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Sample records for clear cell renal-cell

  1. Breast metastasis from clear cell renal cell carcinoma

    OpenAIRE

    Botticelli, A.; De Francesco, G. P.; D. Di Stefano

    2013-01-01

    In Western countries, breast cancer is the most common cancer in women, whereas metastases to the breast from extramammary malignancies are extremely rare. We present the case of a 60-year-old woman, who underwent surgery in 2007 for clear cell renal cell carcinoma and who 4 years later presented with a breast metastasis from clear cell renal cell carcinoma.

  2. Aberrant expression of metallothioneins in clear cell renal cell carcinomas

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    Rymar V. I.

    2015-12-01

    Full Text Available Aim. To find candidate tumor suppressor genes among metallothioneins for clear cell renal cell carcinoma. Methods. Analysis of the microarray data, quantitative PCR. Results. We found three genes encoding metallothioneines that showed reduced expression in different types of renal tumors, using protocol of the cross-platform meta-analysis of microarray data with normalization on several reference genes. Decreased expression of the MT1G, MT1F, and MT1H genes in clear cell renal cell carcinoma was confirmed by qPCR. Conclusions. The MT1G, MT1F and MT1H genes as well as may be considered as the candidate tumor suppressor genes for ccRCC.

  3. Clear Cell Papillary Renal Cell Carcinoma: A Potential Mimic of Conventional Clear Cell Renal Carcinoma on Core Biopsy

    OpenAIRE

    Heath Liddell; Anton Mare; Sean Heywood; Genevieve Bennett; Hin Fan Chan

    2015-01-01

    Clear cell papillary renal cell carcinoma (CCP-RCC) is a recently described, relatively uncommon variant of renal cell carcinoma (RCC) with a reported incidence of 4.1%. Thought to only arise in those with end stage renal disease, CCP-RCC is increasingly identified in those without renal impairment. CCP-RCCs have unique morphologic, genetic, and immunohistochemical features distinguishing them from both conventional clear cell renal cell carcinomas and papillary renal cell carcinomas. Immunoh...

  4. A Study of Varlilumab (Anti-CD27) and Sunitinib in Patients With Metastatic Clear Cell Renal Cell Carcinoma

    Science.gov (United States)

    2016-06-07

    Carcinoma, Renal Cell; Kidney Diseases; Kidney Neoplasms; Urogenital Neoplasms; Urologic Diseases; Urologic Neoplasms; Neoplasms; Neoplasms by Histologic Type; Clear-cell Metastatic Renal Cell Carcinoma

  5. Gene expression profile of renal cell carcinoma clear cell type

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    Marcos F. Dall’Oglio

    2010-08-01

    Full Text Available PURPOSE: The determination of prognosis in patients with renal cell carcinoma (RCC is based, classically, on stage and histopathological aspects. The metastatic disease develops in one third of patients after surgery, even in localized tumors. There are few options for treating those patients, and even the new target designed drugs have shown low rates of success in controlling disease progression. Few studies used high throughput genomic analysis in renal cell carcinoma for determination of prognosis. This study is focused on the identification of gene expression signatures in tissues of low-risk, high-risk and metastatic RCC clear cell type (RCC-CCT. MATERIALS AND METHODS: We analyzed the expression of approximately 55,000 distinct transcripts using the Whole Genome microarray platform hybridized with RNA extracted from 19 patients submitted to surgery to treat RCC-CCT with different clinical outcomes. They were divided into three groups (1 low risk, characterized by pT1, Fuhrman grade 1 or 2, no microvascular invasion RCC; (2 high risk, pT2-3, Fuhrman grade 3 or 4 with, necrosis and microvascular invasion present and (3 metastatic RCC-CCT. Normal renal tissue was used as control. RESULTS: After comparison of differentially expressed genes among low-risk, high-risk and metastatic groups, we identified a group of common genes characterizing metastatic disease. Among them Interleukin-8 and Heat shock protein 70 were over-expressed in metastasis and validated by real-time polymerase chain reaction. CONCLUSION: These findings can be used as a starting point to generate molecular markers of RCC-CCT as well as a target for the development of innovative therapies.

  6. Clear cell renal cell tumors: Not all that is "clear" is cancer.

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    Williamson, Sean R; Cheng, Liang

    2016-07-01

    Continued improvement of our understanding of the clinical, histologic, and genetic features of renal cell tumors has progressively evolved renal tumor classification, revealing an expanding array of distinct tumor types with different implications for prognosis, patient counseling, and treatment. Although clear cell renal cell carcinoma is unequivocally the most common adult renal tumor, there is growing evidence that some "clear cell" renal neoplasms, such as exemplified by multilocular cystic clear cell renal neoplasm of low malignant potential (formerly multilocular cystic renal cell carcinoma), do not have the same potential for insidious progression and metastasis, warranting reclassification as low malignant potential tumors or benign neoplasms. Still other novel tumor types such as clear cell papillary renal cell carcinoma have been more recently recognized, which similarly have shown a conspicuous absence of aggressive behavior to date, suggesting that these too may be recategorized as noncancerous or may be premalignant neoplasms. This importance for prognosis is increasingly significant in the modern era, in which renal masses are increasingly found incidentally by imaging techniques at a small tumor size, raising consideration for less aggressive management options guided by renal mass biopsy diagnosis, including imaging surveillance, tumor ablation, or partial nephrectomy. PMID:26988177

  7. Genetic mutations associated with metastatic clear cell renal cell carcinoma

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    Wu, Qingjian; Li, Fengjie; Zhao, Jiang; Wu, Kaijin; Qu, Cunye; Chen, Yibu; Li, Meng; Chen, Xuelian; Stucky, Andres; Zhong, Jiangjian; Li, Longkun; Zhong, Jiang F.

    2016-01-01

    Metastasis is the major cause of death among cancer patients, yet early detection and intervention of metastasis could significantly improve their clinical outcomes. We have sequenced and analyzed RNA (Expression) and DNA (Mutations) from the primary tumor (PT), tumor extension (TE) and lymphatic metastatic (LM) sites of patients with clear cell renal cell carcinoma (CCRCC) before treatment. Here, we report a three-nucleotide deletion near the C-region of Plk5 that is specifically associated with the lymphatic metastasis. This mutation is un-detectable in the PT, becomes detectable in the TE and dominates the LM tissue. So while only a few primary cancer cells carry this mutation, the majority of metastatic cells have this mutation. The increasing frequency of this mutation in metastatic tissue suggests that this Plk5 deletion could be used as an early indicator of CCRCC metastasis, and be identified by low cost PCR assay. A large scale clinical trial could reveal whether a simple PCR assay for this mutation at the time of nephrectomy could identify and stratify high-risk CCRCC patients for treatments. PMID:26908440

  8. Do Clear Cell Papillary Renal Cell Carcinomas Have Malignant Potential?

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    Diolombi, Mairo L; Cheng, Liang; Argani, Pedram; Epstein, Jonathan I

    2015-12-01

    There have been no recurrences or metastases of clear cell papillary renal cell carcinoma (CCPRCC) in 268 reported cases with follow-up in the English-language literature. We identified all our cases of CCPRCC (1990 to 2013), reviewing all cases that preceded the formal designation of the entity. Immunohistochemical stains were performed on 32 cases during their initial workup. In addition, stains for carbonic anhydrase IX and cytokeratin 7 were performed on 2 cases, one with atypical follow-up and the other with a more compact morphology, although not performed initially. An extended panel with AMACR, CD10, and renal cell carcinoma (RCC) was added to the case with atypical follow-up. Fluorescence in situ hybridization for chromosomes 3p, 7, and 17 was performed on the latter case and on another clinically presumed metastatic tumor. In classic cases, immunohistochemical staining was not performed. Fifty-eight patients (31 women; 27 men) with follow-up data were included in our study; 39 cases were from our consult service. The patients' ages ranged from 36 to 83 years. Thirty-five patients had cystic or partially cystic lesions; 6 tumors were multifocal, 3 of which were bilateral. The majority (53 patients; 91.4%) presented with stage pT1 disease (size range, 0.2 to 8 cm), 2 patients presented with pT2 disease (8.5 and 10.3 cm), 1 patient presented with pT3 disease (6.5 cm sarcomatoid RCC focally extending out of the kidney), and pathologic stage was unavailable in 2 cases. Treatment consisted of 29 partial nephrectomies, 26 radical nephrectomies, 2 cryoablations, and 1 cyst ablation. The resection margins were negative in all but one case, with this case disease free after a 26-month period. Two patients had intraoperative tumor disruption and were disease free at 9 and 34 months. Five patients had synchronous ipsilateral renal cell carcinomas (non-CCPRCC). Mean follow-up time was 21 months (range, 1 to 175 mo), with all but 3 patients having no evidence of

  9. The epigenetic landscape of clear-cell renal cell carcinoma

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    Katarzyna Kluzek

    2015-05-01

    Full Text Available Clear cell renal cell carcinoma (ccRCC is the most common subtype of all kidney tumors. During the last few years, epigenetics has emerged as an important mechanism in ccRCC pathogenesis. Recent reports, involving large-scale methylation and sequencing analyses, have identified genes frequently inactivated by promoter methylation and recurrent mutations in genes encoding chromatin regulatory proteins. Interestingly, three of detected genes (PBRM1, SETD2 and BAP1 are located on chromosome 3p, near the VHL gene, inactivated in over 80% ccRCC cases. This suggests that 3p alterations are an essential part of ccRCC pathogenesis. Moreover, most of the proteins encoded by these genes cooperate in histone H3 modifications. The aim of this review is to summarize the latest discoveries shedding light on deregulation of chromatin machinery in ccRCC. Newly described ccRCC-specific epigenetic alterations could potentially serve as novel diagnostic and prognostic biomarkers and become an object of novel therapeutic strategies.

  10. MET Inhibition in Clear Cell Renal Cell Carcinoma

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    Xie, Zuoquan; Lee, Young H.; Boeke, Marta; Jilaveanu, Lucia B.; Liu, Zongzhi; Bottaro, Donald P.; Kluger, Harriet M.; Shuch, Brian

    2016-01-01

    Background: Clear cell renal cell carcinoma (ccRCC) is the most lethal form of kidney cancer. Small molecule VEGFR inhibitors are widely used but are not curative and various resistance mechanisms such as activation of the MET pathway have been described. Dual MET/VEGFR2 inhibitors have recently shown clinical benefit but limited preclinical data evaluates their effects in ccRCC. Methods: An interrogation of the Cancer Genome Atlas (TCGA) dataset was performed to evaluate oncogenic alterations in the MET/VEGFR2 pathway. We evaluated the in vitro effects of Cabozantinib, a dual MET/VEGFR2 inhibitor, using a panel of ccRCC cell lines. Drug effects of cell viability and proliferation, migration, cell scatter, anchorage independent growth, and downstream MET/VEGFR2 signaling pathways were assessed. Results: Twelve percent of TCGA cases had possible MET/HGF oncogenic alterations with co-occurrence noted (p<0.001). MET/HGF altered cases had worse overall survival (p=0.044). Cabozantinib was a potent inhibitor of MET and VEGFR2 in vitro in our cell line panel. PI3K, MAPK and mTOR pathways were also suppressed by cabozantinib, however the effects on cell viability in vitro were modest. At nanomolar concentrations of cabozantinib, HGF-stimulated migration, invasion, cellular scattering and soft agar colony formation were inhibited. Conclusions: We provide further preclinical rationale for dual MET/VEGFR2 inhibition in ccRCC. While the MET pathway is implicated in VEGFR resistance, dual inhibitors may have direct anti-tumor effects in a patient subset with evidence of MET pathway involvement. Cabozantinib is a potent dual MET/VEGFR2 inhibitor, significantly inhibits cell migration and invasion in vitro and likely has anti-angiogenic effects similar to other VEGFR tyrosine kinase inhibitors. Future work involving in vivo models will be useful to better define mechanisms of potential anti-tumor activity. PMID:27390595

  11. Comparative study of MRI appearances in clear cell renal cell carcinoma, papillary renal cell carcinoma and chromophobe renal cell carcinoma

    International Nuclear Information System (INIS)

    Objective: To investigate the differential diagnostic features of subtypes of renal cell carcinoma (RCC) using dynamic contrast-enhanced MRI(DCE-MRI). Methods: The MRI appearances of 77 RCCs, including 55 clear cell RCCs (CCRCC), 14 papillary RCCs (PRCC) and 8 chromophobe RCCs (CRCC), were retrospectively analyzed and compared with findings of pathology. DCE-MRI was conducted in each case after intravenous administration of contrast agent. Region of interest measurements (cortical, nephrographic and delayed Phases) of signals within tumor and uninvolved renal cortex were used to calculate percentage signal intensity change and tumor-to-cortex enhancement index, and the data was analyzed by AVONA and t test. Results: On unenhanced and enhanced MRI, most CRCCs showed homogeneous signal (7/8). CCRCC and PRCC often show inhomogeneous signal with necrosis (36/55, 7/14). Hemorrhage and cystic degeneration were often found in PRCC (9/14). On the cortical, nephrographic and delayed phase images, CCRCCs showed greater signal intensity change [(296.15± 60.27)%, (236.33±58.31)% and (216.83±46.72)%, respectively than PRCCs (79.70±18.84)%, (122.81±27.35)% and (117.55±20.63)%, respectively], and CRCCs showed intermediate change [(119.56±40.76)%, (163.06±33.91)% and (179.72±32.89)%, respectively]. A phenomenon of quick staining and quick fainting was observed in CCRCCs. Both of CRCCs and PRCCs showed delayed enhancement. The tumor-to-cortex enhancement index at the cortical, nephrographic and delayed phases was highest for CCRCCs (1.26±0.34, 0.92±0.23 and 0.76±0.14, respectively), lowest for PRCCs (0.33±0.12, 0.41±0.23 and 0.35±0.11, respectively), and intermediate for CRCCs (0.54±0.10, 0.62±0.15 and 0.69±0.12, respectively, P<0.01). The degree of enhancement was significantly different among the 3 subtypes at the every contrast enhanced phase (F= 940.931, 124.515 and 38.194, P<0.01), so was the tumor-to-cortex enhancement index (F=798.625, 78.308 and 73.699, P

  12. Chromophobe Renal Cell Carcinoma

    OpenAIRE

    Jyotsna Vijaykumar Wader; Sujata S Kumbhar; Huddedar AD; Wasim GM Khatib

    2013-01-01

    Renal cell carcinoma is the most common neoplasm of the kidney comprised of different histological variants. Chromophobe renal cell carcinoma (ChRCC) is a rare subtype of renal cell carcinoma (RCC) mainly diagnosed in the sixth decade of life. It is important to identify this entity because it has significantly better prognosis than the clear cell (conventional) and papillary renal cell carcinomas. The chromophobe renal cell carcinoma should be differentiated from oncocytoma and clear cell ca...

  13. Systemic Therapy for Metastatic Non-Clear Cell Renal Cell Carcinoma: Recent Progress and Future Directions

    OpenAIRE

    Chowdhury, Simon; Matrana, Marc; Tsang, Christopher; Atkinson, Bradley; Choueiri, Toni K.; Tannir, Nizar M.

    2011-01-01

    Renal cell carcinoma (RCC) encompasses a heterogeneous group of histological subtypes of which clear-cell RCC (CCRCC) is the most common comprising more than 70–80% of all cases. Papillary renal cell carcinoma (PRCC) is the next most common comprising 10–15% of cases. PRCC is refractory to chemotherapy, immunotherapy and hormonal therapy.

  14. Lactate Dehydrogenase A is a potential prognostic marker in clear cell renal cell carcinoma

    OpenAIRE

    Girgis, Hala; Masui, Olena; White, Nicole MA; Scorilas, Andreas; Rotondo, Fabio; Seivwright, Annetta; Gabril, Manal; Filter, Emily R; Girgis, Andrew HA; Bjarnason, Georg A.; Jewett, Michael AS; Evans, Andrew; Al-Haddad, Sahar; Siu, KW Michael; Yousef, George M.

    2014-01-01

    Background Over 90% of cancer-related deaths in clear cell renal cell carcinoma (RCC) are caused by tumor relapse and metastasis. Thus, there is an urgent need for new molecular markers that can potentiate the efficacy of the current clinical-based models of prognosis assessment. The objective of this study is to evaluate the potential significance of lactate dehydrogenase A (LDHA), assessed by immunohistochemical staining, as a prognostic marker in clear cell renal cell carcinoma in relation...

  15. Acanthosis Nigricans associated with clear-cell renal cell carcinoma.

    Science.gov (United States)

    Ferraz de Campos, Fernando Peixoto; Narvaez, Margarita Rosa Aveiga; Reis, Paola Vasconcellos Soares; Gomes, Augusto Cesar Marins; Paraskevopoulos, Daniela Kallíope de Sá; Santana, Frederico; Fugita, Oscar Eduardo Hidetoshi

    2016-01-01

    Acanthosis nigricans (AN), an entity recognized since the 19th century, is a dermatopathy associated with insulin-resistant conditions, endocrinopathies, drugs, chromosome abnormalities and neoplasia. The latter, also known as malignant AN, is mostly related to abdominal neoplasms. Malignant AN occurs frequently among elderly patients. In these cases, the onset is subtle, and spreading involves the flexural regions of the body, particularly the axillae, palms, soles, and mucosa. Gastric adenocarcinoma is the most frequent associated neoplasia, but many others have been reported. Renal cell carcinoma (RCC), although already reported, is rarely associated with malignant AN. The authors report the case of a woman who was being treated for depression but presented a long-standing and marked weight loss, followed by darkening of the neck and the axillary regions. Physical examination disclosed a tumoral mass in the left flank and symmetrical, pigmented, velvety, verrucous plaques on both axillae, which is classical for AN. The diagnostic work-up disclosed a huge renal mass, which was resected and further diagnosed as a RCC. The post-operative period was uneventful and the skin alteration was evanescent at the first follow-up consultation. The authors call attention to the association of AN with RCC. PMID:27284539

  16. Synchronous clear cell renal cell carcinoma and multilocular cystic renal cell neoplasia of low malignant potential: A clinico-pathologic and molecular study.

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    Raspollini, Maria Rosaria; Castiglione, Francesca; Cheng, Liang; Montironi, Rodolfo; Lopez-Beltran, Antonio

    2016-05-01

    We report a rare case of synchronous clear cell renal cell carcinoma and multilocular cystic renal cell neoplasia of low malignant potential in the same kidney. The tumors were seen incidentally in a 45-year-old man. Pathologic study revealed that the former tumor was nucleolar grade 2, and the multilocular cystic renal cell neoplasia of low malignant potential was nucleolar grade 1. At immunohistochemistry, the clear cells in both tumors were positive for CD10 and CA IX. Interestingly, these uncommon synchronous tumors showed a different KRAS/NRAS mutation analysis that was characterized by KRAS mutation at codon p.G12C in the clear cell renal cell carcinoma, while this mutation was not present in the case of multilocular cystic renal cell neoplasia of low malignant potential. NRAS mutation was not seen in any of the tumors. PMID:26874573

  17. Decreased expression of mucin 18 is associated with unfavorable postoperative prognosis in patients with clear cell renal cell carcinoma

    OpenAIRE

    Bai, Qi; Liu, Li; Long, Qilai; Xia, Yu; Wang, Jiajun; Xu, Jiejie; Guo, Jianming

    2015-01-01

    Background: MUC18 is correlated with tumor progression and metastasis in types of malignancy. But the role of MUC18 in clear cell renal cell carcinoma remains unclear. In this study, we aimed to investigate the expression of MUC18 and its correlation with clinical outcomes in clear cell renal cell carcinoma. Patients and Methods: Immunohistochemical staining was performed in samples from 288 patients with clear cell renal cell carcinoma. We used Kaplan-Meier method and Cox proportional hazard...

  18. Ultrasonographic Pattern of Testicular Metastasis of Clear Cell Renal Cell Carcinoma with Pathological Correlation

    OpenAIRE

    Libert, Florent; Cabri-Wiltzer, Mathieu; Dardenne, Emmanuel; Draguet, Anne-Philippe; Puttemans, Thierry

    2016-01-01

    Two cases of testicular metastases of a clear cell renal cell carcinoma sharing a very similar ultrasonographic pattern are reported. The observed pattern – masses containing multiple tiny cyst-like areas – is very similar to that of a previously described ovarian metastasis of clear cell renal parenchymal tumor and can be explained by histopathologic features. Despite the small number of cases, this ultrasonographic pattern of testicular mass may be specific for metastasis of clear cell rena...

  19. Clear cell papillary renal cell carcinoma and clear cell renal cell carcinoma arising in acquired cystic disease of the kidney: an immunohistochemical and genetic study.

    Science.gov (United States)

    Kuroda, Naoto; Shiotsu, Tomoyuki; Kawada, Chiaki; Shuin, Taro; Hes, Ondrej; Michal, Michal; Ohe, Chisato; Mikami, Shuji; Pan, Chin-Chen

    2011-08-01

    Clear cell papillary renal cell carcinoma (RCC) is a recently established disease entity. However, there are few reports on genetic study of this entity. We report such a case with focus on genetic study. A 57-year-old Japanese man was found to have 3 renal tumors. Histologically, two tumors showed findings of clear cell RCC; and the other tumor showed findings of clear cell papillary RCC that was characterized by papillary growth pattern of neoplastic cells in cystic space with purely clear cell cytology. Immunohistochemically, tumor cells of clear cell papillary RCC were diffusely positive for PAX2 and cytokeratin 7, but negative for CD10, RCC Ma, and AMACR. In fluorescence in situ hybridization study for one clear cell papillary RCC, we detected polysomy for chromosome 7 and monosomy for chromosomes 17, 16, and 20. In addition, we detected mutation of VHL gene in clear cell RCC, but found no VHL gene mutation in clear cell papillary RCC. Finally, our results provide further evidence that clear cell papillary RCC may be both morphologically and genetically distinct entity from clear cell RCC and papillary RCC. PMID:20952286

  20. Clear cell renal cell carcinoma with vaginal and brain metastases: a case report and literature review

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    Tobe Samuel Momah; Dhanan Etwaru; Phillip Xiao; Vasantha Kondamudi

    2009-01-01

    There are very few cases of clear cell renal cell carcinoma with metastases to the vagina and brain reported in the literature. Our case study highlights this rare clinical occurrence and its associated complications including pulmonary embolism. In addition we discuss current management guidelines for treating and diagnosing the disease, and how this management improves prognosis.

  1. Clear cell renal carcinoma with areas of chromophobe renal cell carcinoma

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    Rekha Thodavadi Subbanna; Nandini Nandish Manoli

    2012-01-01

    The classification of renal cell carcinoma (RCC) is based upon various histological features which aids in determining the treatment and prognosis. We report a unique case of RCC displaying features of predominantly clear cell RCC with areas of chromophobe RCC in an unusual edematous background. The tumor cells from chromophobe RCC were positive for Hales colloidal iron stain. On Immunohistochemistry majority of them were positive for vimentin and CD10, the markers of clear cell RCC with scat...

  2. Metastatic Renal cell Carcinoma Presenting as a clear-cell Tumor in Tongue: A Case Report

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    Hamid Abbaszadeh-Bidokhty

    2014-07-01

    Full Text Available Introduction: Metastatic lesions of the oral cavity are extremely rare, accounting for approximately 1% of all malignant oral tumors. The most common primary sources of metastatic tumors in the oral region are, from the most to the least common, the breast, lung, kidney, bone, and colon. Renal cell carcinoma accounts for nearly 3% of all adult malignancies. It usually metastasizes to the lungs, bone, adrenal glands, and regional lymph nodes. The incidence of metastasis from renal cell carcinoma to the head and neck region is very low. The tongue is considered a very rare atypical ear, nose, and throat (ENT location for metastasis of renal cell carcinoma. The present case from Iran reports tongue metastasis of renal cell carcinoma (RCC.   Case Report: The following report is based on an 80-year old male patient with a tongue lesion and ambiguous past medical history that ultimately leads to diagnosis of a metastatic RCC. We also updated a previous literature review that was published 2008. A histopathological differential diagnosis for clear-cell tumors is also discussed.   Conclusion:  Because of the rarity of metastatic tumors of the oral region as well as the presence of other lesions with clear cells, diagnosis of metastatic clear-cell RCC in the oral cavity can be very difficult and challenging.  

  3. Renal cell carcinoma: evolving approaches to advanced non-clear cell carcinoma

    OpenAIRE

    Bukowski, Ronald M; Heng, Daniel Y.C.

    2011-01-01

    The treatment of metastatic renal cell carcinoma (RCC) has changed dramatically with the introduction of targeted therapies including sunitinib, sorafenib, and temsirolimus. Because patients with conventional clear cell histology account for 75- 80% of all patients with RCC, there has been little accumulated evidence on the treatment of patients with non-clear cell histologies. Most clinical trials have excluded them from enrolment, except for randomized studies investigating temsirolimus. Ma...

  4. Full-Length Enrich c-DNA Libraries-Clear Cell-Renal Cell Carcinoma

    OpenAIRE

    Sai-Wen Tang; Jung-Yaw Lin

    2012-01-01

    Clear cell renal cell carcinoma (ccRCC), the most common subtype of RCC, is characterized by high metastasis potential and strong resistance to traditional therapies, resulting in a poor five-year survival rate of patients. Several therapies targeted to VEGF pathway for advanced RCC have been developed, however, it still needs to discover new therapeutic targets for treating RCC. Genome-wide gene expression analyses have been broadly used to identify unknown molecular mechanisms of cancer pro...

  5. 'Prechronous' metastasis in clear cell renal cell carcinoma: a case report

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    Chong Tsung; Mohd Zam Nor; Lim Wan; Chuang Xue; Ong Sin; Poon Eileen; Al Jajeh Issam; Mancer Kent; Tan Min-Han

    2011-01-01

    Abstract Introduction Although metastatic carcinoma in the presence of an occult primary tumor is well recognized, underlying reasons for the failure of the primary tumor to manifest are uncertain. Explanations for this phenomenon have ranged from spontaneous regression of the primary tumor to early metastasis of the primary tumor before manifestation of a less aggressive primary tumor. We report a case of 'prechronous' metastasis arising from clear cell renal cell carcinoma, where metastatic...

  6. Transglutaminase 2 Expression and Its Prognostic Significance in Clear Cell Renal Cell Carcinoma

    OpenAIRE

    Park, Min Jee; Baek, Hae Woon; Rhee, Ye-Young; Lee, Cheol; Park, Jeong Whan; Kim, Hwal Woong; Moon, Kyung Chul

    2015-01-01

    Background: A few recent studies have demonstrated a possible role of transglutaminase 2 (TG2) in tumorigenesis or progression of renal cell carcinoma (RCC). The aim of this study was to examine TG2 expression and its clinicopathologic significance in a large number of human clear cell RCCs (CCRCCs). Methods: We analyzed 638 CCRCC patients who underwent partial or radical nephrectomy between 1995 and 2005. The expression of TG2 was determined by immunohistochemistry and categorized into four ...

  7. Systematic Evaluation of the Prognostic Impact and Intratumour Heterogeneity of Clear Cell Renal Cell Carcinoma Biomarkers

    DEFF Research Database (Denmark)

    Gulati, Sakshi; Martinez, Pierre; Joshi, Tejal; Birkbak, Nicolai Juul; Santos, Claudio R.; Rowan, Andrew J.; Pickering, Lisa; Gore, Martin; Larkin, James; Szallasi, Zoltan Imre; Bates, Paul A.; Swanton, Charles; Gerlinger, Marco

    2014-01-01

    BackgroundCandidate biomarkers have been identified for clear cell renal cell carcinoma (ccRCC) patients, but most have not been validated. ObjectiveTo validate published ccRCC prognostic biomarkers in an independent patient cohort and to assess intratumour heterogeneity (ITH) of the most promising...... the ability of published biomarkers to predict the survival of patients with clear cell kidney cancer in an independent patient cohort. Only one molecular test adds prognostic information to routine clinical assessments. This marker showed good and poor prognosis results within most individual cancers...

  8. The Notch and TGF-beta Signaling Pathways Contribute to the Aggressiveness of Clear Cell Renal Cell Carcinoma.

    OpenAIRE

    Sjölund, Jonas; Boström, Anna-Karin; Lindgren, David; Manna, Sugata; Moustakas, Aristidis; Ljungberg, Börje; Johansson, Martin; Fredlund, Erik; Axelson, Håkan

    2011-01-01

    Despite recent progress, therapy for metastatic clear cell renal cell carcinoma (CCRCC) is still inadequate. Dysregulated Notch signaling in CCRCC contributes to tumor growth, but the full spectrum of downstream processes regulated by Notch in this tumor form is unknown.

  9. Renal cell carcinoma: evolving approaches to advanced non-clear cell carcinoma

    Directory of Open Access Journals (Sweden)

    Daniel Y.C. Heng

    2011-12-01

    Full Text Available The treatment of metastatic renal cell carcinoma (RCC has changed dramatically with the introduction of targeted therapies including sunitinib, sorafenib, and temsirolimus. Because patients with conventional clear cell histology account for 75- 80% of all patients with RCC, there has been little accumulated evidence on the treatment of patients with non-clear cell histologies. Most clinical trials have excluded them from enrolment, except for randomized studies investigating temsirolimus. Many retrospective studies on the use of all three of these targeted therapies in patients with non-clear cell histology have demonstrated response rates ranging from 3.7%–16%. Although response rates may not be as high compared to patients with clear cell histologies, targeted therapy does provide a clinically meaningful response.

  10. Engrailed-2 might play an anti-oncogenic role in clear-cell renal cell carcinoma.

    Science.gov (United States)

    Lai, Cai-Yong; Xu, Yin; Yu, Gan-Shen; Wu, Xun; Li, Yun-Fei; Pan, Bin; Heng, Bao-Li; Xue, Yi-Jun; Su, Ze-Xuan

    2016-06-01

    Our preliminary study indicated that Engrailed-2 (EN2) is downregulated but also ectopically expressed in clear-cell renal cell carcinoma (CCRCC), and the absence of EN2 expression was associated with poor histological grade. However, the specific roles of EN2 in CCRCC have yet to be elucidated. In the present study, we examined the effects of inhibiting EN2 expression by human renal tubular epithelial cells (HK-2) and overexpressing EN2 by human clear-cell renal cells (786-O). Results showed that EN2 inhibition accelerated HK-2 cell proliferation, shortened the cell cycle, reduced apoptosis, and acted more invasively. By contrast, EN2 overexpression in 786-O cells decelerated the proliferative ability of 786-O, increased the percentage of cell apoptosis, and weakened the invasive ability. Overall, the results demonstrated that EN2 might play an anti-oncogenic role in oncogenesis and development of CCRCC, thereby maintaining the normal growth of human renal tubular epithelial cells. PMID:26948025

  11. High expression of FER tyrosine kinase predicts poor prognosis in clear cell renal cell carcinoma

    OpenAIRE

    Wei, Can; WU, SONG; Li, Xianxin; Wang, Yadong; Ren, Rui; LAI, YONGQING; YE, JIONGXIAN

    2012-01-01

    FER tyrosine kinase (FER) has been demonstrated to play a critical role in tumorigenesis and metastasis; however, its potential value as a novel prognostic marker for clear cell renal cell carcinoma (ccRCC) remains unclear. In 48 paired samples of ccRCCs and normal adjacent tissues (ADTs), real-time PCR was used to evaluate the expression of FER mRNA. The expression of FER protein was assessed in 87 ADTs and 206 samples of ccRCC using immunohistochemical methods. Statistical analysis was used...

  12. Coexisting Papillary and Clear Renal Cell Carcinoma in the Same Kidney

    OpenAIRE

    Murat Ustuner; Busra Yaprak; Kerem Teke; Seyfettin Ciftci; Mucahit Kart; Kursat Yildiz; Melih Culha

    2014-01-01

    Renal cell carcinoma (RCC) is the most common solid lesion of the kidney. Bilateral synchronous benign and malignant renal tumors have been defined in some reports. However, unilateral concordance of malignant renal tumors is very rare and there are only a few cases that had synchronous different subtypes of malignant renal tumors arising within the same kidney. Herein, we describe a 67-year-old male patient who had clear cell RCC and papillary RCC in his right kidney that were successfully t...

  13. Clear cell papillary renal cell carcinoma, renal angiomyoadenomatous tumor and renal cell carcinoma with leiomyomatous stroma-relationship of three types of renal tumors: A review

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    Hes, Ondrej; Compérat, Eva Maria; Rioux-Leclerc, Nathalie

    2015-01-01

    Renal angiomyoadenomatous tumor has been described in 2000, followed by description of clear cell papillary renal cell carcinoma in 2006. Discussion about possible relationship of both tumors were published since their description. As the main differencial diagnostic feature was considered presence/absence of fibroleiomyomatous stroma favoring diagnosis of RAT in stroma-rich tumors. However it was shown, that stroma is reactive, non-neoplastic by its nature and that all other histologic, immu...

  14. Incidence of Clear Cell Papillary Renal Cell Carcinoma in Low-Grade Renal Cell Carcinoma Cases: A 12-Year Retrospective Clinicopathologic Study From a Single Cancer Center.

    Science.gov (United States)

    Gill, Simpal; Kauffman, Eric C; Kandel, Sirisa; George, Saby; Schwaab, Thomas; Xu, Bo

    2016-05-01

    Clear cell papillary renal cell carcinoma (CCPRCC) is a recently recognized subtype of renal cell carcinoma entity after 2004 World Health Organization classification of renal tumors. CCPRCC has unique histomorphological and immunohistochemical characteristics. The distinction of CCPRCC from renal cell carcinoma (RCC) with clear cell morphology is crucial because the former is considered to have a favorable clinical outcome. CCPRCC may be interpreted in the past as other renal cell carcinomas, particularly low-grade clear cell RCC. In this study, the frequency of CCPRCC in previously diagnosed low-grade RCC and its clinicopathologic features were examined. A total of 126 cases of stage T1a with low nuclear grade RCC were identified from 625 consecutive RCCs removed by radical/partial nephrectomy over 12-year period (2000-2011). Archival tissue sections were retrospectively reviewed along with patient medical charts. Eight cases (1.3% of all RCC, 6.3% of pT1a low grade RCC) with characteristic histologic features of CCPRCC were confirmed by immunohistochemical studies. Seven cases were previously diagnosed as clear cell RCC and one as multilocular cystic RCC. Radiographically, CCPRCC favored a mid-pole location in the kidneys. At a median follow-up period of 52 months (range 20-114.5 months), there were no cases of local or distant recurrence. In conclusion, CCPRCC is not uncommon among small low-grade RCC tumors. CCPRCC can be correctly recognized by its unique histomorphological features and confirmed by immunohistochemistry studies, which is important due to the excellent clinical outcome following resection. PMID:26510859

  15. Cancer stem cells are underestimated by standard experimental methods in clear cell renal cell carcinoma

    Science.gov (United States)

    Gedye, Craig; Sirskyj, Danylo; Lobo, Nazleen C.; Meens, Jalna; Hyatt, Elzbieta; Robinette, Michael; Fleshner, Neil; Hamilton, Robert J; Kulkarni, Girish; Zlotta, Alexandre; Evans, Andrew; Finelli, Antonio; Jewett, Michael A. S.; Ailles, Laurie E.

