to 1.2 in tumor specimens. Statistical analysis also revealed an association of TAp63 expression with high body mass index (p = 0.034), late menopause (p = 0.020), and lower tumor grade (p = 0.034). ΔNp63 was also correlated with grade I/II tumors (p = 0.044). These results indicate that both p63 isoforms and especially ΔNp63 play an important role in the development and progression of grade I/II endometrial adenocarcinoma, especially in obese and late-menopause women.

  5. Heterologous Liposarcomatous Differentiation in Malignant Phyllodes Tumor is Histologically Similar but Immunohistochemically and Molecularly Distinct from Well-differentiated Liposarcoma of Soft Tissue.

    Science.gov (United States)

    Inyang, Alero; Thomas, Dafydd G; Jorns, Julie

    2016-05-01

    Malignant phyllodes tumor (PT) infrequently displays heterologous differentiation, and when present is most often liposarcomatous. We identified five cases of malignant PT with regions identical to well-differentiated liposarcoma (WDLS) of soft tissue and evaluated them for MDM2 and CDK4 gene expression and amplification using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), respectively. Despite indistinguishable morphology all cases of malignant PT with WDLS-like liposarcomatous differentiation were negative for MDM2 and CDK4 IHC and FISH, supporting different underlying pathogenesis. © 2016 Wiley Periodicals, Inc.

  6. Time course of apoptotic tumor response after a single dose of chemotherapy: comparison with 99mTc-annexin V uptake and histologic findings in an experimental model.

    Science.gov (United States)

    Takei, Toshiki; Kuge, Yuji; Zhao, Songji; Sato, Masayuki; Strauss, H William; Blankenberg, Francis G; Tait, Jonathan F; Tamaki, Nagara

    2004-12-01

    In tumors the process of apoptosis occurs over an interval of time after chemotherapy. To determine the best timing for detecting apoptosis in vivo with (99m)Tc-annexin V after chemotherapy, we examined the changes in (99m)Tc-annexin V accumulation over time in comparison with those of caspase-3 and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) expression level after cyclophosphamide treatment in an experimental model. Hydrazinonicotinamide (HYNIC)-annexin V was labeled with (99m)Tc ((99m)Tc-annexin V). Rats were inoculated with allogenic hepatoma cells (KDH-8) into the left calf muscle. Eleven days after the inoculation, the rats were randomly divided into the group receiving a single dose of cyclophosphamide (150 mg/kg intraperitoneally) and the control group. (99m)Tc-Annexin V (18.5 MBq [0.5 mCi] per rat) was injected intravenously in the rats 4, 12, and 20 h after the treatment and also to the control rats (n = 5 in each group). Radioactivity in tissues was determined 6 h after (99m)Tc-annexin V injection. Immunostaining of caspase-3 and TUNEL were performed to detect apoptosis, and the rates of positively stained cells were calculated. (99m)Tc-Annexin V accumulation in tumors significantly increased at 20 h (0.077 +/- 0.007 [%ID/g] x kg, where %ID/g = percentage injected dose per gram) but not at 4 or 12 h (0.048 +/- 0.008 and 0.052 +/- 0.014 [%ID/g] x kg, respectively) after cyclophosphamide treatment. (99m)Tc-Annexin V accumulation in tumors and the rate of apoptotic cells determined by caspase-3 immunostaining and TUNEL were significantly higher in treated rats 20 h after cyclophosphamide treatment as compared with control rats. The effective detection of apoptotic tumor response with (99m)Tc-annexin V required 20 h after cyclophosphamide treatment in an experimental model. The present results provide an important basis for determining the best timing of annexin V imaging after the start of chemotherapy

  7. Glioma supratentorial de baixo grau em adulto: experiência com 23 pacientes operados Supratentorial low grade tumors in adults: an experience with 23 surgical cases

    Directory of Open Access Journals (Sweden)

    José Carlos Lynch

    2004-06-01

    Full Text Available Os astrocitomas e oligodendrogliomas supratentoriais dos adultos são tumores infrequentes. Analisamos retrospectivamente 23 pacientes com este tipo de neoplasia que foram operados entre 1986 e 2002. Não ocorreu nenhum óbito no pós-operatório. A sobrevida de 5 e 10 anos de todo o grupo foi 67 e 30% respectivamente, semelhante a outras experiências. Em 14 pacientes obtivemos a remoção completa da lesão (60,8% e em 9 (39,2% ocorreu remoção parcial do tumor. No subgrupo da ressecção total do tumor, 89% sobreviveram 5 anos e 45% alcançaram 10 anos de sobrevida, em contraste com o subgrupo da remoção parcial em que somente 35% alcançaram os 5 anos de sobrevida e nenhum, 10 anos. Devido aos efeitos deletérios da radioterapia, nós preferimos prescrevê-la apenas nos casos de recorrência tumoral.Low-grade supratentorial astrocytomas and oligodendrogliomas in adults are uncommon tumors of the central nervous system. We analyzed retrospectively 23 patients with this type of neoplasia, who were operated on between 1986 and 2002. There were no post-operative deaths. The survival rate at 5 and 10 years post-surgery for the entire sample was 67 and 30% respectively, similar to other outcomes. With 14 patients we achieved a complete removal of the lesion (60.8% and with 9 (39.2% partial removal of the tumor. In the sub-group which underwent total resection of the tumor, 89% survived 5 years and 45% attained 10 years of survival, in contrast with the sub-group that underwent partial removal in which only 35% attained 5 years of survival and none 10 years. Due to the deleterious effects of radiation therapy, we preferred to prescribe it only in cases of tumor recurrence.

  8. Breast Cancer Survival Defined by the ER/PR/HER2 Subtypes and a Surrogate Classification according to Tumor Grade and Immunohistochemical Biomarkers

    Directory of Open Access Journals (Sweden)

    Carol A. Parise

    2014-01-01

    Full Text Available Introduction. ER, PR, and HER2 are routinely available in breast cancer specimens. The purpose of this study is to contrast breast cancer-specific survival for the eight ER/PR/HER2 subtypes with survival of an immunohistochemical surrogate for the molecular subtype based on the ER/PR/HER2 subtypes and tumor grade. Methods. We identified 123,780 cases of stages 1–3 primary female invasive breast cancer from California Cancer Registry. The surrogate classification was derived using ER/PR/HER2 and tumor grade. Kaplan-Meier survival analysis and Cox proportional hazards modeling were used to assess differences in survival and risk of mortality for the ER/PR/HER2 subtypes and surrogate classification within each stage. Results. The luminal B/HER2− surrogate classification had a higher risk of mortality than the luminal B/HER2+ for all stages of disease. There was no difference in risk of mortality between the ER+/PR+/HER2− and ER+/PR+/HER2+ in stage 3. With one exception in stage 3, the ER-negative subtypes all had an increased risk of mortality when compared with the ER-positive subtypes. Conclusions. Assessment of survival using ER/PR/HER2 illustrates the heterogeneity of HER2+ subtypes. The surrogate classification provides clear separation in survival and adjusted mortality but underestimates the wide variability within the subtypes that make up the classification.

  9. The impact of bleomycin on retroperitoneal histology at post-chemotherapy retroperitoneal lymph node dissection of good risk germ cell tumors.

    Science.gov (United States)

    Cary, K Clint; Pedrosa, Jose A; Kaimakliotis, Hristos Z; Masterson, Timothy A; Einhorn, Lawrence H; Foster, Richard S

    2015-02-01

    Induction chemotherapy for International Germ Cell Cancer Collaborative Group (IGCCCG) good risk metastatic testicular cancer includes 3 cycles of bleomycin, etoposide and cisplatin (BEP x3) or 4 cycles of etoposide and cisplatin (EP x4). We examine differences in active cancer in the retroperitoneum between patients receiving BEP x3 compared to EP x4. The Indiana University Testis Cancer database was queried to identify IGCCCG good risk patients who received BEP x3 or EP x4 induction chemotherapy before retroperitoneal lymph node dissection. The primary outcome of interest was retroperitoneal histology. The association between the use of bleomycin in the induction regimen with active cancer in the retroperitoneal specimen was tested using a propensity score adjusted analysis. A total of 179 men (79%) received BEP x3 while 47 (21%) received EP x4. Median age of the bleomycin, etoposide and cisplatin group was 27 years (range 15 to 50) vs 30 years (range 18 to 71) in the etoposide and cisplatin group. The incidence of active cancer in the retroperitoneal specimen at post-chemotherapy retroperitoneal lymph node dissection was significantly higher in the EP x4 group compared to the BEP x3 group (31.9% vs 7.8%, p retroperitoneal specimen in good risk patients who received 4 cycles of induction etoposide and cisplatin chemotherapy compared to 3 cycles of bleomycin, etoposide and cisplatin in this retrospective analysis. The overall burden of treatment may be higher for men receiving EP x4 for induction chemotherapy. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  10. Is Needle Biopsy Clinically Useful in Preoperative Grading of Central Chondrosarcoma of the Pelvis and Long Bones?

    Science.gov (United States)

    Roitman, Pablo D; Farfalli, Germán L; Ayerza, Miguel A; Múscolo, D Luis; Milano, Federico E; Aponte-Tinao, Luis A

    2017-03-01

    Central chondrosarcoma of bone is graded on a scale of 1 to 3 according to histological criteria. Clinically, these tumors can be divided into low-grade (Grade 1) and high-grade (Grade 2, Grade 3, and dedifferentiated) chondrosarcomas. Although en bloc resection has been the most widely used treatment, it has become generally accepted that in selected patients with low-grade chondrosarcomas of long bones, curettage is safe and effective. This approach requires an accurate preoperative estimation of grade to avoid under- or overtreatment, but prior reports have indicated that both imaging and biopsy do not always give an accurate prediction of grade. (1) What is the concordance of image-guided needle preoperative biopsy and postoperative grading in central (intramedullary) chondrosarcomas of long bones, and how does this compare with the concordance of image-guided needle preoperative biopsy and postoperative grading in central pelvic chondrosarcomas? (2) What is the concordance of preoperative image-guided needle biopsy and postoperative findings in differentiating low-grade from high-grade central chondrosarcomas of long bones, and how does this compare with the concordance in central pelvic chondrosarcomas? Between 1997 and 2014, in our institution, we treated 126 patients for central chondrosarcomas located in long bones and the pelvis. Of these 126 cases, 41 were located in the pelvis and the remaining 85 cases were located in long bones. This study considers 39 (95%) and 40 (47%) of them, respectively. We included all cases in which histological information was complete regarding preoperative and postoperative tumor grading. We excluded all cases with incomplete data sets or nondiagnostic preoperative biopsies. To evaluate the needle biopsy accuracy, we compared the histological tumor grade, obtained from the preoperative biopsy, with the final histological grade obtained from the postoperative surgical specimen. The weighted and nonweighted kappa statistics

  11. Comparison of cytogenetic abnormalities and deoxyribonucleic acid ploidy of benign, borderline malignant, and different grades of malignant soft tissue tumors.

    NARCIS (Netherlands)

    van den Berg, Eva; Oven, M W Van; de Jong, Bauke; Dam, Anke; Wiersema, J; Dijkhuizen, T; Hoekstra, H J; Molenaar, W M

    1994-01-01

    BACKGROUND: Both DNA flow cytometry and cytogenetic analysis have been used to study soft tissue tumors. With flow cytometry, the DNA content of a relatively large number of cells can be examined, but cytogenetic analysis gives more detailed information about genomic changes. EXPERIMENTAL DESIGN: In

  12. Different expression of EZH2, BMI1 and Ki67 in low and high grade neuroendocrine tumors of the lung

    DEFF Research Database (Denmark)

    Bondgaard, Anna-Louise Reinert Ørsum; Poulsen, Thomas Tuxen; Poulsen, Hans Skovgaard

    2012-01-01

    Enhancer of Zeste Homolog 2 (EZH2) and B lymphoma Mo-MLV Insertion region 1 polycomb ring finger (BMI1) are involved in malignant transformation of many human carcinomas. Still, in neuroendocrine tumors of the lung (NELT) their expression pattern is largely unknown. This study evaluated...

  13. Imaging and histologic prognostic factors in triple-negative breast cancer and carcinoma in situ as a prognostic factor.

    Science.gov (United States)

    Sebastián Sebastián, C; García Mur, C; Cruz Ciria, S; Rosero Cuesta, D S; Gros Bañeres, B

    2016-01-01

    To analyze what factors in magnetic resonance imaging (MRI) and histological study of triple-negative breast cancers are related to tumor recurrence and to shorter disease-free survival. To analyze survival and recurrence in function of the presence of an in situ component. This was a retrospective study of MRI staging examinations in 122 women with triple-negative breast cancer done from 2007 through 2014. In the MRI, we evaluated morphological variables (size, margins, morphology, internal signal in T2-weighted sequences) and dynamic variables (perfusion and diffusion). In the histological study, we evaluated Ki67, p53, CK5/6, nuclear grade, and Scarff-Bloom grade, as well as the presence of an in situ component and tumor grade (high grade or not high grade). We compared the variables between patients with tumor recurrence and those without, and we conducted a survival analysis. Non-nodular enhancement was more common in patients with tumor recurrence (p=0.038) and was associated with shorter disease-free survival (p=0.023). Neither diffusion restriction (p=0.079) nor ki67 (p=0.052) was associated with a worse prognosis. An in situ component was detected in 44% of triple-negative tumors, and a greater proportion of patients in the group with tumor recurrence had an in situ component; however, the presence of an in situ component was not associated with shorter survival (p = 0.185). Non-nodular enhancement was associated with a worse prognosis. Diffusion restriction, ki67, and the presence of an in situ component were not associated with shorter disease-free survival. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Loss of the Urothelial Differentiation Marker FOXA1 Is Associated with High Grade, Late Stage Bladder Cancer and Increased Tumor Proliferation

    Science.gov (United States)

    DeGraff, David J.; Clark, Peter E.; Cates, Justin M.; Yamashita, Hironobu; Robinson, Victoria L.; Yu, Xiuping; Smolkin, Mark E.; Chang, Sam S.; Cookson, Michael S.; Herrick, Mary K.; Shariat, Shahrokh F.; Steinberg, Gary D.; Frierson, Henry F.; Wu, Xue-Ru; Theodorescu, Dan; Matusik, Robert J.