    2016-01-01

    Rare cancer stem cells (CSC) are proposed to be responsible for tumour propagation and re-initiation and are functionally defined by identifying tumour-initiating cells (TICs) using the xenotransplantation limiting dilution assay (LDA). While TICs in clear cell renal cell carcinoma (ccRCC) appeared rare in NOD/SCID/IL2Rγ−/− (NSG) mice, xenografts formed more efficiently from small tumour fragments, indicating the LDA underestimated ccRCC TIC frequency. Mechanistic interrogation of the LDA identified multiple steps that influence ccRCC TIC quantitation. For example, tissue disaggregation destroys most ccRCC cells, common assays significantly overestimate tumour cell viability, and microenvironmental supplementation with human extracellular factors or pharmacological inhibition of anoikis increase clonogenicity and tumourigenicity of ccRCC cell lines and primary tumour cells. Identification of these previously uncharacterized concerns that cumulatively lead to substantial underestimation of TICs in ccRCC provides a framework for development of more accurate TIC assays in the future, both for this disease and for other cancers. PMID:27121191

  16. Cancer stem cells are underestimated by standard experimental methods in clear cell renal cell carcinoma.

    Science.gov (United States)

    Gedye, Craig; Sirskyj, Danylo; Lobo, Nazleen C; Meens, Jalna; Hyatt, Elzbieta; Robinette, Michael; Fleshner, Neil; Hamilton, Robert J; Kulkarni, Girish; Zlotta, Alexandre; Evans, Andrew; Finelli, Antonio; Jewett, Michael A S; Ailles, Laurie E

    2016-01-01

    Rare cancer stem cells (CSC) are proposed to be responsible for tumour propagation and re-initiation and are functionally defined by identifying tumour-initiating cells (TICs) using the xenotransplantation limiting dilution assay (LDA). While TICs in clear cell renal cell carcinoma (ccRCC) appeared rare in NOD/SCID/IL2Rγ(-/-) (NSG) mice, xenografts formed more efficiently from small tumour fragments, indicating the LDA underestimated ccRCC TIC frequency. Mechanistic interrogation of the LDA identified multiple steps that influence ccRCC TIC quantitation. For example, tissue disaggregation destroys most ccRCC cells, common assays significantly overestimate tumour cell viability, and microenvironmental supplementation with human extracellular factors or pharmacological inhibition of anoikis increase clonogenicity and tumourigenicity of ccRCC cell lines and primary tumour cells. Identification of these previously uncharacterized concerns that cumulatively lead to substantial underestimation of TICs in ccRCC provides a framework for development of more accurate TIC assays in the future, both for this disease and for other cancers. PMID:27121191

  17. Metastatic Renal cell Carcinoma Presenting as a clear-cell Tumor in Tongue: A Case Report

    OpenAIRE

    Hamid Abbaszadeh-Bidokhty; Mina Motallebnejad; Mahdieh Rajabi-Moghaddam

    2014-01-01

    Introduction: Metastatic lesions of the oral cavity are extremely rare, accounting for approximately 1% of all malignant oral tumors. The most common primary sources of metastatic tumors in the oral region are, from the most to the least common, the breast, lung, kidney, bone, and colon. Renal cell carcinoma accounts for nearly 3% of all adult malignancies. It usually metastasizes to the lungs, bone, adrenal glands, and regional lymph nodes. The incidence of metastasis from renal cell carcino...

  18. Potential Approaches and Recent Advances in Biomarker Discovery in Clear-Cell Renal Cell Carcinoma

    Science.gov (United States)

    Majer, Weronika; Kluzek, Katarzyna; Bluyssen, Hans; Wesoły, Joanna

    2015-01-01

    The early diagnosis and monitoring of clear-cell Renal Cell Carcinoma (ccRCC), which is the most common renal malignancy, remains challenging. The late diagnosis and lack of tools that can be used to assess the progression of the disease and metastasis significantly influence the chance of survival of ccRCC patients. Molecular biomarkers have been shown to aid the diagnosis and disease monitoring for other cancers, but such markers are not currently available for ccRCC. Recently, plasma and serum circulating nucleic acids, nucleic acids present in urine, and plasma and urine proteins gained interest in the field of cancer biomarker discovery. Here, we describe the applicability of plasma and urine nucleic acids as cancer biomarkers with a particular focus on DNA, small RNA, and protein markers for ccRCC. PMID:26516358

  19. Clear cell renal cell carcinoma with hemangioblastoma-like features: A recently described pattern with unusual immunohistochemical profile

    Directory of Open Access Journals (Sweden)

    Sankalp Sancheti

    2015-01-01

    Full Text Available The diagnosis of clear cell renal cell carcinoma may sometimes pose challenges because of the presence of uncharacteristic morphology, varied immunophenotypic patterns and due to lack of molecular or genetic determinants. More often, the morphological variations can be easily overlooked in routine practice and a more common diagnosis is usually put forward. Solid, acinar and alveolar are the common patterns described in the literature. We report a recently described pattern of clear cell renal cell carcinoma which has hemangioblastoma-like morphology and an unusual immunoprofile. In our case, the tumor showed a diffuse hemangioblastoma-like pattern and diffuse positivity for Alpha-inhibin on immunohistochemistry. A thorough literature search, extensive sampling and an expanded immunohistochemistry panel revealed a clear cell renal cell carcinoma component. Presence of renal vein thrombosis and focal necrosis were other helpful features in discerning the malignant nature of tumor.

  20. Sarcomatoid renal cell carcinoma

    OpenAIRE

    Kafil Akhtar; Ahmad Shamshad; Zaheer Sufian; Mansoor Tariq

    2011-01-01

    Sarcomatoid renal cell carcinoma (SRCC) is an aggressive tumor variant thought to arise predominantly from differentiation of clear cell carcinoma. A few reports of SRCC asso-ciated with non-clear cell tumors led to the presumption that SRCC may arise from any renal cell carcinoma, although direct evidence of this is lacking. We report a case of a 70-year-old male patient, who presented with acute left upper quadrant abdominal pain and was diagnosed to have SRCC after pathological examination...

  1. Primary extra-renal clear cell renal cell carcinoma masquerading as an adrenal mass: A diagnostic challenge

    Directory of Open Access Journals (Sweden)

    Roumina Hasan

    2015-01-01

    Full Text Available We present the first case of a nonmetastasizing renal cell carcinoma (RCC masquerading as an adrenal mass, in the presence of normal bilateral native kidneys, in a young adult. The possibility of this mass developing in a supernumerary kidney was ruled out, since no identifiable renal tissue, pelvis or ureters was seen within the mass, nor was any separate systemic arterial supply to the mass seen. The diagnosis of extra-renal clear cell RCC was based on cyto-morphological features, further confirmed by immunohistochemistry findings. The origin of this extra-renal clear cell renal cell is proposed to be from the mesodermal embryonic rests.

  2. Primary extra-renal clear cell renal cell carcinoma masquerading as an adrenal mass: A diagnostic challenge

    Science.gov (United States)

    Hasan, Roumina; Kumar, Sandeep; Monappa, Vidya; Ayachit, Anurag

    2015-01-01

    We present the first case of a nonmetastasizing renal cell carcinoma (RCC) masquerading as an adrenal mass, in the presence of normal bilateral native kidneys, in a young adult. The possibility of this mass developing in a supernumerary kidney was ruled out, since no identifiable renal tissue, pelvis or ureters was seen within the mass, nor was any separate systemic arterial supply to the mass seen. The diagnosis of extra-renal clear cell RCC was based on cyto-morphological features, further confirmed by immunohistochemistry findings. The origin of this extra-renal clear cell renal cell is proposed to be from the mesodermal embryonic rests. PMID:26692677

  3. CD 9 and vimentin distinguish clear cell from chromophobe renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Ljunberg Börje

    2009-11-01

    Full Text Available Abstract Background Clear cell renal cell carcinoma (ccRCC and chromophobe renal cell carcinoma (chRCC can usually be distinguished by histologic characteristics. Occasionally, diagnosis proves challenging and diagnostic difficulty will likely increase as needle biopsies of renal lesions become more common. Methods To identify markers that aid in differentiating ccRCC from chRCC, we used gene expression profiles to identify candidate markers that correlate with histology. 39 antisera and antibodies, including 35 for transcripts identified from gene expression profiling, were evaluated. Promising markers were tested on a tissue microarray (TMA containing 428 renal neoplasms. Strength of staining of each core on the TMA was formally scored and the distribution of staining across different types of renal neoplasms was analyzed. Results Based on results from initial immunohistochemical staining of multitissue titer arrays, 23 of the antisera and antibodies were selected for staining of the TMA. For 7 of these markers, strength of staining of each core on the TMA was formally scored. Vimentin (positive in ccRCC and CD9 (positive in chRCC best distinguished ccRCC from chRCC. The combination of vimentin negativity and CD9 positivity was found to distinguish chRCC from ccRCC with a sensitivity of 100.0% and a specificity of 95.2%. Conclusion Based on gene expression analysis, we identify CD9 and vimentin as candidate markers for distinguishing between ccRCC and chRCC. In difficult cases and particularly when the amount of diagnostic tissue is limited, vimentin and CD9 staining could serve as a useful adjunct in the differential diagnosis of ccRCC and chRCC.

  4. Klotho plays a critical role in clear cell renal cell carcinoma progression and clinical outcome.

    Science.gov (United States)

    Kim, Ji-Hee; Hwang, Kyu-Hee; Lkhagvadorj, Sayamaa; Jung, Jae Hung; Chung, Hyun Chul; Park, Kyu-Sang; Kong, In Deok; Eom, Minseob; Cha, Seung-Kuy

    2016-05-01

    Klotho functions as a tumor suppressor predominantly expressed in renal tubular cells, the origin of clear cell renal cell carcinoma (ccRCC). Altered expression and/or activity of growth factor receptor have been implicated in ccRCC development. Although Klotho suppresses a tumor progression through growth factor receptor signaling including insulin-like growth factor-1 receptor (IGF-1R), the role of Klotho acting on IGF-1R in ccRCC and its clinical relevance remains obscure. Here, we show that Klotho is favorable prognostic factor for ccRCC and exerts tumor suppressive role for ccRCC through inhibiting IGF-1R signaling. Our data shows the following key findings. First, in tumor tissues, the level of Klotho and IGF-1R expression are low or high, respectively, compared to that of adjacent non-neoplastic parenchyma. Second, the Klotho expression is clearly low in higher grade of ccRCC and is closely associated with clinical outcomes in tumor progression. Third, Klotho suppresses IGF-1-stimulated cell proliferation and migration by inhibiting PI3K/Akt pathway. These results provide compelling evidence supporting that Klotho acting on IGF-1R signaling functions as tumor suppressor in ccRCC and suggest that Klotho is a potential carcinostatis substance for ccRCC. PMID:27162484

  5. Non-Clear Cell Renal Cell Carcinoma: Does the Mammalian Target of Rapamycin Represent a Rational Therapeutic Target?

    OpenAIRE

    Albiges, Laurence; Molinie, Vincent; Escudier, Bernard

    2012-01-01

    The disparate subtypes of non-clear cell renal cell carcinoma, the criteria for diagnosis, and the prognoses associated with each subtype, in addition to evaluating the potential use of mammalian target of rapamycin inhibitors in treating patients with this type of cancer are reviewed.

  6. Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway components in clear cell renal cell carcinoma

    DEFF Research Database (Denmark)

    Guo, Guangwu; Gui, Yaoting; Gao, Shengjie;

    2012-01-01

    We sequenced whole exomes of ten clear cell renal cell carcinomas (ccRCCs) and performed a screen of similar to 1,100 genes in 88 additional ccRCCs, from which we discovered 12 previously unidentified genes mutated at elevated frequencies in ccRCC. Notably, we detected frequent mutations in the u...... of the hypoxia regulatory network....

  7. Variation in genomic landscape of clear cell renal cell carcinoma across Europe.

    Science.gov (United States)

    Scelo, Ghislaine; Riazalhosseini, Yasser; Greger, Liliana; Letourneau, Louis; Gonzàlez-Porta, Mar; Wozniak, Magdalena B; Bourgey, Mathieu; Harnden, Patricia; Egevad, Lars; Jackson, Sharon M; Karimzadeh, Mehran; Arseneault, Madeleine; Lepage, Pierre; How-Kit, Alexandre; Daunay, Antoine; Renault, Victor; Blanché, Hélène; Tubacher, Emmanuel; Sehmoun, Jeremy; Viksna, Juris; Celms, Edgars; Opmanis, Martins; Zarins, Andris; Vasudev, Naveen S; Seywright, Morag; Abedi-Ardekani, Behnoush; Carreira, Christine; Selby, Peter J; Cartledge, Jon J; Byrnes, Graham; Zavadil, Jiri; Su, Jing; Holcatova, Ivana; Brisuda, Antonin; Zaridze, David; Moukeria, Anush; Foretova, Lenka; Navratilova, Marie; Mates, Dana; Jinga, Viorel; Artemov, Artem; Nedoluzhko, Artem; Mazur, Alexander; Rastorguev, Sergey; Boulygina, Eugenia; Heath, Simon; Gut, Marta; Bihoreau, Marie-Therese; Lechner, Doris; Foglio, Mario; Gut, Ivo G; Skryabin, Konstantin; Prokhortchouk, Egor; Cambon-Thomsen, Anne; Rung, Johan; Bourque, Guillaume; Brennan, Paul; Tost, Jörg; Banks, Rosamonde E; Brazma, Alvis; Lathrop, G Mark

    2014-01-01

    The incidence of renal cell carcinoma (RCC) is increasing worldwide, and its prevalence is particularly high in some parts of Central Europe. Here we undertake whole-genome and transcriptome sequencing of clear cell RCC (ccRCC), the most common form of the disease, in patients from four different European countries with contrasting disease incidence to explore the underlying genomic architecture of RCC. Our findings support previous reports on frequent aberrations in the epigenetic machinery and PI3K/mTOR signalling, and uncover novel pathways and genes affected by recurrent mutations and abnormal transcriptome patterns including focal adhesion, components of extracellular matrix (ECM) and genes encoding FAT cadherins. Furthermore, a large majority of patients from Romania have an unexpected high frequency of A:T>T:A transversions, consistent with exposure to aristolochic acid (AA). These results show that the processes underlying ccRCC tumorigenesis may vary in different populations and suggest that AA may be an important ccRCC carcinogen in Romania, a finding with major public health implications. PMID:25351205

  8. Identification of DNA Methylation-Independent Epigenetic Events Underlying Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Becket, Elinne; Chopra, Sameer; Duymich, Christopher E; Lin, Justin J; You, Jueng Soo; Pandiyan, Kurinji; Nichols, Peter W; Siegmund, Kimberly D; Charlet, Jessica; Weisenberger, Daniel J; Jones, Peter A; Liang, Gangning

    2016-04-01

    Alterations in chromatin accessibility independent of DNA methylation can affect cancer-related gene expression, but are often overlooked in conventional epigenomic profiling approaches. In this study, we describe a cost-effective and computationally simple assay called AcceSssIble to simultaneously interrogate DNA methylation and chromatin accessibility alterations in primary human clear cell renal cell carcinomas (ccRCC). Our study revealed significant perturbations to the ccRCC epigenome and identified gene expression changes that were specifically attributed to the chromatin accessibility status whether or not DNA methylation was involved. Compared with commonly mutated genes in ccRCC, such as the von Hippel-Lindau (VHL) tumor suppressor, the genes identified by AcceSssIble comprised distinct pathways and more frequently underwent epigenetic changes, suggesting that genetic and epigenetic alterations could be independent events in ccRCC. Specifically, we found unique DNA methylation-independent promoter accessibility alterations in pathways mimicking VHL deficiency. Overall, this study provides a novel approach for identifying new epigenetic-based therapeutic targets, previously undetectable by DNA methylation studies alone, that may complement current genetic-based treatment strategies. Cancer Res; 76(7); 1954-64. ©2016 AACR. PMID:26759245

  9. Renal cell carcinoma

    Science.gov (United States)

    Renal cell carcinoma is a type of kidney cancer that starts in the lining of very small tubes (tubules) in the kidney. ... cancer; Kidney cancer; Hypernephroma; Adenocarcinoma of renal cells; Cancer - kidney

  10. Metastatic Non-Clear Cell Renal Cell Carcinoma: An Evidence Based Review of Current Treatment Strategies

    OpenAIRE

    Sankin, Alexander; Hakimi, A. Ari; Hsieh, James J.; Molina, Ana M.

    2015-01-01

    Much progress has been made in the treatment of metastatic renal cell carcinoma (RCC) over the last decade, with the development of agents that block the vascular endothelial growth factor (VEGF) pathway or the mammalian target of rapamycin (mTOR) pathway. The incorporation of these agents into treatment algorithms has been the result of carefully conducted clinical trials leading to Food and Drug Administration (FDA) approval and subsequent adoption as the current standard of care. These tri...

  11. Orai1 Expression Is Closely Related with Favorable Prognostic Factors in Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Lkhagvadorj, Sayamaa; Kim, Ji-Hee; Oh, Sung-Soo; Lee, Mi-Ra; Jung, Jae Hung; Chung, Hyun Chul; Cha, Seung-Kuy; Eom, Minseob

    2016-06-01

    Store-operated calcium (Ca(2+)) entry (SOCE) is the principal Ca(2+) entry route in non-excitable cells, including cancer cells. We previously demonstrated that Orai1 and STIM1, the molecular components of SOCE, are involved in tumorigenesis of clear cell renal cell carcinoma (CCRCC). However, a clinical relevance of Orai1 and STIM1 expression in CCRCC has been ill-defined. Here, we investigated the expression of Orai1 and STIM1 in CCRCC, and compared their expression with clinico-pathological parameters of CCRCC and the patients' outcome. Immunohistochemical staining for Orai1 and STIM1 was performed on 126 formalin fixed paraffin embedded tissue of CCRCC and western blot analysis for Orai1 was performed on the available fresh tissue. The results were compared with generally well-established clinicopathologic prognostic factors in CCRCC and patient survival. Membrane protein Orai1 is expressed in the nuclei in CCRCC, whereas STIM1 shows the cytosolic expression pattern in immunohistochemical staining. Orai1 expression level is inversely correlated with CCRCC tumor grade, whereas STIM1 expression level is not associated with tumor grade. The higher Orai1 expression is significantly associated with lower Fuhrman nuclear grade, pathologic T stage, and TNM stage and with favorable prognosis. The expression level of STIM1 is not correlated with CCRCC grade and clinical outcomes. Orai1 expression in CCRCC is associated with tumor progression and with favorable prognostic factors. These results suggest that Orai1 is an attractive prognostic marker and therapeutic target for CCRCC. PMID:27247496

  12. Neoantigen Load, Antigen Presentation Machinery, and Immune Signatures Determine Prognosis in Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Matsushita, Hirokazu; Sato, Yusuke; Karasaki, Takahiro; Nakagawa, Tohru; Kume, Haruki; Ogawa, Seishi; Homma, Yukio; Kakimi, Kazuhiro

    2016-05-01

    Tumors commonly harbor multiple genetic alterations, some of which initiate tumorigenesis. Among these, some tumor-specific somatic mutations resulting in mutated protein have the potential to induce antitumor immune responses. To examine the relevance of the latter to immune responses in the tumor and to patient outcomes, we used datasets of whole-exome and RNA sequencing from 97 clear cell renal cell carcinoma (ccRCC) patients to identify neoepitopes predicted to be presented by each patient's autologous HLA molecules. We found that the number of nonsilent or missense mutations did not correlate with patient prognosis. However, combining the number of HLA-restricted neoepitopes with the cell surface expression of HLA or β2-microglobulin(β2M) revealed that an A-neo(hi)/HLA-A(hi) or ABC-neo(hi)/β2M(hi) phenotype correlated with better clinical outcomes. Higher expression of immune-related genes from CD8 T cells and their effector molecules [CD8A, perforin (PRF1) and granzyme A (GZMA)], however, did not correlate with prognosis. This may have been due to the observed correlation of these genes with the expression of other genes that were associated with immunosuppression in the tumor microenvironment (CTLA-4, PD-1, LAG-3, PD-L1, PD-L2, IDO1, and IL10). This suggested that abundant neoepitopes associated with greater antitumor effector immune responses were counterbalanced by a strongly immunosuppressive microenvironment. Therefore, immunosuppressive molecules should be considered high-priority targets for modulating immune responses in patients with ccRCC. Blockade of these molecular pathways could be combined with immunotherapies targeting neoantigens to achieve synergistic antitumor activity. Cancer Immunol Res; 4(5); 463-71. ©2016 AACR. PMID:26980598

  13. Clear cell renal cell carcinoma: Contrast-enhanced ultrasound features relation to tumor size

    International Nuclear Information System (INIS)

    Objectives: To analyze the contrast-enhanced ultrasound (CEUS) features of clear cell renal cell carcinoma (CCRCC) in relation to tumor size. Materials and methods: The CEUS appearance of 92 CCRCCs confirmed pathologically were retrospectively analyzed. Tumor size was stratified into six groups with a 1 cm interval. For each lesion, the degree of enhancement, the homogeneity of enhancement and the presence of pseudocapsule sign were evaluated and compared with the pathologic findings. Results: The tumors of groups I-VI were counted for 13, 26, 21, 11, 10 and 11, respectively. All the CCRCCs mainly showed a marked enhancement, and there was no statistically significance between the degree of enhancement and tumor size (P > 0.05). However, both homogeneity of enhancement and frequency of pseudocapsule correlated well with the tumor size (P 3 cm (9%; P 5 cm (66%, 23%, 24%, respectively; P < 0.01). On the pathologic examinations, the mean MVD was significantly higher in marked enhancement tumors than slight enhancement tumors (46.0 ± 15.9, 27.5 ± 8.3, respectively; P < 0.01). Any tumors with a heterogeneous enhancement pattern were accompanied by intratumoral necrosis or cysts on histologic specimen. A pseudocapsule was seen at pathology in all the 46 cases with perilesional enhancement and 4 of 46 tumors without perilesional enhancement at CEUS. Conclusion: CEUS features of CCRCCs vary with the size of the tumor, especially in the homogeneity of enhancement and the presence of pseudocapsule sign. CEUS is effective in demonstrating the sonographic visualization of tumoral characteristics.

  14. Characteristic findings of renal oncocytoma and clear-cell renal cell carcinoma with multiphase CT

    International Nuclear Information System (INIS)

    Objective: To evaluate characteristic imaging findings of tumor attenuation in 4-phase CT between renal oncocytoma (RO) and clear-cell renal cell carcinoma (ccRCC) of small tumor size (≤ 5 cm). Methods: Fifty-six patients with histologically confirmed renal masses (11 ROs and 45 ccRCCs) were included in this study. Heterogeneous enhancement was found all tumors during the corticomedullary phase (CMP). The CT values of the normal renal cortex, the relatively high enhanced region and the relatively less-enhanced region of the tumor were measured in each phase. Statistical comparison was carried out by Chi-square test or Mann-Whitney test. Results: In CMP, the CT value of the relatively high enhanced region in RO [163.0 HU (141.0-178.0 HU)] was significantly lower than that in ccRCC [194.0 HU (166.5-235.0 HU); Z=-2.847, P=0.004] Compared CMP with the excretory phase, the attenuation of the relatively highly enhanced region in RO [70.0 HU (41.0-86.0 HU)] were significantly lower than that in ccRCC [87.0 HU (65.0-126.5 HU)] (Z=-2.032, P=0.042). In the excretory phase, 9 of 11 ROs had a further enhancement with its relatively less-enhanced region which was significantly higher than that in ccRCC (21/45; χ2=4.391, P=0.036). Conclusions: In CMP, the CT value of the relatively high enhanced region in RO was significantly lower than that in ccRCC. Compared with ccRCC, in the excretory phase, the RO had less attenuation of the relatively highly enhanced region with homogeneous density. (authors)

  15. MicroRNA-194 is a Marker for Good Prognosis in Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Nofech-Mozes, Roy; Khella, Heba W Z; Scorilas, Andreas; Youssef, Leza; Krylov, Sergey N; Lianidou, Evi; Sidiropoulos, Konstantinos G; Gabril, Manal; Evans, Andrew; Yousef, George M

    2016-04-01

    Clear cell renal cell carcinoma (ccRCC) is the most prevalent adult kidney cancer. Prognostic markers are needed to guide patient management toward aggressive versus more conservative approaches, especially for small tumors ≤4 cm. miR-194 was reported to be downregulated in several cancers and is involved in epithelial to mesenchymal transition. We evaluated miR-194 as a prognostic marker in ccRCC. In a cohort of 234 patients with primary ccRCC, we correlated miR-194 expression level with multiple clinicopathological features including disease-free and overall survival, tumor size, clinical stage, and histological grade. Our results shows a stepwise decrease in miR-194 expression from normal kidney to primary ccRCC (P = 0.0032) and a subsequent decrease from primary to metastatic lesions. Additionally, patients with higher miR-194 expression has significantly longer disease-free survival (P = 0.041) and overall survival (P = 0.031) compared to those with lower expression. In multivariate analysis, miR-194-positive tumors retain significance in disease-free survival and overall survival, suggesting miR-194 is an independent marker for good prognosis in ccRCC. Moreover, miR-194 is a marker for good prognosis for patients with small renal masses (P = 0.014). These findings were validated on an independent data set from The Cancer Genome Atlas. We also compared miR-194 expression between RCC subtypes. ccRCC had the highest levels, whereas chromophobe RCC and oncocytoma had comparable lower levels. Target prediction coupled with pathway analysis show that miR-194 is predicted to target key molecules and pathways involved in RCC progression. miR-194 represents a prognostic biomarker in ccRCC. PMID:26860079

  16. Molecular Stratification of Clear Cell Renal Cell Carcinoma by Consensus Clustering Reveals Distinct Subtypes and Survival Patterns

    OpenAIRE

    Brannon, A. Rose; Reddy, Anupama; Seiler, Michael; Arreola, Alexandra; Moore, Dominic T.; Pruthi, Raj S.; Wallen, Eric M.; Nielsen, Matthew E; Liu, Huiqing; Nathanson, Katherine L.; Ljungberg, Börje; Zhao, Hongjuan; BROOKS, JAMES D.; Ganesan, Shridar; Bhanot, Gyan

    2010-01-01

    Clear cell renal cell carcinoma (ccRCC) is the predominant RCC subtype, but even within this classification, the natural history is heterogeneous and difficult to predict. A sophisticated understanding of the molecular features most discriminatory for the underlying tumor heterogeneity should be predicated on identifiable and biologically meaningful patterns of gene expression. Gene expression microarray data were analyzed using software that implements iterative unsupervised consensus cluste...

  17. Primary extra-renal clear cell renal cell carcinoma masquerading as an adrenal mass: A diagnostic challenge

    OpenAIRE

    Roumina Hasan; Sandeep Kumar; Vidya Monappa; Anurag Ayachit

    2015-01-01

    We present the first case of a nonmetastasizing renal cell carcinoma (RCC) masquerading as an adrenal mass, in the presence of normal bilateral native kidneys, in a young adult. The possibility of this mass developing in a supernumerary kidney was ruled out, since no identifiable renal tissue, pelvis or ureters was seen within the mass, nor was any separate systemic arterial supply to the mass seen. The diagnosis of extra-renal clear cell RCC was based on cyto-morphological features, further ...

  18. Orai1 and STIM1 are critical for cell migration and proliferation of clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    Highlights: • Orai1 channel is highly expressed in clear cell renal cell carcinoma (ccRCC) tissues. • Orai1 and STIM1 constitute a native store-operated Ca2+ entry in ccRCC cells. • Orai1 and STIM1 promote cell migration and proliferation of ccRCC cells. - Abstract: The intracellular Ca2+ regulation has been implicated in tumorigenesis and tumor progression. Notably, store-operated Ca2+ entry (SOCE) is a major Ca2+ entry mechanism in non-excitable cells, being involved in cell proliferation and migration in several types of cancer. However, the expression and biological role of SOCE have not been investigated in clear cell renal cell carcinoma (ccRCC). Here, we demonstrate that Orai1 and STIM1, not Orai3, are crucial components of SOCE in the progression of ccRCC. The expression levels of Orai1 in tumor tissues were significantly higher than those in the adjacent normal parenchymal tissues. In addition, native SOCE was blunted by inhibiting SOCE or by silencing Orai1 and STIM1. Pharmacological blockade or knockdown of Orai1 or STIM1 also significantly inhibited RCC cell migration and proliferative capability. Taken together, Orai1 is highly expressed in ccRCC tissues illuminating that Orai1-mediated SOCE may play an important role in ccRCC development. Indeed, Orai1 and STIM1 constitute a native SOCE pathway in ccRCC by promoting cell proliferation and migration

  19. Lutetium-177-G250 radioimmunotherapy in an intraperitoneal clear cell renal cell carcinoma xenograft model

    International Nuclear Information System (INIS)

    Full text of publication follows. Aim: Despite the good results achieved with agents targeting the VEGF and mTOR pathways, the treatment of advanced clear cell renal cell carcinoma (ccRCC) still poses a great challenge. A new approach in the treatment of ccRCC is radioimmunotherapy (RIT) using anti-carbonic anhydrase IX (CAIX) antibody G250. To investigate the potential of RIT with Lutetium-177 (Lu177) labeled G250, we conducted protein dose escalation study and subsequently a RIT study with Lu177-G250 in an intraperitoneal ccRCC mouse model. Materials and methods: 25 athymic female BALB/c mice were injected intraperitoneally with 3 x 106 SK-RC-52 cells. To determine the optimal G250 protein dose, 3 weeks after inoculation the mice were injected with either 1, 3, 10, 30 or 100 μg G250 radiolabeled with 15 MBq indium-111 (In111). SPECT/CT images were made with the micro SPECT USPECT II camera 48 hours p.i. After imaging, the mice are killed and the biodistribution of In111-G250 was determined. The optimal protein dose was used in a subsequent therapy experiment in 3 groups of mice with i.p. SK-RC-52 tumors. One group (n=10) was injected with 13 MBq Lu177-G250, a control group received nonspecific antibody MOPC21 labeled with 13 MBq Lu177 (n=10) and the second control group received 20 MBq In111-G250 (n=10). Tumor growth was monitored with SPECT/CT imaging before treatment and with 3 week intervals. Primary endpoints were overall survival and toxicity. Results: The optimal G250 protein dose to target ccRCC in this model was 10 μg G250, as determined with SPECT/CT imaging and biodistribution. Treatment with 13 MBq Lu177-G250 was well tolerated. Treatment with Lu177-G250 resulted in significantly prolonged median survival of 139 days, in comparison with 49 days (Lu177-MOPC21) and 53 days In111-G250 (p=0.015). Conclusion: this is the first RIT study with radiolabeled G250 protein in mice with i.p. growing ccRCC. Treatment with Lu177-G250 resulted in significantly

  20. EGFR kinase-dependent and kinase-independent roles in clear cell renal cell carcinoma.

    Science.gov (United States)

    Cossu-Rocca, Paolo; Muroni, Maria R; Sanges, Francesca; Sotgiu, Giovanni; Asunis, Anna; Tanca, Luciana; Onnis, Daniela; Pira, Giovanna; Manca, Alessandra; Dore, Simone; Uras, Maria G; Ena, Sara; De Miglio, Maria R

    2016-01-01

    Epidermal growth factor receptor (EGFR) is associated with progression of many epithelial malignancies and represents a significant therapeutic target. Although clear cell renal cell carcinoma (CCRCC) has been widely investigated for EGFR molecular alterations, genetic evidences of EGFR gene activating mutations and/or gene amplification have been rarely confirmed in the literature. Therefore, until now EGFR-targeted therapies in clinical trials have been demonstrated unsuccessful. New evidence has been given about the interactions between EGFR and the sodium glucose co-transporter-1 (SGLT1) in maintaining the glucose basal intracellular level to favour cancer cell growth and survival; thus a new functional role may be attributed to EGFR, regardless of its kinase activity. To define the role of EGFR in CCRCC an extensive investigation of genetic changes and functional kinase activities was performed in a series of tumors by analyzing the EGFR mutational status and expression profile, together with the protein expression of downstream signaling pathways members. Furthermore, we investigated the co-expression of EGFR and SGLT1 proteins and their relationships with clinic-pathological features in CCRCC. EGFR protein expression was identified in 98.4% of CCRCC. Furthermore, it was described for the first time that SGLT1 is overexpressed in CCRCC (80.9%), and that co-expression with EGFR is appreciable in 79.4% of the tumours. Moreover, the activation of downstream EGFR pathways was found in about 79.4% of SGLT1-positive CCRCCs. The mutational status analysis of EGFR failed to demonstrate mutations on exons 18 to 24 and the presence of EGFR-variantIII (EGFRvIII) in all CCRCCs analyzed. FISH analysis revealed absence of EGFR amplification, and high polysomy of chromosome 7. Finally, the EGFR gene expression profile showed gene overexpression in 38.2% of CCRCCs. Our study contributes to define the complexity of EGFR role in CCRCC, identifying its bivalent kinase

  1. Increased Expression of the Very Low-Density Lipoprotein Receptor Mediates Lipid Accumulation in Clear-Cell Renal Cell Carcinoma

    OpenAIRE

    Sundelin, Jeanna Perman; Ståhlman, Marcus; Lundqvist, Annika; Levin, Max; Parini, Paolo; Johansson, Martin E.; Borén, Jan

    2012-01-01

    Clear-cell renal cell carcinoma (RCC) is, in most cases, caused by loss of function of the tumor suppressor gene von Hippel-Lindau, resulting in constitutive activation of hypoxia-inducible factor (HIF)-1 alpha and expression of hypoxia-induced genes in normoxic conditions. Clear-cell RCC cells are characterized histologically by accumulation of cholesterol, mainly in its ester form. The origin of the increased cholesterol remains unclear, but it is likely explained by an HIF-1 alpha-driven i...