    2012-01-01

    Approximately 50% of patients with muscle-invasive bladder cancer (MIBC) develop metastatic disease, which is almost invariably lethal. However, our understanding of pathways that drive aggressive behavior of MIBC is incomplete. Members of the FOXA subfamily of transcription factors are implicated in normal urogenital development and urologic malignancies. FOXA proteins are implicated in normal urothelial differentiation, but their role in bladder cancer is unknown. We examined FOXA expression in commonly used in vitro models of bladder cancer and in human bladder cancer specimens, and used a novel in vivo tissue recombination system to determine the functional significance of FOXA1 expression in bladder cancer. Logistic regression analysis showed decreased FOXA1 expression is associated with increasing tumor stage (pcell carcinoma (SCC) exhibited loss of FOXA1 expression. Furthermore, 81% of cases of SCC of the bladder were negative for FOXA1 staining compared to only 40% of urothelial cell carcinomas. In addition, we showed that a subpopulation of FOXA1 negative urothelial tumor cells are highly proliferative. Knockdown of FOXA1 in RT4 bladder cancer cells resulted in increased expression of UPK1B, UPK2, UPK3A, and UPK3B, decreased E-cadherin expression and significantly increased cell proliferation, while overexpression of FOXA1 in T24 cells increased E-cadherin expression and significantly decreased cell growth and invasion. In vivo recombination of bladder cancer cells engineered to exhibit reduced FOXA1 expression with embryonic rat bladder mesenchyme and subsequent renal capsule engraftment resulted in enhanced tumor proliferation. These findings provide the first evidence linking loss of FOXA1 expression with histological subtypes of MIBC and urothelial cell proliferation, and suggest an important role for FOXA1 in the malignant phenotype of MIBC. PMID:22590586

  15. Pathological classification of brain tumors.

    Science.gov (United States)

    Pollo, B

    2012-04-01

    The tumors of the central nervous system are classified according to the last international classification published by World Health Organization. The Classification of Tumors of the Central Nervous System was done on 2007, based on morphological features, growth pattern and molecular profile of neoplastic cells, defining malignancy grade. The neuropathological diagnosis and the grading of each histotype are based on identification of histopathological criteria and immunohistochemical data. The histopathology, also consisting of findings with prognostic or predictive relevance, plays a critical role in the diagnosis and treatment of brain tumors. The recent progresses on radiological, pathological, immunohistochemical, molecular and genetic diagnosis improved the characterization of brain tumors. Molecular and genetic profiles may identify different tumor subtypes varying in biological and clinical behavior. To investigate new therapeutic approaches is important to study the molecular pathways that lead the processes of proliferation, invasion, angiogenesis, anaplastic transformation. Different molecular biomarkers were identified by genetic studies and some of these are used in neuro-oncology for the evaluation of glioma patients, in particular combined deletions of the chromosome arms 1p and 19q in oligodendroglial tumors, methylation status of the O-6 methylguanine- DNA methyltransferase gene promoter and alterations in the epidermal growth factor receptor pathway in adult malignant gliomas, isocitrate dehydrogenase 1 (IDH1) and IDH2 gene mutations in diffuse gliomas, as well as BRAF status in pilocytic astrocytomas. The prognostic evaluation and the therapeutic strategies for patients depend on synthesis of clinical, pathological and biological data: histological diagnosis, malignancy grade, gene-molecular profile, radiological pictures, surgical resection and clinical findings (age, tumor location, "performance status").

  16. Correlation between PET/CT results and histological and immunohistochemical findings in breast carcinomas

    Directory of Open Access Journals (Sweden)

    Almir Galvão Vieira Bitencourt

    2014-04-01

    Full Text Available Objective To correlate the results of 18F-fluoro-2-deoxy-D-glucose (18F-FDG positron emission tomography/computed tomography (PET/CT performed with a specific protocol for assessment of breasts with histological/immunohistochemical findings in breast carcinoma patients. Materials and Methods Cross-sectional study with prospective data collection, where patients with biopsy-confirmed breast carcinomas were studied. The patients underwent PET/CT examination in prone position, with a specific protocol for assessment of breasts. PET/CT findings were compared with histological and immunohistochemical data. Results The authors identified 59 malignant breast lesions in 50 patients. The maximum diameter of the lesions ranged from 6 to 80 mm (mean: 32.2 mm. Invasive ductal carcinoma was the most common histological type (n = 47; 79.7%. At PET/CT, 53 (89.8% of the lesions demonstrated anomalous concentrations of 18F-FDG, with maximum SUV ranging from 0.8 to 23.1 (mean: 5.5. A statistically significant association was observed between higher values of maximum SUV and histological type, histological grade, molecular subtype, tumor diameter, mitotic index and Ki-67 expression. Conclusion PET/CT performed with specific protocol for assessment of breasts has demonstrated good sensitivity and was associated with relevant histological/immunohistochemical factors related to aggressiveness and prognosis of breast carcinomas.

  17. Metanephric Adenoma: clinical, imaging, and histological findings

    Energy Technology Data Exchange (ETDEWEB)

    Torricelli, Fabio Cesar Miranda; Marchini, Giovanni Scala, E-mail: fabio_torri@yahoo.com.b [Universidade de Sao Paulo (USP), SP (Brazil). Faculdade de Medicina. Dept. de Urologica; Campos, Rodrigo Sousa Madeira [Hospital do Servidor Publico Estadual, Sao Paulo, SP (Brazil). Dept. de Urologia; Gil, Antonio Otero [Instituto Dante Pazanezzi, Sao Paulo, SP (Brazil)

    2011-07-01

    Metanephric adenoma (MA), also designated nephrogenic nephroma or renal epithelial tumor resembling immature nephron, has just been recently recognized as a special type of benign renal epithelial tumor. Only few reports are found in the literature regarding this rare renal tumor. The purpose of this paper is to describe our clinical, imaging and histological / immunohistochemical observations of MA diagnosed in two patients and compare these data to previous information reported in medical databases (author)

  18. Prognostic value of metabolic tumor volume on {sup 11}C-methionine PET in predicting progression-free survival in high-grade glioma

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Min Young; Paeng, Jin Chul; Cheon, Gi Jeong; Lee, Dong Soo; Chung, June Key; Kang, Keon Wook [Dept. of Nuclear Medicine, Seoul National University Hospital, Seoul (Korea, Republic of); Kim, E. Edmund [Dept. of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul (Korea, Republic of)

    2015-12-15

    C-11 methionine (MET) PET is commonly used for diagnosing high-grade glioma (HGG). Recently, volumetric analysis has been widely applied to oncologic PET imaging. In this study, we investigated the prognostic value of metabolic tumor volume (MTV) on MET PET in HGG. A total of 30 patients with anaplastic astrocytoma (n = 12) and glioblastoma multiforme (n = 18) who underwent MET PET before treatment (surgery followed by chemo-radiotherapy) were retrospectively enrolled. Maximal tumor-to-normal brain ratio (TNR{sub max}, maximum tumor activity divided by mean of normal tissue) and MTV (volume of tumor tissue that shows uptake >1.3-fold of mean uptake in normal tissue) were measured on MET PET. Adult patients were classified into two subgroups according to Radiation Therapy Oncology Group Recursive Partitioning Analysis (RTOG RPA) classification. Prognostic values of TNR{sub max}, MTV and clinicopathologic factors were evaluated with regard to progression-free survival (PFS). Median PFS of all patients was 7.9 months (range 1.0–53.8 months). In univariate analysis, MTV (cutoff 35 cm{sup 3}) was a significant prognostic factor for PFS (P = 0.01), whereas TNR{sub max} (cutoff 3.3) and RTOG RPA class were not (P = 0.80 and 0.61, respectively). Treatment of surgical resection exhibited a borderline significance (P = 0.06). In multivariate analysis, MTV was the only independent prognostic factor for PFS (P = 0.03). MTV on MET PET is a significant and independent prognostic factor for PFS in HGG patients, whereas TNR{sub max} is not. Thus, performing volumetric analysis of MET PET is recommended in HGG for better prognostication.

  19. Tumor regression grading after preoperative chemoradiotherapy for locally advanced rectal carcinoma revisited: updated results of the CAO/ARO/AIO-94 trial.

    Science.gov (United States)

    Fokas, Emmanouil; Liersch, Torsten; Fietkau, Rainer; Hohenberger, Werner; Beissbarth, Tim; Hess, Clemens; Becker, Heinz; Ghadimi, Michael; Mrak, Karl; Merkel, Susanne; Raab, Hans-Rudolf; Sauer, Rolf; Wittekind, Christian; Rödel, Claus

    2014-05-20

    We previously described the prognostic impact of tumor regression grading (TRG) on the outcome of patients with rectal carcinoma treated with preoperative chemoradiotherapy (CRT) in the CAO/ARO/AIO-94 trial. Here we report long-term results after a median follow-up of 132 months. TRG after preoperative CRT was determined in 386 surgical specimens by the amount of viable tumor cells versus fibrosis, ranging from TRG 4 (no viable tumor cells) to TRG 0 (no signs of regression). Clinicopathologic parameters and TRG were correlated to the cumulative incidence of local recurrence, distant metastasis, and disease-free survival (DFS). Ten-year cumulative incidence of distant metastasis and DFS were 10.5% and 89.5% for patients with TRG 4 (complete regression), 29.3% and 73.6% for TRG 2 and 3 (intermediate regression), and 39.6% and 63% for TRG 0 and 1 (poor regression), respectively (P = .005 and P = .008, respectively). On multivariable analysis, residual lymph node metastasis (ypN+) and TRG were the only independent prognostic factors for cumulative incidence of distant metastasis (P < .001 and P = .035, respectively) and DFS (P < .001 and P = .039, respectively), whereas local recurrence was significantly affected by ypN status (P < .001) and lymphatic invasion (P = .026). Complete and intermediate tumor regressions were associated with improved long-term outcome in patients with rectal carcinoma after preoperative CRT independent of clinicopathologic parameters. This classification system needs to be prospectively tested in multiple data sets to validate its reproducibility in a wider setting. © 2014 by American Society of Clinical Oncology.

  20. Current Management and Treatment Modalities for Intramedullary Spinal Cord Tumors.

    Science.gov (United States)

    Juthani, Rupa G; Bilsky, Mark H; Vogelbaum, Michael A

    2015-08-01

    Intramedullary spinal cord tumors are rare central nervous system tumors with unique challenges due to the eloquence of the surrounding tissue. Their treatment and prognosis is largely dependent on tumor histology and patient functionality. The introduction and advancement of microsurgical techniques have made surgery the mainstay of treatment for intramedullary tumors. Tumors that are well demarcated (e.g., ependymomas, hemangioblastomas) can be resected for cure, while more infiltrative tumors (e.g., high-grade astrocytomas) are typically managed with biopsies or limited resections in order to minimize the significant risk of damage to the spinal cord. The use of more aggressive surgical resection for astrocytoma is controversial but may have an increasing role in select cases. The use of intraoperative neurophysiologic monitoring and intraoperative ultrasound may help guide the extent of surgery while minimizing damage to normal tissue. Advances in MRI technology have greatly aided the diagnosis and preoperative planning of intramedullary tumors. Further advances in intraoperative MRI may make this a useful tool in guiding extent of resection. Preoperative functional status is the most important predictor of neurologic outcome, while histology and extent of resection are the most important predictors of progression-free survival. The use of adjuvant radiation and chemotherapy is dependent on patient age and histology but is largely reserved for high-grade tumor histologies or systemic involvement. Children are particularly at risk of radiation-induced injury, and these cases may benefit from more focused stereotactic radiation where necessary. Further studies are needed to support new surgical strategies minimizing destabilization and to investigate new forms of adjuvant therapy to minimize toxicity.

  1. High Grade Myofibroblastic Sarcoma of Paratesticular Soft Tissues

    Directory of Open Access Journals (Sweden)

    Ioannis Anastasiou

    2014-01-01

    Full Text Available Tumors of the paratesticular region most often arise from the soft tissue surrounding the spermatic cord and the epididymis or from the soft tissue (dartos muscle of the scrotal wall. Paratesticular tumors, despite their rarity, present a high incidence of malignancy (30%, and the therapeutic approach of choice is surgical resection with negative margin. The grade, the histology type, the presence of metastases during the diagnosis, the size of the tumor, the age of the patients, and the surgical margins are all important prognostic factors. We present a case report of a 86-year-old patient with a high grade paratesticular and scrotum sarcoma of soft tissues which was presented as a hard painful mass of the scrotum. The patient was subjected to high ligation of the spermatic cord and received no further treatment and 6 months after the operation no local or systematic recurrence was observed.

  2. A nationwide study of serous “borderline” ovarian tumors in Denmark 1978–2002

    DEFF Research Database (Denmark)

    Hannibal, Charlotte Gerd; Vang, Russell; Junge, Jette

    2014-01-01

    diagnosed with SBTs from 1978 to 2002. The histologic slides were collected from Danish pathology departments and reviewed by expert pathologists and classified as SBT/atypical proliferative serous tumor (APST) or noninvasive low-grade serous carcinoma (LGSC). Associated implants were classified......, overall survival of women with SBT/APST (pdate this is the largest nationwide cohort of SBTs where all tumors have been verified by expert pathologists. Only in women with advanced stage SBT...