  2. Clear cell renal cell carcinoma: Contrast-enhanced ultrasound features relation to tumor size

    Energy Technology Data Exchange (ETDEWEB)

    Jiang Jun [Department of ultrasound, Sixth People' s Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233 (China)], E-mail: tenine@163.com; Chen Yaqing [Department of ultrasound, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092 (China)], E-mail: joychen1266@126.com; Zhou Yongchang [Department of ultrasound, Sixth People' s Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233 (China)], E-mail: zhouyongchang1130@163.com; Zhang Huizhen [Department of pathology, Sixth People' s Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233 (China)], E-mail: h_z_zhang@163.com

    2010-01-15

    Objectives: To analyze the contrast-enhanced ultrasound (CEUS) features of clear cell renal cell carcinoma (CCRCC) in relation to tumor size. Materials and methods: The CEUS appearance of 92 CCRCCs confirmed pathologically were retrospectively analyzed. Tumor size was stratified into six groups with a 1 cm interval. For each lesion, the degree of enhancement, the homogeneity of enhancement and the presence of pseudocapsule sign were evaluated and compared with the pathologic findings. Results: The tumors of groups I-VI were counted for 13, 26, 21, 11, 10 and 11, respectively. All the CCRCCs mainly showed a marked enhancement, and there was no statistically significance between the degree of enhancement and tumor size (P > 0.05). However, both homogeneity of enhancement and frequency of pseudocapsule correlated well with the tumor size (P < 0.01). Homogeneous enhancement was shown in 85%, 65%, 19%, 9%, 0% and 0% of the tumors in the six groups, respectively. In tumors {<=}3 cm the frequency (72%) of homogeneity was significantly higher than in tumors >3 cm (9%; P < 0.01). The detection rate of pseudocapsule sign in the six group was 23%, 62%, 71%, 64%, 50% and 0%, respectively. The frequency of pseudocapsule sign was significantly higher in tumors 2.1-5 cm than <2 cm and >5 cm (66%, 23%, 24%, respectively; P < 0.01). On the pathologic examinations, the mean MVD was significantly higher in marked enhancement tumors than slight enhancement tumors (46.0 {+-} 15.9, 27.5 {+-} 8.3, respectively; P < 0.01). Any tumors with a heterogeneous enhancement pattern were accompanied by intratumoral necrosis or cysts on histologic specimen. A pseudocapsule was seen at pathology in all the 46 cases with perilesional enhancement and 4 of 46 tumors without perilesional enhancement at CEUS. Conclusion: CEUS features of CCRCCs vary with the size of the tumor, especially in the homogeneity of enhancement and the presence of pseudocapsule sign. CEUS is effective in demonstrating the

  3. Clear Cell Papillary Renal Cell Carcinoma in the Bilateral Native Kidneys after 2 Years of Renal Transplantation: Report of a Case and Review of the Literature

    OpenAIRE

    Zhanyong Bing; Tomaszewski, John E.

    2011-01-01

    Renal transplantation increases the probability of malignant tumors by about 2–4-fold overall with a much higher rate for renal epithelial malignancy. Renal tumors in renal transplant recipients are commonly conventional clear cell or papillary renal cell carcinoma. Clear cell papillary renal cell carcinoma is a recently described unique renal epithelial neoplasm with scant eosinophilic or moderate amount of clear cytoplasm and pyknotic small nuclei oriented commonly toward the apical surface...

  4. Renal-cell carcinomas in end-stage kidneys: a clinicopathological study with emphasis on clear-cell papillary renal-cell carcinoma and acquired cystic kidney disease-associated carcinoma.

    Science.gov (United States)

    Bhatnagar, Ramneesh; Alexiev, Borislav A

    2012-02-01

    Clear-cell papillary renal-cell carcinoma (CCPC) and acquired cystic kidney disease-associated carcinoma (ACDAC) are neoplasms with distinct morphological characteristics that behave less aggressively than conventional renal-cell carcinomas. End-stage kidney specimens from 61 patients (47 males and 14 females) with 109 renal-cell carcinomas were selected. Papillary renal-cell carcinoma was the most common malignancy (61/109, 56%), followed by CCPC (20/109, 18%). The CCPC showed a papillary or tubular/solid architecture, clear cytoplasm, low nuclear grade, and a distinct immunohistochemical profile (RCC-, vimentin+, CK7+, p504S-). ACDAC displayed a variety of architectural patterns, eosinophilic cytoplasm, high nuclear grade, intratumoral calcium oxalate deposits, and an immunohistochemical profile similar to type 2 papillary renal-cell carcinoma (RCC+, vimentin+, CK7-/+, p504S+). Less than 5% (3/69) of pathologically staged renal-cell carcinomas in end-stage kidneys presented with lymphogenous and/or hematogenous metastases. PMID:21791489

  5. PD-L1 expression in renal cell carcinoma clear cell type is related to unfavorable prognosis

    OpenAIRE

    Katia R. M. Leite; Reis, Sabrina T.; Junior, José Pontes; Zerati, Marcelo; Gomes, Daniel de Oliveira; Luiz H. Camara-Lopes; Srougi, Miguel

    2015-01-01

    Background PD-L1 is a glycoprotein from the family of T-cell co-stimulatory molecules that are constitutively expressed by macrophages. Aberrant expression of PD-L1 is observed in human cancers associated with inhibition of the tumor-directed T-cell immune response. There are few reports in the literature evaluating PD-L1 expression in association to prognosis specifically in renal cell cancer clear cell type (RCC-CC). Methods Immunohistochemistry using a PD-L1 polyclonal antibody was perform...

  6. Ultrastructural appearance and cytoskeletal architecture of the clear, chromophilic, and chromophobe types of human renal cell carcinoma in vitro.

    OpenAIRE

    Gerharz, C D; Moll, R.; Störkel, S.; Ramp, U; Thoenes, W.; Gabbert, H E

    1993-01-01

    The clear, chromophilic, and chromophobe types of human renal cell carcinoma have been defined as distinct morphological entities and can be clearly separated by differences of ultrastructural appearance, cytoskeletal architecture, enzyme synthesis, and cytogenetic aberrations. In this report, the cytomorphological aspects of these tumor types are compared in vitro, showing that essential ultrastructural and cytoskeletal characteristics of each tumor type are expressed even after prolonged in...

  7. Stage-dependent prognostic impact of molecular signatures in clear cell renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Weber T

    2014-05-01

    Full Text Available Thomas Weber,1,2 Matthias Meinhardt,3 Stefan Zastrow,1 Andreas Wienke,4 Kati Erdmann,1 Jörg Hofmann,1 Susanne Fuessel,1 Manfred P Wirth11Department of Urology, Technische Universität Dresden, Dresden, Germany; 2Department of Oncology and Hematology, Martin-Luther-University Halle-Wittenberg, Halle (Saale, Germany; 3Institute of Pathology, Technische Universität Dresden, Dresden, Germany; 4Institute of Medical Epidemiology, Biostatistics, and Informatics, Martin-Luther-University Halle-Wittenberg, Halle (Saale, GermanyPurpose: To enhance prognostic information of protein biomarkers for clear cell renal cell carcinomas (ccRCCs, we analyzed them within prognostic groups of ccRCC harboring different tumor characteristics of this clinically and molecularly heterogeneous tumor entity.Methods: Tissue microarrays from 145 patients with primary ccRCC were immunohistochemically analyzed for VHL (von Hippel-Lindau tumor suppressor, Ki67 (marker of proliferation 1, p53 (tumor protein p53, p21 (cyclin-dependent kinase inhibitor 1A, survivin (baculoviral IAP repeat containing 5, and UEA-1 (ulex europaeus agglutinin I to assess microvessel-density.Results: When analyzing all patients, nuclear staining of Ki67 (hazard ratio [HR] 1.08, 95% confidence interval [CI] 1.04–1.12 and nuclear survivin (nS; HR 1.04, 95% CI 1.01–1.08 were significantly associated with disease-specific survival (DSS. In the cohort of patients with advanced localized or metastasized ccRCC, high staining of Ki67, p53 and nS predicted shorter DSS (Ki67: HR 1.07, 95% CI 1.02–1.11; p53: HR 1.05, 95% CI 1.01–1.09; nS: HR 1.08, 95% CI 1.02–1.14. In organ-confined ccRCC, patients with high p21-staining had a longer DSS (HR 0.96, 95% CI 0.92–0.99. In a multivariate model with stepwise backward elimination, tumor size and p21-staining showed a significant association with DSS in patients with "organ-confined" ccRCCs. The p21-staining increased the concordance index of tumor size from

  8. Comparative Studies of the Proteome, Glycoproteome, and N-Glycome of Clear Cell Renal Cell Carcinoma Plasma before and after Curative Nephrectomy

    OpenAIRE

    Gbormittah, Francisca O.; Lee, Ling Y.; Taylor, KyOnese; Hancock, William S.; Iliopoulos, Othon

    2014-01-01

    Clear cell renal cell carcinoma is the most prevalent of all reported kidney cancer cases, and currently there are no markers for early diagnosis. This has stimulated great research interest recently because early detection of the disease can significantly improve the low survival rate. Combining the proteome, glycoproteome, and N-glycome data from clear cell renal cell carcinoma plasma has the potential of identifying candidate markers for early diagnosis and prognosis and/or to monitor dise...

  9. Comparison of digital image analysis versus visual assessment to assess survivin expression as an independent predictor of survival for patients with clear cell renal cell carcinoma✩

    OpenAIRE

    Parker, Alexander S.; Lohse, Christine M.; Leibovich, Bradley C.; Cheville, John C; Sheinin, Yuri M.; Kwon, Eugene D.

    2008-01-01

    We previously used quantitative digital image analysis to report that high immunohistochemical tumor expression levels of survivin independently predict poor outcome among patients with clear cell renal cell carcinoma. However, given the cumbersome and costly nature of digital image analysis, we evaluated simple visual assessment as an alternative to digital image analysis for assessing survivin as a predictor of clear cell renal cell carcinoma patient outcomes. We identified 310 patients tre...

  10. PD-L1 Expression in Clear Cell Renal Cell Carcinoma: An Analysis of Nephrectomy and Sites of Metastases

    OpenAIRE

    Jilaveanu, L.B.; Shuch, B.; Zito, C. R.; Parisi, F.; Barr, M.; Kluger, Y.; Chen, L; Kluger, H. M.

    2014-01-01

    Background: Expression of programmed death ligand (PD-L1/B7-H1/CD274) represents a mechanism of immune escape for renal cell carcinoma (RCC) cells. Drugs blocking PD-L1 or its receptor are in clinical development and early data suggests that tumor PD-L1 expression may predict response. Patients and Methods: A tissue microarray (TMA) consisting of four biopsy cores from 34 matched pairs of nephrectomy and metastatic sites of clear cell RCC was used to assess PD-L1 expression by quantitative im...

  11. Orai1 and STIM1 are critical for cell migration and proliferation of clear cell renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji-Hee [Department of Physiology, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of); Lkhagvadorj, Sayamaa; Lee, Mi-Ra [Department of Pathology, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of); Hwang, Kyu-Hee [Department of Physiology, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of); Chung, Hyun Chul; Jung, Jae Hung [Department of Urology, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of); Cha, Seung-Kuy, E-mail: skcha@yonsei.ac.kr [Department of Physiology, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of); Institute of Lifestyle Medicine, and Nuclear Receptor Research Consortium, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of); Eom, Minseob, E-mail: eomm@yonsei.ac.kr [Department of Pathology, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of)

    2014-05-23

    Highlights: • Orai1 channel is highly expressed in clear cell renal cell carcinoma (ccRCC) tissues. • Orai1 and STIM1 constitute a native store-operated Ca{sup 2+} entry in ccRCC cells. • Orai1 and STIM1 promote cell migration and proliferation of ccRCC cells. - Abstract: The intracellular Ca{sup 2+} regulation has been implicated in tumorigenesis and tumor progression. Notably, store-operated Ca{sup 2+} entry (SOCE) is a major Ca{sup 2+} entry mechanism in non-excitable cells, being involved in cell proliferation and migration in several types of cancer. However, the expression and biological role of SOCE have not been investigated in clear cell renal cell carcinoma (ccRCC). Here, we demonstrate that Orai1 and STIM1, not Orai3, are crucial components of SOCE in the progression of ccRCC. The expression levels of Orai1 in tumor tissues were significantly higher than those in the adjacent normal parenchymal tissues. In addition, native SOCE was blunted by inhibiting SOCE or by silencing Orai1 and STIM1. Pharmacological blockade or knockdown of Orai1 or STIM1 also significantly inhibited RCC cell migration and proliferative capability. Taken together, Orai1 is highly expressed in ccRCC tissues illuminating that Orai1-mediated SOCE may play an important role in ccRCC development. Indeed, Orai1 and STIM1 constitute a native SOCE pathway in ccRCC by promoting cell proliferation and migration.

  12. Study of the role of SETD2 mutations in clear cell renal cell carninoma (ccRCC)

    OpenAIRE

    Almeida, Catarina Faria de

    2013-01-01

    Trabalho de projecto de mestrado em Bioestatística, apresentado à Universidade de Lisboa, através da Faculdade de Ciências, 2013 Clear cell Renal Cell Carcinoma, ccRCC, is the most common form of Renal Cancer, accounting for 90% of these cancers cases. It is well established that the majority of these cancers happen when both alleles of VHL (Von Hippel Lindau) tumour suppressor gene are mutated. It has also been observed that patients with this form of cancer present mutations on the SETD2...

  13. Differential expression of PD-L1 between primary and metastatic sites in clear cell Renal Cell Carcinoma

    OpenAIRE

    Callea, Marcella; Albiges, Laurence; Gupta, Mamta; Cheng, Su-Chun; Genega, Elizabeth M.; Fay, André P.; Song, Jiaxi; Carvo, Ingrid; Bhatt, Rupal S.; Atkins, Michael B.; Hodi, F. Stephen; Choueiri, Toni K.; McDermott, David F.; Freeman, Gordon J; Signoretti, Sabina

    2015-01-01

    PD-L1 expression in primary clear cell renal cell carcinoma (ccRCC) increases the likelihood of response to anti-PD-1 inhibition, but fails to identify all responders. We hypothesized that PD-L1 levels assessed in randomly selected areas of the primary tumors may not accurately reflect expression levels in metastatic lesions, which are the target of systemic therapy. Therefore, we compared PD-L1 expression in a series of primary ccRCC and their metastases. Tissue blocks from 53 primary ccRCCs...

  14. B7-H3 is a new cancer-specific endothelial marker in clear cell renal cell carcinoma

    OpenAIRE

    Qin XJ; Zhang HL; Ye DW; Dai B; Zhu Y; Shi GH

    2013-01-01

    Xiaojian Qin,1,2 Hailiang Zhang,1,2 Dingwei Ye,1,2 Bo Dai,1,2 Yao Zhu,1,2 Guohai Shi1,2 1Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; 2Department of Oncology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China Background: The purpose of this study was to validate B7-H3 as a new cancer-specific endothelial marker in clear cell renal cell carcinoma. Methods: B7-H3 expression patterns were compared betw...

  15. Gene set enrichment analysis and ingenuity pathway analysis of metastatic clear cell renal cell carcinoma cell line.

    Science.gov (United States)

    Khan, Mohammed I; Dębski, Konrad J; Dabrowski, Michał; Czarnecka, Anna M; Szczylik, Cezary

    2016-08-01

    In recent years, genome-wide RNA expression analysis has become a routine tool that offers a great opportunity to study and understand the key role of genes that contribute to carcinogenesis. Various microarray platforms and statistical approaches can be used to identify genes that might serve as prognostic biomarkers and be developed as antitumor therapies in the future. Metastatic renal cell carcinoma (mRCC) is a serious, life-threatening disease, and there are few treatment options for patients. In this study, we performed one-color microarray gene expression (4×44K) analysis of the mRCC cell line Caki-1 and the healthy kidney cell line ASE-5063. A total of 1,921 genes were differentially expressed in the Caki-1 cell line (1,023 upregulated and 898 downregulated). Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) approaches were used to analyze the differential-expression data. The objective of this research was to identify complex biological changes that occur during metastatic development using Caki-1 as a model mRCC cell line. Our data suggest that there are multiple deregulated pathways associated with metastatic clear cell renal cell carcinoma (mccRCC), including integrin-linked kinase (ILK) signaling, leukocyte extravasation signaling, IGF-I signaling, CXCR4 signaling, and phosphoinositol 3-kinase/AKT/mammalian target of rapamycin signaling. The IPA upstream analysis predicted top transcriptional regulators that are either activated or inhibited, such as estrogen receptors, TP53, KDM5B, SPDEF, and CDKN1A. The GSEA approach was used to further confirm enriched pathway data following IPA. PMID:27279483

  16. Genetic mutations in accordance with a low malignant potential tumour are not demonstrated in clear cell papillary renal cell carcinoma.

    Science.gov (United States)

    Raspollini, Maria Rosaria; Castiglione, Francesca; Cheng, Liang; Montironi, Rodolfo; Lopez-Beltran, Antonio

    2016-06-01

    Clear cell papillary renal cell carcinoma (CCPRCC) cases were evaluated for mutations on the following genes: KRAS, NRAS, BRAF, PIK3CA, ALK, ERBB2, DDR2, MAP2K1, RET and EGFR. Four male and three female patients of age 42-74 years were evaluated. All cases were incidentally detected by ultrasound and ranged 1.8-3.5 cm. Microscopic examination showed variably tubulopapillary, tubular acinar, cystic architecture and the characteristic linear arrangement of nuclei. The cells were reactive with CK7 (strong), CA IX (cup-shape) and 34 β E12. CD10, AMACR/RACEMASE and GATA3 were negative. There were no mutations on any of the investigated genes. This preliminary observation supports the concept that CCPRCC might be indeed an indolent tumour worth it to be named as clear cell papillary neoplasm of low potential. PMID:26941183

  17. Urinary KIM-1 and AQP-1 in patients with clear renal cell carcinoma: Potential noninvasive biomarkers

    Directory of Open Access Journals (Sweden)

    Mijušković Mirjana

    2016-01-01

    Full Text Available Background/Aim. Kidney injury molecule-1 (KIM-1 and aquaporin-1 (AQP-1 are potential early urinary biomarkers of clear renal cell carcinoma (cRCC. The aim of this study was to ascertain relationship between the urine concentrations KIM-1 and AQP-1 with tumor size, grade, pT stage and type of operation (radical or partial nephrectomy in patients with cRCC. Methods. Urinary concentrations of urinary KIM-1 (uKIM-1 and urinary AQP-1 (uAQP-1 were determined by commercially available ELISA kits. The analysis included 40 patients undergoing partial or radical nephrectomy for cRCC and 40 age- and sex-matched healthy adult volunteers. Results. The median preoperative concentrations of KIM-1 in the cRCC group [0.724 ± 1.120 ng/mg urinary creatinine (Ucr] were significantly greater compared with controls (healthy volunteers (0.210 ± 0.082 ng/mgUcr (p = 0.0227. Postoperatively, uKIM-1 concentration decreased significantly to control values (0.177 ± 0.099 ng/mgUcr vs 0.210 ± 0.082 ng/mgUcr, respectively. The size, grade and stage of tumor were correlated positively with preoperative uKIM-1 concentrations. Contrary to these results, concentrations of uAQP-1 in the cRCC group were significantly lower (0.111 ± 0.092 ng/mgUcr compared with the control group (0.202 ± 0.078 ng/mgUcr (p = 0.0014. Postoperatively, the concentrations of uAQP-1 increased progressively up to control values, approximately. We find no significant correlation between preoperative uAQP-1 concentrations and tumor size, grade and stage. Conclusion. uKIM-1 was found to be a reliable diagnostic marker of cRCC, based on its significantly increased values before and decreased values after the nephrectomy. [Projekat Ministarstva nauke Republike Srbije, br. III41018

  18. Sunitinib treatment for patients with clear-cell metastatic renal cell carcinoma: clinical outcomes and plasma angiogenesis markers

    International Nuclear Information System (INIS)

    Sunitinib is a protein tyrosine kinase-inhibitor targeting VEGFR, c-kit and PDGFR. It has been approved for the treatment of metastatic renal-cell carcinoma and gastrointestinal stromal tumors. Although it has been shown to prolong disease-free and overall survival in renal-cell carcinoma patients, only 70% of the treated population receive a clinical benefit (CB) from the treatment. Markers that could predict clinical benefit to sunitinib would be an important aid in monitoring and following their treatment. We assessed the outcome and plasma proangiogenic factors in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib in our institution. We have treated 42 patients with metastatic clear-cell renal carcinoma with sunitinib. Plasma concentrations of VEGF-A, sVEGFR2 and PDGF were determined by ELISA. At the time of analysis 39 patients were evaluable for response and 30 patients had obtained a clinical benefit (CB). Median progression-free survival was 268 days (8.93 months) and median overall survival was 487 days (16.23 months). Interestingly, disease stabilization or objective response resulted in comparable overall survival. Most treatment-related adverse events were of mild-to-moderate intensity with one treatment-related death. Plasma sVEGFR2 and PDGF levels had no predictive value. Fold-increase in plasma VEGF was significantly lower in patients that obtained a CB as compared to patients that progressed after two cycles of treatment. Plasma VEGF did not increase in patients with initial CB at the time of progression. Sunitinib showed substantial activity in mRCC. Disease stabilization or objective response resulted in comparable overall survival and both outcomes should be considered positive. Fold-increase in plasma VEGF predicts for CB and could be a candidate marker. Progression after initial CB is not associated with elevated plasma VEGF, implying a different mechanism of resistance

  19. Prognostic significance of modified Glasgow Prognostic Score in patients with non-metastatic clear cell renal cell carcinoma.

    Science.gov (United States)

    Cho, Dae Sung; Kim, Sun Il; Choo, Seol Ho; Jang, Seok Heun; Ahn, Hyun Soo; Kim, Se Joong

    2016-06-01

    Objective The aim of this study was to evaluate the usefulness of the modified Glasgow Prognostic Score (mGPS) as a prognostic factor in patients with non-metastatic clear cell renal cell carcinoma (RCC). Materials and methods Between June 1994 and July 2012, 469 patients with RCC underwent radical or partial nephrectomy at two hospitals. Among these patients, 65 with non-clear cell type histology and 16 with lymph-node or distant metastasis were excluded. The medical records of the remaining 388 patients were retrospectively reviewed. The mGPS was calculated using a selective combination of C-reactive protein (CRP) and albumin as previously described. The prognostic significance of various clinicopathological variables including mGPS was analyzed using univariate and multivariate analyses. Results Of the total 388 patients, 40 patients (10.3%) developed local recurrence or distant metastasis and 18 patients (4.6%) died of disease during the follow-up period. The univariate analysis identified CRP, mGPS, thrombocytosis, T stage, Fuhrman's nuclear grade and lymphovascular invasion as significant prognostic factors for recurrence-free survival (RFS) and cancer-specific survival (CSS). The multivariate analysis indicated that mGPS (p clear cell RCC treated with radical or partial nephrectomy. These findings suggest that mGPS should be used for predicting recurrence or survival in patients undergoing nephrectomy for non-metastatic clear cell RCC. PMID:26878156

  20. Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing

    OpenAIRE

    Gerlinger, Marco; Horswell, Stuart; Larkin, James; Rowan, Andrew J.; Salm, Max P; Varela, Ignacio; Fisher, Rosalie; McGranahan, Nicholas; Matthews, Nicholas; Santos, Claudio R; Martinez, Pierre; Phillimore, Benjamin; Begum, Sharmin; Rabinowitz, Adam; Spencer-Dene, Bradley

    2014-01-01

    Clear cell renal carcinomas (ccRCCs) can display intratumor heterogeneity (ITH). We applied multiregion exome sequencing (M-seq) to resolve the genetic architecture and evolutionary histories of ten ccRCCs. Ultra-deep sequencing identified ITH in all cases. We found that 73–75% of identified ccRCC driver aberrations were subclonal, confounding estimates of driver mutation prevalence. ITH increased with the number of biopsies analyzed, without evidence of saturation in most tumors. Chromosome ...

  1. Infiltration of tumor-associated macrophages is involved in CD44 expression in clear cell renal cell carcinoma.

    Science.gov (United States)

    Ma, Chaoya; Komohara, Yoshihiro; Ohnishi, Koji; Shimoji, Tetsu; Kuwahara, Nao; Sakumura, Yasuo; Matsuishi, Kozue; Fujiwara, Yukio; Motoshima, Takanobu; Takahashi, Wataru; Yamada, Sohsuke; Kitada, Shohei; Fujimoto, Naohiro; Nakayama, Toshiyuki; Eto, Masatoshi; Takeya, Motohiro

    2016-05-01

    Cancer stem-like cells (CSC) or cancer-initiating cells are now considered to be an important cell population related to cancer recurrence and the resistance to anti-cancer therapy. Tumor-associated macrophages (TAM) are a main component of stromal cells and are related to cancer progression in clear cell renal cell carcinoma (ccRCC). Because the detailed mechanisms allowing the maintenance of CSC in cancer tissues remain unclear, we investigated the relationship between TAM and CD44-expressing cancer cells in ccRCC. CD44 was used as a marker for CSC, and CD163 and CD204 were used as markers for TAM. CD44-positive cancer cells were detected in 37 of the 103 cases. Although statistical analysis showed no relationship between CD44-positive cancer cells and the clinical course, the distribution of CD44-positive cancer cells was significantly associated with a high density of TAM. Our in vitro study using RCC cell lines and human macrophages demonstrated that CD44 expression was upregulated by direct co-culture with macrophages. Silencing of TNF-alpha on macrophages abrogated the upregulation of CD44 expression in cancer cells. Macrophage-induced CD44 overexpression was also suppressed by NF-κB inhibitors. These results suggest that TNF-alpha derived from TAM is linked to CD44 overexpression via NF-κB signaling in ccRCC. PMID:26918621

  2. Role of chromosome 3p12–p21 tumour suppressor genes in clear cell renal cell carcinoma: analysis of VHL dependent and VHL independent pathways of tumorigenesis

    OpenAIRE

    Martinez, A.; Fullwood, P; Kondo, K.; Kishida, T.; Yao, M.; Maher, E R; Latif, F

    2000-01-01

    Aims—Chromosome 3p deletions and loss of heterozygosity (LOH) for 3p markers are features of clear cell renal cell carcinoma but are rare in non-clear cell renal cell carcinoma. The VHL tumour suppressor gene, which maps to 3p25, is a major gatekeeper gene for clear cell renal cell carcinoma and is inactivated in most sporadic cases of this disease. However, it has been suggested that inactivation of other 3p tumour suppressor genes might be crucial for clear cell renal cell carcinoma tumorig...

  3. The antioxidant protein PARK7 plays an important role in cell resistance to Cisplatin-induced apoptosis in case of clear cell renal cell carcinoma.

    Science.gov (United States)

    Trivedi, Rachana; Dihazi, Gry H; Eltoweissy, Marwa; Mishra, Durga P; Mueller, Gerhard A; Dihazi, Hassan

    2016-08-01

    Clear cell renal cell carcinoma (ccRCC) is the most malignant tumor in the adult kidney. Many factors are responsible for the development and progression of this tumor. Increased reactive oxygen species accumulation and altered redox status have been observed in cancer cells and this biochemical property of cancer cells can be exploited for therapeutic benefits. In earlier work we identified and characterize Protein DJ-1 (PARK7) as an oxidative stress squevenger in renal cells exposed to oxidative stress. To investigate whether the PARK7 or other oxidative stress proteins play a role in the renal cell carcinoma and its sensitivity or resistance to cytostatic drug treatment, differential proteomics analysis was performed with a cell model for clear cell renal carcinoma (Caki-2 and A498). Caki-2 cells were treated with cisplatin and differentially expressed proteins were investigated. The cisplatin treatment resulted in an increase in reactive oxygen species accumulation and ultimately apoptosis of Caki-2 and A498 cells. In parallel, the apoptotic effect was accompanied by a significant downregulation of antioxidant proteins especially PARK7. Knockdown of PARK7 using siRNA and overexpression using plasmid highlights the role of PARK7 as a key player in renal cell carcinoma response to cisplatin induced apoptosis. Overexpression of PARK7 resulted in significant decrease in apoptosis, whereas knockdown of the protein was accompanied by an increase in apoptosis in Caki-2 and A498 cells treated with cisplatin. These results highlights for the first time the important role of PARK7 in cisplatin induced apoptosis in clear renal cell carcinoma cells. PMID:27112662

  4. Synchronous Renal Cell Carcinoma and Gastrointestinal Malignancies

    OpenAIRE

    Dafashy, Tamer J.; Cameron K. Ghaffary; Keyes, Kyle T.; Joseph Sonstein

    2016-01-01

    While renal cell carcinoma is the most commonly diagnosed neoplasm of the kidney, its simultaneous diagnosis with a gastrointestinal malignancy is a rare, but well reported phenomenon. This discussion focuses on three independent cases in which each patient was diagnosed with renal cell carcinoma and a unique synchronous gastrointestinal malignancy. Case 1 explores the diagnosis and surgical intervention of a 66-year-old male patient synchronously diagnosed with clear cell renal cell carcinom...

  5. Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing.

    Science.gov (United States)

    Gerlinger, Marco; Horswell, Stuart; Larkin, James; Rowan, Andrew J; Salm, Max P; Varela, Ignacio; Fisher, Rosalie; McGranahan, Nicholas; Matthews, Nicholas; Santos, Claudio R; Martinez, Pierre; Phillimore, Benjamin; Begum, Sharmin; Rabinowitz, Adam; Spencer-Dene, Bradley; Gulati, Sakshi; Bates, Paul A; Stamp, Gordon; Pickering, Lisa; Gore, Martin; Nicol, David L; Hazell, Steven; Futreal, P Andrew; Stewart, Aengus; Swanton, Charles

    2014-03-01

    Clear cell renal carcinomas (ccRCCs) can display intratumor heterogeneity (ITH). We applied multiregion exome sequencing (M-seq) to resolve the genetic architecture and evolutionary histories of ten ccRCCs. Ultra-deep sequencing identified ITH in all cases. We found that 73-75% of identified ccRCC driver aberrations were subclonal, confounding estimates of driver mutation prevalence. ITH increased with the number of biopsies analyzed, without evidence of saturation in most tumors. Chromosome 3p loss and VHL aberrations were the only ubiquitous events. The proportion of C>T transitions at CpG sites increased during tumor progression. M-seq permits the temporal resolution of ccRCC evolution and refines mutational signatures occurring during tumor development. PMID:24487277

  6. RhoB Acts as a Tumor Suppressor That Inhibits Malignancy of Clear Cell Renal Cell Carcinoma

    Science.gov (United States)

    Ma, Xin; Zhang, Peng; Gao, Yu; Fan, Yang; Pang, Haigang; Gong, Huijie; Shen, Donglai; Gu, Liangyou; Zhang, Yu

    2016-01-01

    This study aims to investigate the biological role of RhoB in clear cell renal cell carcinoma (ccRCC). The expression of RhoB was examined in specimens of patients and cell lines by Western blot and Immunohistochemistry. The correlation between RhoB expression and clinicopathologic variables was also analyzed. The effects of RhoB on cell proliferation, cell cycle, cell apoptosis, and invasion/migration were detected by over-expression and knockdown of RhoB level in ccRCC cells via plasmids and RNAi. The results showed that RhoB was low-expressed in ccRCC surgical specimens and cell lines compared with adjacent normal renal tissues and normal human renal proximal tubular epithelial cell lines (HKC), and its protein expression level was significantly associated with the tumor pathologic parameter embracing tumor size(P = 0.0157), pT stage(P = 0.0035), TNM stage(P = 0.0024) and Fuhrman tumor grade(P = 0.0008). Further, over-expression of RhoB remarkably inhibited the cancer cell proliferation, colony formation and promoted cancer cell apoptosis, and aslo reduced the invasion and migration ability of ccRCC cells. Interestingly, up-regulation of RhoB could induce cell cycle arrest in G2/M phase and led to cell cycle regulators(CyclineB1,CDK1) and pro-apoptotic protein(casp3,casp9) aberrant expression. Moreover, knockdown of RhoB in HKC cells promoted cell proliferation and migration. Taken together, our study indicates that RhoB expression is decreased in ccRCC carcinogenesis and progression. Up-regulation of RhoB significantly inhibits ccRCC cell malignant phenotype. These findings show that RhoB may play a tumor suppressive role in ccRCC cells, raising its potential value in futural therapeutic target for the patients of ccRCC. PMID:27384222

  7. Renal Cell Carcinoma Presenting as Dysphagia

    OpenAIRE

    Chauhan, Sharad; Yadav, Sher Singh; Tomar, Vinay

    2015-01-01

    Renal cell carcinoma presenting with dysphagia is rare. We report a case who presented with dysphagia as the only manifestations of renal malignancy. Biopsy from the pyriform fossa nodules revealed a clear cell neoplasm. Immuno-histochemical analysis of tissue confirmed metastasis of renal cell carcinoma.