  3. Exploratory Study to Identify Radiomics Classifiers for Lung Cancer Histology

    OpenAIRE

    Wu, Weimiao; Parmar, Chintan; Grossmann, Patrick; Quackenbush, John; Lambin, Philippe; Bussink, Johan; Mak, Raymond; Aerts, Hugo J. W. L.

    2016-01-01

    Background Radiomics can quantify tumor phenotypic characteristics non-invasively by applying feature algorithms to medical imaging data. In this study of lung cancer patients, we investigated the association between radiomic features and the tumor histologic subtypes (adenocarcinoma and squamous cell carcinoma). Furthermore, in order to predict histologic subtypes, we employed machine-learning methods and independently evaluated their prediction performance. Methods Two independen...

  4. Multiparametric analysis of magnetic resonance images for glioma grading and patient survival time prediction

    Energy Technology Data Exchange (ETDEWEB)

    Garzon, Benjamin (Dept. of Circulation and Medical Imaging, NTNU, Trondheim (Norway)), email: benjamin.garzon@ntnu.no; Emblem, Kyrre E. (The Interventional Center, Rikshospitalet, Oslo Univ. Hospital, Oslo (Norway); Dept. of Radiology, MGH-HST AA Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston (United States)); Mouridsen, Kim (Center of Functionally Integrative Neuroscience, Aarhus Univ., Aarhus (Denmark)); Nedregaard, Baard; Due-Toennessen, Paulina; Nome, Terje; Hald, John K. (Dept. of Radiology and Nuclear Medicine, Rikshospitalet, Oslo Univ. Hospital, Oslo (Norway)); Bjoernerud, Atle (The Interventional Center, Rikshospitalet, Oslo Univ. Hospital, Oslo (Norway)); Haaberg, Asta K. (Dept. of Circulation and Medical Imaging, NTNU, Trondheim (Norway); Dept. of Medical Imaging, St Olav' s Hospital, Trondheim (Norway)); Kvinnsland, Yngve (NordicImagingLab, Bergen (Norway))

    2011-11-15

    Background. A systematic comparison of magnetic resonance imaging (MRI) options for glioma diagnosis is lacking. Purpose. To investigate multiple MR-derived image features with respect to diagnostic accuracy in tumor grading and survival prediction in glioma patients. Material and Methods. T1 pre- and post-contrast, T2 and dynamic susceptibility contrast scans of 74 glioma patients with histologically confirmed grade were acquired. For each patient, a set of statistical features was obtained from the parametric maps derived from the original images, in a region-of-interest encompassing the tumor volume. A forward stepwise selection procedure was used to find the best combinations of features for grade prediction with a cross-validated logistic model and survival time prediction with a cox proportional-hazards regression. Results. Presence/absence of enhancement paired with kurtosis of the FM (first moment of the first-pass curve) was the feature combination that best predicted tumor grade (grade II vs. grade III-IV; median AUC 0.96), with the main contribution being due to the first of the features. A lower predictive value (median AUC = 0.82) was obtained when grade IV tumors were excluded. Presence/absence of enhancement alone was the best predictor for survival time, and the regression was significant (P < 0.0001). Conclusion. Presence/absence of enhancement, reflecting transendothelial leakage, was the feature with highest predictive value for grade and survival time in glioma patients

  5. Transcriptome analysis reveals distinct gene expression profiles in astrocytoma grades II-IV.

    Science.gov (United States)

    Narsia, Nato; Ramagiri, Pradeep; Ehrmann, Jiri; Kolar, Zdenek

    2017-09-01

    Astrocytoma is the most prevalent form of primary brain cancer categorized into four histological grades by the World Health Organization. Investigation into individual grades of astrocytoma by previous studies has provided some insight into dysregulation of regulatory networks associated with increasing astrocytoma grades. However, further understanding of key mechanisms that distinguish different astrocytoma grades is required to facilitate targeted therapies. In this study, we utilized a large cohort of publicly available RNA sequencing data from patients with diffuse astrocytoma (grade II), anaplastic astrocytoma (grade III), primary glioblastoma (grade IV), secondary glioblastoma (grade IV), recurrent glioblastoma (grade IV), and normal brain samples to identify genetic similarities and differences between these grades using bioinformatics applications. Our analysis revealed a distinct gene expression pattern between grade II astrocytoma and grade IV glioblastoma (GBM). We also identified genes that were exclusively expressed in each of the astrocytoma grades. Furthermore, we identified known and novel genes involved in key pathways in our study. Gene set enrichment analysis revealed a distinct expression pattern of transcriptional regulators in primary GBM. Further investigation into molecular processes showed that the genes involved in cell proliferation and invasion were shared across all subtypes of astrocytoma. Also, the number of genes involved in metastasis, regulation of cell proliferation, and apoptosis increased with tumor grade. We confirmed existing findings and shed light on some important genes and molecular processes that will improve our understanding of glioma biology.

  6. Comparisons of the Efficacy of a Jak1/2 Inhibitor (AZD1480 with a VEGF Signaling Inhibitor (Cediranib and Sham Treatments in Mouse Tumors Using DCE-MRI, DW-MRI, and Histology

    Directory of Open Access Journals (Sweden)

    Mary E. Loveless

    2012-01-01

    Full Text Available Jak1/2 inhibition suppresses STAT3 phosphorylation that is characteristic of many cancers. Activated STAT3 promotes the transcription of factors that enhance tumor growth, survival, and angiogenesis. AZD1480 is a novel small molecule inhibitor of Jak1/2, which is a key mediator of STAT3 activation. This study examined the use of diffusion-weighted (DW and dynamic contrast-enhanced (DCE magnetic resonance imaging (MRI biomarkers in assessing early tumor response to AZD1480. Cediranib (AZD2171, a vascular endothelial growth factor signaling inhibitor, was used as a comparator. Thirty mice were injected with Calu-6 lung cancer cells and randomized into the three treatment groups: AZD1480, cediranib, and sham. DW-MRI and DCE-MRI protocols were performed at baseline and at days 3 and 5 after treatment. The percent change from baseline measurements for Ktrans, ADC, and ve were calculated and compared with hematoxylin and eosin (H&E, CD31, cParp, and Ki-67 histology data. Decreases in Ktrans of 29% (P < .05 and 53% (P < .05 were observed at days 3 and 5, respectively, for the cediranib group. No significant changes in Ktrans occurred for the AZD1480 group, but a significant increase in ADC was demonstrated at days 3 (63%, P < .05 and 5 (49%, P < .05. CD31 staining indicated diminished vasculature in the cediranib group, whereas significantly increased cParp staining for apoptotic activity and extracellular space by image analysis of H&E were present in the AZD1480 group. These imaging biomarker changes, and corresponding histopathology, support the use of ADC, but not Ktrans, as a pharmacodynamic biomarker of response to AZD1480 at these time points.

  7. Some Renal Masses Did Not “Read the Book”: A Case of a High Grade Hybrid Renal Tumor Masquerading as a Renal Cyst on Non-contrast Imaging

    Directory of Open Access Journals (Sweden)

    Hal D. Kominsky

    2015-11-01

    Full Text Available Hybrid renal tumors (HRT are rare neoplasms that contain both benign and malignant components. Sporadic solitary HRT that contain high-grade malignant pathology appear to be extremely rare [1]. We describe a case at our institution of a tumor that was characterized as a type-2 papillary RCC and atypical oncocytoma hybrid that mimicked a simple cyst on non-contrast computed tomography.

  8. Cerebellar metastases of recurrent phyllodes tumor breast; a rare phenomenon reflecting the unpredictable outcome.

    Science.gov (United States)

    Singh, Jyotsna; Majumdar, Kaushik; Gupta, Rahul; Batra, Vineeta Vijay

    2015-01-01

    Carcinomas of lung, breast, colon, kidney, and malignant melanomas are the most common malignancies that metastasize to the central nervous system (CNS). Phyllodes tumor is a rare fibroepithelial tumor of the breast, often having unpredictable recurrences, with increasing histological grade and distant metastasis. Malignant forms exist, which may develop distant metastases usually to the lung, pleura, bone, and liver. CNS metastasis of phyllodes tumor is rare and associated with a poor prognosis, with resistance to chemotherapy and radiation. We present a rare case of cerebellar metastasis in recurrent phyllodes tumor breast with subsequent rapid downhill course.

  9. Warthin's tumor of parotid gland on Tc-99m pertechnetate scintigraphy with lemon juice stimulation: Tc-99m uptake, size, and pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Miyake, Hidetoshi; Matsumoto, Akira; Hori, Yuko; Takeoka, Hiroshi; Kiyosue, Hiro; Hori, Yuzo; Mori, Hiromu [Dept. of Radiology, Oita Medical Univ., Oita (Japan); Ueyama, Shigehiro [Dept. of Otorhinolaryngology, Oita Medical Univ. (Japan); Kashima, Kenji [Dept. of Pathology, Oita Medical Univ. (Japan)

    2001-12-01

    The aim of this study was to evaluate the usefulness of technetium-99m (Tc-99m) pertechnetate scintigraphy with lemon juice stimulation in the diagnosis of Warthin's tumor and its correlation with Tc-99m uptake, tumor size, and histologic subtype. Tc-99m pertechnetate scintigraphy before and after lemon juice stimulation and pathologic specimens of 34 Warthin's tumors and 47 non-Warthin's lesions were retrospectively evaluated. Tc-99m uptake of Warthin's tumors before and after stimulation was visually graded as follows: absent; indeterminate; low grade; definite; and strong. Tumor size was defined as maximum diameter of the tumor measured from the surgical specimen. Warthin's tumors were classified into three histologic subtypes according to the ratio of epithelial and lymphoid stromal components: predominant epithelial; intermediate; and low-grade epithelial types. Eighteen of 34 (53%) Warthin's tumors and one benign lymphoepithelial cyst showed higher uptake than that of the normal parotid gland on Tc-99m scintigraphy before lemon juice stimulation. Thirty-two of the 34 (94%) Warthin's tumors, one benign lymphoepithelial cyst, one pleomorphic adenoma, and one oncocytoma revealed higher uptake than that of the normal parotid gland on Tc-99m scintigraphy after lemon juice stimulation. The mean size was 37 mm in strong uptake Warthin's tumors, 24 mm in definite uptake tumors, 19 mm in low-grade uptake tumors, and 12 mm in low-grade uptake tumors excluding those tumors with large cystic component. There was a significant correlation between tumor size and degree of Tc-99m uptake after lemon juice stimulation. However, there was no correlation between histologic subtype and Tc-99m uptake, and histologic subtype and tumor size in Warthin's tumors. Our study concludes that Tc-99m pertechnetate scintigraphy with lemon juice stimulation is useful for the detection and diagnosis of Warthin's tumor. The degree of uptake in

  10. Treatment Regimen, Surgical Outcome, and T-cell Differentiation Influence Prognostic Benefit of Tumor-Infiltrating Lymphocytes in High-Grade Serous Ovarian Cancer.

    Science.gov (United States)

    Wouters, Maartje C A; Komdeur, Fenne L; Workel, Hagma H; Klip, Harry G; Plat, Annechien; Kooi, Neeltje M; Wisman, G Bea A; Mourits, Marian J E; Arts, Henriette J G; Oonk, Maaike H M; Yigit, Refika; de Jong, Steven; Melief, Cornelis J M; Hollema, Harry; Duiker, Evelien W; Daemen, Toos; de Bruyn, Marco; Nijman, Hans W

    2016-02-01

    Tumor-infiltrating lymphocytes (TIL) are associated with a better prognosis in high-grade serous ovarian cancer (HGSC). However, it is largely unknown how this prognostic benefit of TIL relates to current standard treatment of surgical resection and (neo-)adjuvant chemotherapy. To address this outstanding issue, we compared TIL infiltration in a unique cohort of patients with advanced-stage HGSC primarily treated with either surgery or neoadjuvant chemotherapy. Tissue microarray slides containing samples of 171 patients were analyzed for CD8(+) TIL by IHC. Freshly isolated CD8(+) TIL subsets were characterized by flow cytometry based on differentiation, activation, and exhaustion markers. Relevant T-cell subsets (CD27(+)) were validated using IHC and immunofluorescence. A prognostic benefit for patients with high intratumoral CD8(+) TIL was observed if primary surgery had resulted in a complete cytoreduction (no residual tissue). By contrast, optimal (<1 cm of residual tumor) or incomplete cytoreduction fully abrogated the prognostic effect of CD8(+) TIL. Subsequent analysis of primary TIL by flow cytometry and immunofluorescence identified CD27 as a key marker for a less-differentiated, yet antigen-experienced and potentially tumor-reactive CD8(+) TIL subset. In line with this, CD27(+) TIL were associated with an improved prognosis even in incompletely cytoreduced patients. Neither CD8(+) nor CD27(+) cell infiltration was of prognostic benefit in patients treated with neoadjuvant chemotherapy. Our findings indicate that treatment regimen, surgical result, and the differentiation of TIL should all be taken into account when studying immune factors in HGSC or, by extension, selecting patients for immunotherapy trials. ©2015 American Association for Cancer Research.

  11. Tumor Budding in Intestinal Type Gastric Adenocarcinoma is Associated with Nodal Metastasis and Recurrence.

    Science.gov (United States)

    Olsen, Stephen; Linda, Jin; Fields, Ryan C; Yan, Yan; Nalbantoglu, ILKe

    2017-04-17

    Gastric adenocarcinoma (GAC) is a common cause of cancer-related death worldwide. GAC can be classified as intestinal or diffuse. Intestinal type cancers are common and reported to have a better prognosis compared to diffuse cancers. Studies have shown the presence and amount of tumor budding in intestinal carcinomas of the colon and esophagus to predict nodal metastasis and recurrence. Our aim is to determine if tumor budding in intestinal type GAC correlates with prognostic features. One hundred four patients treated with primary surgical excision between 1999-2013 were identified. Histologic type (intestinal, diffuse, or mixed), tumor grade, T-stage, and lymph node status were evaluated. Tumor bud scores were assigned to all intestinal type cancers using methods previously described for colorectal adenocarcinoma. Scores of Tumor characteristics were as follows: 52 intestinal (50%), 36 diffuse (35%) and 16 mixed (15%). Of the 52 cases with intestinal histology, 4 were well (8%), 28 were moderately (54%), and 20 were poorly differentiated (38%). Thirty-three (63%) of the intestinal tumors had high tumor bud scores. Cases with high scores were associated with higher T-stage, N-stage, and grade (Ptumor bud scores in intestinal type GAC have higher T-stage, N-stage, grade, and likelihood of recurrence. Assessment of tumor budding may guide clinical management in a subset of patients. Copyright © 2017. Published by Elsevier Inc.

  12. Estadios precoces de cancer oral: pronóstico en relación con gradación histológica, linfagiogénesis intratumoral y expresión de factor de crecimiento endotelial vascular Tipo-C (VEGF-C Early stage oral cancer: prognosis with regard to histological grading, intratumoral lymphangiogenesis, and the expression of vascular endothelial growth factor-C (VEGF-C

    Directory of Open Access Journals (Sweden)

    M.F. Muñoz-Guerra

    2006-02-01

    Bryne systems (p<0.001. Our study demonstrated an inverse relationship between the values of the Anneroth system (p<0.01 - Bryne system (p<0.001 and the presence of intratumoral lymphangiogenesis. Conclusion. The clinical value of the histological grading systems can increase by including new parameters that take into account the biological behavior of the tumor. Expression of VEGF-C and intratumoral lymphatics may thus be useful prognostic markers for oral squamous cell carcinoma.

  13. Morphology and prognostic value of tumor budding in rectal cancer after neoadjuvant radiotherapy.

    Science.gov (United States)

    Du, Changzheng; Xue, Weicheng; Li, Jiyou; Cai, Yong; Gu, Jin

    2012-07-01

    Tumor budding is an acknowledged prognostic marker in colorectal cancer. This study was conducted to investigate the morphology and prognostic significance of budding in rectal cancer after neoadjuvant radiotherapy. Surgical specimens from 96 consecutive patients who underwent neoadjuvant radiotherapy and curative resection were retrieved to assess budding and other clinicopathologic factors. The morphology and prognostic significance of postirradiation tumor budding were closely associated with tumor regression grade. In the tumor regression grade 1 group, tumor budding presented as "false budding" and did not have a significant association with prognosis. In the tumor regression grade 2 and 3 groups, budding was observed surrounded by radiation-induced fibrosis and large populations of infiltrating inflammatory cells, and budding intensity was significantly associated with histologic differentiation, ypN stage, and lymphovascular invasion (P budding subgroup showed a significantly higher rate of 5-year disease-free survival than the high-grade budding subgroup (87.5% versus 55.6%, P tumor regression grade, and tumor budding were the major independent factors affecting long-term disease-free survival. In conclusion, postirradiation budding has distinct morphology and prognostic significance in rectal cancer after neoadjuvant radiotherapy. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. B-cell clonal detection in gastric low-grade lymphomas and regional lymph nodes: an immunohistologic and molecular study.

    Science.gov (United States)

    Sanchez, L; Algara, P; Villuendas, R; Martinez, P; Orradre, J L; Morente, M; Piris, M A

    1993-03-01

    Gastric low-grade B cell lymphomas originating in mucosa-associated lymphoid tissues are composed of reactive hyperplastic germinal centers and interfollicular centrocyte-like cells. Their polymorphic, histologic composition and infrequent dissemination beyond the gastric wall led to the denomination of these tumors as "pseudolymphomas." To elucidate their clonal character, a Southern blot study of DNA and immunohistological study was carried out on 14 cases of surgical specimens from gastrectomy (11 low-grade and three high-grade tumors). Monoclonal and polyclonal antibodies were used on frozen and paraffin sections. A mucosa-associated lymphoid tissue origin for the tumors was assigned due to their centrocyte-like morphology and the presence of lymphoepithelial lesions. Southern blot analysis of DNA and immunohistological results confirm the monoclonal composition of gastric low-grade lymphomas in all cases. Although both types of technique correlated well on the predominant light-chain, Southern blot DNA study was nevertheless more sensitive than the immunohistochemical techniques. Surprisingly, in two cases of gastric low-grade lymphoma, Southern blot DNA analysis of histologically reactive regional lymph nodes showed an unexpected immunoglobulin heavy chain gene rearrangement. This coincided with that found in the gastric wall. Results confirm the monoclonal nature of the low-grade gastric lymphoma. This supports consideration of this tumor as an indolent primary lymphoma of the stomach, confirming the suitability of excluding the term "pseudolymphoma." Involvement of regional lymph nodes may be a more frequent occurrence than previously detected through morphological study.

  15. Odontogenic tumors.

    Science.gov (United States)

    Chrysomali, Evanthia; Leventis, Minas; Titsinides, Savas; Kyriakopoulos, Vasileios; Sklavounou, Alexandra

    2013-09-01

    This study aims to analyze the frequency and distribution of odontogenic tumors in a Greek population and compare the findings with those reported in the recent literature. Records of the Department of Oral Medicine and Pathology, Dental School, University of Athens, with histologic diagnosis of odontogenic tumors (based on the World Health Organization 2005 classification) were reviewed retrospectively from January 1970 to December 2011. A total of 652 cases of odontogenic tumors were reported. Of these, 651 (99.8%) were benign and only 1 (0.2%) was malignant. Keratocystic odontogenic tumor was the most frequent lesion (52.7%), followed by odontoma (18.9%) and ameloblastoma (16.1%). The mean age of patients was 38.0 years with a wide range (2.5-92 years). Odontogenic tumors are rare lesions and appear to show a definite geographic variation. In Athens, Greece, they are presented mainly by the keratocystic odontogenic tumor, odontoma, and ameloblastoma.

  16. Multiparametric MR assessment of pediatric brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Tzika, A.A. [Department of Radiology, Children' s Hospital, Harvard Medical School, Boston, MA 02114 (United States); NMR Surgical Laboratory, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, 51 Blossom Street, Boston, MA 02114 (United States); Astrakas, L.G.; Zarifi, M.K.; Petridou, N.; Young-Poussaint, T. [Department of Radiology, Children' s Hospital, Harvard Medical School, Boston, MA 02114 (United States); Goumnerova, L.; Black, P.McL. [Department of Neurosurgery, Children' s Hospital, Harvard Medical School, Boston, MA 02114 (United States); Zurakowski, D. [Department of Biostatistics, Children' s Hospital, Harvard Medical School, Boston, MA 02114 (United States); Anthony, D.C. [Department of Pathology, Children' s Hospital, Harvard Medical School, Boston, MA 02114 (United States)

    2003-01-01

    MR assessment of pediatric brain tumors has expanded to include physiologic information related to cellular metabolites, hemodynamic and diffusion parameters. The purpose of this study was to investigate the relationship between MR and proton MR spectroscopic imaging in children with primary brain tumors. Twenty-one patients (mean age 9 years) with histologically verified brain tumors underwent conventional MR imaging, hemodynamic MR imaging (HMRI) and proton MR spectroscopic imaging (MRSI). Fourteen patients also had diffusion-weighted MR imaging (DWMRI). Metabolic indices including choline-containing compounds (Cho), total creatine (tCr) and lipids/lactate (L) were derived by proton MRSI, relative cerebral blood volume (rCBV) by HMRI, and apparent tissue water diffusion coefficients (ADC) by DWMRI. Variables were examined by linear regression and correlation as well as by ANOVA. Cho (suggestive of tumor cellularity and proliferative activity) correlated positively with rCBV, while the relationship between Cho and ADC (suggestive of cellular density) was inverse (P<0.001). The relationship between rCBV and ADC was also inverse (P=0.004). Cho and lipids (suggestive of necrosis and/or apoptosis) were not significantly correlated (P=0.51). A positive relationship was found between lipids and ADC (P=0.002). The relationships between Cho, rCBV, ADC and lipids signify that tumor physiology is influenced by the tumor's physical and chemical environment. Normalized Cho and lipids distinguished high-grade from low-grade tumors (P<0.05). Multiparametric MR imaging using MRSI, HMRI and DWMRI enhances assessment of brain tumors in children and improves our understanding of tumor physiology while promising to distinguish higher- from lower-malignancy tumors, a distinction that is particularly clinically important among inoperable tumors. (orig.)

  17. [Bladder transitional cell carcinoma rating, systematization of grading and value of DNA ploidy].

    Science.gov (United States)

    Hierro Martín, I; Alvarez Pérez, M; Blanes Berenguel, A; Quiñonero Díaz, A; Díaz Cano, S; García González, I; Matilla Vicente, A

    1999-06-01

    TCCs are an heterogenous group of tumors with an uncertain biologic behaviour, especially intermediate grade (G2). Histologic grade and pathologic stage have revealed only partially useful on predicting the outcome. Search and statement of objective and cuantitative parameters able to define prognostic subgroups to TCCs. We studied consecutive 106 patients with TCC in order to: 1) Identify every variable with independent predictive value in classifying cases of TCC in a three (1,2,3) or two (high/low) grades systems. 2) Make a correlation between DNA ploidy obtained by image analysis and DNA ploidy and S-phase obtained by flow cytometry. Every variable used to define the histologic grade showed significative correlation with both gradation systems. In multivariate analysis, the presence of superficial cells and the mitotic counts revealed us the most valuable variables in predicting the histologic grade. DNA-ploidy (both obtained by static an flow cytometry) correlated well with grade, stage, growth pattern and necrosis, whereas S-phase did so with grade, mitotic index and DNA ploidy. Image cytometry showed similars results to those of flow cytometry and also was able to detect aneuploidy when an situ carcinoma or dysplasia were present in the adyacent mucosa.

  18. Phosphorylated p70S6K in noninvasive low-grade urothelial carcinoma of the bladder: correlation with tumor recurrence.

    Science.gov (United States)

    Kim, Soon-Ja; Kim, Jung Hoon; Jung, Hui Seok; Lee, Tae-Jin; Lee, Kyung Mee; Chang, In Ho

    2014-01-01

    We investigated whether inhibiting phosphorylated p70S6K (p-p70S6K) suppresses the proliferation and growth of noninvasive low-grade urothelial carcinoma (LG-URCa) in vitroand whether p-p70S6K can serve as a predictive biomarker for the recurrence of noninvasive LG-URCa of the bladder in patients. We constructed a tissue microarray (TMA) for 95 LG-URCa and 35 benign urothelium samples and performed immunohistochemical staining for p-p70S6K and p-4E-BP1. A Cox regression model was used to investigate the predictive factors for recurrence of LG-URCa. We investigated the dose-dependent antiproliferative effect of rapamycin, its antiproliferative effect and the growth-inhibition effect of p70S6K siRNA transfection in RT4 and 253J cell lines. The pT1 staged group (P RT4 and 253J cell proliferation in a dose-dependent manner (r = -0.850, PRT4 cells; r = -0.835, Pcells). RT4 and 253J cell proliferation and growth were inhibited by the transfection of p70S6K siRNA and rapamycin, respectively (P cell proliferation and growth that were similar to those of rapamycin. Our results suggest that inhibiting p70S6K phosphorylation is important to prevent recurrence and that p70S6K phosphorylation can be used as a molecular biomarker to predict recurrence of certain LG-URCa of the bladder.

  19. Ring chromosomes and low-grade gene amplification in an atypical lipomatous tumor with minimal nuclear atypia.

    Science.gov (United States)

    Storlazzi, Clelia Tiziana; Mertens, Fredrik; Domanski, Henryk; Fletcher, Christopher D M; Wiegant, Joop; Mandahl, Nils

    2003-07-01

    Atypical lipomatous tumors (ALTs) are characterized by supernumerary ring chromosomes and/or giant marker chromosomes, which typically are composed of interspersed, amplified 12q-sequences, are C-band negative, lack alpha-satellite sequences, and display high copy numbers of several oncogenes, including HMGA2 (a.k.a. HMGIC) and MDM2, from the 12q13-15 region. In the present study, we report the cytogenetic and molecular genetic findings in an ALT with minimal nuclear atypia from a 16-year-old boy. At G-banding analysis, 1-3 supernumerary ring chromosomes were detected. Combined binary ratio labeling fluorescence in situ hybridization (COBRA-FISH) showed that the rings were entirely composed of material from chromosome 12, and by further FISH analysis with locus-specific probes it was revealed that they consisted of two tandemly arranged copies of the segment 12p11.2-p13.2 to 12q21.2-q23.1. Within that segment of chromosome 12, there was a small deletion including the HMGA2 locus. There was no variation in ring size and no interphase bridges could be detected, indicating that the ring chromosomes were mitotically relatively stable. The present case thus adds support to the concept that there exists a subset of ALT with limited or minimal nuclear atypia and low-level amplification of 12q sequences, further suggesting the possibility of a molecular genetic continuum between lipoma and classical examples of ALT. Furthermore, the present data strongly imply that it is the composition of the rings rather than the ring chromosome formation as such that causes the genetic instability and nuclear atypia frequently seen in ALTs.

  20. Differences in the architecture of low-grade and high-grade gliomas evaluated using fiber density index and fractional anisotropy.