  8. P2X7 receptor predicts postoperative cancer-specific survival of patients with clear-cell renal cell carcinoma.

    Science.gov (United States)

    Liu, Zheng; Liu, Yidong; Xu, Le; An, Huimin; Chang, Yuan; Yang, Yuanfeng; Zhang, Weijuan; Xu, Jiejie

    2015-09-01

    The P2X7 receptor, an ATP-gated plasma membrane ion channel, is involved in inflammation, apoptosis and cell proliferation, and thereby plays a crucial role during oncogenic transformation in various malignancies. This study aims to evaluate the impact of P2X7 receptor expression on postoperative cancer-specific survival of patients with clear-cell renal cell carcinoma (ccRCC). A total of 273 patients with ccRCC undergoing nephrectomy at a single institution were retrospectively enrolled in this study, among which 86 patients died of this disease and six patients died of other causes. Clinicopathologic features and cancer-specific survival (CSS) were recorded. P2X7 expression was assessed by immunohistochemistry in clinical specimens. Kaplan-Meier method with log rank test was performed to compare survival curves. Cox regression models were used to evaluate the prognostic values of variables on CSS. Concordance index was calculated to assess prognostic accuracy of prognostic models. Median follow-up period was 90 months (range, 11-120 months). Intratumoral P2X7 expression was significantly lower than peritumoral tissues (P independent prognostic factor for CSS (hazard ratio [HR], 1.693; P = 0.034). The prognostic accuracy of TNM stage, UISS and SSIGN scoring models was improved when intratumoral P2X7 expression was added. Intratumoral P2X7 expression is a potential independent adverse prognostic indicator for postoperative CSS of patients with ccRCC. PMID:26179886

  9. Synergy between von Hippel-Lindau and P53 contributes to chemosensitivity of clear cell renal cell carcinoma.

    Science.gov (United States)

    Zhao, Ziyi; Chen, Changjin; Lin, Junzhi; Zeng, Wentong; Zhao, Juan; Liang, Yindan; Tan, Qinrui; Yang, Chao; Li, Hui

    2016-09-01

    The von Hippel-Lindau tumor suppressor (VHL; E3 ubiquitin ligase gene) is frequently mutated or undetectable in clear cell renal cell carcinoma (CCRCC), and therefore these tumors are highly resistant to chemotherapeutic agents, including adriamycin (ADM) and sunitinib. A mutation in the tumor protein p53 (TP53) also leads to chemoresistance in tumors; however, in CCRCC, TP53 is frequently functional, yet the tumors remain highly insensitive to chemotherapy. This indicates the possibility of a synergistic effect of VHL and P53 in CCRCC. The present study aimed to detect the chemosensitivity of CCRCC. The expression of VHL in the MZ1257 cell line sensitized these cells to ADM and sunitinib, and a knockdown of VHL in the ACHN cells increased their chemoresistance. To confirm that VHL and P53 are both required for chemosensitivity, VHL and P53 were co‑expressed in 786‑O cells. The results of the functional antagonist assay (which assessed the IC50 values, i.e. the half maximal inhibitory concentration) confirmed that VHL and P53 act in synergy to promote chemosensitivity. Cell cycle arrest was measured by propidium iodide staining following treatment with ADM or sunitinib. Further analysis indicated that co‑expression of VHL and P53 inhibited cell proliferation by completely inhibiting the cell cycle at the G0/G1 phase, and promoted apoptosis following treatment with ADM or sunitinib. These findings demonstrated that VHL and P53 act synergistically in the regulation of cell proliferation and apoptosis in CCRCC. Overall, VHL and P53 have important roles in the regulation of cell proliferation and apoptosis in CCRCC. Furthermore, the regulatory role of VHL is dependant on the activation P53. PMID:27485825

  10. Glycosaminoglycan Profiling in Patients' Plasma and Urine Predicts the Occurrence of Metastatic Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Gatto, Francesco; Volpi, Nicola; Nilsson, Helén; Nookaew, Intawat; Maruzzo, Marco; Roma, Anna; Johansson, Martin E; Stierner, Ulrika; Lundstam, Sven; Basso, Umberto; Nielsen, Jens

    2016-05-24

    Metabolic reprogramming is a hallmark of clear cell renal cell carcinoma (ccRCC) progression. Here, we used genome-scale metabolic modeling to elucidate metabolic reprogramming in 481 ccRCC samples and discovered strongly coordinated regulation of glycosaminoglycan (GAG) biosynthesis at the transcript and protein levels. Extracellular GAGs are implicated in metastasis, so we speculated that such regulation might translate into a non-invasive biomarker for metastatic ccRCC (mccRCC). We measured 18 GAG properties in 34 mccRCC samples versus 16 healthy plasma and/or urine samples. The GAG profiles were distinctively altered in mccRCC. We derived three GAG scores that distinguished mccRCC patients with 93.1%-100% accuracy. We validated the score accuracies in an independent cohort (up to 18 mccRCC versus nine healthy) and verified that the scores normalized in eight patients with no evidence of disease. In conclusion, coordinated regulation of GAG biosynthesis occurs in ccRCC, and non-invasive GAG profiling is suitable for mccRCC diagnosis. PMID:27184840

  11. Cytoplasmic fat detection utilizing chemical shift gradient. Echo MR imaging in cases of clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    We investigated whether cytoplasmic fat in clear cell renal cell carcinoma (CCC) can be identified by chemical shift gradient-echo magnetic resonance imaging (CSI). CSI was performed for 22 cases of CCC and 30 cases of other renal tumors (including 16 cases of non-CCC), all of which were surgically proven. Signal reduction in out-of-phase images of these tumors was retrospectively evaluated and compared. The signal loss ratio (SLR) was defined and calculated. Fat staining of specimens from 16 tumors was performed and correlated with SLR. SLR was found to be significantly higher in CCC than in non-CCC (p<0.002). There was a significant correlation between the degree of fat staining positively of the specimens and SLR (p<0.01). When signal reduction in out-of-phase images suggested a diagnosis of CCC, a correct diagnosis of this entity was made in the resected renal tumors with a sensitivity, specificity, and accuracy of 82%, 93%, and 88%, respectively. CSI can demonstrate cytoplasmic fat in CCC, which helps to differentiate this entity from other renal tumors. (author)

  12. Diffusion-weighted magnetic resonance imaging in the differentiation of angiomyolipoma with minimal fat from clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    The aim of the present study was to evaluate diffusion-weighted (DW) magnetic resonance imaging (MRI) in differentiating between minimal fat angiomyolipoma (MFAML) and clear cell renal cell carcinoma (CCRCC). Forty-one solid renal tumors without visible macroscopic fat on unenhanced computed tomography images were evaluated by MRI, including DW-MRI, and were diagnosed pathologically as CCRCC (n=36) or MFAML (n=5). To evaluate the heterogeneity of diffusion in each tumor, the signals of the tumors on DW-MRI were analyzed subjectively and the apparent diffusion coefficient (ADC) values and histograms assessed objectively. Thirty-three of 36 CCRCC (92%) exhibited a heterogeneous signal on DW-MRI and several peaks in the ADC value histogram, whereas four of five MFAML exhibited a homogeneous signal on DW-MRI and a single prominent peak in the histogram. The standard deviations of the ADC values were significantly smaller for MFAML than for CCRCC (P=0.0015). In conclusion, DW-MRI can be considered a useful and noninvasive addition to the preoperative differentiation of CCRCC and MFAML. (author)

  13. Microvessel density and heparanase over-expression in clear cell renal cell cancer: correlations and prognostic significances

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    Ren Juchao

    2011-12-01

    Full Text Available Abstract Background Tumor angiogenesis is important in the progression of malignancies, and heparanase plays an important role in sustaining the pathology of clear cell renal cell cancer (ccRCC. The study was carried out to investigate the correlations between microvessel density (MVD and heparanase expression containing prognostic significances in the patients with ccRCC. Methods Specimens from 128 patients with ccRCC were investigated by immunohistochemistry for MVD. RT-PCR and immunohistochemistry were used to detect heparanase expression. Correlations between MVD, heparanase expression, and various clinico-pathological factors were studied. The prognostic significances of MVD and heparanase expression were also analysed. Results We discovered a statistically significant prevalence of higher MVD in ccRCC compared with adjacent normal renal tissues. MVD was positively correlated with TNM stage and distant metastasis in ccRCC patients, and was also correlated with the expression level of heparanase. Heparanase is over-expressed and correlated with TNM stage, histologic grade, distant metastasis and lymphatic metastasis in ccRCC. High MVD and heparanase over-expression inversely correlate with the survival of ccRCC patients. Conclusions Heparanase contributes to angiogenesis of ccRCC and over-expression of heparanase is an independent predictors of prognosis for ccRCC. MVD is correlated with tumor development and metastasis in ccRCC.

  14. Decreased expression of dual-specificity phosphatase 9 is associated with poor prognosis in clear cell renal cell carcinoma

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    Liu Zhuowei

    2011-09-01

    Full Text Available Abstract Background The molecular mechanisms involved in the development and progression of clear cell renal cell carcinomas (ccRCCs are poorly understood. The objective of this study was to analyze the expression of dual-specificity phosphatase 9 (DUSP-9 and determine its clinical significance in human ccRCCs. Methods The expression of DUSP-9 mRNA was determined in 46 paired samples of ccRCCs and adjacent normal tissues by using real-time qPCR. The expression of the DUSP-9 was determined in 211 samples of ccRCCs and 107 paired samples of adjacent normal tissues by immunohistochemical analysis. Statistical analysis was performed to define the relationship between the expression of DUSP-9 and the clinical features of ccRCC. Results The mRNA level of DUSP-9, which was determined by real-time RT-PCR, was found to be significantly lower in tumorous tissues than in the adjacent non-tumorous tissues (p Conclusion To our knowledge, this is the first study that determines the relationship between DUSP-9 expression and prognosis in ccRCC. We found that decreased expression of DUSP-9 is associated with poor prognosis in ccRCC. DUSP-9 may represent a novel and useful prognostic marker for ccRCC.

  15. Prognostic significance of ubiquinol-cytochrome c reductase hinge protein expression in patients with clear cell renal cell carcinoma

    Science.gov (United States)

    Liu, Wei-Si; Liu, Yi-Dong; Fu, Qiang; Zhang, Wei-Juan; Xu, Le; Chang, Yuan; Xu, Jie-Jie

    2016-01-01

    Ubiquinol-cytochrome c reductase hinge protein (UQCRH), as a connecter between cytochrome c1 with cytochrome c in complex III of respiratory chain, is top-ranked hypermethylated gene in clear cell renal cell carcinoma (ccRCC). This study aims to evaluate the impact of UQCRH on recurrence and survival of 424 ccRCC patients enrolled retrospectively from a single institution after surgical resection using immunohistochemistry method. UQCRH was specifically downregulated in ccRCC, compared with papillary and chromophobe RCC. Moreover, patients with low UQCRH were prone to possess high T stage and TNM stage and associated with poor survival and early recurrence. UQCRH remained an independent favorable prognosticator for OS (Hazard rate [HR]: 0.510, 95% CI: 0.328-0.795, p=0.003) and RFS (HR: 0.506, 95% CI: 0.334-0.767, p=0.001) adjusting with other well-established factors using backward Cox model. Furthermore, in stratified subgroups, patients with low UQCRH had an increased risk of recurrence (HR: 0.452, 95% CI: 0.261-0.783, p=0.005) and mortality (HR: 0.386, 95% CI: 0.205-0.726, p=0.003) in subgroup of early TNM stage. Taken together, UQCRH is a potential independent favorable prognostic factor for recurrence and survival of patients with ccRCC after nephrectomy.

  16. MET Expression in Primary and Metastatic Clear Cell Renal Cell Carcinoma: Implications of Correlative Biomarker Assessment to MET Pathway Inhibitors

    Directory of Open Access Journals (Sweden)

    Brian Shuch

    2015-01-01

    Full Text Available Aims. Inhibitors of the MET pathway hold promise in the treatment for metastatic kidney cancer. Assessment of predictive biomarkers may be necessary for appropriate patient selection. Understanding MET expression in metastases and the correlation to the primary site is important, as distant tissue is not always available. Methods and Results. MET immunofluorescence was performed using automated quantitative analysis and a tissue microarray containing matched nephrectomy and distant metastatic sites from 34 patients with clear cell renal cell carcinoma. Correlations between MET expressions in matched primary and metastatic sites and the extent of heterogeneity were calculated. The mean expression of MET was not significantly different between primary tumors when compared to metastases (P=0.1. MET expression weakly correlated between primary and matched metastatic sites (R=0.5 and a number of cases exhibited very high levels of discordance between these tumors. Heterogeneity within nephrectomy specimens compared to the paired metastatic tissues was not significantly different (P=0.39. Conclusions. We found that MET expression is not significantly different in primary tumors than metastatic sites and only weakly correlates between matched sites. Moderate concordance of MET expression and significant expression heterogeneity may be a barrier to the development of predictive biomarkers using MET targeting agents.

  17. Papillary renal cell carcinoma

    International Nuclear Information System (INIS)

    Between 1976 and 1987, 395 patients with kidney tumors were studied with radiological techniques and sonography. In 37 cases (9.4%) histopathology diagnosed pure papillary renal cell carcinoma. Analyzing the radiographic patterns of these neoplasms, the authors observed constantly diminished vascularity (100%) frequent calcifications (35.1%) and necrotic areas (51.3%). Such X-ray features are not specific: nevertheless, their coexistence is strongly suggestive of papillary renal cell cancer. No consistent US pattern was found; however, necrotic areas were easily demonstrated in most cases. It must be stressed how patients with papillary carcinoma experienced a longer post-operative survival; it has not yet been established whether such favorable behavior is due to low biological aggressiveness or to earlier diagnosis

  18. Characterization of clear cell renal cell carcinoma with diffusion kurtosis imaging: correlation between diffusion kurtosis parameters and tumor cellularity.

    Science.gov (United States)

    Dai, Yongming; Yao, Qiuying; Wu, Guangyu; Wu, Dongmei; Wu, Lianming; Zhu, Li; Xue, Rong; Xu, Jianrong

    2016-07-01

    The aim of this study was to evaluate the role of diffusion kurtosis imaging (DKI) in the characterization of clear cell renal cell carcinoma (ccRCC) and to correlate DKI parameters with tumor cellularity. Fifty-nine patients with pathologically diagnosed ccRCCs were evaluated by DKI on a 3-T scanner. Regions of interest were drawn on the maps of the mean diffusion coefficient (MD) and mean diffusion kurtosis (MK). All ccRCCs were histologically graded according to the Fuhrman classification system. Tumor cellularity was measured by the nuclear-to-cytoplasm (N/C) ratio and the number of tumor cell nuclei (NTCN). ccRCCs were classified as grade 1 (n = 23), grade 2 (n = 24), grade 3 (n = 10) and grade 4 (n = 3). Both MD and MK could readily discriminate between normal renal parenchyma and ccRCCs (p  0.05) for both MD and MK. With regard to NTCN, no significant difference was found between any two grades (p > 0.05), and the N/C ratio changed significantly with grade (p correlations were found between MK and MD (r = -0.56, p r = -0.36, p correlated (r = 0.45, p = 0.003). DKI could quantitatively characterize ccRCC with different grades by probing non-Gaussian diffusion properties related to changes in the tumor microenvironment or tissue complexities in the tumor. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27119793

  19. Downregulation of SAV1 plays a role in pathogenesis of high-grade clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    Clinical outcome of patients with high-grade ccRCC (clear cell renal cell carcinoma) remains still poor despite recent advances in treatment strategies. Molecular mechanism of pathogenesis in developing high-grade ccRCC must be clarified. In the present study, we found that SAV1 was significantly downregulated with copy number loss in high-grade ccRCCs. Therefore, we investigated the SAV1 function on cell proliferation and apoptosis in vitro. Furthermore, we attempted to clarify the downstream signaling which is regulated by SAV1. We performed array CGH and gene expression analysis of 8 RCC cell lines (786-O, 769-P, KMRC-1, KMRC-2, KMRC-3, KMRC-20, TUHR4TKB, and Caki-2), and expression level of mRNA was confirmed by quantitative RT-PCR (qRT-PCR) analysis. We next re-expressed SAV1 in 786-O cells, and analyzed its colony-forming activity. Then, we transfected siRNAs of SAV1 into the kidney epithelial cell line HK2 and renal proximal tubule epithelial cells (RPTECs), and analyzed their proliferation and apoptosis. Furthermore, the activity of YAP1, which is a downstream molecule of SAV1, was evaluated by western blot analysis, reporter assay and immunohistochemical analysis. We found that SAV1, a component of the Hippo pathway, is frequently downregulated in high-grade ccRCC. SAV1 is located on chromosome 14q22.1, where copy number loss had been observed in 7 of 12 high-grade ccRCCs in our previous study, suggesting that gene copy number loss is responsible for the downregulation of SAV1. Colony-forming activity by 786-O cells, which show homozygous loss of SAV1, was significantly reduced when SAV1 was re-introduced exogenously. Knockdown of SAV1 promoted proliferation of HK2 and RPTEC. Although the phosphorylation level of YAP1 was low in 786-O cells, it was elevated in SAV1-transduced 786-O cells. Furthermore, the transcriptional activity of the YAP1 and TEAD3 complex was inhibited in SAV1-transduced 786-O cells. Immunohistochemistry frequently demonstrated nuclear

  20. High expression of pituitary tumor-transforming gene-1 predicts poor prognosis in clear cell renal cell carcinoma

    Science.gov (United States)

    WEI, CAN; YANG, XIAOLIANG; XI, JUNHUA; WU, WEI; YANG, ZHENXING; WANG, WEI; TANG, ZHIGUO; YING, QUANSHENG; ZHANG, YANBIN

    2015-01-01

    Pituitary tumor-transforming gene-1 (PTTG1) is a recently identified oncogene involved in the progression of malignant tumors; however, the expression level of PTTG1 in clear cell renal cell carcinoma (ccRCC) and its potential value as a novel prognostic marker for ccRCC remains unclear. In this study, PTTG1 mRNA and protein levels were assessed in 44 paired ccRCC tissues and adjacent normal tissues by quantitative polymerase chain reaction (qPCR) and immunohistochemistry, respectively. Further immunohistochemical analysis was implemented in 192 samples of ccRCC to evaluate the associations between PTTG1 levels and the clinical characteristics in ccRCC. Reverse transcription qPCR and immunohistochemical analysis demonstrated that the PTTG1 mRNA and protein levels were significantly higher in ccRCC compared to normal tissues. In addition, the PTTG1 protein level in 192 ccRCC samples was found to be significantly correlated with T stage, N classification, metastasis, recurrence and Fuhrman grade, whereas it was not associated with age and gender. Patients with low PTTG1 levels exhibited a better survival outcome compared to those with a higher PTTG1 level. PTTG1 expression and N stage were identified as independent prognostic factors for the overall survival of ccRCC patients. The results suggested that the overexpression of PTTG1 indicates a poor prognosis in ccRCC patients and, therefore, PTTG1 may serve as a novel prognostic marker for ccRCC. PMID:25798272

  1. Prognostic impact of epidermal growth factor receptor on clear cell renal cell carcinoma: Does it change with different expression patterns?

    Directory of Open Access Journals (Sweden)

    Duygu Kankaya

    2016-01-01

    Full Text Available Introduction: The aim of this study was to assess whether epidermal growth factor receptor (EGFR overexpression was a significant prognostic factor in clear cell renal cell carcinoma (CRCC and whether its prognostic significance was affected by immunohistochemical expression patterns. Materials and Methods: Immunohistochemistry was performed on 100 cases of CRCC using an antibody against EGFR. Tumors were grouped by nuclear grade (NG as low-NG (NG1, 2 or high NG (NG3, 4, and by pathological stage as localized (pT1, 2, or locally invasive (pT3, 4. Clinical disease was grouped by clinical stage as early stage (stage I, II, or late stage (stage III, IV. Evaluation of the EGFR overexpression was based on cytoplasmic (EGFR Cyt , and membranous (EGFR Mem staining. Results: EGFR Cyt correlated with high NG (P = 0.001, lymphovascular invasion (P = 0.028, regional lymph node involvement (P = 0.027, metastasis (P = 0.001, late stage (P = 0.003, cancer-specific death (P = 0.036, and was a predictor for disease-specific survival (P = 0.012 whereas EGFR Mem correlated with only local invasion (P = 0.021 and perirenal invasion (P = 0.009 and did not show any correlation with cancer-specific death or disease specific survival. Conclusion: Our findings suggest that EGFR overexpression is an important prognostic factor in CRCC, and its prognostic value differs significantly with respect to the location of EGFR immunostaining. This prognostic difference may give direction on the management and treatment of CRCC patients.

  2. Overexpression of FoxM1 is associated with tumor progression in patients with clear cell renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Xue Yi-Jun

    2012-09-01

    Full Text Available Abstract Background Fork head box M1 (FoxM1 is a proliferation-associated transcription factor essential for cell cycle progression. Numerous studies have documented that FoxM1 has multiple functions in tumorigenesis and its elevated levels are frequently associated with cancer progression. The present study was conducted to investigate the expression of FoxM1 and its prognostic significance in clear cell renal cell carcinoma (ccRCC. Meanwhile, the function of FoxM1 in human ccRCC was further investigated in cell culture models. Methods Real-time quantitative PCR, western blot and immunohistochemistry were used to explore FoxM1 expression in ccRCC cell lines and primary ccRCC clinical specimens. FoxM1 expression was knocked down by small interfering RNA (siRNA in Caki-1 and 786-O cells; proliferation, colony formation, cell cycle, migration, invasion, and angiogenesis were assayed. Results FoxM1 expression was up-regulated in the majority of the ccRCC clinical tissue specimens at both mRNA and protein levels. Clinic pathological analysis showed that FoxM1 expression was significantly correlated with primary tumor stage (P P = 0.01, distant metastasis (P = 0.01, TNM stage (P P = 0.003. The Kaplan–Meier survival curves revealed that high FoxM1 expression was associated with poor prognosis in ccRCC patients (P P = 0.008. Experimentally, we found that down-regulation of FoxM1 inhibited cell proliferation and induced cell cycle arrest with reduced expression of cyclin B1, cyclin D1, and Cdk2, and increased expression of p21 and p27. Also, down-regulation of FoxM1 reduced expression and activity of matrix metalloproteinase-2 (MMP-2, MMP-9 and vascular endothelial growth factor (VEGF, resulting in the inhibition of migration, invasion, and angiogenesis. Conclusions These results suggest that FoxM1 expression is likely to play important roles in ccRCC development and progression, and that FoxM1 is a prognostic biomarker and a

  3. Lipid-poor renal angiomyolipoma: Differentiation from clear cell renal cell carcinoma using wash-in and washout characteristics on contrast-enhanced computed tomography

    OpenAIRE

    XIE, PINGKUN; Yang, Zhihui; Yuan, Zheng

    2016-01-01

    In the present study, a total of 82 patients (42 men and 40 women; age range, 24–84 years), including 34 patients with lipid-poor renal angiomyolipoma (AML) and 49 with clear cell renal cell carcinoma (RCC), who had undergone multiphase contrast-enhanced computed tomography (CT) (i.e., CT with unenhanced, corticomedullary, nephrographic and 5-min delay phase scanning) were evaluated. The peak enhancement attenuation value, net enhancement attenuation value, enhancement ratio, washout value an...

  4. Synchronous clear cell renal cell carcinoma and tubulocystic carcinoma: genetic evidence of independent ontogenesis and implications of chromosomal imbalances in tumor progression

    OpenAIRE

    Quiroga-Garza Gabriela; Piña-Oviedo Sergio; Cuevas-Ocampo Karime; Goldfarb Richard; Schwartz Mary R; Ayala Alberto G; Monzon Federico A

    2012-01-01

    Abstract Seven percent of renal cell carcinoma (RCC) cases are diagnosed as "unclassified" RCC by morphology. Genetic profiling of RCCs helps define renal tumor subtypes, especially in cases where morphologic diagnosis is inconclusive. This report describes a patient with synchronous clear cell RCC (ccRCC) and a tubulocystic renal carcinoma (TCRC) in the same kidney, and discusses the pathologic features and genetic profile of both tumors. A 67 year-old male underwent CT scans for an unrelate...

  5. Metastatic renal cell carcinoma management

    Directory of Open Access Journals (Sweden)

    Flavio L. Heldwein

    2009-06-01

    Full Text Available PURPOSE: To assess the current treatment of metastatic renal cell carcinoma, focusing on medical treatment options. MATERIAL AND METHODS: The most important recent publications have been selected after a literature search employing PubMed using the search terms: advanced and metastatic renal cell carcinoma, anti-angiogenesis drugs and systemic therapy; also significant meeting abstracts were consulted. RESULTS: Progress in understanding the molecular basis of renal cell carcinoma, especially related to genetics and angiogenesis, has been achieved mainly through of the study of von Hippel-Lindau disease. A great variety of active agents have been developed and tested in metastatic renal cell carcinoma (mRCC patients. New specific molecular therapies in metastatic disease are discussed. Sunitinib, Sorafenib and Bevacizumab increase the progression-free survival when compared to therapy with cytokines. Temsirolimus increases overall survival in high-risk patients. Growth factors and regulatory enzymes, such as carbonic anhydrase IX may be targets for future therapies. CONCLUSIONS: A broader knowledge of clear cell carcinoma molecular biology has permitted the beginning of a new era in mRCC therapy. Benefits of these novel agents in terms of progression-free and overall survival have been observed in patients with mRCC, and, in many cases, have become the standard of care. Sunitinib is now considered the new reference first-line treatment for mRCC. Despite all the progress in recent years, complete responses are still very rare. Currently, many important issues regarding the use of these agents in the management of metastatic renal cancer still need to be properly addressed.

  6. Analyses of Potential Predictive Markers and Response to Targeted Therapy in Patients with Advanced Clear-cell Renal Cell Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yan Song; Jing Huang; Ling Shan; Hong-Tu Zhang

    2015-01-01

    Background:Vascular endothelial growth factor-targeted agents are standard treatments in advanced clear-cell renal cell carcinoma (ccRCC),but biomarkers of activity are lacking.The aim of this study was to investigate the association of Von Hippel-Lindau (VHL) gene status,vascular endothelial growth factor receptor (VEGFR) or stem cell factor receptor (KIT) expression,and their relationships with characteristics and clinical outcome of advanced ccRCC.Methods:A total of 59 patients who received targeted treatment with sunitinib or pazopanib were evaluated for determination at Cancer Hospital and Institute,Chinese Academy of Medical Sciences between January 2010 and November 2012.Paraffin-embedded tumor samples were collected and status of the VHL gene and expression of VEGFR and KIT were determined by VHL sequence analysis and immunohistochemistry.Clinical-pathological features were collected and efficacy such as response rate and Median progression-free survival (PFS) and ovcrall survival (OS) were calculated and then compared based on expression status.The Chi-square test,the KaplanMeier method,and the Lon-rank test were used for statistical analyses.Results:Of 59 patients,objective responses were observed in 28 patients (47.5%).The median PFS was 13.8 months and median OS was 39.9 months.There was an improved PFS in patients with the following clinical features:Male gender,number of metastatic sites 2 or less,VEGFR-2 positive or KIT positive.Eleven patients (18.6%) had evidence of VHL mutation,with an objective response rate of 45.5%,which showed no difference with patients with no VHL mutation (47.9%).VHL mutation status did not correlate with either overall response rate (P =0.938) or PFS (P =0.277).The PFS was 17.6 months and 22.2 months in VEGFR-2 positive patients and KIT positive patients,respectively,which was significantly longer than that of VEGFR-2 or KIT negative patients (P =0.026 and P =0.043).Conclusion:VHL mutation status could not predict

  7. Analyses of Potential Predictive Markers and Response to Targeted Therapy in Patients with Advanced Clear-cell Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Yan Song

    2015-01-01

    Full Text Available Background: Vascular endothelial growth factor-targeted agents are standard treatments in advanced clear-cell renal cell carcinoma (ccRCC, but biomarkers of activity are lacking. The aim of this study was to investigate the association of Von Hippel-Lindau (VHL gene status, vascular endothelial growth factor receptor (VEGFR or stem cell factor receptor (KIT expression, and their relationships with characteristics and clinical outcome of advanced ccRCC. Methods: A total of 59 patients who received targeted treatment with sunitinib or pazopanib were evaluated for determination at Cancer Hospital and Institute, Chinese Academy of Medical Sciences between January 2010 and November 2012. Paraffin-embedded tumor samples were collected and status of the VHL gene and expression of VEGFR and KIT were determined by VHL sequence analysis and immunohistochemistry. Clinical-pathological features were collected and efficacy such as response rate and Median progression-free survival (PFS and overall survival (OS were calculated and then compared based on expression status. The Chi-square test, the Kaplan-Meier method, and the Lon-rank test were used for statistical analyses. Results: Of 59 patients, objective responses were observed in 28 patients (47.5%. The median PFS was 13.8 months and median OS was 39.9 months. There was an improved PFS in patients with the following clinical features: Male gender, number of metastatic sites 2 or less, VEGFR-2 positive or KIT positive. Eleven patients (18.6% had evidence of VHL mutation, with an objective response rate of 45.5%, which showed no difference with patients with no VHL mutation (47.9%. VHL mutation status did not correlate with either overall response rate (P = 0.938 or PFS (P = 0.277. The PFS was 17.6 months and 22.2 months in VEGFR-2 positive patients and KIT positive patients, respectively, which was significantly longer than that of VEGFR-2 or KIT negative patients (P = 0.026 and P = 0.043. Conclusion

  8. Proteotranscriptomic Analysis Reveals Stage Specific Changes in the Molecular Landscape of Clear-Cell Renal Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Benjamin A Neely

    Full Text Available Renal cell carcinoma comprises 2 to 3% of malignancies in adults with the most prevalent subtype being clear-cell RCC (ccRCC. This type of cancer is well characterized at the genomic and transcriptomic level and is associated with a loss of VHL that results in stabilization of HIF1. The current study focused on evaluating ccRCC stage dependent changes at the proteome level to provide insight into the molecular pathogenesis of ccRCC progression. To accomplish this, label-free proteomics was used to characterize matched tumor and normal-adjacent tissues from 84 patients with stage I to IV ccRCC. Using pooled samples 1551 proteins were identified, of which 290 were differentially abundant, while 783 proteins were identified using individual samples, with 344 being differentially abundant. These 344 differentially abundant proteins were enriched in metabolic pathways and further examination revealed metabolic dysfunction consistent with the Warburg effect. Additionally, the protein data indicated activation of ESRRA and ESRRG, and HIF1A, as well as inhibition of FOXA1, MAPK1 and WISP2. A subset analysis of complementary gene expression array data on 47 pairs of these same tissues indicated similar upstream changes, such as increased HIF1A activation with stage, though ESRRA and ESRRG activation and FOXA1 inhibition were not predicted from the transcriptomic data. The activation of ESRRA and ESRRG implied that HIF2A may also be activated during later stages of ccRCC, which was confirmed in the transcriptional analysis. This combined analysis highlights the importance of HIF1A and HIF2A in developing the ccRCC molecular phenotype as well as the potential involvement of ESRRA and ESRRG in driving these changes. In addition, cofilin-1, profilin-1, nicotinamide N-methyltransferase, and fructose-bisphosphate aldolase A were identified as candidate markers of late stage ccRCC. Utilization of data collected from heterogeneous biological domains strengthened

  9. Prognostic significance of two lipid metabolism enzymes, HADHA and ACAT2, in clear cell renal cell carcinoma.

    Science.gov (United States)

    Zhao, Zuohui; Lu, Jiaju; Han, Liping; Wang, Xiaoqing; Man, Quanzhan; Liu, Shuai

    2016-06-01

    Renal cell carcinoma (RCC) is one of the leading causes of cancer mortality in adults, but there is still no acknowledged biomarker for its prognostic evaluation. Our previous proteomic data had demonstrated the dysregulation of some lipid metabolism enzymes in clear cell RCC (ccRCC). In the present study, we elucidated the expression of two lipid metabolism enzymes, hydroxyl-coenzyme A dehydrogenase, alpha subunit (HADHA) and acetyl-coenzyme A acetyltransferase 2 (ACAT2), using Western blotting analysis, then assessed the prognostic potential of HADHA and ACAT2 using immunohistochemistry (IHC) on a tissue microarray of 145 ccRCC tissues. HADHA and ACAT2 were downregulated in ccRCC (P < 0.05); further IHC analysis revealed that HADHA expression was significantly associated with tumor grade, stage, size, metastasis, and cancer-specific survival (P = 0.004, P < 0.001, P < 0.001, P = 0.049, P < 0.001, respectively) and ACAT2 expression was significantly associated with tumor stage, size, and cancer-specific survival (P < 0.001, P = 0.001, P < 0.001, respectively). In addition, a strong correlation was found between HADHA and ACAT2 expression (R = 0.655, P < 0.001). Further univariate survival analysis demonstrated that high stage, big tumor size, metastasis, and HADHA and ACAT2 down-expression were associated with poorer prognosis on cancer-specific survival (P = 0.007, P = 0.005, P = 0.006, P < 0.001, P = 0.001, respectively), and multivariate analysis revealed that HADHA, stage, and metastasis were identified as independent prognostic factors for cancer-specific survival in patients with ccRCC (P = 0.018, P = 0.046, P = 0.001, respectively). Collectively, these findings indicated that HADHA could serve as a promising prognostic marker in ccRCC, which indicated lipid metabolism abnormality might be involved in ccRCC tumorigenesis. PMID:26715271

  10. NF-KappaB expression correlates with apoptosis and angiogenesis in clear cell renal cell carcinoma tissues

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    Erkus Muhan

    2008-10-01

    Full Text Available Abstract Background Clear cell renal cell carcinoma (ccRCC is the most frequently encountered tumor in the adult kidney. Many factors are known to take part in the development and progression of this tumor. Nuclear factor kappa B (NF-κB is a family of the genes that includes five members acting in events such as inflammation and apoptosis. In this study, the role of NF-κB (p50 subunit in ccRCC and its relation to angiogenesis and apoptosis were investigated. Methods Formalin-fixed and paraffin embedded tissue blocks from 40 patients with ccRCC were studied. Expressions of NF-κB (p50, VEGF, EGFR, bc1-2 and p53 were detected immunohistochemically. The relationship of NF-κB with these markers and clinicopathological findings were evaluated. Results The expression of NF-κB was detected in 35 (85%, VEGF in 37 (92.5%, EGFR in 38 (95%, bc1-2 in 33 (82.5% and p53 in 13 (32.5% of 40 ccRCC patients. Statistical analyses revealed a significant relation between NF-κB expression and VEGF (p = 0.001, EGFR (p = 0.004, bc1-2 (p = 0.010 and p53 (p = 0.037. There was no significant correlation between NF-κB and such parameters as tumor grade, stage, age and sex. Conclusion The results of this study indicated that in ccRCC cases NF-κB was associated with markers of angiogenesis and apoptosis such as VEGF, EGFR, bc1-2 and p53. In addition, the results did not only suggest a close relationship between NF-κB and VEGF, EGFR, bc1-2 and p53 in ccRCC, but also indicate that NF-κB was a potential therapeutic target in the treatment of ccRCC resistant to chemotherapy.