    Science.gov (United States)

    Chen, Yiyong; Shi, Yonghong; Song, Zhijian

    2010-07-01

    Accurate pre-operative assessment of tumor grade is important for the selection of appropriate treatment strategies. The aim of this study was to retrospectively evaluate whether the fiber density index (FDi) and fractional anisotropy (FA) via diffusion tensor MRI (DTI) could assist with pre-operative diagnosis of glioma grade. A total of 31 patients who had histologically confirmed gliomas underwent DTI performed using a 1.5-Tesla magnetic resonance scanner. To reconstruct the white matter adjacent to the tumor, DTI fiber tracking (DTI-FT) using an FA threshold of 0.15 was implemented. Regions of interest (ROIs) were defined (i-iv) as: the tumor center (ROI i); white matter adjacent to the tumor (ROI ii); contralateral centrum semiovale (ROI iii); and the homologous fiber tracts to ROI ii in the contralateral hemisphere (ROI iv). We calculated six parameters from different ROIs and compared high-grade and low-grade gliomas: FA values and ratios; FDi values and ratios with an FA threshold of 0.15; and FDi values and ratios with an FA threshold of 0.25. The results showed that FA ratios and FDi ratios with FA thresholds of 0.25 were significantly different between patients with high-grade and low-grade gliomas. This may be useful for developing surgical strategies and appraising patient prognosis.

  1. Phosphorylated p70S6K in noninvasive low-grade urothelial carcinoma of the bladder: correlation with tumor recurrence

    Directory of Open Access Journals (Sweden)

    Soon-Ja Kim

    2014-08-01

    Full Text Available We investigated whether inhibiting phosphorylated p70S6K (p-p70S6K suppresses the proliferation and growth of noninvasive low-grade urothelial carcinoma (LG-URCa in vitroand whether p-p70S6K can serve as a predictive biomarker for the recurrence of noninvasive LG-URCa of the bladder in patients. We constructed a tissue microarray (TMA for 95 LG-URCa and 35 benign urothelium samples and performed immunohistochemical staining for p-p70S6K and p-4E-BP1. A Cox regression model was used to investigate the predictive factors for recurrence of LG-URCa. We investigated the dose-dependent antiproliferative effect of rapamycin, its antiproliferative effect and the growth-inhibition effect of p70S6K siRNA transfection in RT4 and 253J cell lines. The pT1 staged group (P < 0.05; hazard ratio (HR, 2.415 and the high p-p70S6K staining group (P < 0.05; HR, 2.249 were independent factors for predicting recurrence. Rapamycin inhibited RT4 and 253J cell proliferation in a dose-dependent manner (r = −0.850, P< 0.001 in RT4 cells; r = −0.835, P< 0.001 in 253J cells. RT4 and 253J cell proliferation and growth were inhibited by the transfection of p70S6K siRNA and rapamycin, respectively (P < 0.05. Transfection of p70S6K siRNA resulted in inhibitory effects on cell proliferation and growth that were similar to those of rapamycin. Our results suggest that inhibiting p70S6K phosphorylation is important to prevent recurrence and that p70S6K phosphorylation can be used as a molecular biomarker to predict recurrence of certain LG-URCa of the bladder.

  2. Tumor metabolism and perfusion ratio assessed by 18F-FDG PET/CT and DCE-MRI in breast cancer patients: Correlation with tumor subtype and histologic prognostic factors

    Energy Technology Data Exchange (ETDEWEB)

    An, Young-Sil [Department of Nuclear Medicine and Molecular Imaging, Ajou University School of Medicine (Korea, Republic of); Kang, Doo Kyoung [Department of Radiology, Ajou University School of Medicine (Korea, Republic of); Jung, Yong Sik; Han, Sehwan [Department of Surgery, Ajou University School of Medicine (Korea, Republic of); Kim, Tae Hee, E-mail: medhand@ajou.ac.kr [Department of Radiology, Ajou University School of Medicine (Korea, Republic of)

    2015-07-15

    Highlights: • In non-triple negative breast cancer, metabolic parameter (SUVmax) was significantly correlated with perfusion parameters (Kep and Ve). • In triple negative cancers, any perfusion parameters did not correlated with metabolic parameters. • Higher SUVmax, higher SUVmax/Ktrans, higher MTV50/Ktrans, higher TLG50/Ktrans, higher TLG50/Ve ratios were significantly correlated with TNBC. • In triple negative breast cancer, perfusion and metabolic parameters are not significantly correlated. • Triple negative breast cancer showed higher metabolic–perfusion ratios compared to non-triple negative breast cancer. - Abstract: Objective: Our purpose was to evaluate whether breast cancer with high metabolic–perfusion ratio would be associated with poor histopathologic prognostic factors and whether triple negative breast cancer (TNBC) would show high metabolic–perfusion ratio compared to non-triple negative breast cancer (non-TNBC). Methods: From March 2011 to November 2011, 67 females with invasive ductal carcinoma of breast who underwent both MRI and 18F-FDG PET/CT were included. Perfusion parameters including Ktrans, Kep and Ve were acquired from Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Metabolic parameters including the standardized uptake value (SUV) and volumetric metabolic parameters including metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were obtained from F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). Results: In non-TNBC, SUVmax was significantly correlated with Kep (ρ = 0.298, p = 0.036) and Ve (ρ = −0.286, p = 0.044). In TNBC, there was no significant correlation between all perfusion and metabolic parameters. Compared to non-TNBC, higher SUVmax (10.2 vs 5.3, p < 0.001), higher SUVmax/Ktrans (56.02 vs 20.3, p < 0.001), higher MTV50/Ktrans (7.8 vs 16.54, p < 0.001), higher TLG50/Ktrans (36.49 vs 12.3, p < 0.001), higher TLG50/Ve (91.34 vs 27.1 p = 0.022) were

  3. Giant cell tumor-like lesion of the urinary bladder: a report of two cases and literature review; giant cell tumor or undifferentiated carcinoma?

    Directory of Open Access Journals (Sweden)

    Oznur Meltem

    2009-12-01

    Full Text Available Summary Giant cell tumor, excluding its prototype in bone, is usually a benign but local aggressive neoplasm originating from tendon sheath or soft tissue. Malignant behavior is uncommon. Visceral organ involvement including urinary bladder is rare. Giant cell tumors in visceral organs usually accompany epithelial tumors and the clinical behavior of giant cell tumor in urinary bladder is similar to its bone counterpart. Here, we report two cases of giant cell tumor located in urinary bladder in comparison with nine reported cases in the English literature. Concurrent noninvasive urothelial carcinoma was also described in all these previous reports and only one patient with follow-up died of disease. One of the two cases we present had no concurrent urothelial tumor at the time of diagnosis but had a history of a low grade noninvasive urothelial carcinoma with three recurrences. The histology of these two cases was similar to the giant cell tumor of bone and composed of oval to spindle mononuclear cells with evenly spaced osteoclast-like giant cells. Immunohistochemically, the giant cells showed staining with osteoclastic markers including CD68, TRAP, and LCA. Immunohistochemical expression of vimentin, CD68, LCA, and smooth muscle actin in mononuclear cells supported a mesenchymal origin with histiocytic lineage. The histologic and immunohistochemical properties in our cases as well as their clinical courses were consistent with a giant cell tumor. Consequently, tumors in urinary bladder showing features of giant cell tumor of bone may also be considered and termed "giant cell tumor".

  4. Next-Gen Sequencing Exposes Frequent MED12 Mutations and Actionable Therapeutic Targets in Phyllodes Tumors.

    Science.gov (United States)

    Cani, Andi K; Hovelson, Daniel H; McDaniel, Andrew S; Sadis, Seth; Haller, Michaela J; Yadati, Venkata; Amin, Anmol M; Bratley, Jarred; Bandla, Santhoshi; Williams, Paul D; Rhodes, Kate; Liu, Chia-Jen; Quist, Michael J; Rhodes, Daniel R; Grasso, Catherine S; Kleer, Celina G; Tomlins, Scott A

    2015-04-01

    Phyllodes tumors are rare fibroepithelial tumors with variable clinical behavior accounting for a small subset of all breast neoplasms, yet little is known about the genetic alterations that drive tumor initiation and/or progression. Here, targeted next-generation sequencing (NGS) was used to identify somatic alterations in formalin-fixed paraffin-embedded (FFPE) patient specimens from malignant, borderline, and benign cases. NGS revealed mutations in mediator complex subunit 12 (MED12) affecting the G44 hotspot residue in the majority (67%) of cases spanning all three histologic grades. In addition, loss-of-function mutations in p53 (TP53) as well as deleterious mutations in the tumor suppressors retinoblastoma (RB1) and neurofibromin 1 (NF1) were identified exclusively in malignant tumors. High-level copy-number alterations (CNA) were nearly exclusively confined to malignant tumors, including potentially clinically actionable gene amplifications in IGF1R and EGFR. Taken together, this study defines the genomic landscape underlying phyllodes tumor development, suggests potential molecular correlates to histologic grade, expands the spectrum of human tumors with frequent recurrent MED12 mutations, and identifies IGF1R and EGFR as potential therapeutic targets in malignant cases. Integrated genomic sequencing and mutational profiling provides insight into the molecular origin of phyllodes tumors and indicates potential druggable targets in malignant disease. Visual Overview: http://mcr.aacrjournals.org/content/early/2015/04/02/1541-7786.MCR-14-0578/F1.large.jpg. ©2015 American Association for Cancer Research.

  5. Epithelial ovarian tumors: Clinicopathological correlation and immunohistochemical study

    Directory of Open Access Journals (Sweden)

    Pooja S Naik

    2015-01-01

    Full Text Available Background: Ovarian cancer is the third leading site of cancer among women, trailing behind cervix and breast cancer. Aim: This study was undertaken to analyze the immunohistochemical (IHC profile of estrogen receptors (ER, progesterone receptors (PR, Ki-67, and p53 in various ovarian epithelial tumors and attempt correlation with clinical and histopathological findings. Materials and Methods: The present study was conducted over a period of 4 years. A technique of manual tissue array was employed for cases subjected for IHC. The primary antibodies used were ER, PR, p53, and Ki-67. A correlation was attempted between histopathological and IHC findings. Results were subjected to statistical analysis. Software program "the primer of biostatistics 5.0" was used for calculation of interrelationships between the analyzed ER, PR, p53, and Ki-67 expression and histological factors by Pearson′s Chi-square test. The results were considered to be significant when the P < 0.05. Results: There were 110 cases of surface epithelial ovarian tumors (SEOT encountered over the period of 4 years. The expression of ER was more in malignant tumors (13/16, 81.25% than borderline (9/12, 75% and benign (20/82, 24.39%. As compared to ER, the expression of PR was more in benign (51/82, 62.19% than borderline (8/12, 66.67% and malignant tumors (9/16, 56.25%. The expression of PR was more in benign tumors than borderline and malignant tumors. However, this was not statistically significant (Chi-square = 0.335 with 2 degrees of freedom; P = 0.846. The expression of p53 was less in benign (5/82, 6.1% than borderline (9/12, 75% and malignant tumors (13/16, 81.25%. The expression of Ki-67 was more in malignant (4/82, 4.88% than borderline (10/12, 83.33% and benign tumors (15/16, 93.75%. In all the above cases, the difference was statistically significant (P < 0.05. There was statistically significant difference in the expression of ER, PR, p53, and Ki-67 in the patients with

  6. High grade hemangioendothelioma of the temporal bone in a child: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyo Lim; Im, Soo Ah; Lim, Gye Yeon; Chun, Ho Jong; Lee, Hee Jeong; Park, Hyun Jin; Byun, Jae Young [The Catholic University of Korea, College of Medicine, Seoul (Korea, Republic of)

    2004-09-15

    Hemangioendothelioma is a rare vascular tumor characterized by endothelial tumor cells and variable malignant behavior, and it's not common for this lesion to involve the bone. Although there are a few reports of cranial involvement by hemangioendothelioma, only rare cases arising in temporal bone have been published. We present the radiologic findings of a 7-year-old boy who had a high grade hemangioendothelioma involving the temporal bone with intracranial extension. Evidence of flow voids on MR images suggested a tumor of vascular origin, and the ill-defined margins, cortical destruction and intracranial extension on the CT and MR images were correlated with the tumor's high histologic grade.

  7. Identifying grade/stage-related active modules in human co-regulatory networks: a case study for breast cancer.

    Science.gov (United States)

    Feng, Chenchen; Chen, Lina; Li, Wan; Wang, Hong; Zhang, Liangcai; Jia, Xu; Miao, Zhengqiang; Qu, Xiaoli; Li, Weiguo; He, Weiming

    2012-12-01

    The histological grade/stage of tumor is widely acknowledged as an important clinical prognostic factor for cancer progression. Recent experimental studies have explored the following two topics at the molecular level: (1) whether or not gene expression levels vary by different degrees among different tumor grades/stages, and (2) whether some well-defined modules could distinguish one grade/stage from another. In this article, using breast cancer as an example, we investigated this topic and identified grade/stage-related active modules under the framework of a weighted network integrated from a human protein interaction network and a transcriptional regulatory network. Our results enabled us to draw the conclusion that the gene expression profile could provide more clues about tumor grade, but reveals less evidence about tumor stage. In addition, we found that our modular biomarker method had additional advantages in identifying some tumor grade/stage-related genes with slightly altered expression. According to our case study, the framework we introduced could be used for other cancers to identify their modules during grading or staging.

  8. Vascular grading of angiogenesis

    DEFF Research Database (Denmark)

    Hansen, S; Grabau, D A; Sørensen, Flemming Brandt

    2000-01-01

    The study aimed to evaluate the prognostic value of angiogenesis by vascular grading of primary breast tumours, and to evaluate the prognostic impact of adding the vascular grade to the Nottingham Prognostic Index (NPI). The investigation included 836 patients. The median follow-up time was 11...... years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. Angiogenesis was graded semiquantitatively by subjective scoring into three groups according to the expected number of microvessels in the most vascular tumour area. The vascular grading between observers...... was moderately reproduced (kappa = 0.59). Vascular grade was significantly associated with axillary node involvement, tumour size, malignancy grade, oestrogen receptor status and histological type. In univariate analyses vascular grade significantly predicted recurrence free survival and overall survival for all...