  11. Soluble Serum αKlotho Is a Potential Predictive Marker of Disease Progression in Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Gigante, Margherita; Lucarelli, Giuseppe; Divella, Chiara; Netti, Giuseppe Stefano; Pontrelli, Paola; Cafiero, Cesira; Grandaliano, Giuseppe; Castellano, Giuseppe; Rutigliano, Monica; Stallone, Giovanni; Bettocchi, Carlo; Ditonno, Pasquale; Gesualdo, Loreto; Battaglia, Michele; Ranieri, Elena

    2015-11-01

    Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies, and clear cell RCC (ccRCC), that has a high metastatic index and high relapse rate, is the most common histological subtype. The identification of new biomarkers in ccRCC is fundamental for stratifying patients into prognostic risk groups and to guide therapy. The renoprotective antiaging gene, αKlotho, has recently been found to work as a tumor suppressor in different human cancers. Here, we evaluated αKlotho expression in tissue and serum of ccRCC patients and correlated it with disease progression. Tissue αKlotho expression was studied by quantitative RT-PCR and immunohistochemistry. In addition, soluble serum αKlotho levels were preoperatively measured in 160 patients who underwent nephrectomy for RCC with ELISA. Estimates of cancer-specific (CSS) and progression-free survival (PFS) were calculated according to the Kaplan-Meier method. Multivariate analysis was performed to identify the most significant variables for predicting CSS and PFS. αKlotho protein levels were significantly decreased in RCC tissues compared with normal tissues (P < 0.01) and the more advanced the disease, the more evident the down-regulation. This trend was also observed in serum samples. Statistically significant differences resulted between serum αKlotho levels and tumor size (P = 0.003), Fuhrman grade (P = 0.007), and clinical stage (P = 0.0004). CSS and PFS were significantly shorter in patients with lower levels of αKlotho (P < 0.0001 and P = 0.0004, respectively). At multivariate analysis low serum levels of αKlotho were independent adverse prognostic factors for CSS (HR = 2.11; P = 0.03) and PFS (HR = 2.18; P = 0.03).These results indicate that a decreased αKlotho expression is correlated with RCC progression, and suggest a key role of declining αKlotho in the onset of cancer metastasis. PMID:26559258

  12. Decreased expression of dual-specificity phosphatase 9 is associated with poor prognosis in clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    The molecular mechanisms involved in the development and progression of clear cell renal cell carcinomas (ccRCCs) are poorly understood. The objective of this study was to analyze the expression of dual-specificity phosphatase 9 (DUSP-9) and determine its clinical significance in human ccRCCs. The expression of DUSP-9 mRNA was determined in 46 paired samples of ccRCCs and adjacent normal tissues by using real-time qPCR. The expression of the DUSP-9 was determined in 211 samples of ccRCCs and 107 paired samples of adjacent normal tissues by immunohistochemical analysis. Statistical analysis was performed to define the relationship between the expression of DUSP-9 and the clinical features of ccRCC. The mRNA level of DUSP-9, which was determined by real-time RT-PCR, was found to be significantly lower in tumorous tissues than in the adjacent non-tumorous tissues (p < 0.001). An immunohistochemical analysis of 107 paired tissue specimens showed that the DUSP-9 expression was lower in tumorous tissues than in the adjacent non-tumorous tissues (p < 0.001). Moreover, there was a significant correlation between the DUSP-9 expression in ccRCCs and gender (p = 0.031), tumor size (p = 0.001), pathologic stage (p = 0.001), Fuhrman grade (p = 0.002), T stage (p = 0.001), N classification (p = 0.012), metastasis (p = 0.005), and recurrence (p < 0.001). Patients with lower DUSP-9 expression had shorter overall survival time than those with higher DUSP-9 expression (p < 0.001). Multivariate analysis indicated that low expression of the DUSP-9 was an independent predictor for poor survival of ccRCC patients. To our knowledge, this is the first study that determines the relationship between DUSP-9 expression and prognosis in ccRCC. We found that decreased expression of DUSP-9 is associated with poor prognosis in ccRCC. DUSP-9 may represent a novel and useful prognostic marker for ccRCC

  13. Proteotranscriptomic Analysis Reveals Stage Specific Changes in the Molecular Landscape of Clear-Cell Renal Cell Carcinoma

    Science.gov (United States)

    Wilkins, Christopher E.; Marlow, Laura A.; Malyarenko, Dariya; Kim, Yunee; Ignatchenko, Alexandr; Sasinowska, Heather; Sasinowski, Maciek; Nyalwidhe, Julius O.; Kislinger, Thomas; Copland, John A.; Drake, Richard R.

    2016-01-01

    Renal cell carcinoma comprises 2 to 3% of malignancies in adults with the most prevalent subtype being clear-cell RCC (ccRCC). This type of cancer is well characterized at the genomic and transcriptomic level and is associated with a loss of VHL that results in stabilization of HIF1. The current study focused on evaluating ccRCC stage dependent changes at the proteome level to provide insight into the molecular pathogenesis of ccRCC progression. To accomplish this, label-free proteomics was used to characterize matched tumor and normal-adjacent tissues from 84 patients with stage I to IV ccRCC. Using pooled samples 1551 proteins were identified, of which 290 were differentially abundant, while 783 proteins were identified using individual samples, with 344 being differentially abundant. These 344 differentially abundant proteins were enriched in metabolic pathways and further examination revealed metabolic dysfunction consistent with the Warburg effect. Additionally, the protein data indicated activation of ESRRA and ESRRG, and HIF1A, as well as inhibition of FOXA1, MAPK1 and WISP2. A subset analysis of complementary gene expression array data on 47 pairs of these same tissues indicated similar upstream changes, such as increased HIF1A activation with stage, though ESRRA and ESRRG activation and FOXA1 inhibition were not predicted from the transcriptomic data. The activation of ESRRA and ESRRG implied that HIF2A may also be activated during later stages of ccRCC, which was confirmed in the transcriptional analysis. This combined analysis highlights the importance of HIF1A and HIF2A in developing the ccRCC molecular phenotype as well as the potential involvement of ESRRA and ESRRG in driving these changes. In addition, cofilin-1, profilin-1, nicotinamide N-methyltransferase, and fructose-bisphosphate aldolase A were identified as candidate markers of late stage ccRCC. Utilization of data collected from heterogeneous biological domains strengthened the findings from

  14. Correlation between apparent diffusion coefficient value and pathological grading in pT1b clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    Objective: To evaluate the correlation of ADC values on 3.0 T MR with the pathological grades in pT1b clear cell renal cell carcinoma (CCRCC). Methods: Conventional MR images, ADC values and Fuhrman pathological grading of pT1b CCRCC were performed in 30 patients. Grade Ⅰ and Ⅱ were defined as low-grade group; grade Ⅲ and Ⅳ were defined as high-grade group. The differences of ADC values among four different pathologic grades were compared with a one-way analysis of variance. The comparison of ADC values of two different grade groups was performed with t test, and the ROC curve was performed to evaluate the diagnostic efficacy of ADC value. Correlation between pathological grading and ADC values was assessed with Spearman rank correlation analysis. Results: (1) The mean ADC value of grading Ⅰ (10 patients), Ⅱ (8 patients), Ⅲ (7 patients), Ⅳ (5 patients) was (0.94 ± 0.11) ×10-3 mm2/s, (0.82 ±0.13) × 10-3 mm2/s,(0.68 ±0.09) × 10-3 mm2/s, (0.59 ±0.03) × 10-3 mm2/s, respectively. Significant differences of ADC values among the four grades were present (F=16.422, P=0.000). (2) The mean ADC value of the low-grade group was significantly higher than that of the high-grade group (t=5.738, P=0.000). Sensitivity and specificity of diagnosing the low-grade group was 88.9% and 83.3% respectively. There was a negative correlation between pathological grading and ADC value (r=-0.807, P<0.05). Conclusions: The ADC values of pT1b CCRCC have close correlation with pathological grading. They can be used to predict the degree of tumor malignancy preoperatively and guide surgical planning. (authors)

  15. Renal cell carcinoma of clear type: correlation of CT features with tumor size, architectural patterns, and pathologic staging

    International Nuclear Information System (INIS)

    The purpose of this study was to report the CT findings of renal cell carcinoma of clear type (RCCCT) and to determine if there are characteristic morphologic features in RCCCT with respect to tumor size, architectural patterns, and pathologic stage. The CT scans of 35 patients with RCCCT were reviewed retrospectively. The CT findings (tumor size, attenuation patterns, presence of calcifications, encapsulation, margins of neoplasms, venous involvement by neoplasms) were correlated with tumor size, architectural patterns, and pathologic staging. Of the 35 neoplasms, 28 (80 %) were solid, 4 (11 %) were papillary, and 3 (9 %) were cystic. Complete encapsulation was more frequent in lower pathologic stages (40 % in stages 1 and 2 vs 0 % in stages 3 and 4; p < 0.05). Venous involvement was less frequent with completely encapsulated neoplasms (0 of 10, 0 %) than with incompletely or nonencapsulated neoplasms (8 of 25, 32 %; p < 0.05). Encapsulated RCCCT are more likely to have lower pathologic stage. Nonencapsulated neoplasms are more likely to have a higher pathologic stage. (orig.). With 4 figs., 3 tabs

  16. MRI analysis of renal cell carcinoma

    International Nuclear Information System (INIS)

    Objective: To analyze MRI manifestation and enhancement of renal cell carcinoma, and to improve the diagnosis of renal cell carcinoma. Methods: 48 cases of renal cell carcinoma proven by surgery and pathology were reviewed. MRI scans including T1WI, T2WI, TRUFI and contrast enhancement were carried out in all cases and dynamic contrast-enhanced MRI was performed in 15. Results: Of the 48 cases, there were clear cell carcinoma in 41, chromophobe cell carcinoma in 4 and papillary cell carcinoma in 3. The tumors were homogeneously T1 iso- or hypointense in 33 and heterogeneous in 15; homogeneously T2 hyperintense in 14, isointense in 6 and heterogeneous in 28 patients. Pseudocapsule was found in 10 cases. Contrast enhancement was homogeneous in 6, heterogeneous in 34, irregularly peripheral within the wall in 5, and homogeneously circular in 3. Conclusion: MRI can accurately diagnose renal cell carcinoma and help to determine the cell subsets. (authors)

  17. Stages of Renal Cell Cancer

    Science.gov (United States)

    ... cell cancer is a disease in which malignant (cancer) cells form in tubules of the kidney. Renal cell ... diagnosed, tests are done to find out if cancer cells have spread within the kidney or to other ...

  18. Fast clearance of lipid droplets through MAP1S-activated autophagy suppresses clear cell renal cell carcinomas and promotes patient survival

    Science.gov (United States)

    Liu, Xian-De; Yue, Fei; Li, Wenjiao; Li, Xun; He, Yongzhong; Jiang, Xianhan; Huang, Hai; Chen, Qi; Jonasch, Eric; Liu, Leyuan

    2016-01-01

    Clear cell renal cell carcinoma (ccRCC) is composed of cells whose cytoplasm filled with lipid droplets, subcellular organelles coated with adipocyte differentiation-related protein (ADFP) for the storage of triacylglycerol converted from excess free fatty acids. Mammalian cells primarily use the autophagy-lysosome system to degrade misfolded/aggregated proteins and dysfunctional organelles such as lipid droplets. MAP1S (originally named C19ORF5) is an autophagy activator and promotes the biogenesis and degradation of autophagosomes. Previously, we reported that MAP1S suppresses hepatocellular carcinogenesis in a mouse model and promoted the survival of patients with prostate adenocarcinomas by increasing the degradation of aggregated proteins and dysfunctional mitochondria. Here we show that a suppression of MAP1S in renal cells causes an impairment of autophagic clearance of lipid droplets. In contrast, an overexpression of MAP1S causes an activation of autophagy flux and a reduction of lipid droplets so less DNA double strand breakage is induced. The levels of MAP1S in normal renal cells are dramatically higher than those in the ccRCC tissues and cell lines derived from renal cell carcinomas. High levels of MAP1S are associated with a reduced malignancy and metastasis of ccRCC and predict a better survival of ccRCC patients. Therefore, autophagy defects in the degradation of lipid droplets triggered by the MAP1S deficiency may enhance the initiation and development of ccRCC and reduce the survival of ccRCC patients. PMID:26701856

  19. Carbonic Anhydrase IX is Not a Predictor of Outcomes in Non-Metastatic Clear Cell Renal Cell Carcinoma - A Digital Analysis of Tissue Microarray

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    Marcelo Zerati

    2013-07-01

    Full Text Available Introduction The knowledge about the molecular biology of clear cell renal cell carcinoma (ccRCC is evolving, and Carbonic Anhydrase type IX (CA-IX has emerged as a potential prognostic marker in this challenging disease. However, most of the literature about CA-IX on ccRCC comes from series on metastatic cancer, with a lack of series on non-metastatic cancer. The objective is to evaluate the expression of CA-IX in a cohort of non-metastatic ccRCC, correlating with 1 overall survival, and 2 with established prognostic parameters (T stage, tumor size, Fuhrman nuclear grade, microvascular invasion and peri-renal fat invasion. Materials and Methods This is a retrospective cohort study. We evaluated 95 patients with non-metastatic clear cell renal cell carcinoma, as to the expression of CA-IX. The analyzed parameters where: overall survival (OS, TNM stage, tumor size (TS, Fuhrman nuclear grade (FNG, microvascular invasion (MVI, peri-renal fat invasion (PFI. We utilized a custom built tissue microarray, and the immunoexpression was digitally quantified using the Photoshop® software. Results: Th e mean follow-up time was 7.9 years (range 1.9 to 19.5 years. The analysis of CA-IX expression against the selected prognostic parameters showed no correlation. The results are as follows: Overall survival (p = 0.790; T stage (p = 0.179; tumor size (p = 0.143; grouped Fuhrman nuclear grade (p = 0.598; microvascular invasion (p = 0.685, and peri-renal fat invasion (p = 0.104. Conclusion Carbonic anhydrase type IX expression does not correlate with overall survival and conventional prognostic parameters in non-metastatic clear cell renal cell carcinoma.

  20. CLINICAL VALUE OF THE MARKERS OF PROLIFERATION AND APOPTOSIS IN PATIENTS WITH CLEAR CELL RENAL CELL CARCINOMA

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    N. A. Gorban

    2014-07-01

    Full Text Available Renal cell carcinoma (RCC is a heterogeneous disease in which the patients survive for months to years. At the present time the prognostic models have no sufficient information or exact prognostic value. Cell proliferation and apoptosis play a key role in cell cycle regulation; and impairment in these processes is commonly detected in different human tumors. The investigation enrolled 76 patients (49 men, 27 women aged 32 to 73 years (mean age 56 ± 7.6 years diagnosed with RCC. The follow-up was 8 to 116 months (mean 36.5 months. All the patients underwent nephrectomy; antibodies against р53, Bcl-2, and Ki-67 were investigated by immunohistochemistry. The expression of p53 and none or reduced expression of Bcl-2 are poor prognostic factors and associated with the metastatic potential of a tumor and with low relapse-free survival. High Ki-67 levels are a risk factor for metastases. A combination of p53 expression and high proliferative activity reflects the aggressive potential of a tumor and suggests the high risk of metastases just at the disease diagnosis and early tumor dissemination. 

  1. Renal cell carcinoma in childhood

    International Nuclear Information System (INIS)

    The authors present five cases of renal cell carcinoma in children, describing its aspects on excretory urography, ultra-sonography and computerized tomography. The clinical, pathological and radiological features are compared with those of the literature. (author)

  2. Emergency Pancreatoduodenectomy with Preservation of Gastroduodenal Artery for Massive Gastrointestinal Bleeding due to Duodenal Metastasis by Clear Cell Renal Cell Carcinoma in a Patient with Celiac Artery Stenosis

    Directory of Open Access Journals (Sweden)

    Kyriakos Neofytou

    2014-01-01

    Full Text Available Duodenal metastasis from renal cell carcinoma is rare, and even rarer is a massive gastrointestinal bleeding from such tumours. Coeliac occlusive disease, although rarely symptomatic, can lead to ischaemic changes with anastomotic dehiscence and leaks when a patient undergoes pancreatoduodenectomy. A 41-year-old man with known metastasis to the adrenal glands and the second part of the duodenum close to the ampulla of Vater from clear cell renal cell carcinoma was admitted to our department due to massive gastrointestinal bleeding from the duodenal metastasis. Endoscopic control of the bleed was not possible, while the bleeding vessel embolization was able to control the haemorrhage only temporarily. An angiography during the embolization demonstrated the presence of stenosis of the coeliac artery and also hypertrophic inferior pancreaticoduodenal arteries supplying the proper hepatic artery via the gastroduodenal artery (GDA. The patient underwent emergency pancreatoduodenectomy with preservation of the gastroduodenal artery. The patient had an uneventful recovery and did not experience further bleeding. Also the blood flow to the liver was compromised as shown by the normal liver function tests (LFTs postoperatively. To the best of our knowledge, this is the first report of a preservation of the GDA during an emergency pancreatoduodenectomy.

  3. Intratumoral Morphologic and Molecular Heterogeneity of Rhabdoid Renal Cell Carcinoma: Challenges for Personalized Therapy

    OpenAIRE

    Singh, Rajesh R.; Murugan, Paari; Patel, Lalit R; Voicu, Horatiu; Yoo, Suk-Young; Majewski, Tadeusz; Mehrotra, Meenakshi; Wani, Khalida; Tannir, Nizar; Karam, Jose A.; Jonasch, Eric; Wood, Christopher G; Creighton, Chad J.; Medeiros, L. Jeffrey; Broaddus, Russell R.

    2015-01-01

    Rhabdoid histology in clear cell renal cell carcinoma is associated with a poor prognosis. The prognosis of patients with clear cell renal cell carcinoma may also be influenced by molecular alterations. The aim of this study was to evaluate the association between histologic features and salient molecular changes in rhabdoid clear cell renal cell carcinoma. We macrodissected the rhabdoid and clear cell epithelioid components from 12 cases of rhabdoid clear cell renal cell carcinoma. We assess...

  4. Multilocular Cystic Renal Cell Carcinoma: An Unusual Gross Appearance

    OpenAIRE

    Nikumbh, Dhiraj B.; Sunil V. Jagtap; Gaurav Jain; Roopali K Mali

    2011-01-01

    Multilocular Cystic Renal Cell Carcinoma (MCRCC) represents a rare variant of clear cell (conventional) renal cell carcinomas. Attributable to its distinct characteristics in prognosis and its natural history, MCRCC was recognised as a separate subtype of renal cell carcinoma in the 2004 WHO classification of adult renal tumors. We report this case of MCRCC from antemortem surgical specimen, due to its unusual gross appearance and a rare clinical entity.

  5. Sarcomatoid chromophobe renal cell carcinoma: Cytohistopathological correlation of a case

    OpenAIRE

    Chakrabarti Indranil; Giri Amita; Majumdar Kaushik; DE, Anuradha

    2010-01-01

    Sarcomatoid renal cell carcinomas of the kidney are rare neoplasms constituting about 1-5% of all renal malignant neoplasms. These are aggressive tumors and are commonly associated with conventional (clear cell) renal cell carcinomas, but cases associated with chromophobe renal cell carcinomas are sparse. Cytological features of such lesions have rarely been reported. Here, we report a unique case of a 48-year-old male patient who presented with right flank lump and pain. A fine needle...

  6. Multilocular Cystic Renal Cell Carcinoma: An Unusual Gross Appearance

    Directory of Open Access Journals (Sweden)

    Dhiraj B Nikumbh

    2011-04-01

    Full Text Available Multilocular Cystic Renal Cell Carcinoma (MCRCC represents a rare variant of clear cell (conventional renal cell carcinomas. Attributable to its distinct characteristics in prognosis and its natural history, MCRCC was recognised as a separate subtype of renal cell carcinoma in the 2004 WHO classification of adult renal tumors. We report this case of MCRCC from antemortem surgical specimen, due to its unusual gross appearance and a rare clinical entity.

  7. Optimizing lutetium 177-anti-carbonic anhydrase IX radioimmunotherapy in an intraperitoneal clear cell renal cell carcinoma xenograft model

    NARCIS (Netherlands)

    Muselaers, C.H.J.; Oosterwijk, E.; Bos, D.L.; Oyen, W.J.G.; Mulders, P.F.A.; Boerman, O.C.

    2014-01-01

    A new approach in the treatment of clear cell renal carcinoma (ccRCC) is radioimmunotherapy (RIT) using anti-carbonic anhydrase IX (CAIX) antibody G250. To investigate the potential of RIT with lutetium 177 (177Lu)-labeled G250, we conducted a protein dose escalation study and subsequently an RIT st

  8. Treatment Option Overview (Renal Cell Cancer)

    Science.gov (United States)

    ... Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  9. Treatment Options for Renal Cell Cancer

    Science.gov (United States)

    ... Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  10. Case Report: Multifocal biphasic squamoid alveolar renal cell carcinoma

    Science.gov (United States)

    Lopez, Jose Ignacio

    2016-01-01

    A multifocal biphasic squamoid alveolar renal cell carcinoma in a 68-year-old man is reported. Four different peripheral tumor nodules were identified on gross examination. A fifth central tumor corresponded to a conventional clear cell renal cell carcinoma. Biphasic squamoid alveolar renal cell carcinoma is a rare tumor that has been very recently characterized as a distinct histotype within the spectrum of papillary renal cell carcinoma. Immunostaining with cyclin D1 seems to be specific of this tumor subtype. This is the first reported case with multifocal presentation. PMID:27158455

  11. Evaluation of the efficiency of combination palliative treatment in patients with metastatic clear-cell renal cell carcinoma

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    P. S. Borisov

    2015-01-01

    Full Text Available Background. Experience with combination treatment, i.e. systemic therapy in combination with palliative surgery, in the treatment of metastatic kidney cancer is very rarely described in world literature.Objective: to evaluate the efficiency of combination treatment in combination with palliative cytoreductive surgery and targeted therapy and to define optimal indications for combination treatment.Subjects and methods. Data on 47 patients with metastatic renal cell carcinoma (mRCC who received systemic (targeted therapy in combination or after incomplete cytoreduction (iCR were analyzed in this retrospective study. The proportion of men and women was 72.3 % and 27.7 %, respectively; their ratio was 2.6:1. All the patients (100% underwent surgical treatment as nephrectomy or kidney resection for primary tumor. In the patients who had received radical treatment in different periods, the median relapse-free survival was 25.3 (0-187 months; the mean follow-up duration in the study was 33.2 (27.4–39.0 months. Out of the histological characteristics of a primary tumor, its Fuhrman grade was studied. Prior to initiation of mRCC therapy, Memorial Sloan Kettering Cancer Center (MSKCC prognosis groups were assessed; the patients were divided into good (n = 9 (19.1 %, interim (n = 28 (59.6 %, and bad (n = 10 (21.3 % prognosis groups. Their total somatic status was separately rated using the ECOG scale: 0, (n = 10 (21.3%, 1 (n = 24 (51.1 %, and 2, (n = 13 (27.6 %. The sites of metastases were as follows: the lung (n = 29, bones (n = 18, adrenals (n = 11, recurrence in the removed kidney bed (n = 10, and liver (n = 10. Multiple organ involvements were detected in 22 (46.8 % patients. There were more than 5 metastases in one organ in 18 (40.0 % patients and only 15 (33.3 % were found to have a single focus in one organ. Whether iCR might be used as a separate line treatment was studied. A comparative analysis was made between 2 groups of

  12. Clinical evaluation of microRNA-145 expression in renal cell carcinoma: a promising molecular marker for discriminating and staging the clear cell histological subtype.

    Science.gov (United States)

    Papadopoulos, Emmanuel I; Petraki, Constantina; Gregorakis, Alkiviadis; Fragoulis, Emmanuel G; Scorilas, Andreas

    2016-06-01

    The vast majority of malignancies detected in renal parenchyma are diagnosed as renal cell carcinoma (RCC), whose subtype discrimination and determination of prognosis may contribute to the selection of the adequate therapy. Recently, a new class of small non-coding RNAs, known as microRNAs, has proven to be among the most promising biomarkers for providing this information. Herein, we sought to add up to this knowledge by evaluating the expression levels of microRNA-145 (miR-145) in RCC. For that purpose, total RNA from 58 cancerous and 44 adjacent non-cancerous renal tissues was firstly extracted and then polyadenylated and reverse transcribed to cDNA. MiR-145 levels were finally analyzed by developing and applying a highly sensitive real-time PCR protocol, while their clinical significance was determined via comprehensive statistical analysis. Our data showed that miR-145 was significantly downregulated in cancerous samples and could discriminate between clear cell and non-clear cell subtypes. Moreover, miR-145 expression was found to be correlated with primary tumor staging of cancerous samples, something also noticed in the clear cell RCC subset, in which miR-145 levels were negatively correlated with tumor size as well. Overall, these results indicate that miR-145 might constitute a promising molecular marker for RCC classification and staging. PMID:26866880

  13. Variants of SCARB1 and VDR Involved in Complex Genetic Interactions May Be Implicated in the Genetic Susceptibility to Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Pośpiech, Ewelina; Ligęza, Janusz; Wilk, Wacław; Gołas, Aniela; Jaszczyński, Janusz; Stelmach, Andrzej; Ryś, Janusz; Blecharczyk, Aleksandra; Wojas-Pelc, Anna; Jura, Jolanta; Branicki, Wojciech

    2015-01-01

    The current data are still inconclusive in terms of a genetic component involved in the susceptibility to renal cell carcinoma. Our aim was to evaluate 40 selected candidate polymorphisms for potential association with clear cell renal cell carcinoma (ccRCC) based on independent group of 167 patients and 200 healthy controls. The obtained data were searched for independent effects of particular polymorphisms as well as haplotypes and genetic interactions. Association testing implied position rs4765623 in the SCARB1 gene (OR = 1.688, 95% CI: 1.104-2.582, P = 0.016) and a haplotype in VDR comprising positions rs739837, rs731236, rs7975232, and rs1544410 (P = 0.012) to be the risk factors in the studied population. The study detected several epistatic effects contributing to the genetic susceptibility to ccRCC. Variation in GNAS1 was implicated in a strong synergistic interaction with BIRC5. This effect was part of a model suggested by multifactor dimensionality reduction method including also a synergy between GNAS1 and SCARB1 (P = 0.036). Significance of GNAS1-SCARB1 interaction was further confirmed by logistic regression (P = 0.041), which also indicated involvement of SCARB1 in additional interaction with EPAS1 (P = 0.008) as well as revealing interactions between GNAS1 and EPAS1 (P = 0.016), GNAS1 and MC1R (P = 0.031), GNAS1 and VDR (P = 0.032), and MC1R and VDR (P = 0.035). PMID:25945350

  14. Combined effects of DNA methyltransferase 1 and 3A polymorphisms and urinary total arsenic levels on the risk for clear cell renal cell carcinoma.

    Science.gov (United States)

    Yang, Shu-Mei; Huang, Chao-Yuan; Shiue, Horng-Sheng; Pu, Yeong-Shiau; Hsieh, Yi-Hsun; Chen, Wei-Jen; Lin, Ying-Chin; Hsueh, Yu-Mei

    2016-08-15

    Our previous study showed that high urinary total arsenic levels were associated with higher odds ratio (OR) for renal cell carcinoma (RCC). Single nucleotide polymorphisms (SNPs) of DNA methyltransferases (DNMTs) might influence DNMT enzyme activity associated with tumorigenesis. In this study, we investigated the association of five SNPs from DNMT1 (rs8101626 and rs2228611), DNMT3A (rs34048824 and rs1550117), and DNMT3B (rs1569686) with the risk of clear cell renal cell carcinoma (ccRCC). We also examined the combined effects of DNMT genotypes and urinary arsenic levels on ccRCC risk. We conducted a hospital-based case-control study, which included 293 subjects with ccRCC and 293 age- and gender-matched controls. The urinary arsenic species were determined by a high performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Genotypes were investigated using polymerase chain reaction and restriction fragment length polymorphism analyses. We observed that the DNMT1 rs8101626 G/G genotype was significantly associated with reduced odds ratio (OR) of ccRCC [OR=0.38, 95% confidence interval (CI) 0.14-0.99]. Subjects with concurrent DNMT1 rs8101626 A/A+A/G and DNMT3A rs34048824 T/T+T/C genotypes had significantly higher OR for ccRCC [OR=2.88, 95% CI 1.44-5.77]. Participants with the high-risk genotype of DNMT1 rs8101626 and DNMT3A rs34048824 with concurrently high urinary total arsenic levels had even higher OR of ccRCC in a dose-response manner. This is the first study to evaluate variant DNMT1 rs8101626 and DNMT3A rs34048824 genotypes that modify the arsenic-related ccRCC risk in a geographic area without significant arsenic exposure in Taiwan. PMID:27292127

  15. Long non-coding RNA Linc00152 is a positive prognostic factor for and demonstrates malignant biological behavior in clear cell renal cell carcinoma

    Science.gov (United States)

    Wu, Yong; Tan, Cong; Weng, Wei-Wei; Deng, Yu; Zhang, Qiong-Yan; Yang, Xiao-Qun; Gan, Hua-Lei; Wang, Tao; Zhang, Pei-Pei; Xu, Mi-Die; Wang, Yi-Qin; Wang, Chao-Fu

    2016-01-01

    Accumulating evidence demonstrates that lncRNAs play important roles in regulating gene expression and are involved in various pathological processes. In the present study, we screened the lncRNAs profile in clear cell renal cell carcinoma (ccRCC) from The Cancer Genome Atlas (TCGA) database, and got linc00152, a differentially expressed lncRNA that haven’t been reported in ccRCC. To further explore its role in ccRCC, the level of Linc00152 was detected in 77 paired ccRCC tissues and renal cancer cell lines by qRT-PCR, and its association with overall survival was assessed by statistical analysis. Linc00152 expression was significantly up-regulated in cancerous tissues and cell lines compared with normal counterparts, and high Linc00152 expression was closely associated with advanced TNM stage. Moreover, Linc00152 was found to be able to serve as an independent predictor of overall survival. Further experiments demonstrated that overexpression of Linc00152 can significantly promote cell proliferation and invasion, inhibit cell cycle arrest in G1 phase and dramatically decrease apoptosis in both 786O and Caki-2 cell lines, whereas the opposite results were observed with attenuated Linc00152 expression. Our data suggest that Linc00152 is a novel molecule involved in ccRCC progression as well as a potential prognostic biomarker and therapeutic target.

  16. Sunitinib for advanced renal cell cancer

    Directory of Open Access Journals (Sweden)

    Chris Coppin

    2008-03-01

    Full Text Available Chris CoppinBC Cancer Agency and University of British Columbia, Vancouver, CanadaAbstract: Renal cell cancer has been refractory to drug therapy in the large majority of patients. Targeted agents including sunitinib have been intensively evaluated in renal cell cancer over the past 5 years. Sunitinib is an oral small molecule inhibitor of several targets including multiple tyrosine kinase receptors of the angiogenesis pathway. This review surveys the rationale, development, validation, and clinical use of sunitinib that received conditional approval for use in North America and Europe in 2006. In patients with the clear-cell subtype of renal cell cancer and metastatic disease with good or moderate prognostic factors for survival, sunitinib 50 mg for 4 weeks of a 6-week cycle provides superior surrogate and patient-reported outcomes when compared with interferon-alfa, the previous commonly used first-line drug. Overall survival has not yet shown improvement over interferon and is problematic because of patient crossover from the control arm to sunitinib at disease progression. Toxicity is significant but manageable with experienced monitoring. Sunitinib therapy is an important step forward for this condition. High cost and limited efficacy support the ongoing search for further improved therapy.Keywords: renal cell cancer, targeted therapy, sunitinib

  17. Metastatic Renal Cell Carcinoma Initially Presented as a Tongue Mass

    Directory of Open Access Journals (Sweden)

    Deniz ALTINEL

    2010-09-01

    Full Text Available Renal cell carcinoma is one of the most common tumours after lung and breast cancer to metastasize to the head and neck. Initial presentation by tongue metastasis is extremely rare. A 67-year-oldmale presented with a 4.8 cm mass on his tongue. The result of the punch biopsy from the tongue was diagnosed as a clear cell variant of squamous cell carcinoma. The biopsy was reevaluated due to the renal mass found during the check-up and the rapid enlargement of the mass. The excision of the tongue mass and the radical nephrectomy material confirmed the diagnosis of a metastatic renal cell carcinoma in the tongue and renal cell carcinoma in the kidney. Since metastasis of renal cell carcinoma to the tongue is uncommon it may cause difficulties in diagnosis and proper management. The metastasis of renal cell carcinoma should always be considered in the differential diagnosis among the clear cell neoplasms.