  9. Oesophageal sarcomas in dogs: histological and clinical evaluation.

    Science.gov (United States)

    Ranen, Eyal; Dank, Gillian; Lavy, Eran; Perl, Samuel; Lahav, Dan; Orgad, Uri

    2008-10-01

    A histological grading system of oesophageal sarcomas has not been established. Thirty-two cases of oesophageal sarcomas have been reviewed for tumour characteristics and clinical outcome. Nineteen dogs underwent surgical intervention to remove oesophageal tumours; ten of them survived (median 278 days). Primary tumour types included osteosarcoma (47%), osteosarcoma with tumour giant cells (7%), fibroblastic osteosarcoma (13%), chondroblastic osteosarcoma (7%) fibrosarcoma (23%) and undifferentiated sarcoma (3%). Histological grade evaluation revealed 33% grade 1 sarcoma, 50% grade 2 and 17% grade 3. No correlation could be found between survival and signalment, duration of clinical signs, tumour type, tumour grade and chemotherapy. Chemotherapy was found to reduce lung metastases' histological scores in three cases (P=0.0007). Surgery seems to be the treatment of choice but the effect of chemotherapy warrants further investigation. Additional research of cases should be performed in order to further define prognostic factors of oesophageal sarcomas.

  10. Correlation of SUV-Derived Indices With Tumoral Aggressiveness of Gliomas in Static 18F-FDOPA PET: Use in Clinical Practice.

    Science.gov (United States)

    Janvier, Lucile; Olivier, Pierre; Blonski, Marie; Morel, Olivier; Vignaud, Jean-Michel; Karcher, Gilles; Taillandier, Luc; Verger, Antoine

    2015-09-01

    Glioma grading is necessary for prognostic evaluation and optimal treatment decisions. The aims of this study were to establish whether a correlation between F-FDOPA uptake with tumor grade was observed and to determine which of the SUV-derived indices was the best correlated. Thirty-one patients were retrospectively included (mean [SD] age, 36.8 [12.1] years) including 21 proven low-grade tumors due to histology, imaging, and clinical follow-up and 10 histologically proven high-grade tumors. Static PET acquisitions were postreconstructed between the 10th and 30th minute after injection of F-FDOPA. Regions of interest of 20 mm were applied to tumors, and isocontoured volumes were defined at levels of 50% and 80% of the peak intensity voxel. Background was quantified with 30-mm-diameter regions of interest on contralateral striatum and centrum semioval. Tumoral uptake was evaluated with the following SUV-derived indices: SUVmax, SUVmean, SUVmax, and SUVmean of isocontoured volume, tumor/striatum ratio (T/S), and tumor/normal brain ratio (T/N). All the SUV-derived indices tested were significantly correlated with tumor grade, considering low-grade and high-grade groups (P < 0.05), except for the SUVmean 50%. The 2 best-correlated indices were SUVmean T/N and SUVmean T/S, with correlation coefficients of 0.561 and 0.522, respectively. Receiver operating characteristic analysis defined optimal thresholds of 1.33 and 1 for sensitivity and specificity of 71% and 100% and 67% and 100%, respectively. F-FDOPA PET SUV-derived indices are routinely available information that enables accurate discrimination of low-grade and high-grade gliomas. The best-correlated indices were SUVmean T/N and SUVmean T/S with thresholds of 1.33 and 1.

  11. N-Acetylcysteine Supplementation Controls Total Antioxidant Capacity, Creatine Kinase, Lactate, and Tumor Necrotic Factor-Alpha against Oxidative Stress Induced by Graded Exercise in Sedentary Men

    Directory of Open Access Journals (Sweden)

    Donrawee Leelarungrayub

    2011-01-01

    Full Text Available Aim of this study was to evaluate the effects of short-term (7 days N-acetylcysteine (NAC at 1,200 mg daily supplementation on muscle fatigue, maximal oxygen uptake (VO2max, total antioxidant capacity (TAC, lactate, creatine kinase (CK, and tumor necrotic factor-alpha (TNF-α. Twenty-nine sedentary men (13 controls; 16 in the supplement group from a randomized control were included. At before and after supplementation, fatigue index (FI was evaluated in the quadriceps muscle, and performed a graded exercise treadmill test to induce oxidative stress, and as a measure of VO2max. Blood samples were taken before exercise and 20 minutes after it at before and after supplementation, to determine TAC, CK, lactate, and TNF-α levels. Results showed that FI and VO2max increased significantly in the supplement group. After exercise decreased the levels of TAC and increased lactate, CK, and TNF-α of both groups at before supplementation. After supplementation, lactate, CK, and TNF-α levels significantly increased and TAC decreased after exercise in the control group. Whereas the TAC and lactate levels did not change significantly, but CK and TNF-α increased significantly in the supplement group. Therefore, this results showed that NAC improved the muscle fatigue, VO2max, maintained TAC, controlled lactate production, but had no influence on CK and TNF-α.

  12. N-acetylcysteine supplementation controls total antioxidant capacity, creatine kinase, lactate, and tumor necrotic factor-alpha against oxidative stress induced by graded exercise in sedentary men.

    Science.gov (United States)

    Leelarungrayub, Donrawee; Khansuwan, Raphiphat; Pothongsunun, Prapas; Klaphajone, Jakkrit

    2011-01-01

    Aim of this study was to evaluate the effects of short-term (7 days) N-acetylcysteine (NAC) at 1,200 mg daily supplementation on muscle fatigue, maximal oxygen uptake (VO(2max)), total antioxidant capacity (TAC), lactate, creatine kinase (CK), and tumor necrotic factor-alpha (TNF-α). Twenty-nine sedentary men (13 controls; 16 in the supplement group) from a randomized control were included. At before and after supplementation, fatigue index (FI) was evaluated in the quadriceps muscle, and performed a graded exercise treadmill test to induce oxidative stress, and as a measure of VO(2max). Blood samples were taken before exercise and 20 minutes after it at before and after supplementation, to determine TAC, CK, lactate, and TNF-α levels. Results showed that FI and VO(2max) increased significantly in the supplement group. After exercise decreased the levels of TAC and increased lactate, CK, and TNF-α of both groups at before supplementation. After supplementation, lactate, CK, and TNF-α levels significantly increased and TAC decreased after exercise in the control group. Whereas the TAC and lactate levels did not change significantly, but CK and TNF-α increased significantly in the supplement group. Therefore, this results showed that NAC improved the muscle fatigue, VO(2max), maintained TAC, controlled lactate production, but had no influence on CK and TNF-α.

  13. HistologiQuiz

    DEFF Research Database (Denmark)

    Brent, Mikkel Bo

    2015-01-01

    HistologiQuiz er en quiz-app udviklet til almen og speciel histologi. Den består af mere end 1400 spørgsmål og over 320 histologiske billeder. Alle spørgsmål tager udgangspunkt i lærebogen Genesers Histologi af Annemarie Brüel m.fl.......HistologiQuiz er en quiz-app udviklet til almen og speciel histologi. Den består af mere end 1400 spørgsmål og over 320 histologiske billeder. Alle spørgsmål tager udgangspunkt i lærebogen Genesers Histologi af Annemarie Brüel m.fl....

  14. Tumor budding is associated with an increased risk of lymph node metastasis and poor prognosis in superficial esophageal adenocarcinoma.

    Science.gov (United States)

    Landau, Michael S; Hastings, Steven M; Foxwell, Tyler J; Luketich, James D; Nason, Katie S; Davison, Jon M

    2014-12-01

    The treatment approach for superficial (stage T1) esophageal adenocarcinoma critically depends on the pre-operative assessment of metastatic risk. Part of that assessment involves evaluation of the primary tumor for pathologic characteristics known to predict nodal metastasis: depth of invasion (intramucosal vs submucosal), angiolymphatic invasion, tumor grade, and tumor size. Tumor budding is a histologic pattern that is associated with poor prognosis in early-stage colorectal adenocarcinoma and a predictor of nodal metastasis in T1 colorectal adenocarcinoma. In a retrospective study, we used a semi-quantitative histologic scoring system to categorize 210 surgically resected, superficial (stage T1) esophageal adenocarcinomas according to the extent of tumor budding (none, focal, and extensive) and also evaluated other known risk factors for nodal metastasis, including depth of invasion, angiolymphatic invasion, tumor grade, and tumor size. We assessed the risk of nodal metastasis associated with tumor budding in univariate analyses and controlled for other risk factors in a multivariate logistic regression model. In all, 41% (24 out of 59) of tumors with extensive tumor budding (tumor budding in ≥3 20X microscopic fields) were metastatic to regional lymph nodes, compared with 10% (12 out of 117) of tumors with no tumor budding, and 15% (5 out of 34) of tumors with focal tumor budding (Ptumor budding remains an independent risk factor for lymph node metastasis in superficial esophageal adenocarcinoma associated with a 2.5-fold increase (95% CI=1.1-6.3, P=0.039) in the risk of nodal metastasis. Extensive tumor budding is also a poor prognostic factor with respect to overall survival and time to recurrence in univariate and multivariate analyses. As an independent risk factor for nodal metastasis and poor prognosis after esophagectomy, tumor budding should be evaluated in superficial (T1) esophageal adenocarcinoma as a part of a comprehensive pathologic risk

  15. Reproducibility of two malignancy grading systems with reportedly prognostic value for oral cancer patients.

    Science.gov (United States)

    Bryne, M; Nielsen, K; Koppang, H S; Dabelsteen, E

    1991-09-01

    Supplementary prognostic factors should be added to the TNM classification for oral squamous cell carcinomas in order to optimize its clinical value. We have recently published two prognostically valuable malignancy grading systems based on histopathology and immunohistology of the most invasive cells in oral squamous cell carcinomas (OSCCs). However, a major problem with classifications based on histologic features is frequent lack of interobserver agreement which limits the clinical value of subjective histologic classifications. Thirty-eight file cases of OSCCs were therefore graded by three pathologists according to criteria of the histologic malignancy grading system which includes 5 morphologic features, each graded from 1 to 4. Agreement was calculated by kappa statistics, which showed that interobserver agreement was not optimal, but significantly better than by chance alone. We also studied the reproducibility of grading of immunohistologic membrane expression of a tumor-associated marker (blood group antigen H), and found a similar level of agreement. We conclude that the clinical value of our grading systems will increase by improving reproducibility.

  16. Sclerosing PEComa: A Histologic Surprise | Valiathan | African ...

    African Journals Online (AJOL)

    Sclerosing PEComa: A Histologic Surprise. M Valiathan, BP Sunil, L Rao, V Geetha, P Hedge. Abstract. PEComa represents a group of mesenchymal tumors consisting of perivascular epithelioid cells. We present a 50-year old female patient with a rare distinctive variant, sclerosing PEComa, characterized by extensive ...

  17. Tumor budding is an independent predictor of outcome in AJCC/UICC stage II colorectal cancer.

    Science.gov (United States)

    Betge, Johannes; Kornprat, Peter; Pollheimer, Marion J; Lindtner, Richard A; Schlemmer, Andrea; Rehak, Peter; Vieth, Michael; Langner, Cord

    2012-11-01

    In colorectal cancer, the morphology of the invasive tumor margin may reflect aggressiveness of tumor growth, thus providing important prognostic information. The tumor growth pattern according to Jass and the extent of tumor budding were analyzed in patients with American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) stage II disease. Tumors of 120 randomly selected patients with AJCC/UICC stage II disease were retrospectively reviewed for tumor growth pattern (expanding vs. infiltrating) and the extent of tumor budding, with high-grade budding reflecting presence of 10 or more budding foci scattered at the invasive tumor margin. Progression-free and cancer-specific survivals were determined by the Kaplan-Meier method. For multivariable analysis, Cox's proportional hazards regression models were performed. The infiltrating growth pattern was significantly associated with histological subtype and lymphovascular invasion, while high-grade budding was significantly associated with tumor grade and lymphovascular invasion. High-grade budding, but not the infiltrating growth pattern, was significantly associated with outcome in univariable analysis. Cox's proportional hazards regression models proved tumor budding to be an independent predictor of disease progression (hazard ratio 3.91, 95 % confidence interval 1.3-11.77; P = 0.02) and cancer-related death (hazard ratio 5.90, 95 % confidence interval 1.62-21.51; P = 0.007). The combination of infiltrating growth pattern and high-grade budding did not have a stronger prognostic significance than tumor budding alone. Tumor budding independently predicted patient outcome in patients with AJCC/UICC stage II colorectal cancer and may therefore be used for accurate prognostication, patient counseling, and design of clinical trials by using integrated multimodal therapy.

  18. Correlating Tumor Stiffness with Immunohistochemical Subtypes of Breast Cancers: Prognostic Value of Comb-Push Ultrasound Shear Elastography for Differentiating Luminal Subtypes.

    Directory of Open Access Journals (Sweden)

    Max Denis

    Full Text Available The purpose of our study is to correlate quantitatively measured tumor stiffness with immunohistochemical (IHC subtypes of breast cancer. Additionally, the influence of prognostic histologic features (cancer grade, size, lymph node status, and histological type and grade to the tumor elasticity and IHC profile relationship will be investigated.Under an institutional review board (IRB approved protocol, B-mode ultrasound (US and comb-push ultrasound shear elastography (CUSE were performed on 157 female patients with suspicious breast lesions. Out of 157 patients 83 breast cancer patients confirmed by pathology were included in this study. The association between CUSE mean stiffness values and the aforementioned prognostic features of the breast cancer tumors were investigated.Our results demonstrate that the most statistically significant difference (p = 0.0074 with mean elasticity is tumor size. When considering large tumors (size ≥ 8mm, thus minimizing the statistical significance of tumor size, a significant difference (p 20% subtypes.Tumor size is an independent factor influencing mean elasticity. The Ki-67 proliferation index and histological grade were dependent factors influencing mean elasticity for the differentiation between luminal subtypes. Future studies on a larger group of patients may broaden the clinical significance of these findings.