  18. Increased expression of system large amino acid transporter (LAT)-1 mRNA is associated with invasive potential and unfavorable prognosis of human clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    The system L amino acid transporter (LAT) has an important role in the transport of various amino acids, and there have been reports about the relation of this system to cancer. Although LATs are highly expressed in the kidneys, little is known about their influence on human renal cancer. To clarify the role of LATs in human clear cell renal cell carcinoma (RCC), we investigated the expression of mRNAs for LAT1, LAT2, LAT3, LAT4, and 4F2hc in clear cell RCC tissues. The mRNAs of these five genes were analyzed by the real-time reverse transcription polymerase chain reaction in matched sets of tumor and non-tumor tissues obtained at operation from 82 Japanese patients with clear cell RCC. We also measured phosphorylated S6 ribosomal protein (Ser-235/236) proteins levels in 18 paired tumor and non-tumor tissues of the patients by Western blotting. Expression of LAT1 mRNA was significantly increased in tumor tissue compared with non-tumor tissue, while expression of LAT2 and LAT3 mRNAs was reduced. There was no difference in the expression of LAT4 and 4F2hc mRNAs between tumor and non-tumor tissues. Increased expression of LAT1 mRNA was associated with less differentiated tumors, local invasion, microscopic vascular invasion, and metastasis. Kaplan-Meier survival analysis showed that a higher serum LAT1 mRNA level was associated with a shorter overall survival time. Phosphorylated S6 ribosomal protein levels were associated with metastatic potential. LAT1 mRNA levels positively correlated with phosphorylated S6 ribosomal protein proteins levels in primary tumors. These findings suggest that LAT1 mRNA is related to the invasive and progressive potential of clear cell RCC

  19. Diagnosis value of dual-phase contrast enhancement CT combined with virtual non-enhanced images by dual-energy CT in clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    Objective: To explore the diagnostic value of dual-phase contrast enhancement CT combined with virtual non-enhanced images by dual-energy CT in clear cell renal cell carcinoma. Methods: Sixty patients who were suspected of clear cell renal cell carcinoma underwent non-enhanced CT and contrast enhancement CT of early interface-phase between cortex -medulla and parenchymal phase on a dual-energy CT. The true non-enhanced kidney CT (TNCT) was performed in a single-energy acquisition mode, but the dual-phase contrast enhancement CT were performed in a dual-energy mode of 80 kV and 140 kV respectively. The virtual non-enhanced CT (VNCT) images were derived from the data of early interface phase using liver virtual non-contrast software. The diagnose according to VNCT combined dual-phase contrast enhancement CT and dual-phase contrast enhancement CT only were made respectively and compared with χ2 test. Between the true non-contrast CT and the virtual non-contrast CT, the image quality was compared with Wilcoxon test; The radiation dose of volume CT dose index (CTDIvol) and dose length product(DLP) in a single-phase and total examination, the mean CT HU values of the tumours were compared with t test. Results: The accuracy of VNCT combined dual-phase contrast enhancement CT was higher than that of dual-phase contrast enhancement CT only [93.3% (56/60) vs.78.3% (47/60); χ2=5.6, P<0.05]. The detective ability (score) of VNCT was near to that of TNCT and the difference was not obvious (Z=0.00, P>0.05). The radiation dose of volume CT dose index (CTDIvol) and dose length product (DLP) in a single phase and total examination of VNCT [(8.85 ± 1.28) mGy, (196.45 ±21.12) mGy·cm, (17.69±2.35) mGy, (392.90±42.25) mGy · cm] were lower than that of TNCT [(10.20 ± 1.44) mGy,(218.29 ± 29.60) mGy · cm, (30.61 ± 3.27) mGy and (654.86 ± 88.81) mGy ·cm], t=4.21, 3.58, 23.63, 16.12 respectively, P<0.05. The mean CT HU values of tumours on VNCT images was higher than that on

  20. Metastatic renal cell cancer treatments.

    Science.gov (United States)

    Sternberg, C N

    2003-01-01

    Metastatic renal cell carcinoma has been considered to be resistant to chemotherapy, with responses observed in only limited numbers of patients. For this reason, therapeutic options have ranged from no treatment, to immunotherapy with cytokines such as IL-2 and interferon-alpha, chemotherapy alone or in combination with cytokines, and to a variety of new investigational approaches. Interferon and interleukin-2 (IL-2) have led to long-term survival in selected patients. Immunotherapy with cytokines, monoclonal antibodies, new agents, dendritic cell therapy, and allotransplantation offer promise. Novel therapeutic strategies include combining cytokines, and antiangiogenic approaches such as thalidomide and antivascular endothelial growth factor therapy. Pathologic, cytogenic and molecular studies have proven that renal cell carcinoma is not a single tumor entity. Efforts to improve results also include the identification of prognostic factors, which allow treatment to be better directed towards those patients most likely to benefit. Increasing understanding of cancer biology is beginning to allow for a more targeted approach to the therapy of metastatic renal cell carcinoma. Adequate positioning of known treatments is essential and many trials of new targeted therapies are underway. PMID:14988745

  1. Immunotherapy in renal cell carcinoma.

    Science.gov (United States)

    Bukowski, R M

    1999-06-01

    Patients with metastatic renal cell carcinoma continue to present a therapeutic challenge. Current therapeutic approaches involve surgery and various types of immunotherapy. The rationale for this latter form of therapy include the observations of spontaneous tumor regression, the presence of a T-cell-mediated immune response, and the tumor responses observed in patients receiving cytokine therapy. Analysis of prognostic factors in these patients demonstrates that clinical responses occur most frequently in individuals with good performance status. The cytokines interleukin-2 (IL-2, aldesleukin [Proleukin], interferon-alfa (Intron A, Roferon-A), or the combination produce responses in 15% to 20% of patients. Randomized trials suggest that administration of interferon-alfa may result in a modest improvement in median survival. Investigation of the molecular genetics of renal cell carcinoma and the presence of T-lymphocyte immune dysregulation have suggested new therapeutic strategies. Further preclinical and clinical studies investigating inhibitors of angiogenesis or pharmacologic methods to reverse immune dysregulation are ongoing. Therapeutic results in patients with renal cell carcinoma remain limited, and investigational approaches are warranted. PMID:10378218

  2. HtrA3 is regulated by 15-deoxy-{Delta}12,14-prostaglandin J2 independently of PPAR{gamma} in clear cell renal cell carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Theoleyre, Sandrine; Mottier, Stephanie [CNRS UMR 6061, Faculte de Medecine, Rennes (France); Masson, Damien [CNRS UMR 6061, Faculte de Medecine, Rennes (France); INSERM UMR 913, Faculte de Medecine, Nantes (France); Denis, Marc G., E-mail: marc.denis@univ-nantes.fr [CNRS UMR 6061, Faculte de Medecine, Rennes (France); INSERM UMR 913, Faculte de Medecine, Nantes (France)

    2010-04-09

    Peroxisome proliferator-activated receptor gamma (PPAR{gamma}) ligands have been shown to possess anti-proliferative effects in many types of cancer. In clear cell renal cell carcinoma (CCRCC), the targets involved in these effects are not known. In this study, we demonstrated that, in CCRCC cell lines, the endogenous PPAR{gamma} ligand 15-deoxy-{Delta}12,14-prostaglandin J2 (15dPGJ2) induces the expression, both at the mRNA and the protein levels, of the HtrA3 gene. This gene belongs to the High-Temperature Requirement Factor A family of serine proteases that repress signaling by TGF-{beta} family members and inhibit cell migration. Rosiglitazone or ciglitazone, synthetic PPAR{gamma} agonists, did not induce HtrA3 expression, and the PPAR{gamma} antagonist GW9662 did not prevent 15dPGJ2 induction, suggesting that the up-regulation of HtrA3 by 15dPGJ2 is independent of PPAR{gamma}. The MEK/ERK inhibitor PD98059 dramatically repressed HtrA3 induction. Altogether, these data indicate that 15dPGJ2 is able to stimulate the expression of HtrA3 through an indirect mechanism involving the MEK/ERK pathway but independent of PPAR{gamma}. Our results provide a better understanding of the mechanisms involved in the regulation of HtrA3, a potential tumor suppressor gene.

  3. HtrA3 is regulated by 15-deoxy-Δ12,14-prostaglandin J2 independently of PPARγ in clear cell renal cell carcinomas

    International Nuclear Information System (INIS)

    Peroxisome proliferator-activated receptor gamma (PPARγ) ligands have been shown to possess anti-proliferative effects in many types of cancer. In clear cell renal cell carcinoma (CCRCC), the targets involved in these effects are not known. In this study, we demonstrated that, in CCRCC cell lines, the endogenous PPARγ ligand 15-deoxy-Δ12,14-prostaglandin J2 (15dPGJ2) induces the expression, both at the mRNA and the protein levels, of the HtrA3 gene. This gene belongs to the High-Temperature Requirement Factor A family of serine proteases that repress signaling by TGF-β family members and inhibit cell migration. Rosiglitazone or ciglitazone, synthetic PPARγ agonists, did not induce HtrA3 expression, and the PPARγ antagonist GW9662 did not prevent 15dPGJ2 induction, suggesting that the up-regulation of HtrA3 by 15dPGJ2 is independent of PPARγ. The MEK/ERK inhibitor PD98059 dramatically repressed HtrA3 induction. Altogether, these data indicate that 15dPGJ2 is able to stimulate the expression of HtrA3 through an indirect mechanism involving the MEK/ERK pathway but independent of PPARγ. Our results provide a better understanding of the mechanisms involved in the regulation of HtrA3, a potential tumor suppressor gene.

  4. pVHL co-ordinately regulates CXCR4/CXCL12 and MMP2/MMP9 expression in human clear-cell renal cell carcinoma

    DEFF Research Database (Denmark)

    Struckmann, K; Mertz, Kd; Steu, S; Storz, M; Staller, P; Krek, W; Schraml, P; Moch, H

    2008-01-01

    Loss of pVHL function, characteristic for clear-cell renal cell carcinoma (ccRCC), causes increased expression of CXCR4 chemokine receptor, which triggers expression of metastasis-associated MMP2/MMP9 in different human cancers. The impact of pVHL on MMP2/MMP9 expression and their relationship to...... CXCR4 and its ligand CXCL12 in ccRCC is unclear. By using reverse transcription PCR, immunofluorescence and immunohistochemistry, strong mRNA and protein expression of CXCR4, CXCL12, MMP2, MMP9 and MMP inhibitors TIMP1 and TIMP2 was found in VHL-null 786-O ccRCC cells. Loss of CXCR4/CXCL12 expression...... after restoration of VHL function in these cells was accompanied by a significant reduction of MMP2 and MMP9 expression, whereas neither TIMP1 nor TIMP2 expression was affected. Using real-time PCR analysis, higher MMP2 (p = 0.0134) and MMP9 (p = 0.067) mRNA expression levels were detected in primary cc...

  5. Metastatic Renal Cell Carcinoma Masquerading as a Primary Ovarian Mass in a Post-Operative Case of Meningioma and Renal Cell Carcinoma

    OpenAIRE

    Sangita Bohara; Biswajit Dey; Swapnil Agarwal; Jyotsna Naresh Bharti; Nita Khurana; Poonam Sachdeva

    2015-01-01

    The clinical presentation of metastatic renal cell carcinoma to ovary is extremely rare as well as confusing due to its close resemblance to primary ovarian tumors, especially clear cell carcinoma. We present a case of metastatic renal cell carcinoma diagnosed in a 48-year-old female, who had renal cell carcinoma of the right kidney and right sphenoid wing meningioma of transitional type.

  6. Collision Tumor With Renal Cell Carcinoma and Plasmacytoma: Further Evidence of a Renal Cell and Plasma Cell Neoplasm Relationship?

    Science.gov (United States)

    Berquist, Sean W; Hassan, Abd-Elrahman Said; Miakicheva, Olga; Dufour, Catherine; Hamilton, Zachary; Shabaik, Ahmed; Derweesh, Ithaar H

    2016-05-01

    Renal solitary extramedullary plasmacytomas belong to a group of plasma cell neoplasms, which generally have been associated with renal cell carcinoma. We present a case report of a patient with collision tumor histology of extramedullary plasmacytoma and clear cell renal cell carcinoma, the first in the known literature. Standard work-up for a plasma cell neoplasm was conducted and the mass was resected. The patient remains disease-free at 28 months post-surgery. The report calls into question pre-surgical renal mass biopsy protocol and suggests a relationship between renal cell carcinoma and plasma cell neoplasms. PMID:27175345

  7. Prognostic significance of lymphocyte-to-monocyte ratio and CRP in patients with nonmetastatic clear cell renal cell carcinoma: a retrospective multicenter analysis

    Science.gov (United States)

    Xia, Wen-Kai; Wu, Xia; Yu, Tang-Hong; Wu, Yu; Yao, Xia-Juan; Hu, Hong

    2016-01-01

    Background Inflammation has been reported to be involved in carcinogenesis and cancer progression. This study was designed to explore the prognostic significance of lymphocyte-to-monocyte ratio (LMR) and serum C-reactive protein (CRP) in nonmetastatic clear cell renal cell carcinoma (ccRCC) patients after treatment. Methods The retrospective study consisted of 985 patients with ccRCC who had undergone nephrectomy from 2005 to 2010 at multiple centers. The patients were divided into four groups using a quartile of LMR or CRP, and their associations with clinical characteristics and outcome were systematically estimated. Results Both low LMR and high CRP significantly diminished overall survival (OS) and metastasis-free survival (MFS) in patients with ccRCC. Further investigation indicated that LMR and CRP were independent prognostic factors of both OS and MFS. Integration of LMR and CRP into a predictive model, including significant variables in multivariate analysis, established a nomogram to predict accurately the 3- and 5-year survival for nonmetastatic patients with ccRCC. Conclusion LMR and CRP represent independent prognostic factors of OS and MFS for patients with ccRCC. Incorporation of LMR and CRP into the traditional TNM staging system may improve their predictive performance.

  8. Elevated expression of IFN-inducible CXCR3 ligands predicts poor prognosis in patients with non-metastatic clear-cell renal cell carcinoma.

    Science.gov (United States)

    Liu, Weisi; Liu, Yidong; Fu, Qiang; Zhou, Lin; Chang, Yuan; Xu, Le; Zhang, Weijuan; Xu, Jiejie

    2016-03-22

    IFN-inducible CXCR3 ligands (ICL), namely CXCL9, CXCL10 and CXCL11, exhibit pleiotropic roles in orchestrating immunity and angiogenesis. However, the prognosis value of them in renal cell carcinoma (RCC) was still obscure. Thus, we retrospectively used immunohistochemistry approach to evaluate the impact of these ligands on recurrence and survival of non-metastatic clear cell RCC (ccRCC) patients after nephrectomy. We systemically built a prespecified ICL score based on these ligands, and found specimens with high ICL score were prone to possess high Fuhrman grade, necrosis, and high-risk level of SSIGN. Moreover, ICL score stratified patients into different risk subgroups, and remained an independent adverse prognosticator for overall survival (OS) and recurrence-free survival (RFS). Meanwhile, in TCGA database, the increasing ICL mRNA predicted poor survival and early recurrence. Furthermore, after adding ICL score into SSIGN, the C-index for OS and RFS increased from 0.705 to 0.746 and 0.712 to 0.765, respectively. In conclusion, the ICL score based on expression of CXCL9, CXCL10 and CXCL11 stratified non-metastatic ccRCC patients into different risk subgroups of recurrence and death, which might benefit preoperative risk stratification and guide immune therapy in the future. PMID:26910919

  9. The evolving classification of renal cell neoplasia.

    Science.gov (United States)

    Delahunt, Brett; Srigley, John R

    2015-03-01

    The classification of renal cell neoplasia is morphologically based; however, this has evolved over the last 35 years with the incorporation of genetic characteristics into the diagnostic features of some tumors. The 2013 Vancouver classification recognized 17 morphotypes of renal parenchymal malignancy and two benign tumors. This classification included the newly established entities tubulocystic renal cell carcinoma (RCC)), acquired cystic disease-associated RCC, clear cell (tubulo) papillary RCC, microphthalmia transcription factor family translocation RCC and hereditary leiomyomatosis RCC syndrome-associated RCC. In addition to these newly described forms of RCC there are a number of novel tumors that are currently recognized as emerging entities. These are likely to be incorporated into subsequent classifications and include thyroid-like follicular RCC, succinate dehydrogenase B mutation-associated RCC, ALK translocation RCC, tuberous sclerosis complex-associated RCC, and RCC with (angio) leiomyomatous stroma. PMID:25753529

  10. CD133 Staining Detects Acute Kidney Injury and Differentiates Clear Cell Papillary Renal Cell Carcinoma from Other Renal Tumors

    OpenAIRE

    Schwartz, John D.; Francis Dumler; Hafron, Jason M.; Wilson, George D.; Wolforth, Stacy C.; Michele T. Rooney; Wei Li; Zhang, Ping L.

    2013-01-01

    CD133 has recently been characterized as a progenitor cell marker in the kidney. However, the expression of this marker has not been thoroughly investigated in kidney injury and variants of renal tumors for pathology practice. We quantified CD133 expression in kidney biopsies from patients with acute renal failure and compared staining intensity with serum creatinine levels. CD133 expression levels were also evaluated in several subtypes of renal neoplasms. Normal adult renal parenchyma showe...

  11. PD-L1 expression is regulated by hypoxia inducible factor in clear cell renal cell carcinoma.

    Science.gov (United States)

    Ruf, Melanie; Moch, Holger; Schraml, Peter

    2016-07-15

    In our study, we demonstrate that ccRCC cell lines with impaired function of pVHL to degrade HIFα express elevated levels of PD-L1. In vitro analysis provided evidence that both reconstitution of pVHL and silencing of HIF2α, but not of HIF1α, lead to reduced PD-L1 expression. The strong correlation of expression between the HIF2α-specific HIF target Glut1 and PD-L1 confirmed this finding in ccRCC cell lines and tissue. Soluble PD-L1 levels remained constant in the sera of ccRCC patients regardless of the PD-L1 expression status in their tumors. In conclusion, our data suggest PD-L1 as HIF2α target, which is upregulated in pVHL deficient ccRCC. The combination of PD-L1 targeting drugs with HIF inhibiting agents may be an additional option for the treatment of ccRCC. PMID:26945902

  12. Case of hereditary papillary renal cell carcinoma

    OpenAIRE

    Mustafa, Sadaf; Jadidi, Nima; Faraj, Sheila F.; Rodriquez, Ronald

    2012-01-01

    Renal cell carcinoma is the most common type of renal malignancy and it originates from the renal tubular epithelium. Due to the diversity in the histopathological and molecular characteristics, it is typically subclassified into five different categories. Papillary renal cell carcinoma is one subclassification and it includes two variants: sporadic and hereditary. Although the hereditary form comprises a smaller number of cases of papillary renal cell carcinoma, an understanding of the molec...

  13. Renal cell carcinoma presenting as mandibular metastasis

    Directory of Open Access Journals (Sweden)

    Hassan Ahmadnia

    2013-01-01

    Full Text Available Renal clear cell carcinoma (RCC has different manifestations, including uncommon metastasis and paraneoplastic syndromes. Here we report a rare case of RCC presenting as metastasis to the mandible. A 57-year-old patient with mandibular swelling was referred to the dentist. After necessary evaluations, an incisional biopsy of mandible showed metastatic RCC. The patient was referred to the urologist. The patient underwent right radical nephrectomy. Pathological examination showed clear renal cell carcinoma. Every abnormal bone lesion in the oral cavity should be evaluated carefully and the possibility of a malignant lesion should always be considered.

  14. Synchronous clear cell renal cell carcinoma and tubulocystic carcinoma: genetic evidence of independent ontogenesis and implications of chromosomal imbalances in tumor progression

    Directory of Open Access Journals (Sweden)

    Quiroga-Garza Gabriela

    2012-02-01

    Full Text Available Abstract Seven percent of renal cell carcinoma (RCC cases are diagnosed as "unclassified" RCC by morphology. Genetic profiling of RCCs helps define renal tumor subtypes, especially in cases where morphologic diagnosis is inconclusive. This report describes a patient with synchronous clear cell RCC (ccRCC and a tubulocystic renal carcinoma (TCRC in the same kidney, and discusses the pathologic features and genetic profile of both tumors. A 67 year-old male underwent CT scans for an unrelated medical event. Two incidental renal lesions were found and ultimately removed by radical nephrectomy. The smaller lesion had multiple small cystic spaces lined by hobnail cells with high nuclear grade separated by fibrous stroma. This morphology and the expression of proximal (CD10, AMACR and distal tubule cell (CK19 markers by immunohistochemistry supported the diagnosis of TCRC. The larger lesion was a typical ccRCC, with Fuhrman's nuclear grade 3 and confined to the kidney. Molecular characterization of both neoplasms using virtual karyotyping was performed to assess relatedness of these tumors. Low grade areas (Fuhrman grade 2 of the ccRCC showed loss of 3p and gains in chromosomes 5 and 7, whereas oncocytic areas displayed additional gain of 2p and loss of 10q; the high grade areas (Fuhrman grade 3 showed several additional imbalances. In contrast, the TCRC demonstrated a distinct profile with gains of chromosomes 8 and 17 and loss of 9. In conclusion, ccRCC and TCRC show distinct genomic copy number profiles and chromosomal imbalances in TCRC might be implicated in the pathogenesis of this tumor. Second, the presence of a ccRCC with varying degrees of differentiation exemplifies the sequence of chromosomal imbalances acquired during tumor progression. Virtual Slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1790525735655283

  15. Downregulation of NDUFB6 due to 9p24.1-p13.3 loss is implicated in metastatic clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    This study was conducted to clarify the genomic profiles of metastatic clear cell renal cell carcinomas (ccRCCs) and identify the genes responsible for development of metastasis. We analyzed the genomic profiles of 20 cases of primary ccRCC and their corresponding metastases using array-based comparative genomic hybridization, and identified 32 chromosomal regions in which gene copy number alterations were detected more frequently in metastases than in the primary tumors. Among these 32 regions, 9p24.1-p13.3 loss was the most statistically significant alteration. Furthermore, we found that patients with 9p24.1-p13.3 loss in primary tumors exhibited significantly lower rates of recurrence-free and cancer-specific survival, suggesting that 9p loss in the primary tumor is a potential biomarker predicting early recurrence of metastasis. Interestingly, the genomic profiles of primary tumors with 9p loss resembled those of their corresponding metastases, though 9p loss was accumulated in the metastases derived from the primary tumors without 9p loss. Comparison of the mRNA expression levels revealed that 2 of 58 genes located at 9p24.1-p13.3 were downregulated due to gene copy number loss in ccRCCs. An overexpression study of these two genes in ccRCC cell lines revealed that downregulation of NDUFB6 due to loss at 9p24.1-p13.3 may confer a growth advantage on metastatic ccRCC cells. These results were confirmed by analyzing the data of 405 cases of ccRCC obtained from The Cancer Genome Atlas (TCGA). On the basis of our present data, we propose that NDUFB6 is a possible tumor suppressor of metastatic ccRCCs

  16. Epithelial-mesenchymal transition-associated microRNA/mRNA signature is linked to metastasis and prognosis in clear-cell renal cell carcinoma

    Science.gov (United States)

    Mlcochova, Hana; Machackova, Tana; Rabien, Anja; Radova, Lenka; Fabian, Pavel; Iliev, Robert; Slaba, Katerina; Poprach, Alexandr; Kilic, Ergin; Stanik, Michal; Redova-Lojova, Martina; Svoboda, Marek; Dolezel, Jan; Vyzula, Rostislav; Jung, Klaus; Slaby, Ondrej

    2016-01-01

    Clear-cell renal cell carcinomas (ccRCCs) are genetically heterogeneous tumors presenting diverse clinical courses. Epithelial-mesenchymal transition (EMT) is a crucial process involved in initiation of metastatic cascade. The aim of our study was to identify an integrated miRNA/mRNA signature associated with metastasis and prognosis in ccRCC through targeted approach based on analysis of miRNAs/mRNAs associated with EMT. A cohort of 230 ccRCC was included in our study and further divided into discovery, training and validation cohorts. EMT markers were evaluated in ccRCC tumor samples, which were grouped accordingly to EMT status. By use of large-scale miRNA/mRNA expression profiling, we identified miRNA/mRNA with significantly different expression in EMT-positive tumors and selected 41 miRNAs/mRNAs for training phase of the study to evaluate their diagnostic and prognostic potential. Fifteen miRNAs/mRNAs were analyzed in the validation phase, where all evaluated miRNA/mRNA candidates were confirmed to be significantly deregulated in tumor tissue. Some of them significantly differed in metastatic tumors, correlated with clinical stage, with Fuhrman grade and with overall survival. Further, we established an EMT-based stage-independent prognostic scoring system enabling identification of ccRCC patients at high-risk of cancer-related death. Finally, we confirmed involvement of miR-429 in EMT regulation in RCC cells in vitro. PMID:27549611

  17. Do programmed death 1 (PD-1) and its ligand (PD-L1) play a role in patients with non-clear cell renal cell carcinoma?

    Science.gov (United States)

    Abbas, Mahmoud; Steffens, Sandra; Bellut, Maria; Becker, Jan U; Großhennig, Anika; Eggers, Hendrik; Wegener, Gerd; Kuczyk, Markus A; Kreipe, Hans H; Grünwald, Viktor; Schrader, Andres J; Ivanyi, Philipp

    2016-06-01

    Clinical trials targeting programmed death 1 (PD-1) and its ligand PD-L1 (PD-L1) for metastatic renal cell cancer (RCC) are ongoing. The aim of this study is to validate their roles as prognostic markers in non-clear cell (non-cc) RCC. Sixty-four non-cc RCC tissue specimens were collected from patients undergoing renal tumor surgery. Expressions of biomarkers were assessed using immunohistochemistry and compared with clinical characteristics. Survival analyses were performed with a median follow-up of 77.5 (range: 0-176) months. No significant correlations were found for PD-1(+) tumor-infiltrating mononuclear cells (TIMC) or PD-L1(+) expression and clinical attributes in patients with non-cc RCC. Kaplan-Meier analysis revealed no differences in 5- and 10-year cancer-specific survival (CSS) for PD-1(-) TIMC compared to PD-1(+) TIMC (71.4 and 63 % versus 72.2 and 61.9 %; p = 0.88). Intratumoral expression of PD-L1 did not appear to influence the 5- and 10-year CSS significantly, even though a trend was identified (68 and 53.6 % versus 80.1 and 75.7 %; p = 0.08). In multivariate analysis, neither PD-1(+) TIMC nor intratumoral PD-L1(+) expression proved to be independent predictors of CSS (p = 0.99 and p = 0.68, respectively). Our study demonstrates that PD-1(+) TIMC and intratumoral PD-L1(+) expression did not significantly impact tumor aggressiveness or clinical outcome in non-ccRCC specimens. Due to rare incidence of non-cc RCC in particular according to PD-L1 expression, further analyzes are warranted. PMID:27165272

  18. Integrative genome-wide gene expression profiling of clear cell renal cell carcinoma in Czech Republic and in the United States.

    Directory of Open Access Journals (Sweden)

    Magdalena B Wozniak

    Full Text Available Gene expression microarray and next generation sequencing efforts on conventional, clear cell renal cell carcinoma (ccRCC have been mostly performed in North American and Western European populations, while the highest incidence rates are found in Central/Eastern Europe. We conducted whole-genome expression profiling on 101 pairs of ccRCC tumours and adjacent non-tumour renal tissue from Czech patients recruited within the "K2 Study", using the Illumina HumanHT-12 v4 Expression BeadChips to explore the molecular variations underlying the biological and clinical heterogeneity of this cancer. Differential expression analysis identified 1650 significant probes (fold change ≥2 and false discovery rate <0.05 mapping to 630 up- and 720 down-regulated unique genes. We performed similar statistical analysis on the RNA sequencing data of 65 ccRCC cases from the Cancer Genome Atlas (TCGA project and identified 60% (402 of the downregulated and 74% (469 of the upregulated genes found in the K2 series. The biological characterization of the significantly deregulated genes demonstrated involvement of downregulated genes in metabolic and catabolic processes, excretion, oxidation reduction, ion transport and response to chemical stimulus, while simultaneously upregulated genes were associated with immune and inflammatory responses, response to hypoxia, stress, wounding, vasculature development and cell activation. Furthermore, genome-wide DNA methylation analysis of 317 TCGA ccRCC/adjacent non-tumour renal tissue pairs indicated that deregulation of approximately 7% of genes could be explained by epigenetic changes. Finally, survival analysis conducted on 89 K2 and 464 TCGA cases identified 8 genes associated with differential prognostic outcomes. In conclusion, a large proportion of ccRCC molecular characteristics were common to the two populations and several may have clinical implications when validated further through large clinical cohorts.

  19. A divide-and-conquer strategy in tumor sampling enhances detection of intratumor heterogeneity in routine pathology: A modeling approach in clear cell renal cell carcinoma

    Science.gov (United States)

    Lopez, José I.; Cortes, Jesús M.

    2016-01-01

    Intratumor heterogeneity (ITH) is an inherent process in cancer development which follows for most of the cases a branched pattern of evolution, with different cell clones evolving independently in space and time across different areas of the same tumor. The determination of ITH (in both spatial and temporal domains) is nowadays critical to enhance patient treatment and prognosis. Clear cell renal cell carcinoma (CCRCC) provides a good example of ITH. Sometimes the tumor is too big to be totally analyzed for ITH detection and pathologists decide which parts must be sampled for the analysis. For such a purpose, pathologists follow internationally accepted protocols. In light of the latest findings, however, current sampling protocols seem to be insufficient for detecting ITH with significant reliability. The arrival of new targeted therapies, some of them providing promising alternatives to improve patient survival, pushes the pathologist to obtain a truly representative sampling of tumor diversity in routine practice. How large this sampling must be and how this must be performed are unanswered questions so far.  Here we present a very simple method for tumor sampling that enhances ITH detection without increasing costs. This method follows a divide-and-conquer (DAC) strategy, that is, rather than sampling a small number of large-size tumor-pieces as the routine protocol (RP) advises, we suggest sampling many small-size pieces along the tumor. We performed a computational modeling approach to show that the usefulness of the DAC strategy is twofold: first, we show that DAC outperforms RP with similar laboratory costs, and second, DAC is capable of performing similar to total tumor sampling (TTS) but, very remarkably, at a much lower cost. We thus provide new light to push forward a shift in the paradigm about how pathologists should sample tumors for achieving efficient ITH detection. PMID:27127618

  20. Type 1 plasminogen activator inhibitor (PAI-1 in clear cell renal cell carcinoma (CCRCC and its impact on angiogenesis, progression and patient survival after radical nephrectomy

    Directory of Open Access Journals (Sweden)

    Seidal Tomas

    2010-12-01

    Full Text Available Abstract Background To examine the expression of type 1 plasminogen inhibitor (PAI-1 in clear cell renal cell carcinoma (CCRCC, and its possible association with microvessel density (MVD, the expression of thrombospondin-1 (TSP-1, nuclear grade, tumour stage, continuously coded tumour size (CCTS and to assess the value of PAI as a prognostic marker in 162 patients with CCRCC treated with radical nephrectomy. Methods A total of 172 consecutive patients with CCRCC treated with radical nephrectomy were enrolled in the study. The expression of PAI-1, TSP-1 and factor VIII were analysed on formalin-fixed, paraffin-embedded tissues without knowledge of the clinical outcome. Ten cases, where PAI-1 immunohistochemistry was not possible due to technical problems and lack of material, were excluded. Sixty-nine patients (43% died of RCC, while 47 patients (29% died of other diseases. Median follow-up was 13.8 years for the surviving 46 patients (28%. Results Nine percent of the tumours showed PAI-1 positivity. High expression of PAI-1 was significantly inversely correlated with TSP-1 (p = 0.046 and directly with advanced stage (p = 0.008, high NG (3+4 (p = 0.002, tumour size (p = 0.011, microvessel density (p = 0.049 and disease progression (p = 0.002. In univariate analysis PAI-1 was a significant prognosticator of cancer-specific survival (CSS (p Conclusions PAI-1 was found to be an independently significant prognosticator of CSS and a promoter of tumour angiogenesis, aggressiveness and progression in CCRCC.

  1. Assessment of survival of patients with metastatic clear cell renal cell carcinoma after radical cytoreductive nephrectomy versus no surgery: a SEER analysis

    Directory of Open Access Journals (Sweden)

    Wen-Jun Xiao

    2015-04-01

    Full Text Available Purposes To examine the factors related to the choice of cytoreductive nephrectomy (CN for patients with metastatic clear cell renal cell carcinoma (mCCRCC, and compare the population-based survival rates of patients treated with or without surgery in the modern targeted therapy era. Materials and Methods From 2006 to 2009, patients with mCCRCC were identified from SEER database. The factors that affected patients to be submitted to CN were examined and propensity scores for each patient were calculated. Then patients were matched based upon propensity scores. Univariable and multivariable cox regression models were used to compare survival rates of patients treated with or without surgery. Finally, sensitivity analysis for the cox model on a hazard ratio scale was performed. Results Age, race, tumor size, T stage and N stage were associated with nephrectomy univariablely. After the match based upon propensity scores, the 1-, 2-, and 3-year cancer-specific survival rate estimates were 45.1%, 27.9%, and 21.7% for the no-surgery group vs 70.6%, 52.2%, and 41.7% for the surgery group, respectively (hazard ratio 0.42, 95%CI: 0.35-0.52, log-rank P<0.001. In multivariable Cox proportional hazard regression model, race, T stage, N stage and median household income were significantly associated with survival. Sensitivity analysis on a hazard ratio scale indicated that the hazard ratio might be above 1.00 only when the unknown factor had an opposite effect on survival which was 3-fold than CN. Conclusion The results of our study showed that CN significantly improves the survival of patients with metastatic CCRCC even in the targeted therapy era.

  2. Decreased GATA5 mRNA expression associates with CpG island methylation and shortened recurrence-free survival in clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    GATA-5, a zinc-finger transcription factor and member of the GATA family proteins 1–6, is known to be involved in cellular differentiation. We recently found that tumor-specific hypermethylation of the GATA5 CpG island (CGI) occurs in renal cell carcinoma (RCC) and is associated with an adverse clinical outcome. In this study, we investigated whether epigenetic GATA5 alterations may result in changes in GATA5 mRNA expression levels and correlate with the observed prognostic impact of epigenetic changes in GATA5 in RCC. Quantitative real-time reverse-transcribed polymerase chain reaction was applied to measure relative GATA5 mRNA expression levels in 135 kidney tissue samples, including 77 clear cell RCC (ccRCC) tissues and 58 paired adjacent normal renal tissue samples. Relative GATA5 expression levels were determined using the ΔΔCt method and detection of three endogenous control genes then compared to previously measured values of relative methylation. The mean relative GATA5 mRNA expression level exhibited an approximately 31-fold reduction in tumor specimens compared with corresponding normal tissues (p < 0.001, paired t-test). Decreased GATA5 mRNA expression was inversely correlated with increased GATA5 CGI methylation (p < 0.001) and was associated with shortened recurrence-free survival in ccRCC patients (p = 0.023, hazard ratio = 0.25). GATA5 mRNA expression is decreased in ccRCC, likely due to gene silencing by methylation of the GATA5 CGI. Moreover, reduced GATA5 mRNA levels were associated with a poor clinical outcome, indicating a possible role of GATA5 for the development of aggressive ccRCC phenotypes

  3. CT feature analysis of renal cell carcinoma: report of 300 cases

    International Nuclear Information System (INIS)

    Objective: To analyze the CT features of renal cell carcinoma, so as to improve the diagnostic accuracy of renal cell carcinoma. Methods: Three hundred cases of renal cell carcinoma proved by pathology were examined by means of CT. There were 214 male and 86 female in this group. Their age ranged from 9 to 81 years, with a mean of 53.7 years. Their CT features were retrospectively reviewed. Results: The masses were 1.5-16.0 cm (mean, 4.8 cm) in greatest dimension, 125 masses on left kidney and 175 masses on right kidney. According to WHO histological classification of tumours of the kidney in 2004, there were 238 cases of clear cell renal cell carcinoma, 6 cases of multilocular clear cell renal cell carcinomas, 23 cases of papillary renal cell carcinoma, 14 cases of chromophobe renal cell carcinoma and 19 eases of renal cell carcinoma, unclassified. The above subtype of renal cell carcinoma demonstrated characteristic features. Clear cell renal cell carcinoma exhibited inhomogenous (due to hemorrhage, necrosis or cystic degeneration) and hypervascular. Multilocular clear cell renal cell carcinoma presented as a multilocular cystic mass lacking an expansile nodule, and with regular thin cyst wall and septa. Papillary renal cell carcinoma exhibited inhomogenous and hypovascular. Chromophobe renal cell carcinoma was relatively homogenous and hypovascular. Renal cell carcinoma, unclassified showed inhomogenous and hypervascular, and was more invading growth compared to clear cell renal cell carcinoma. Conclusion: Common subtype of renal cell carcinoma demonstrated characteristic features in CT and it is helpful for differentiation. (authors)

  4. Pituitary metastasis from a renal cell carcinoma progressed after sorafenib treatment

    OpenAIRE

    Guang-Yuan Hu; Shi-Ying Yu; Lin Yang

    2013-01-01

    Pituitary metastasis from renal cell carcinoma is rare and has never been reported for renal cell carcinoma primarily treated with sorafenib. Herein, we present a case of an advanced clear-cell renal cell carcinoma in which pituitary metastasis progressed but extracerebral metastases showed partial response to sorafenib treatment.

  5. Pituitary metastasis from a renal cell carcinoma progressed after sorafenib treatment

    Directory of Open Access Journals (Sweden)

    Guang-Yuan Hu

    2013-06-01

    Full Text Available Pituitary metastasis from renal cell carcinoma is rare and has never been reported for renal cell carcinoma primarily treated with sorafenib. Herein, we present a case of an advanced clear-cell renal cell carcinoma in which pituitary metastasis progressed but extracerebral metastases showed partial response to sorafenib treatment.

  6. Expression of parafibromin in major renal cell tumors

    OpenAIRE

    Cui, C.; Lal, P; Master, S.; Ma, Y.; Baradet, T.; Bing, Z.

    2012-01-01

    Parafibromin, encoded by HRPT2 gene, is a recently identified tumor suppressor. Complete and partial loss of its expression have been observed in hyperparathyroidism-jaw tumor (HPT-JT), parathyroid carcinoma, breast carcinoma, lung carcinoma, gastric and colorectal carcinoma. However, little has been known about its expression in renal tumors. In order to study the expression of parafibromin in a series of the 4 major renal cell tumors - clear cell renal cell carcinoma (ccRCC), papillary ren...

  7. Choroidal metastasis from tubulopapillary renal cell carcinoma: a case report

    OpenAIRE

    Elghissassi, Ibrahim; Inrhaoun, Hanane; Ismaili, Nabil; Errihani, Hassan

    2009-01-01

    Choroidal metastases from renal carcinoma are rare. Most reported cases describe a clear cell carcinoma histologic subtype. Metastatic tubulopapillary renal cell carcinoma to the choroid plexus is very exceptional. We report the case of a 31-year-old man with a history of tubulopapillary renal cell carcinoma who presented two years later with metastatic disease to lungs and presternal soft tissue and three months after with choroidal metastasis revealed on ophtalmoscopic examination and magne...

  8. Current treatments for renal cell carcinoma

    OpenAIRE

    Noble, Helen; Walsh, Ian

    2015-01-01

    Renal cell carcinoma (RCC), also known as kidney cancer, renal adenocarcinoma or hypernephroma, and metastatic renal cell carcinoma is a global burden. This article aims to provide a brief overview of RCC. It outlines epidemiology and presentation; invesitgation and staging; treatments and prognosis. The article also includes a focus on currently available drug treatments, and serves as an introduction to the topic.

  9. Renal cell carcinoma presenting with malignant ascites

    OpenAIRE

    Jennison, Erica; Wathuge, Gayathri W; Gorard, David A

    2015-01-01

    Lesson It is rare for renal cell carcinoma to involve the peritoneum and cause malignant ascites. Furthermore, it is uncommon for malignant ascites to be a presenting feature of this cancer. An unusual case of renal cell carcinoma presenting with malignant ascites is reported, and its response to sunitinib described.

  10. Renal Cell Carcinoma in Transplanted Kidney

    OpenAIRE

    M. Naroienejad; Salouti, R

    2005-01-01

    Immunosuppressive drugs are prescribed routinely to kidney transplant recipients to prevent rejection. These medications are associated wi th an increased risk of secondary malignancies,including renal cell carcinoma in the transplanted kidney itself. We present a case of renal cell carcinoma in a transplanted kidney.

  11. Atypical presentations and rare metastatic sites of renal cell carcinoma: a review of case reports

    OpenAIRE

    Cindolo Luca; Metaxa Linda; Sountoulides Petros

    2011-01-01

    Abstract Renal cell carcinoma is a potentially lethal cancer with aggressive behavior and a propensity for metastatic spread. Due to the fact that the patterns of metastases from renal cell carcinomas are not clearly defined, there have been several reports of cases of renal cell carcinoma associated with rare metastatic sites and atypical presenting symptoms. The present review focuses on these atypical rare clinical presentations of renal cell carcinomas both at the time of diagnosis of the...

  12. MicroRNA-22 is downregulated in clear cell renal cell carcinoma, and inhibits cell growth, migration and invasion by targeting PTEN.

    Science.gov (United States)

    Fan, Wenxing; Huang, Jie; Xiao, Hua; Liang, Zhang

    2016-06-01

    MicroRNA (miR)-22 has previously been reported to be frequently downregulated in certain types of cancer. The present study examined the expression and effects of miR-22 in renal cell carcinoma (RCC). The results indicated that miR‑22 was downregulated in tumor tissue from patients with RCC. In addition, lower miR‑22 expression levels were associated with histological grade, tumor stage and lymph node metas-tasis. Following transfection of RCC cells with miR‑22, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, cell migration, cell invasion and luciferase assays, and western blotting were conducted. The results demonstrated that miR‑22 was able to inhibit cell proliferation, migration and invasion in 786‑O and A498 cells. Furthermore, the results indicated that miR‑22 may directly target phosphatase and tensin homolog (PTEN) in RCC. In conclusion, the present study suggested that the miR-22/PTEN axis may be considered a novel therapeutic target in RCC. These findings may be beneficial for the development of an effective therapy against RCC. PMID:27082730

  13. Clinical presentation of renal cell carcinoma

    International Nuclear Information System (INIS)

    Most common malignant tumour of the kidney is Renal Cell Carcinoma (RCC) and is known for its unpredictable clinical behaviour. Aetiology and risk factors are not completely understood. Extensive workup is being done in the understanding of the disease, especially to diagnose early and to treat promptly. The objective of this study was to determine the clinical presentation and pathological pattern of RCC. Methods: After approval from ethical committee a retrospective review of records was conducted extending from January 2012 to January 2014 to identify clinical characteristics of renal cell carcinomas. The study included all renal cancer patients presented to Sheikh Zayed Hospital Lahore with in this specified period. The data was retrieved regarding, history, physical examination and necessary investigations such as ultrasonography of abdomen and pelvis and CT scan of abdomen and pelvis. Results: There were total of 50 cases. The male to female ratio was 3:2. Mean age of patients were 52.38 (18-93) years old. Most common clinical presentation was gross haematuria(66%).The mean tumour size was 8.34 (3-24) cm. Tumour histology were clear cell (84%), papillary transitional cell carcinoma (12%) and oncosytoma contributed 4%. Conclusion: We observed that large number of the patients with RCC presented with haematuria and most of them were male. Common pathological type was clear cell carcinoma. (author)

  14. Transcriptome Sequencing (RNAseq) Enables Utilization of Formalin-Fixed, Paraffin-Embedded Biopsies with Clear Cell Renal Cell Carcinoma for Exploration of Disease Biology and Biomarker Development

    Science.gov (United States)

    Eikrem, Oystein; Beisland, Christian; Hjelle, Karin; Flatberg, Arnar; Scherer, Andreas; Landolt, Lea; Skogstrand, Trude; Leh, Sabine; Beisvag, Vidar; Marti, Hans-Peter

    2016-01-01

    Formalin-fixed, paraffin-embedded (FFPE) tissues are an underused resource for molecular analyses. This proof of concept study aimed to compare RNAseq results from FFPE biopsies with the corresponding RNAlater® (Qiagen, Germany) stored samples from clear cell renal cell carcinoma (ccRCC) patients to investigate feasibility of RNAseq in archival tissue. From each of 16 patients undergoing partial or full nephrectomy, four core biopsies, such as two specimens with ccRCC and two specimens of adjacent normal tissue, were obtained with a 16g needle. One normal and one ccRCC tissue specimen per patient was stored either in FFPE or RNAlater®. RNA sequencing libraries were generated applying the new Illumina TruSeq® Access library preparation protocol. Comparative analysis was done using voom/Limma R-package. The analysis of the FFPE and RNAlater® datasets yielded similar numbers of detected genes, differentially expressed transcripts and affected pathways. The FFPE and RNAlater datasets shared 80% (n = 1106) differentially expressed genes. The average expression and the log2 fold changes of these transcripts correlated with R2 = 0.97, and R2 = 0.96, respectively. Among transcripts with the highest fold changes in both datasets were carbonic anhydrase 9 (CA9), neuronal pentraxin-2 (NPTX2) and uromodulin (UMOD) that were confirmed by immunohistochemistry. IPA revealed the presence of gene signatures of cancer and nephrotoxicity, renal damage and immune response. To simulate the feasibility of clinical biomarker studies with FFPE samples, a classifier model was developed for the FFPE dataset: expression data for CA9 alone had an accuracy, specificity and sensitivity of 94%, respectively, and achieved similar performance in the RNAlater dataset. Transforming growth factor-ß1 (TGFB1)-regulated genes, epithelial to mesenchymal transition (EMT) and NOTCH signaling cascade may support novel therapeutic strategies. In conclusion, in this proof of concept study, RNAseq data

  15. Combination of expression levels of miR-21 and miR-126 is associated with cancer-specific survival in clear-cell renal cell carcinoma

    International Nuclear Information System (INIS)

    Renal cell carcinoma (RCC) is marked by high mortality rate. To date, no robust risk stratification by clinical or molecular prognosticators of cancer-specific survival (CSS) has been established for early stages. Transcriptional profiling of small non-coding RNA gene products (miRNAs) seems promising for prognostic stratification. The expression of miR-21 and miR-126 was analysed in a large cohort of RCC patients; a combined risk score (CRS)-model was constructed based on expression levels of both miRNAs. Expression of miR-21 and miR-126 was evaluated by qRT-PCR in tumour and adjacent non-neoplastic tissue in n = 139 clear cell RCC patients. Relation of miR-21 and miR-126 expression with various clinical parameters was assessed. Parameters were analysed by uni- and multivariate COX regression. A factor derived from the z-score resulting from the COX model was determined for both miRs separately and a combined risk score (CRS) was calculated multiplying the relative expression of miR-21 and miR-126 by this factor. The best fitting COX model was selected by relative goodness-of-fit with the Akaike information criterion (AIC). RCC with and without miR-21 up- and miR-126 downregulation differed significantly in synchronous metastatic status and CSS. Upregulation of miR-21 and downregulation of miR-126 were independently prognostic. A combined risk score (CRS) based on the expression of both miRs showed high sensitivity and specificity in predicting CSS and prediction was independent from any other clinico-pathological parameter. Association of CRS with CSS was successfully validated in a testing cohort containing patients with high and low risk for progressive disease. A combined expression level of miR-21 and miR-126 accurately predicted CSS in two independent RCC cohorts and seems feasible for clinical application in assessing prognosis

  16. Transcriptome Sequencing (RNAseq) Enables Utilization of Formalin-Fixed, Paraffin-Embedded Biopsies with Clear Cell Renal Cell Carcinoma for Exploration of Disease Biology and Biomarker Development.

    Science.gov (United States)

    Eikrem, Oystein; Beisland, Christian; Hjelle, Karin; Flatberg, Arnar; Scherer, Andreas; Landolt, Lea; Skogstrand, Trude; Leh, Sabine; Beisvag, Vidar; Marti, Hans-Peter

    2016-01-01

    Formalin-fixed, paraffin-embedded (FFPE) tissues are an underused resource for molecular analyses. This proof of concept study aimed to compare RNAseq results from FFPE biopsies with the corresponding RNAlater® (Qiagen, Germany) stored samples from clear cell renal cell carcinoma (ccRCC) patients to investigate feasibility of RNAseq in archival tissue. From each of 16 patients undergoing partial or full nephrectomy, four core biopsies, such as two specimens with ccRCC and two specimens of adjacent normal tissue, were obtained with a 16g needle. One normal and one ccRCC tissue specimen per patient was stored either in FFPE or RNAlater®. RNA sequencing libraries were generated applying the new Illumina TruSeq® Access library preparation protocol. Comparative analysis was done using voom/Limma R-package. The analysis of the FFPE and RNAlater® datasets yielded similar numbers of detected genes, differentially expressed transcripts and affected pathways. The FFPE and RNAlater datasets shared 80% (n = 1106) differentially expressed genes. The average expression and the log2 fold changes of these transcripts correlated with R2 = 0.97, and R2 = 0.96, respectively. Among transcripts with the highest fold changes in both datasets were carbonic anhydrase 9 (CA9), neuronal pentraxin-2 (NPTX2) and uromodulin (UMOD) that were confirmed by immunohistochemistry. IPA revealed the presence of gene signatures of cancer and nephrotoxicity, renal damage and immune response. To simulate the feasibility of clinical biomarker studies with FFPE samples, a classifier model was developed for the FFPE dataset: expression data for CA9 alone had an accuracy, specificity and sensitivity of 94%, respectively, and achieved similar performance in the RNAlater dataset. Transforming growth factor-ß1 (TGFB1)-regulated genes, epithelial to mesenchymal transition (EMT) and NOTCH signaling cascade may support novel therapeutic strategies. In conclusion, in this proof of concept study, RNAseq data

  17. Combined GSTM1-Null, GSTT1-Active, GSTA1 Low-Activity and GSTP1-Variant Genotype Is Associated with Increased Risk of Clear Cell Renal Cell Carcinoma

    Science.gov (United States)

    Coric, Vesna M.; Simic, Tatjana P.; Pekmezovic, Tatjana D.; Basta-Jovanovic, Gordana M.; Savic Radojevic, Ana R.; Radojevic-Skodric, Sanja M.; Matic, Marija G.; Dragicevic, Dejan P.; Radic, Tanja M.; Bogdanovic, Ljiljana M.; Dzamic, Zoran M.; Pljesa-Ercegovac, Marija S.

    2016-01-01

    The aim of this study was to evaluate specific glutathione S-transferase (GST) gene variants as determinants of risk in patients with clear cell renal cell carcinoma (cRCC), independently or simultaneously with established RCC risk factors, as well as to discern whether phenotype changes reflect genotype-associated risk. GSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 199 cRCC patients and 274 matched controls. Benzo(a)pyrene diolepoxide (BPDE)-DNA adducts were determined in DNA samples obtained from cRCC patients by ELISA method. Significant association between GST genotype and risk of cRCC development was found for the GSTM1-null and GSTP1-variant genotype (p = 0.02 and p<0.001, respectively). Furthermore, 22% of all recruited cRCC patients were carriers of combined GSTM1-null, GSTT1-active, GSTA1-low activity and GSTP1-variant genotype, exhibiting 9.32-fold elevated cRCC risk compared to the reference genotype combination (p = 0.04). Significant association between GST genotype and cRCC risk in smokers was found only for the GSTP1 genotype, while GSTM1-null/GSTP1-variant/GSTA1 low-activity genotype combination was present in 94% of smokers with cRCC, increasing the risk of cRCC up to 7.57 (p = 0.02). Furthermore, cRCC smokers with GSTM1-null genotype had significantly higher concentration of BPDE-DNA adducts in comparison with GSTM1-active cRCC smokers (p = 0.05). GSTM1, GSTT1, GSTA1 and GSTP1 polymorphisms might be associated with the risk of cRCC, with special emphasis on GSTM1-null and GSTP1-variant genotypes. Combined GSTM1-null, GSTT1-active, GSTA1 low activity and GSTP1-variant genotypes might be considered as “risk-carrying genotype combination” in cRCC. PMID:27500405

  18. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma

    DEFF Research Database (Denmark)

    Motzer, Robert J; Escudier, Bernard; McDermott, David F;

    2015-01-01

    %). CONCLUSIONS: Among patients with previously treated advanced renal-cell carcinoma, overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus. (Funded by Bristol-Myers Squibb; CheckMate 025 ClinicalTrials.gov number, NCT01668784.).......BACKGROUND: Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus...... in patients with renal-cell carcinoma who had received previous treatment. METHODS: A total of 821 patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens of antiangiogenic therapy were randomly assigned (in a 1:1 ratio) to...

  19. Multilocular Cystic Renal Cell Carcinoma: A Rare Entity with Review of Literature

    OpenAIRE

    Wahal, Shailja Puri; Mardi, Kavita

    2014-01-01

    Multilocular cystic renal cell carcinoma (MCRCC) represents a rare variant of clear cell renal cell carcinoma (RCC). MCRCC has been recognized as a separate subtype of RCC in the 2004 World Health Organization (WHO) classification of adult renal tumors. MCRCC is diagnosed on the basis of strict histological criteria according to 2004 WHO classification. The chief differentials diagnosis to be considered include cystic nephroma, cystic clear cell carcinoma, clear cell papillary renal cell carc...

  20. TCEB1-mutated Renal Cell Carcinoma: A Distinct Genomic and Morphologic Subtype

    OpenAIRE

    Hakimi, A. Ari; Tickoo, Satish K; Jacobsen, Anders; Sarungbam, Judy; Sfakianos, John P.; Sato, Yusuke; Morikawa, Teppei; Kume, Haruki; Fukayama, Masashi; Homma, Yukio; Chen, Ying-bei; Sankin, Alexander; Mano, Roy; Coleman, Jonathan A.; Russo, Paul

    2015-01-01

    Integrated sequencing analysis identified a group of tumors among clear cell renal cell carcinomas characterized by hotspot mutations in TCEB1 (a gene that contributes to the VHL complex to ubiquitinate hypoxia inducible factor). We analyzed 11 tumors from two distinct cohorts with TCEB1 mutations along with an expanded cohort to assess whether these should be considered an entity distinct from clear cell renal cell carcinoma and clear cell papillary renal cell carcinoma. All tumors were char...

  1. Simultaneous removal of a tumour of the right atrium and inferior vena cava and coronary bypass-grafting in a patient with recurrent clear renal cell carcinoma

    Science.gov (United States)

    Pietrzyk, Edward; Głuszek, Stanisław; Michta, Kamil; Kot, Marta; Wożakowska-Kapłon, Beata

    2015-01-01

    Metastatic cardiac tumours are the most common malignant cardiac tumours. In the early stages they are usually asymptomatic, but their consequences can be very serious, and the prognosis is poor. We present a patient with recurrent renal cell carcinoma as a tumour of the right atrium and the vena cava inferior in whom cancerous masses were removed with simultaneously coronary artery bypass-grafting. PMID:26855653

  2. Renal cell carcinoma: Evolving and emerging subtypes.

    Science.gov (United States)

    Crumley, Suzanne M; Divatia, Mukul; Truong, Luan; Shen, Steven; Ayala, Alberto G; Ro, Jae Y

    2013-12-16

    Our knowledge of renal cell carcinoma (RCC) is rapidly expanding. For those who diagnose and treat RCC, it is important to understand the new developments. In recent years, many new renal tumors have been described and defined, and our understanding of the biology and clinical correlates of these tumors is changing. Evolving concepts in Xp11 translocation carcinoma, mucinous tubular and spindle cell carcinoma, multilocular cystic clear cell RCC, and carcinoma associated with neuroblastoma are addressed within this review. Tubulocystic carcinoma, thyroid-like follicular carcinoma of kidney, acquired cystic disease-associated RCC, and clear cell papillary RCC are also described. Finally, candidate entities, including RCC with t(6;11) translocation, hybrid oncocytoma/chromophobe RCC, hereditary leiomyomatosis and RCC syndrome, and renal angiomyoadenomatous tumor are reviewed. Knowledge of these new entities is important for diagnosis, treatment and subsequent prognosis. This review provides a targeted summary of new developments in RCC. PMID:24364021

  3. Isolated abdominal wall metastasis from renal cell carcinoma: Unusual presentation

    OpenAIRE

    Suresh Kumar; Pramod Kumar Sharma; Malay Kumar Bera

    2015-01-01

    Fifty-seven-year-old gentleman, who was a known victim of left-sided clear cell renal cell carcinoma (RCC), presented with isolated huge parietal swelling in left anterolateral aspect of abdomen. He had undergone open left radical nephrectomy 2 years back. Parietal swelling was widely excised and histopathology revealed clear cell RCC, nuclear Fuhrman grade 2.

  4. CONVENTIONAL RENAL CELL CARCINOMA WITH GRANULOMATOUS REACTION

    Directory of Open Access Journals (Sweden)

    Srinivas

    2014-09-01

    Full Text Available : Granulomatous inflammation is a distinctive pattern of chronic inflammatory reaction characterized by microscopic aggregation of activated macrophages which often develop epithelioid appearance and multinucleate giant cells. Granulomas are encountered in limited number of infectious and some non-infectious conditions. Granulomas have been described within the stroma of malignancies like carcinomas of the breast and colon, seminoma and Hodgkin’s lymphoma, where they represent T-cell-mediated reaction of the tumor stroma to antigens expressed by the tumor. Granulomatous reaction in association with renal cell carcinoma (RCC is uncommon, with only few published reports in the literature. We describe a case of conventional (clear cell RCC associated with epithelioid cell granulomas within the tumor parenchyma.

  5. Sunitinib benefits patients with renal cell carcinoma

    Science.gov (United States)

    Findings from clinical trial patients with metastatic renal cell carcinoma, a common kidney cancer, show they did not have accelerated tumor growth after treatment with sunitinib, in contrast to some study results in animals.

  6. Aldesleukin in advanced renal cell carcinoma.

    Science.gov (United States)

    Schmidinger, Manuela; Hejna, Michael; Zielinski, Christoph C

    2004-12-01

    Renal cell carcinoma accounts for 2-3% of all malignancies. The most common subtype [85%] is the clear cell variant. A total of 30% of patients present with metastatic disease at diagnosis and another 30-40% will develop metastases during the course of the disease. Conventional cancer treatment is not effective, but cytokines including recombinant interleukin-2 (aldesleukin) have demonstrated clinical activity of various degrees. This drug profile provides a review of the literature on studies using aldesleukin in patients with metastatic renal cell carcinoma. Aldesleukin has been used in different dose schedules applying various administration routes, as either monotherapy or in combination with other cytokines, chemotherapy, endocrine treatment and adoptive cellular immunotherapy. Although a large number of randomized trials have been performed with different treatment strategies, it still remains uncertain whether the dose or combination of aldesleukin with other agents substantially influence treatment outcome. It appears that factors other than those that are treatment related are responsible for the course of the disease. PMID:15606326

  7. Isolated pleural metastases from renal cell carcionoma

    DEFF Research Database (Denmark)

    Eckardt, Jens; Ladegaard, Lars; Licht, Peter Bjorn

    2011-01-01

    A 71-year-old female was referred with three right-sided intrathoracic tumours. In 2003, she underwent radical left nephrectomy for renal cell cancer (RCC) clinical stage 1. She was since followed at her local hospital with annual computed tomography (CT)-scans during the first five years and did....... Histology demonstrated metastases from RCC which apparently can reach the parietal pleura without lung metastases. Keywords: Pleural metastasis; Renal cell cancer....

  8. Renal cell cancer without a renal primary

    OpenAIRE

    Cumani B; Bratcher J; Wang W.; Wayne M.; Kasmin F; Cooperman A

    2010-01-01

    Abstract Renal cell carcinoma has been increasing in incidence over the past two decades. Men are affected more than women and metastatic disease at presentation occurs in up to one third of patients. Metastasis can occur to virtually any organ, and involvement of multiple organs is not uncommon. To date, no reports have been found of metastatic disease without a renal primary. We present a case of renal cell cancer initially presenting as a subcutaneous mass with subsequent pancreatic and pa...

  9. Hereditary papillary renal cell carcinoma primarily diagnosed in a cervical lymph node: a case report of a 30-year-old woman with multiple metastases

    OpenAIRE

    Behnes Carl Ludwig; Schlegel Christina; Shoukier Moneef; Magiera Isabella; Henschke Frank; Schwarz Alexander; Bremmer Felix; Loertzer Hagen

    2013-01-01

    Abstract Background Papillary renal cell carcinoma is a rare cancer. Some cases can be attributed to individuals with hereditary renal cell carcinomas usually consisting of the clear cell subtype. In addition, two syndromes with hereditary papillary renal cell carcinoma have been described. One is the hereditary leiomyomatosis and renal cell carcinoma, which is characterized by cutaneous and uterine leiomyomas and renal cell carcinoma mostly consisting of the papillary renal cell carcinoma ty...

  10. Multidisciplinary management of clear-cell renal cell carcinoma in Africa and the Middle East: current practice and recommendations for improvement

    Directory of Open Access Journals (Sweden)

    Zekri J

    2015-07-01

    Full Text Available Jamal Zekri,1 Lydia M Dreosti,2 Marwan Ghosn,3 Emad Hamada,4 Mohamed Jaloudi,5 Ola Khorshid,6 Blaha Larbaoui7 1College of Medicine, King Faisal Specialist Hospital and Research Centre, Alfaisal University, Jeddah, Saudi Arabia; 2Department of Medical Oncology, University of Pretoria, Pretoria, South Africa; 3Faculty of Medicine Hematology, Oncology Department, Saint Joseph University, Beirut, Lebanon; 4Faculty of Medicine, Cairo University, Kasr Alainy, Cairo, Egypt; 5Oncology Hematology Department, Tawam Hospital, Al Ain, Abu Dhabi, United Arab Emirates; 6National Cancer Institute, Cairo University, Kasr El Ainy, Cairo, Egypt; 7Oncology Service, Université Djillali Liabés, Sidi Bel Abbés, Algeria Abstract: The management of renal cell carcinoma (RCC has evolved considerably in recent years. This report represents the consensus of 22 relevant medical specialists from Africa and the Middle East region engaged in the management of RCC. Partial or radical nephrectomy is the standard of care for most patients with localized RCC. It is essential that patients are followed up appropriately after surgery to enable local and distant relapses to be identified and treated promptly. The treatment of advanced/metastatic disease has changed dramatically with the introduction of targeted therapies. Follow-up of these patients enables therapy optimization and assessment of response to treatment. There was universal agreement on the importance of management of RCC by a multidisciplinary team supported by a multidisciplinary tumor board. Barriers hindering this approach were identified. These included lack of awareness of the benefits of multidisciplinary team role, poor communication among relevant disciplines, time constraints, and specifics of private practice. Other challenges include shortage of expert specialists as urologists and oncologists and lack of local management guidelines in some countries. Solutions were proposed and discussed. Medical

  11. A Novel Protein Is Lower Expressed in Renal Cell Carcinoma

    OpenAIRE

    Ruili Guan; Yongde Xu; Hongen Lei; Zhezhu Gao; Zhongcheng Xin; Yinglu Guo

    2014-01-01

    Engrailed-2 (EN2) has been identified as a candidate oncogene in breast cancer and prostate cancer. It is usually recognized as a mainly nuclear staining in the cells. However, recent studies showed a cytoplasmic staining occurred in prostate cancer, bladder cancer and clear cell renal cell carcinoma. The inconsistency makes us confused. To clarify the localization and expression of EN2 in renal cell carcinoma, anti-EN2 antibody (ab28731) and anti-EN2 antibody (MAB2600) were used for immunohi...

  12. 11C-Acetate PET imaging for renal cell carcinoma

    International Nuclear Information System (INIS)

    In this study, we investigated the effectiveness of positron emission tomography (PET) with 11C-acetate (AC) for evaluation of renal cell carcinoma. Enrolled in the study were 20 patients with suspected renal tumour, one of whom had three renal lesions. In all, 22 renal lesions were evaluated. Following administration of 350 MBq (10 mCi) of AC, whole-body PET images were obtained. Based on these PET findings, kidney lesions were scored as positive or negative. The PET results were correlated with the CT findings and histological diagnosis after surgery. In 18 patients, 20 tumours were diagnosed as renal cell carcinoma. Lesions in the remaining two patients were diagnosed as complicated cyst without malignant tissue. Of the 20 renal cell carcinomas. 14 (70%) showed positive AC PET findings; 6 were negative. The two patients with complicated cyst had negative AC PET findings. Of the 20 renal cell carcinomas, 19 were clear-cell carcinoma and 1 was a papillary cell carcinoma. This papillary cell carcinoma showed high AC uptake. AC demonstrates marked uptake in renal cell carcinoma. These preliminary data show that AC is a possible PET tracer for detection of renal cancer. (orig.)

  13. MicroRNA-187, down-regulated in clear cell renal cell carcinoma and associated with lower survival, inhibits cell growth and migration though targeting B7-H3

    International Nuclear Information System (INIS)

    Highlights: •miR-187 is down-regulated in clear cell renal cell carcinoma (ccRCC). •Down-regulation of miR-187 is associated with poor outcomes in patients with ccRCC. •miR-187 inhibits cell growth and migration though targeting B7-H3 in ccRCC. -- Abstract: Aberrantly expressed microRNAs (miRNAs) are frequently associated with the aggressive malignant behavior of human cancers, including clear cell renal cell carcinoma (ccRCC). Based on the preliminary deep sequencing data, we hypothesized that miR-187 may play an important role in ccRCC development. In this study, we found that miR-187 was down-regulated in both tumor tissue and plasma of ccRCC patients. Lower miR-187 expression levels were associated with higher tumor grade and stage. All patients with high miR-187 expression survived 5 years, while with low miR-187 expression, only 42% survived. Suppressed in vitro proliferation, inhibited in vivo tumor growth, and decreased motility were observed in cells treated with the miR-187 expression vector. Further studies showed that B7 homolog 3 (B7-H3) is a direct target of miR-187. Over-expression of miR-187 decreased B7-H3 mRNA level and repressed B7-H3-3′-UTR reporter activity. Knockdown of B7-H3 using siRNA resulted in similar phenotype changes as that observed for overexpression of miR-187. Our data suggest that miR-187 is emerging as a novel player in the disease state of ccRCC. miR-187 plays a tumor suppressor role in ccRCC

  14. MicroRNA-187, down-regulated in clear cell renal cell carcinoma and associated with lower survival, inhibits cell growth and migration though targeting B7-H3

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Jun [Foshan Maternal and Child Health Care Hospital, Foshan (China); Lei, Ting [Zhongshan People’s Hospital, Zhongshan (China); Xu, Congjie [Department of Urology, Pepole’s Hospital of Hainan Province, Haikou (China); Li, Huan; Ma, Wenmin; Yang, Yunxia; Fan, Shuming [Foshan Maternal and Child Health Care Hospital, Foshan (China); Liu, Yuchen, E-mail: s_ycliu1@stu.edu.cn [Anhui Medical University, Hefei (China)

    2013-08-23

    Highlights: •miR-187 is down-regulated in clear cell renal cell carcinoma (ccRCC). •Down-regulation of miR-187 is associated with poor outcomes in patients with ccRCC. •miR-187 inhibits cell growth and migration though targeting B7-H3 in ccRCC. -- Abstract: Aberrantly expressed microRNAs (miRNAs) are frequently associated with the aggressive malignant behavior of human cancers, including clear cell renal cell carcinoma (ccRCC). Based on the preliminary deep sequencing data, we hypothesized that miR-187 may play an important role in ccRCC development. In this study, we found that miR-187 was down-regulated in both tumor tissue and plasma of ccRCC patients. Lower miR-187 expression levels were associated with higher tumor grade and stage. All patients with high miR-187 expression survived 5 years, while with low miR-187 expression, only 42% survived. Suppressed in vitro proliferation, inhibited in vivo tumor growth, and decreased motility were observed in cells treated with the miR-187 expression vector. Further studies showed that B7 homolog 3 (B7-H3) is a direct target of miR-187. Over-expression of miR-187 decreased B7-H3 mRNA level and repressed B7-H3-3′-UTR reporter activity. Knockdown of B7-H3 using siRNA resulted in similar phenotype changes as that observed for overexpression of miR-187. Our data suggest that miR-187 is emerging as a novel player in the disease state of ccRCC. miR-187 plays a tumor suppressor role in ccRCC.

  15. Sternal metastasis as an initial presentation of renal cell carcinoma: a case report

    OpenAIRE

    Batista, Raquel Ribeiro; Marchiori, Edson; Takayassu, Tatiana Chinem; Cabral, Fernanda Caseira; Cabral, Rafael Ferracini; Zanetti, Gláucia

    2009-01-01

    Renal cell carcinoma accounts for 85% of all solid renal tumors in adults. Nearly one quarter of patients has distant metastasis at presentation while another 50% develop metastasis during follow-up. A small percentage of these are solitary metastasis. We report here a case of solitary bone sternal metastasis as an initial presentation of clear-cell renal cell carcinoma in a 56-year-old woman. The prognosis for patients with metastasized renal cell carcinoma is poor; treatment of metastasis i...

  16. Imaging of renal cell cancer with radiolabelled octreotide

    International Nuclear Information System (INIS)

    Recently the presence of somatostatin receptors on human renal cell carcinomas has been demonstrated by autoradiographic techniques on surgically removed kidneys. In a prospective study we evaluated, by means of 111In-labelled octreotide scintigraphy, the in vivo tumour imaging in a group of patients with biopsy proven renal cell carcinomas at different tumour stages. Seven patients were studied. In three of them, (43%) pathological tracer accumulation was demonstrated. In these patients, 20 out of 23 known tumour localizations were clearly visualized. Tracer uptake could be inhibited by prior administration of cold octreotide. We conclude that 111In-ocreotide scintigraphy can be used to demonstrate, in vivo, metastatic renal cell carcinoma. (author)

  17. Case Report: Multifocal biphasic squamoid alveolar renal cell carcinoma [version 1; referees: 2 approved, 1 approved with reservations

    OpenAIRE

    Jose Ignacio Lopez

    2016-01-01

    A multifocal biphasic squamoid alveolar renal cell carcinoma in a 68-year-old man is reported. Four different peripheral tumor nodules were identified on gross examination. A fifth central tumor corresponded to a conventional clear cell renal cell carcinoma. Biphasic squamoid alveolar renal cell carcinoma is a rare tumor that has been very recently characterized as a distinct histotype within the spectrum of papillary renal cell carcinoma. Immunostaining with cyclin D1 seems to be specific of...