  19. Clinico-Histologic Conferences: Histology and Disease

    Science.gov (United States)

    Shaw, Phyllis A.; Friedman, Erica S.

    2012-01-01

    Providing a context for learning information and requiring learners to teach specific content has been demonstrated to enhance knowledge retention. To enhance students' appreciation of the role of science and specifically histology in clinical reasoning, disease diagnosis, and treatment, a new teaching format was created to provide clinical…

  20. Correlation of the presence and extent of loss of heterozygosity mutations with histological classifications of Barrett’s esophagus

    Directory of Open Access Journals (Sweden)

    Ellsworth Eric

    2012-12-01

    Full Text Available Abstract Background Recent advances in the management of Barrett’s Esophagus (BE have placed greater emphasis on accurate diagnosis of BE as well as better prediction of risk for progression to esophageal adenocarcinoma (EAC. Histological evaluation of BE is particularly challenging with significant inter-observer variability. We explored the presence and extent of genomic instability in BE biopsy specimens as a means to add supplementary information to the histological classification and clinical decision-making related to early disease. Methods We reviewed histology slides from 271 patients known to have BE. Using histological features as a guide, we microdissected target cell populations with various histological classifications of BE (intestinal metaplasia, “indefinite for dysplasia”, low grade dysplasia, or high grade dysplasia. DNA was extracted from microdissected targets and analyzed for loss of heterozygosity (LOH using a panel of 16 LOH mutational markers associated with tumor suppressor genes at chromosomal loci 1p, 3p, 5q, 9p, 10q, 17p, 17q, 18q, 21q, 22q. The presence or absence of mutations and the clonality of each mutation were determined for each marker. Results The presence and clonal expansion of LOH mutations was formulated into mutational load (ML for each microdissected target analyzed. ML correlated with the histological classification of microdissected targets, with increasingly severe histology having higher ML. Three levels of mutation load (no ML, low ML, and high ML were defined based on the population of microdissected targets histologically classified as intestinal metaplasia. All microdissected targets with dysplasia had mutations, with a high ML consistently present in high grade dysplasia targets. Microdissected targets histologically classified as intestinal metaplasia or “indefinite for dysplasia” spanned a range of no, low, and high ML. Conclusions The results of this study reinforce the association

  1. Magnetic resonance imaging of low-grade fibromyxoid sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Torriani, Martin; Ouellette, Hugue [Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States). Dept. of Radiology. Div. of Musculoskeletal Radiology; Etchebehere, Mauricio [Universidade Estadual de Campinas, SP (Brazil). Faculdade de Ciencias Medicas. Dept. de Ortopedia; Amstalden, Eliane M.I. [Universidade Estadual de Campinas, SP (Brazil). Faculdade de Ciencias Medicas. Dept. de Patologia

    2006-06-15

    Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft-tissue tumor with a deceptively benign histologic appearance affecting predominantly young adults during the fourth decade of life. (MR) imaging features of a surgically confirmed case of LGFMS, affecting the shoulder is presented. A 30-year-old man presented with a 20-year history of a painless slow-growing mass in the right shoulder. Magnetic resonance images were obtained on a 2.0T scanner (Elscint, Haifa, Israel), demonstrating a well-defined soft tissue mass measuring 12.0 x 7.0 x 9.0 cm located between the deltoid muscle, rotator-cuff muscles, and proximal humerus. The differential diagnosis of LGFMS includes several benign and malignant neoplasms containing variable amounts of myxoid and fibrous tissue. Histologically, the most important differential diagnosis is with myxofibrosarcoma. Low-grade fibromyxoid sarcoma is a rare soft tissue tumor with slow growth and deceptively benign histologic appearance. The possibility of LGFMS must be considered when elaborating differential diagnostic possibilities for young adults with a large soft tissue mass exhibiting MR imaging characteristics of intermixed fibrous and myxoid tissue.

  2. Next-Gen Sequencing Exposes Frequent MED12 Mutations and Actionable Therapeutic Targets in Phyllodes Tumors

    Science.gov (United States)

    Cani, Andi K.; Hovelson, Daniel H.; McDaniel, Andrew S.; Sadis, Seth; Haller, Michaela J.; Yadati, Venkata; Amin, Anmol M.; Bratley, Jarred; Bandla, Santhoshi; Williams, Paul D.; Rhodes, Kate; Liu, Chia-Jen; Quist, Michael J.; Rhodes, Daniel R.; Grasso, Catherine S.; Kleer, Celina G.; Tomlins, Scott A.

    2016-01-01

    Phyllodes tumors are rare fibroepithelial tumors with variable clinical behavior accounting for a small subset of all breast neoplasms, yet little is known about the genetic alterations that drive tumor initiation and/or progression. Here targeted next generation sequencing (NGS) was used to identify somatic alterations in formalin fixed paraffin embedded (FFPE) patient specimens from malignant, borderline and benign cases. NGS revealed mutations in mediator complex subunit 12 (MED12) affecting the G44 hotspot residue in the majority (67%) of cases spanning all three histological grades. In addition, loss-of-function mutations in p53 (TP53) as well as deleterious mutations in the tumor suppressors retinoblastoma (RB1) and neurofibromin 1 (NF1) were identified exclusively in malignant tumors. High-level copy number alterations (CNAs) were nearly exclusively confined to malignant tumors, including potentially clinically actionable gene amplifications in IGF1R and EGFR. Taken together, this study defines the genomic landscape underlying phyllodes tumor development, suggests potential molecular correlates to histologic grade, expands the spectrum of human tumors with frequent recurrent MED12 mutations, and identifies IGF1R and EGFR as potential therapeutic targets in malignant cases. PMID:25593300

  3. Esophageal Carcinoma Histology Affects Perioperative Morbidity Following Open Esophagogastrectomy

    Directory of Open Access Journals (Sweden)

    Charles E. Woodall

    2008-01-01

    Full Text Available Background. Esophagectomy for esophageal cancer is being practiced routinely with favorable results at many centers. We sought to determine if tumor histology is a powerful surrogate marker for perioperative morbidity. Methods. Seventy three consecutive patients managed operatively were reviewed from our prospectively maintained database. Results. Adenocarcinoma (AC was present in 52 (71% and squamous cell (SCC in 21 (29%. The use of neoadjuvant therapy was similar for the AC (34.62% and SCC (42.86% groups. The SCC group had a higher incidence of prior pulmonary disease than the AC group (23.8% versus 5.8%, resp.; =.03. SCC patients were more likely to have a prolonged ICU stay than AC patients (=.004 despite similar complication rates, EBL, and prognostic nutritional index. The SCC group did, however, experience higher grades of complications (=.0053. Conclusions. Presence of SCC was the single best predictor of prolonged ICU stay and more severe complications as defined by this study. Only a past history of pulmonary disease was different between the two histologic subgroups.

  4. [Histological and molecular classification of endometrial carcinoma and therapeutical implications].

    Science.gov (United States)

    Genestie, Catherine; Leary, Alexandra; Devouassoux, Mojgan; Auguste, Aurélie

    2017-12-01

    Endometrial cancer is the fourth cause of cancer in women in France and is the second most common cancer of the gynecologic cancer after breast cancer with 7275 new cases in 2012. The incidence of this neoplasm tends to increase with population aging, diabetes and obesity's augmentation. In rare cases, a hereditary factor has been described: Lynch's syndrome. The therapeutic management of the patient depends on the endometrial biopsy which specifies the histological type and the histo-prognostic grade as well as the MRI which allow the tumor staging. Within the last decade, improvement in technologies such as genomic, transcriptomic and histological analyses, allowed the establishment of new and finer classifications of endometrial carcinomas. The latest classification proposed by The Cancer Genomic Atlas (TCGA), has been made routinely applicable through the international consortium TransPORTEC. It consists of 4 groups listed from good to poor prognosis: (1) ultra-mutated "POLE"; (2) hyper-mutated "MSI"; (3) low copy number "NSMP" and (4) high number of copies "TP53 mutated" (serous-like). This integrated characterization combined with mutational data opens new opportunities for therapeutic strategies. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  5. c-erbB-2 expression and nuclear pleomorphism in canine mammary tumors

    Directory of Open Access Journals (Sweden)

    Dutra A.P.

    2004-01-01

    Full Text Available The objective of the present investigation was to study the expression of c-erbB-2 and MIB-1 and try to associate them with morphological features of the cell such as nuclear pleomorphism, mitotic count and histological grade in a series of 70 canine mammary gland tumors, 22 of them benign and 48 malignant. Tumors were collected at the Veterinary Hospital of UFMG (Brazil and the Veterinary Faculty of Porto University (Portugal. c-erbB-2 expression was determined according to the guidelines provided by the manufacturer of the HercepTest system and nuclear pleomorphism, mitotic count and histological grade according the Elston and Ellis grading system. The HercepTest is the FDA-approved in vitro diagnostic test marketed by Dako. It is a semi-quantitative immunohistochemical assay used to determine overexpression of HER2 protein (human epidermal growth factor receptor in breast cancer tissue. MIB-1 expression was also evaluated in 28 malignant tumors. Seventeen (35.4% of the malignant tumors were positive for c-erbB-2 expression, which was positively associated with nuclear pleomorphism (P < 0.0001, histological grade (P = 0.0017 and mitotic count (P < 0.05. Nuclear pleomorphism also showed a positive association with MIB-1 index (P < 0.0001. These results suggest that some of the biological and morphological characteristics of the tumor are associated in canine mammary gland tumors, as also reported for human breast cancer. It was also possible to show that the immunoexpression of c-erbB-2 can be a factor in mammary carcinogenesis. This fact opens the possibility of using anti-c-erbB-2 antibodies in the treatment of canine mammary tumors.

  6. Comparison of myometrial invasion and tumor free distance from uterine serosa in endometrial cancer.

    Science.gov (United States)

    Ozbilen, Ozlem; Sakarya, Derya Kilic; Bezircioglu, Incim; Kasap, Burcu; Yetimalar, Hakan; Yigit, Seyran

    2015-01-01

    We aimed to investigate whether the tumor free distance (the distance between the uterine serosa and the tumor at its deepest point) is useful in surgical staging and in predicting prognosis. Data from patients who underwent complete surgical staging for endometrial cancer between January 2006 and June 2011 were reviewed retrospectively. All demographic findings, surgical stages, histological type and grade, myometrial invasion, lymphovascular space invasion as well as abdominal cytology, cervical, adnexal, and omental involvement, and lymph node metastasis were recorded. The relations between myometrial invasion and tumor free distance from uterine serosa with prognostic factors were investigated. Seventy patients were included in the study. Sixty-four (91.5%) had endometrioid type cancers and forty-four (62.9%) were grade 1. The deepest myometrial invasion was less than 1/2 in 42 patients (60%). In 18 patients (25.8%) lymphovascular invasion was noted. Eight (11.4%) were found to have cervical involvement, five (7.1%) had adnexal involvement and in 4 cases (5.7%) the peritoneal washings included malignant cells. Four patients had pelvic and one para-aortic node metastasis. We recognized that an invasion of more than 1/2 was correlated significantly with lymphovascular space involvement, histological grade, positive abdominal washing cytology, nodal and cervical involvement, but not with adnexal involvement. Tumor-free myometrial thickness was negative and statistically significant correlated with surgical stage, histological grade, lymphovascular space involvement, positive abdominal washing cytology, cervical and adnexal involvement. The importance of tumor- free myometrial thickness in determinating the lymphovascular space invasion was found to be highest in terms of sensitivity and specificity when crossing the ROC curve at 11 millimeters. Depth of myometrial invasion is more valuable for predicting lymph node metastasis than tumor-free myometrial thickness

  7. Cognitive outcome after awake surgery for tumors in language areas.

    Science.gov (United States)

    Santini, B; Talacchi, A; Squintani, G; Casagrande, F; Capasso, R; Miceli, G

    2012-06-01

    In surgery for tumors of the dominant hemisphere, the attention devoted to quality of resection and preservation of language function has not been accompanied by comparable interest in preservation of cognitive abilities which may affect quality of life. We studied 22 patients undergoing awake surgery for glioma removal in the language areas of the brain. Besides monitoring tumor variables (size, location, histology, edema), we used a multifaceted battery of tests to investigate mood, cognition, and language in an attempt to assess the burden of disease and treatment, and the relationships between these three dimensions. Baseline assessment showed that 45% of the patients were depressed and 23% anxious; some cognitive and language impairment was noted for 59 and 50%, respectively. A general decline in postoperative cognitive performance (significant for memory and attention only) and language function (significant for picture naming) was observed, whereas depression was unchanged and anxiety decreased. Tumor histology, but not demographic variables or extent of resection, correlated with postoperative cognitive changes: patients undergoing surgery for high-grade tumors were more likely to improve. No correlation was observed between scores for mood, cognition, and language function. A subset of patients with low-grade glioma was followed up for 3-6 months; although some improvement was observed they did not always regain their preoperative performance. In conclusion, we believe that cognitive assessment performed in conjunction with language testing is a necessary step in the global evaluation of brain tumor patients both before and after surgery.

  8. Correlation between 3T apparent diffusion coefficient values and grading of invasive breast carcinoma.

    Science.gov (United States)

    Cipolla, Valentina; Santucci, Domiziana; Guerrieri, Daniele; Drudi, Francesco Maria; Meggiorini, Maria Letizia; de Felice, Carlo

    2014-12-01

    The aim of this study was to evaluate whether the apparent diffusion coefficient (ADC) provided by 3.0T (3T) magnetic resonance diffusion-weighted imaging (DWI) varied according to the grading of invasive breast carcinoma. A total of 92 patients with 96 invasive breast cancer lesions were enrolled; all had undergone 3T magnetic resonance imaging (MRI) for local staging. All lesions were confirmed by histological analysis, and tumor grade was established according to the Nottingham Grading System (NGS). MRI included both dynamic contrast-enhanced and DWI sequences, and ADC value was calculated for each lesion. ADC values were compared with NGS classification using the Mann-Whitney U and the Kruskal-Wallis H tests. Grading was considered as a comprehensive prognostic factor, and Rho Spearman test was performed to determine correlation between grading and tumor size, hormonal receptor status, HER2 expression and Ki67 index. Pearson's Chi square test was carried out to compare grading with the other prognostic factors. ADC values were significantly higher in G1 than in G3 tumors. No significant difference was observed when G1 and G3 were compared with G2. Tumor size, hormonal receptor status, HER2 expression and Ki67 index correlated significantly with grading but there was a significant difference only between G1 and G3 related to the ER and PR status, HER2 expression and Ki67 index. There was no statistically significant difference in lesion size between the two groups. ADC values obtained on 3T DWI correlated with low-grade (G1) and high-grade (G3) invasive breast carcinoma. 3T ADC may be a helpful tool for identifying high-grade invasive breast carcinoma. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Low-grade fibromyxoid sarcoma: case report and immunohistochemical study.

    Science.gov (United States)

    Nichols, G E; Cooper, P H

    1994-08-01

    A case is presented of low-grade fibromyxoid sarcoma involving the arm of a 52-year-old man. Low-grade fibromyxoid sarcoma is a recently described neoplasm of the deep and subcutaneous soft tissue which demonstrates a spectrum of histologic images. The current case demonstrated the typical patterns of intermixed, sweeping bands of fibrous and myxoid tissue, homogeneous foci of fibrous and myxoid tissue, focal areas of storiforming, and concentric perivascular cuffs of slender spindle cells, all lacking the nuclear anaplasia, mitotic activity, and necrosis generally associated with sarcoma. Immunohistochemical analysis performed on paraffin-embedded sections demonstrated strong labeling of the tumor cells by anti-CD34 antibody, moderate labeling for vimentin, and rare, focal positivity for muscle-specific actin. Tumor cells were negative for markers of epithelial, muscular, neural, histiocytic, melanocytic, and vascular differentiation. The constellation of histopathologic features described in this and previous reports is characteristic of low-grade fibromyxoid sarcoma. Based on this case, it appears that the immunohistochemical features of low-grade fibromyxoid sarcoma can help to exclude many cutaneous and deep soft tissue tumors from the differential diagnosis. The findings support the interpretation that the neoplasm is essentially fibroblastic in nature.

  10. the histological effects of formaldehyde vapour on the lungs

    African Journals Online (AJOL)

    Uwaifoh

    2012-12-31

    Dec 31, 2012 ... lung injury, pulmonary fibrosis, bronchiolar epithelia degeneration, acute purulent bronchitis, cellular pyknosis and chronic lungs injury. Thus, 40% formaldehyde inhalation can induce lungs injury and possibly lung tumors. Keywords: Formaldehyde, Inhalation, Pulmonary histology, Lung injury.

  11. Multi-modal image registration: matching MRI with histology

    NARCIS (Netherlands)

    Alić, L.; Haeck, J.C.; Klein, S.; Bol, K.; Tiel, S.T. van; Wielopolski, P.A.; Bijster, M.; Niessen, W.J.; Bernsen, M.; Veenland, J.F.; Jong, M. de

    2010-01-01

    Spatial correspondence between histology and multi sequence MRI can provide information about the capabilities of non-invasive imaging to characterize cancerous tissue. However, shrinkage and deformation occurring during the excision of the tumor and the histological processing complicate the co

  12. Aggressive malignant phyllodes tumor

    OpenAIRE

    Nathan Roberts; Dianne M. Runk

    2015-01-01

    Introduction: Originally described in 1838 by Muller, phyllodes tumor is a rare fibroepithelial neoplasm which represents roughly 0.3–0.9% of all breast cancers. Phyllodes tumor are divided into benign, borderline and malignant histologic categories. Malignant phyllodes tumor represent anywhere from 10–30% of all phyllodes tumors. This group has both the potential to recur locally and metastasize, however not all malignant phyllodes behave this way. The challenge lays in predicting which tumo...

  13. Magnetic resonance characterization of tumor microvessels in experimental breast tumors using a slow clearance blood pool contrast agent (carboxymethyldextran-A2-Gd-DOTA) with histopathological correlation.

    Science.gov (United States)

    Preda, Anda; Novikov, Viktor; Möglich, Martina; Floyd, Eugenia; Turetschek, Karl; Shames, David M; Roberts, Timothy P L; Corot, Claire; Carter, Wayne O; Brasch, Robert C

    2005-11-01

    Carboxymethyldextran (CMD)-A2-Gd-DOTA, a slow clearance blood pool contrast agent with a molecular weight of 52.1 kDa, designed to have intravascular residence for more than 1 h, was evaluated for its potential to characterize and differentiate the microvessels of malignant and benign breast tumors. Precontrast single-slice inversion-recovery snapshot FLASH and dynamic contrast-enhanced MRI using an axial T1-weighted three-dimensional spoiled gradient recalled sequence was performed in 30 Sprague-Dawley rats with chemically induced breast tumors. Endothelial transfer coefficient and fractional plasma volume of the breast tumors were estimated from MRI data acquired with CMD-A2-Gd-DOTA enhancement injected at a dose of 0.1 mmol Gd/kg body weight using a two-compartment bidirectional model of the tumor tissue. The correlation between MRI microvessel characteristics and histopathological tumor grade was determined using the Scarff-Bloom-Richardson method. Using CMD-A2-Gd-DOTA, no significant correlations were found between the MR-estimated endothelial transfer coefficient or plasma volumes with histological tumor grade. Analysis of CMD-A2-Gd-DOTA-enhanced MR kinetic data failed to demonstrate feasibility for the differentiation of benign from malignant tumors or for image-based tumor grading.

  14. ER-positive breast cancer patients with more than three positive nodes or grade 3 tumors are at high risk of late recurrence after 5-year adjuvant endocrine therapy.

    Science.gov (United States)

    Song, Fangbin; Zhang, Jianbing; Li, Shanbao; Wu, Junyi; Jin, Tao; Qin, Jun; Wang, Ye; Wang, Min; Xu, Junming

    2017-01-01

    Currently, although several clinical trials available give strong suggestions that extension of endocrine therapy has benefits, the risk level at which patients may benefit from extended endocrine therapy remains uncertain. This study aimed to identify the proportion of patients at a substantial risk of late recurrence after 5-year adjuvant endocrine therapy. We reviewed 1,056 female patients with primary breast cancer who underwent curative resection between January 2006 and December 2011. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model to identify prognostic factors. A total of 327 eligible patients were eventually enrolled in this study. Among them, 42 (12.8%) patients suffered from distant metastasis and 34 (10.4%) patients experienced locoregional recurrence after 5-year adjuvant endocrine therapy. In multivariate analysis, patients with more than three positive nodes (hazard ratio [HR] =2.176, 95% CI=1.071-4.421; P =0.032) and histologic grade 3 disease (HR=2.098, 95% CI=1.300-3.385; P =0.002) were significantly associated with high risk of late recurrence. However, only histologic grade 3 (HR=2.212, 95% CI=1.166-4.194; P =0.015) was significantly associated with high risk of distant metastasis. Late relapse after completion of 5-year adjuvant endocrine therapy was still common, and grade 3 and more than three positive nodes were the risk factors of late recurrence, while grade 3 was the only risk factor of late distant metastasis. These patients might benefit from extended endocrine therapy.

  15. Low-Grade Uterine Epithelioid Hemangioendothelioma Presented as a Submucosal Leiomyoma during Labor

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    Anastasios V. Koutsopoulos

    2013-01-01

    Full Text Available With the exception of leiomyomas, soft tissue tumors of the uterine corpus are not common. This is particularly true for vascular neoplasms, with the epithelioid hemangioendothelioma being a curiosity; not more than twenty-two cases of malignant hemangioendotheliomas have been reported in the literature so far, all of which were high-grade hemangioendotheliomas (hemangiosarcomas. We present herewith a unique case of low-grade epithelioid hemangioendothelioma of the uterus in a pregnant woman aged 29 years. The clinical, histological, and immunohistochemical characteristics of this entity, together with its differential diagnosis, are discussed.

  16. The response of variant histology bladder cancer to intravesical immunotherapy compared to conventional cancer

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    Ofer Nathan Gofrit

    2016-03-01

    Full Text Available Background: High-grade urothelial carcinomas (UC often show foci of variant differentiation. There is limited information in the literature about the response of these variant urothelial tumors to immunotherapy with Bacillus Calmette Guerin (BCG. We compared the response to treatment with BCG of UC containing glandular, squamous, nested and micropapillary types of differentiation to response of conventional non-muscle invasive high-grade urothelial carcinoma. Methods: A total of 100 patients were diagnosed with variant histology urothelial cancer between June 1995 and December 2013. 41 patients with Ta or T1, confirmed by 2nd look biopsies, received immunotherapy with BCG. Fourteen patients in this group were diagnosed with micropapillary differentiation 13 patients with squamous differentiation, in 9 patients glandular differentiation was seen and in 7 patients nested variant. The control group included 140 patients with conventional high-grade UC. Both groups have been treated and followed similarly. Findings: Patients with variant tumors had similar clinical features to patients with conventional disease including: age, males to female ratio, stage, presence of Tis and median follow-up. Patients with variant tumors had a significantly worse prognosis compared to patients with conventional high-grade UC including: 5-year recurrence-free survival (63.5% Vs. 71.5%, p=0.05, 5-year progression to≥T2 -free survival (60% Vs. 82.5%, p=0.002, 5-year disease-specific survival (73% Vs. 92.5%, p=0.0004 and overall survival (66% Vs. 89.5%, 0.05. Interpretation: A patient with variant bladder cancer treated with intra-vesical immunotherapy has a 27% chance of dying from this disease within 5-years compared to 7.5% for a patient with conventional high-grade UC.

  17. Bortezomib sensitizes primary human astrocytoma cells of WHO grades I to IV for tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis

    NARCIS (Netherlands)

    Koschny, Ronald; Holland, Heidrun; Sykora, Jaromir; Haas, Tobias L.; Sprick, Martin R.; Ganten, Tom M.; Krupp, Wolfgang; Bauer, Manfred; Ahnert, Peter; Meixensberger, Jürgen; Walczak, Henning

    2007-01-01

    Malignant gliomas are the most aggressive human brain tumors without any curative treatment. The antitumor effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in gliomas has thus far only been thoroughly established in tumor cell lines. In the present study, we investigated the

  18. Benign and malignant cartilage tumors of bone and joint: their anatomic and theoretical basis with an emphasis on radiology, pathology and clinical biology. II. Juxtacortical cartilage tumors

    Energy Technology Data Exchange (ETDEWEB)

    Brien, E.W. [Orthopaedic Oncology Service, Orthopaedic Hospital, Los Angeles, CA (United States)]|[Musculoskeletal Tumor Service, Orthopaedic Hospital, Los Angeles, CA (United States); Mirra, J.M.; Luck, J.V. Jr. [Orthopaedic Oncology Service, Orthopaedic Hospital, Los Angeles, CA (United States)

    1999-01-01

    In part I, we reviewed the varied clinical presentations, pathogenesis, histologic findings, radiologic findings, and treatment of intramedullary cartilaginous lesions of bone. In this section, we will evaluate our cases and consultations of juxtacortical cartilaginous tumors. Radiographic differential diagnosis includes the numerous juxtacortical lesions particularly osteochondroma, parosteal chondroma, Trevor`s disease, trauma (fracture and periostitis ossificans), and the low- and high-grade surface osteosarcomas. By emphasizing pathogenesis in conjunction with radiographic and histologic findings, pitfalls in diagnosis and subsequent treatment can be avoided in such cases. (orig.) With 32 figs., 2 tabs., 32 refs.

  19. Comparison of cerebral blood volume and permeability in preoperative grading of intracranial glioma using CT perfusion imaging

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    Ding, Bei; Ling, Hua Wei; Chen, Ke Min [Shanghai Jiaotong University, Department of Radiology, Ruijin Hospital, School of Medicine, Shanghai (China); Jiang, Hong [Shanghai Jiaotong University, Department of Pathology, Ruijin Hospital, School of Medicine, Shanghai (China); Zhu, Yan Bo [Shanghai Jiaotong University, Department of Neurosurgery, Ruijin Hospital, School of Medicine, Shanghai (China)

    2006-10-15

    Regional cerebral blood volume (rCBV) and permeability surfaces (rPS) permit in vivo assessment of glioma microvasculature, which provides quite important pathophysiological information in grading gliomas. The aim of our study was to simultaneously examine rCBV and rPS in glioma patients to determine their correlation with histological grade using CT perfusion imaging. A total of 22 patients with gliomas underwent multislice CT perfusion imaging preoperatively. Low-grade and high-grade groups were categorized corresponding to WHO grade II gliomas and WHO grade III or IV gliomas, respectively, as determined by histopathological examination. rCBVs and rPSs were obtained from regions of maximal abnormality in tumor parenchyma on CBV and PS color perfusion maps. Perfusion parameters were compared using the Kruskal-Wallis test in order to evaluate the differences in relation to tumor grade. The Pearson coefficients of rCBV and rPS for each tumor