  18. Local thermal ablation of renal cell carcinoma

    International Nuclear Information System (INIS)

    Purpose: With evolving local thermal ablation technology, the clinical application of thermal ablation has been actively investigated in the treatment for renal cell carcinoma. We review the evolution and current status of radiofrequency ablation and microwave ablation for renal cell carcinoma. Materials and methods: All articles published in English on radiofrequency ablation or microwave ablation as a treatment for renal cell carcinoma were identified with a MEDLINE® and PubMed® search from 1990 to 2010. Results: Local thermal ablation has several advantages, including keeping more normal renal units, relatively simple operation, easy tolerance, fewer complications, a shorter hospitalization and convalescence period. Long-term data has determined radiofrequency ablation is responsible for poor surgical candidates with renal cell carcinoma, however, tumor size, location and shape might affect the efficacy of radiofrequency ablation. Microwave ablation can induce large ablation volumes and yield good local tumor control. Associated complications appear to be low. Conclusions: Local ablative approaches seem to represent an attractive alternative to extirpative surgery for the treatment of small renal neoplasms in select patients. Potential developments include concepts to improve the accuracy and effectiveness of thermal ablation by improving the guiding, monitoring capabilities and detection capacity of multi-center lesions to provide at least equivalent cancer control to conventional surgery.

  19. Evaluating hemorrhage in renal cell carcinoma using susceptibility weighted imaging.

    Directory of Open Access Journals (Sweden)

    Wei Xing

    Full Text Available BACKGROUND: Intratumoral hemorrhage is a frequent occurrence in renal cell carcinoma and is an indicator of tumor subtype. We hypothesize that susceptibility weighted imaging (SWI is sensitive to hemorrhage in renal cell carcinoma and can give a more diagnostic image when compared to conventional imaging techniques. MATERIALS AND METHODS: A retrospective review of 32 patients with clear cell renal cell carcinoma was evaluated. All patients underwent magnetic resonance imaging (MRI and 22 out of 32 patients also underwent a computed tomography (CT scan. Hemorrhage was classified into 3 different categories according to shape and distribution. Histopathology was obtained from all masses by radical nephrectomy. The ability to detect the presence of hemorrhage using CT, non-contrast conventional MRI and SWI was evaluated, and the patterns of hemorrhage were compared. RESULTS: Using pathologic results as the gold standard, the sensitivities of non-contrast conventional MRI, SWI and CT in detecting hemorrhage in clear cell renal cell carcinoma were 65.6%, 100% and 22.7%, respectively. Accuracy of non-contrast conventional MRI and SWI in evaluating hemorrhagic patterns were 31.3% and 100%, respectively. CONCLUSION: These results demonstrate that SWI can better reveal hemorrhage and characterize the pattern more accurately than either non-contrast conventional MRI or CT. This suggests that SWI is the technique of choice for detecting hemorrhagic lesions in patients with renal cancer.

  20. Risk Factors for Renal Cell Cancer in a Japanese Population

    OpenAIRE

    Washio, Masakazu; Mori, Mitsuru

    2009-01-01

    The incidence of renal cell cancer has been increasing worldwide. Although the incidence of renal cell cancer in Japan is lower than the rates in the other industrialized countries, there is no doubt that it is increasing. In this paper, we would like to introduce the result of our studies, which evaluate the risk factors for renal cell cancer in Japan. Hypertension, diabetes mellitus, kidney diseases, fondness for fatty food and black tea showed an increased risk of renal cell carcinoma whil...

  1. A familial case of renal cell carcinoma and a t(2;3) chromosome translocation

    NARCIS (Netherlands)

    Koolen, MI; van der Meyden, PM; Bodmer, D; Eleveld, M; van der Looij, E; Brunner, H; Smits, A; Smeets, D; van Kessel, AG

    1998-01-01

    Cytogenetic analysis was performed on peripheral blood lymphocytes of members of a family with inherited renal cell cancer. Four family members in three generations developed multiple/bilateral renal cell carcinomas of the clear cell type. In one additional case a bladder carcinoma was diagnosed. In

  2. Molecular characterization of clear cell renal cell carcinoma identifies CSNK2A1, SPP1 and DEFB1 as promising novel prognostic markers

    DEFF Research Database (Denmark)

    Rabjerg, Maj; Bjerregaard, Henriette; Halekoh, Ulrich; Jensen, Boye L; Walter, Steen; Marcussen, Niels

    2016-01-01

    The prognosis associated with clear cell renal carcinoma (ccRCC) can vary widely and novel molecular prognostic markers are needed to assess prognosis at an earlier stage. Several gene products have been investigated for this purpose, but none of them have been implemented in clinical practice...

  3. A Novel Protein Is Lower Expressed in Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Ruili Guan

    2014-04-01

    Full Text Available Engrailed-2 (EN2 has been identified as a candidate oncogene in breast cancer and prostate cancer. It is usually recognized as a mainly nuclear staining in the cells. However, recent studies showed a cytoplasmic staining occurred in prostate cancer, bladder cancer and clear cell renal cell carcinoma. The inconsistency makes us confused. To clarify the localization and expression of EN2 in renal cell carcinoma, anti-EN2 antibody (ab28731 and anti-EN2 antibody (MAB2600 were used for immunohistochemistry (IHC respectively. Interestingly, we found that EN2 detected by ab28731 was mainly presented in cytoplasm while EN2 detected by MAB2600 was mainly presented in nucleus. To further investigate the different patterns observed above, lysates from full-length EN2 over expression in HEK293T cells were used to identify which antibody the EN2 molecule bound by western blot. Results showed ab28731 did not react with the lysates. For this reason, the novel specific protein detected by ab28731 was not the EN2 molecule and was named nonEN2. Then using the renal carcinoma tissue microarray and renal tissues, we found that the protein expression levels of nonEN2 in kidney tumor tissues was significantly lower than that in kidney normal tissues (p < 0.05, so was in renal cell lines. Taken together, nonEN2 is lower expressed and may play an important role in renal cell carcinoma.

  4. Osteoblastic bone metastases from renal cell carcinoma

    International Nuclear Information System (INIS)

    RCC accounts for only 2–3% of all cancers. Due to its’ non-specific symptoms disease is often diagnosed in advanced stage. Disseminated RCC frequently produces bone metastases that are almost always highly destructive, hyper vascularized and purely osteolytic. In this article we describe a case of a 71-year old male patient with disseminated osteoblastic bone metastases from renal cell carcinoma (RCC), and present a short review of published literature reporting cases of osteoblastic bone metastases from RCC. Our patient presented with thoracic pain aggravated by movement. He was diagnosed with predominantly osteoblastic bone metastases in the skeleton of thoracic and lumbar vertebra along with metastases in iliac bones, ribs, humerus and clavicles. Initially, origin of bone metastases was unknown, but later a small tumor in patient’s right kidney was identified. Microscopic evaluation of the open bone biopsy showed clear cell RCC with sarcomatoid differentiation. Although, due to its’ rarity, RCC is not included in the primary differential diagnosis in patients with osteoblastic metastases, such rare cases suggest that RCC may be considered in the diagnosis when there no other primary tumor is found

  5. Diagnostic importance of CT in early stage renal cell carcinoma

    International Nuclear Information System (INIS)

    Our experience of finding a small renal cell carcinoma by CT suggested the diagnostic importance of CT in the early stage of the tumor. The patient was a forty-year-old woman who had suffered several times from pyelonephritis. She consulted us for detailed examination. IVP showed only slight deformity like a calceal diverticulum at the upper. pole of the left kidney. Ultrasonic tomography failed to expose the region. Enhanced CT revealed a small space occupying lesion like a simple renal cyst at the region, though plain CT revealed no abnormal findings. From the comparison of these two CT, she was diagnosed to have renal cell carcinoma which was confirmed by renal arteriography. Subsequently, transabdominal left nephrectomy was performed. Pathological diagnosis was renal cell carcinoma (clear cell type). The tumor size was very small, 1.5 cm in diameter. Comparison of plain and enhanced CT were considered important to diagnose a small tumor, and CT is now the most useful examination to detect early stage renal cell carcinoma. (author)

  6. Imaging characteristics of papillary renal cell carcinoma by computed tomography scan and magnetic resonance imaging

    International Nuclear Information System (INIS)

    The aim of this study was to analyse the differences in the patterns between clear and papillary renal cell carcinomas using magnetic resonance imaging (MRI) and dual-phase helical computed tomography (CT). We examined seven patients with papillary renal cell carcinoma, and six with clear cell carcinoma. The highest attenuation value of tumors in the corticomedullary phase (CMP) and the excretory phase (EP) was measured using the observer-defined region of interest (ROI). MRI consisted of T1-weighted and T2-weighted spin-echo imaging. All five tumors except for one with papillary renal cell carcinoma showed homogenous hypointensity, but all six tumors with clear cell carcinoma showed heterogeneous hyperintensity on their T2-weighted images. In the CMP, the mean CT numbers of the papillary renal cell carcinomas were significantly lower than those of the clear cell carcinomas. The mean enhancement of the papillary renal cell carcinomas in the CMP and the EP was significantly lower than that of the clear renal cell carcinomas. The mean CT numbers of the clear cell carcinomas in the CMP were markedly increased from those on the unenhanced CT; those in the EP were decreased gradually. But the mean CT numbers of the papillary renal cell carcinomas in the EP were still slightly more increased than those in the CMP. The enhancement patterns of the papillary renal cell carcinomas in the CMP and the EP were homogenous, but those of the clear cell carcinomas were heterogeneous. We can speculate the differential diagnosis from clear to papillary renal cell carcinoma using MRI and dual-phase helical CT. (author)

  7. Sorafenib in the management of metastatic renal cell carcinoma

    OpenAIRE

    Guevremont, C.; C. Jeldres; Perrotte, P.; Karakiewicz, P.I.

    2009-01-01

    Purpose Sorafenib represents one of the two standards of care for patients with metastatic renal cell carcinoma (mrcc). In the present review, we provide information regarding the use of sorafenib in first and second lines. We also describe results for dose escalation strategies. Finally, we provide data addressing the efficacy of sorafenib in patients with mrcc of non-clear-cell histology. Recent Findings Sorafenib is a valid first-line agent. Sorafenib response rates and toxicity are not af...

  8. Delayed recurrence of renal cell carcinoma presenting as a haemorrhoid

    OpenAIRE

    Davies, James R.L.; Smith, Gavin; Cornaby, Andrew J.; Thomas, Teresa; Lamparelli, Michael J.

    2015-01-01

    Metastatic non-colorectal cancer of the anal canal is a rare entity. To date, only four cases have been described in the literature. We present a 76-year-old man who was referred with an unusual perianal lesion. He had a history of renal cell carcinoma 7 years previously. Histologically, the lesion revealed clear cell carcinoma in keeping with metastasis. To our knowledge, this is only the second time a renal carcinoma metastasis to the anal canal has been identified.

  9. Metastatic Renal Cell Carcinoma in the Sinonasal Region

    OpenAIRE

    Jyothi A Raj; Mahantachar, V; Rajaram, T

    2013-01-01

    Sinonasal region is an exceptional site for metastatic tumors. Renal cell carcinoma is known to metastasise to the most unusual sites, the sinonasal region being one of them. Clear cell carcinoma is its most common histologic variant. A sixty year old male presented with epistaxis and nasal obstruction. Clinical examination and CT scan revealed a vascular tumor in the right nasal cavity and maxillary sinus. The tumor was resected and sent for histopathological examination. A diagnosis of meta...

  10. Renal Preservation Therapy for Renal Cell Carcinoma

    OpenAIRE

    Yichun Chiu; Allen W. Chiu

    2012-01-01

    Renal preservation therapy has been a promising concept for the treatment of localized renal cell carcinoma (RCC) for 20 years. Nowadays partial nephrectomy (PN) is well accepted to treat the localized RCC and the oncological control is proved to be the same as the radical nephrectomy (RN). Under the result of well oncological control, minimal invasive method gains more popularity than the open PN, like laparoscopic partial nephrectomy (LPN) and robot assisted laparoscopic partial nephrectomy...

  11. Targeted therapy for metastatic renal cell carcinoma

    OpenAIRE

    Patel, P H; Chaganti, R.S.K.; Motzer, R J

    2006-01-01

    Metastatic renal cell carcinoma (RCC) has historically been refractory to cytotoxic and hormonal agents; only interleukin 2 and interferon alpha provide response in a minority of patients. We reviewed RCC biology and explored the ways in which this understanding led to development of novel, effective targeted therapies. Small molecule tyrosine kinase inhibitors, monoclonal antibodies and novel agents are all being studied, and phase II studies show promising activity of sunitinib, sorafenib a...

  12. Sequential Therapy in Metastatic Renal Cell Carcinoma

    OpenAIRE

    Hirsch, Bradford R.; Burke, John M.; Manish Agrawal; Hauke, Ralph J.; Hutson, Thomas E.; Gury Doshi; Mark T Fleming; Vogelzang, Nicholas J.

    2016-01-01

    The treatment of metastatic renal cell carcinoma (mRCC) has changed dramatically in the past decade. As the number of available agents, and related volume of research, has grown, it is increasingly complex to know how to optimally treat patients. The authors are practicing medical oncologists at the US Oncology Network, the largest community-based network of oncology providers in the country, and represent the leadership of the Network's Genitourinary Research Committee. We outline our though...

  13. Systemic adjuvant therapies in renal cell carcinoma

    OpenAIRE

    Sebastiano Buti; Melissa Bersanelli; Maddalena Donini; Andrea Ardizzoni

    2012-01-01

    Renal cell carcinoma (RCC) is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to d...

  14. Renal Cell Cancer Diagnosed at Endoscopy

    OpenAIRE

    Muhammed Hameed Thoufeeq; Nima Maleki; Naeem Jagirdar; Bjorn Rembacken; Jason Jennings

    2012-01-01

    A 59-year-old lady was referred for an open-access endoscopy with a history of dyspepsia. The endoscopy showed a 5 mm sessile nodule in the fundus of the stomach. The histology report suggested that this represented a metastatic deposit from renal cell carcinoma (RCC). Following this, a computerised tomography (CT) of the abdomen showed an 18 × 15 cm RCC. Here we provide a short review on gastric metastases.

  15. Hereditary leiomyomatosis and renal cell carcinoma

    OpenAIRE

    Schmidt LS; Linehan WM

    2014-01-01

    Laura S Schmidt,1,2 W Marston Linehan11Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; 2Basic Science Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USAAbstract: Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an autosomal-dominant hereditary syndrome, which is caused by germline mutations in the FH gene that encodes the tricarboxylic ac...

  16. Thyroid metastases in renal cell cancer: two case reports

    International Nuclear Information System (INIS)

    Non-thyroid cancers rarely metastasize to the thyroid gland. Metastases can be divided into those with clinical expression and those identified at necropsy. Symptom producing thyroid metastases are usually due to a primary renal cell cancer. We report two cases of thyroid metastasis of a clear cell renal carcinoma. In the first case, an 82-year-old woman presented with an enlarged thyroid metastasis and identification of recurrent renal cell carcinoma which had been treated by radiotherapy 24 years earlier. After radiotherapy for a concomitant pulmonary metastasis, the patient is in good general health with no signs of recurrence. In the second case, increased thyroid volume led to signs of compression in a 71-year-old-man. The pathology report after left lobular thyroidectomy suggested trabecular adenoma or metastasis of a clear-cell primary tumour. Abdominal CT-scan revealed a 3.5 cm tumour found to be a clear-cell renal carcinoma at nephrectomy. Another osteolytic metastasis to the femur was also observed three months after surgery. The patient is in good health 15 months after the initial diagnosis. The significance of thyroid metastasis of renal cell carcinoma would vary according to the different cases reported in the literature with survival ranging from 32 months to 3-7 years after surgical exeresis. Prognosis would thus not appear to be as poor as for thyroid metastasis from other primary tumours. (authors). 24 refs

  17. Percutaneous Cryoablation for Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Tsitskari Maria

    2015-06-01

    Full Text Available Renal cell carcinoma (RCC is the most common type of kidney cancer in adults. Nephron sparing resection (partial nephrectomy has been the “gold standard” for the treatment of resectable disease. With the widespread use of cross sectional imaging techniques, more cases of renal cell cancers are detected at an early stage, i.e. stage 1A or 1B.  This has provided an impetus for expanding the nephron sparing options and especially, percutaneous ablative techniques.  Percutaneous ablation for RCC is now performed as a standard therapeutic nephron-sparing option in patients who are poor candidates for resection or when there is a need to preserve renal function due to comorbid conditions, multiple renal cell carcinomas, and/or heritable renal cancer syndromes. During the last few years, percutaneous cryoablation has been gaining acceptance as a curative treatment option for small renal cancers. Clinical studies to date indicate that cryoablation is a safe and effective therapeutic method with acceptable short and long term outcomes and with a low risk, in the appropriate setting.  In addition it seems to offer some advantages over radio frequency ablation (RFA and other thermal ablation techniques for renal masses.

  18. Molecular characterization of clear cell renal cell carcinoma identifies CSNK2A1, SPP1 and DEFB1 as promising novel prognostic markers.

    Science.gov (United States)

    Rabjerg, Maj; Bjerregaard, Henriette; Halekoh, Ulrich; Jensen, Boye L; Walter, Steen; Marcussen, Niels

    2016-05-01

    The prognosis associated with clear cell renal carcinoma (ccRCC) can vary widely and novel molecular prognostic markers are needed to assess prognosis at an earlier stage. Several gene products have been investigated for this purpose, but none of them have been implemented in clinical practice. Here we hypothesized that we, using TaqMan(®) Array, could identify superior prognostic messenger RNA (mRNA)s in long-term follow-up. Messenger RNA level of 19 candidate genes was investigated in 97 patients with ccRCC. Three genes impacted significantly on prognosis in both univariate and multivariate analysis. In univariate analysis, CSNK2A1 was a strong indicator of a poor overall survival (OS) (HR = 5.01, p renal cancer development. PMID:26876164

  19. CT staging of renal cell carcinoma

    International Nuclear Information System (INIS)

    Objective: To assess the usefulness of computerized tomography (CT) in the characterization of renal masses, in order to stage them, determine their prognosis and their appropriate clinical and/or surgical management. Material and Methods: Between 1988 and 2001, we selected 63 patients with renal tumors that had been examined by pathology. Patient's ages ranged from 16 to 88 years (25 women, 38 men). The studies were performed with a sequential helical CT, using 5 mm thickness sections every 5mm evaluating the cortico medullar and nephrographic phases. Renal tumors were characterized and staged without any knowledge about the pathological findings; subsequently the tomographic characteristics were compared to such findings. The following characteristics were evaluated: 1) mixed solid-cystic nature; 2) size; 3) borders; 4) enhancement; 5) necrosis; 6) hemorrhage; 7) central scar; 8) presence of fat; 9) collecting system; 10) capsular invasion; 11) perirenal fat invasion; 12) vessels; 13) Gerota's fascia; 14) lymph nodes; and 15) local and/or distant metastases. Results: Of the 63 tumors, 2 were complicated cysts; of the 61 remaining tumors, 10 were angiomyolipomas, 1 was a renal lymphoma, 1 was a focal xantogranulomatose pyelonephritis, 1 was a metanephric adenoma, 3 papillary renal cell carcinoma (RCC), 4 transitional cell tumors, 4 oncocytomas, 37 clear cell renal carcinoma. The CT could correctly characterize the 2 cystic tumors as such, as well as the 9 angiomyolipomas and the 4 transitional cell tumors. The 48 other tumors (1 angiomyolipoma, 1 lymphoma, 1 focal xantogranulomatose pyelonephritis, 1 metanephric adenoma, 3 papillary RCC, 4 oncocytomas, and 37 cell renal carcinomas) remaining were characterized as renal adenocarcinomas and CT staged. Conclusion: CT is a useful method to characterize renal masses since it determines their solid-cystic or fatty structure; aiding in many cases to define a surgical treatment. For the CT staging of renal tumors, the

  20. Renal cell carcinoma in a setting of chronic lithium toxicity

    OpenAIRE

    Zardawi, Ibrahim; Nagonkar, Santoshi; Patel, Purvish

    2013-01-01

    Patient: Female, 72 Final Diagnosis: Renal cell carcinoma Symptoms: — Medication: — Clinical Procedure: — Specialty: Oncology Objective: Challenging differential diagnosis Background: Lithium salts are widely used in the treatment of affective disorders of the bipolar type. Lithium is a nephrotoxic substance which can cause both acute and chronic renal disease, including cyst formation. Cysts appear to predispose the kidney to renal cell carcinoma. Case Report: A case of renal cell carcinoma ...

  1. Unusual Presentation of Renal Cell Carcinoma: Gluteal Metastasis

    OpenAIRE

    Yunus Emre Goger; Mehmet Mesut Piskin; Mehmet Balasar; Mehmet Kilinc

    2013-01-01

    Renal cell carcinoma (RCC) has widespread and unpredictable metastatic potential. The most common sites of metastatic RCC are the lungs, lymph nodes, bones, liver, and brain; however the soft tissue metastasis is rare (2,3). Here we report a 76-year-old male patient who had renal cell carcinoma presented with gluteal metastasis. To our knowledge this is the first renal cell cancer case with gluteal metastasis at the initial diagnosis.

  2. Sciatica leading to the discovery of a renal cell carcinoma

    OpenAIRE

    Amine Lakmichi, Mohamed; Jarir, Redouane; Kabour, Jamal; Dahami, Zakaria; Said Moudouni, Mohamed; Sarf, Ismail

    2011-01-01

    Metastatic renal cell cancer is not exceptional in kidney cancer (30% of patients with kidneyl cancer). Its prognosis is particularly severe. However, sciatic neuralgia (sciatica) remains an exceptional revealing clinical sign of this disease. The authors report the case of a patient admitted with right sciatica as chief complain, leading to the discovery of a renal cell carcinoma. Although uncommon, renal cell carcinoma spine metastasis should be included in the differential diagnosis of bac...

  3. Painless pulsatile mass as first presentation of renal cell carcinoma

    OpenAIRE

    Kimberley Hoyland; Nikhil Vasdev; Paul Nathan; Damian Hanbury

    2014-01-01

    Renal cell carcinoma rarely presents with typical features of abdominal pain, flank mass and haematuria, and up to 30% of patients present with metastases. We present the case of an 81 year old man who presented with a painless, pulsatile sternal metastasis as an initial presentation of renal cell carcinoma. This case highlights the importance of recognizing even unusual presentations of renal cell carcinoma, and that although sternal metastases are rare, when they do occur there should be a ...

  4. Prolyl hydroxylase 2 dependent and Von-Hippel-Lindau independent degradation of Hypoxia-inducible factor 1 and 2 alpha by selenium in clear cell renal cell carcinoma leads to tumor growth inhibition

    Directory of Open Access Journals (Sweden)

    Chintala Sreenivasulu

    2012-07-01

    Full Text Available Abstract Background Clear cell renal cell carcinoma (ccRCC accounts for more than 80% of the cases of renal cell carcinoma. In ccRCC deactivation of Von-Hippel-Lindau (VHL gene contributes to the constitutive expression of hypoxia inducible factors 1 and 2 alpha (HIF-α, transcriptional regulators of several genes involved in tumor angiogenesis, glycolysis and drug resistance. We have demonstrated inhibition of HIF-1α by Se-Methylselenocysteine (MSC via stabilization of prolyl hydroxylases 2 and 3 (PHDs and a significant therapeutic synergy when combined with chemotherapy. This study was initiated to investigate the expression of PHDs, HIF-α, and VEGF-A in selected solid cancers, the mechanism of HIF-α inhibition by MSC, and to document antitumor activity of MSC against human ccRCC xenografts. Methods Tissue microarrays of primary human cancer specimens (ccRCC, head & neck and colon were utilized to determine the incidence of PHD2/3, HIF-α, and VEGF-A by immunohistochemical methods. To investigate the mechanism(s of HIF-α inhibition by MSC, VHL mutated ccRCC cells RC2 (HIF-1α positive, 786–0 (HIF-2α positive and VHL wild type head & neck cancer cells FaDu (HIF-1α were utilized. PHD2 and VHL gene specific siRNA knockdown and inhibitors of PHD2 and proteasome were used to determine their role in the degradation of HIF-1α by MSC. Results We have demonstrated that ccRCC cells express low incidence of PHD2 (32%, undetectable PHD3, high incidence of HIF-α (92%, and low incidence of VEGF-A compared to head & neck and colon cancers. This laboratory was the first to identify MSC as a highly effective inhibitor of constitutively expressed HIF-α in ccRCC tumors. MSC did not inhibit HIF-1α protein synthesis, but facilitated its degradation. The use of gene knockdown and specific inhibitors confirmed that the inhibition of HIF-1α was PHD2 and proteasome dependent and VHL independent. The effects of MSC treatment on HIF-α were associated with

  5. Prolyl hydroxylase 2 dependent and Von-Hippel-Lindau independent degradation of Hypoxia-inducible factor 1 and 2 alpha by selenium in clear cell renal cell carcinoma leads to tumor growth inhibition

    International Nuclear Information System (INIS)

    Clear cell renal cell carcinoma (ccRCC) accounts for more than 80% of the cases of renal cell carcinoma. In ccRCC deactivation of Von-Hippel-Lindau (VHL) gene contributes to the constitutive expression of hypoxia inducible factors 1 and 2 alpha (HIF-α), transcriptional regulators of several genes involved in tumor angiogenesis, glycolysis and drug resistance. We have demonstrated inhibition of HIF-1α by Se-Methylselenocysteine (MSC) via stabilization of prolyl hydroxylases 2 and 3 (PHDs) and a significant therapeutic synergy when combined with chemotherapy. This study was initiated to investigate the expression of PHDs, HIF-α, and VEGF-A in selected solid cancers, the mechanism of HIF-α inhibition by MSC, and to document antitumor activity of MSC against human ccRCC xenografts. Tissue microarrays of primary human cancer specimens (ccRCC, head & neck and colon) were utilized to determine the incidence of PHD2/3, HIF-α, and VEGF-A by immunohistochemical methods. To investigate the mechanism(s) of HIF-α inhibition by MSC, VHL mutated ccRCC cells RC2 (HIF-1α positive), 786–0 (HIF-2α positive) and VHL wild type head & neck cancer cells FaDu (HIF-1α) were utilized. PHD2 and VHL gene specific siRNA knockdown and inhibitors of PHD2 and proteasome were used to determine their role in the degradation of HIF-1α by MSC. We have demonstrated that ccRCC cells express low incidence of PHD2 (32%), undetectable PHD3, high incidence of HIF-α (92%), and low incidence of VEGF-A compared to head & neck and colon cancers. This laboratory was the first to identify MSC as a highly effective inhibitor of constitutively expressed HIF-α in ccRCC tumors. MSC did not inhibit HIF-1α protein synthesis, but facilitated its degradation. The use of gene knockdown and specific inhibitors confirmed that the inhibition of HIF-1α was PHD2 and proteasome dependent and VHL independent. The effects of MSC treatment on HIF-α were associated with significant antitumor activity against cc

  6. Are primary renal cell carcinoma and metastases of renal cell carcinoma the same cancer?

    Science.gov (United States)

    Semeniuk-Wojtaś, Aleksandra; Stec, Rafał; Szczylik, Cezary

    2016-05-01

    Metastasis is a process consisting of cells spreading from the primary site of the cancer to distant parts of the body. Our understanding of this spread is limited and molecular mechanisms causing particular characteristics of metastasis are still unknown. There is some evidence that primary renal cell carcinoma (RCC) and metastases of RCC exhibit molecular differences that may effect on the biological characteristics of the tumor. Some authors have detected differences in clear cell and nonclear cell component between these 2 groups of tumors. Investigators have also determined that primary RCC and metastases of RCC diverge in their range of renal-specific markers and other protein expression, gene expression pattern, and microRNA expression. There are also certain proteins that are variously expressed in primary RCCs and their metastases and have effect on clinical outcome, e.g., endothelin receptor type B, phos-S6, and CD44. However, further studies are needed on large cohorts of patients to identify differences representing promising targets for prognostic purposes predicting disease-free survival and the metastatic burden of a patient as well as their suitability as potential therapeutic targets. To sum up, in this review we have attempted to summarize studies connected with differences between primary RCC and its metastases and their influence on the biological characteristics of renal cancer. PMID:26850779

  7. Staging and differential diagnosis of renal cell carcinoma

    International Nuclear Information System (INIS)

    The usefulness of magnetic resonance imaging (MRI) was compared with that of computed tomography (CT). Twenty-nine patients with renal cell carcinoma, 3 with angiomyolipomas and 1 with renal pelvic cancer, were examined by both MRI and CT. MRI and CT showed similar results in staging cases of renal cell carcinoma. However, MRI may be more sensitive in detecting the venous extension, metastatic adenopathy, and adjacent organ invasion. In predicting the involvement of perinephric fat, however, MRI is only marginally superior to CT. To demonstrate the usefulness of MRI in differentiating renal cell carcinoma from other renal tumors, the density of renal tumor and that of the psoas muscle were determined using a densitiometer, and the percent (%) contrast (the intensity of the renal tumor / the intensity of the psoas muscle x100) was calculated. In most patients with clear cell type renal carcinoma, the % contrast value in the T1 weighted images was about 100. In the T2 weighted images, the maximum value of the % contrast value was 50 or less in most patients. In one patient with spindle cell type (sarcomatoid type) carcinoma, the % contrast value was 109 in the T1 weighted images, but was 65 - 85, at most, in the T2 weighted images. In patients with renal angiomyolipomas, the % contrast values were calculated exclusive of the fatty components. The % contrast value of the T1 weighted images was 50 or less in all 3 patients, and that of the T2 weighted images was 50 or more in 2 patients and 21 - 38 in the others. Calculation of the % contrast value may possibly enable one to differentiate between various types of renal cell carcinoma and other renal masses. (author)

  8. Choroid plexus metastasis of renal-cell carcinoma

    International Nuclear Information System (INIS)

    A rare case of the choroid plexus metastasis of renal-cell carcinoma is reported. A 58-year-old man was admitted on March 3, 1982, with complaints of mild headache and a transient attack of muscle weakness of the left upper extremity. He had undergone a left nephrectomy because of renal-cell carcinoma 2 years before this admission. A CT scan revealed a small mass in the right lateral ventricle that was markedly enhanced by the contrast medium. A carotid angiogram was normal, but a left vertebral angiogram showed a round tumor stain in the distal portion of the right posterior choroidal artery. To determine the nature of the tumor, it was successfully removed via the right frontal transventricular approach. The immediate recovery from the operation was uneventful, but the patient became semicomatose 6 hours later because of a large subdural hematoma over the left hemisphere. An emergency operation for clot removal and external decompression failed to improve the patient's status, and he died on the 3rd postoperative day. An histological examination of the tumor determined the diagnosis of clear-cell-type renal-cell carcinoma. The CT demonstration of choroid plexus metastasis is quite rare. To our knowledge, only two cases have been described. (author)

  9. Renal cell carcinoma: links and risks

    Directory of Open Access Journals (Sweden)

    Kabaria R

    2016-03-01

    Full Text Available Reena Kabaria, Zachary Klaassen, Martha K Terris Department of Surgery, Section of Urology, Augusta University, Augusta, GA, USA Abstract: This review provides an overview of the incidence of renal cell carcinoma (RCC and a summary of the most commonly associated risk factors. A literature review was performed with a focus on recent studies with a high level of evidence (large prospective cohort studies and meta-analyses. The incidence rate of RCC varies globally, with the rate rising rapidly in more developed regions, demonstrating the effects of increased use of diagnostic imaging and prevalence of modifiable risk factors. Based on the current evidence, cigarette smoking, obesity, and hypertension are the most well-established risk factors for sporadic RCC worldwide. Acquired cystic kidney disease is also a significant risk factor, specifically in dialysis patients. There is increasing evidence for an inverse association between RCC risk and moderate alcohol consumption. Certain analgesics and occupational exposure have been linked to an increased risk of RCC, although data are limited. Diets rich in fruits and vegetables may provide a protective effect. Keywords: renal cell carcinoma, risk factors, incidence, smoking, obesity, hypertension

  10. Metastatic Renal Cell Carcinoma Initially Presented as a Tongue Mass

    OpenAIRE

    Altinel, Deniz; Demet ETİT; Tan, Ayça; Ümit BAYOL; Volkan BULUT; Gökçöl Erdoğan, Işın; Beyhan, Rafet; Yusuf YALÇIN

    2010-01-01

    Renal cell carcinoma is one of the most common tumours after lung and breast cancer to metastasize to the head and neck. Initial presentation by tongue metastasis is extremely rare. A 67-year-oldmale presented with a 4.8 cm mass on his tongue. The result of the punch biopsy from the tongue was diagnosed as a clear cell variant of squamous cell carcinoma. The biopsy was reevaluated due to the renal mass found during the check-up and the rapid enlargement of the mass. The excision of the tongue...

  11. Comparative analysis of novel and conventional Hsp90 inhibitors on HIF activity and angiogenic potential in clear cell renal cell carcinoma: implications for clinical evaluation

    International Nuclear Information System (INIS)

    Perturbing Hsp90 chaperone function targets hypoxia inducible factor (HIF) function in a von Hippel-Lindau (VHL) independent manner, and represents an approach to combat the contribution of HIF to cell renal carcinoma (CCRCC) progression. However, clinical trials with the prototypic Hsp90 inhibitor 17-AAG have been unsuccessful in halting the progression of advanced CCRCC. Here we evaluated a novel next generation small molecule Hsp90 inhibitor, EC154, against HIF isoforms and HIF-driven molecular and functional endpoints. The effects of EC154 were compared to those of the prototypic Hsp90 inhibitor 17-AAG and the histone deacetylase (HDAC) inhibitor LBH589. The findings indicate that EC154 is a potent inhibitor of HIF, effective at doses 10-fold lower than 17-AAG. While EC154, 17-AAG and the histone deacetylase (HDAC) inhibitor LBH589 impaired HIF transcriptional activity, CCRCC cell motility, and angiogenesis; these effects did not correlate with their ability to diminish HIF protein expression. Further, our results illustrate the complexity of HIF targeting, in that although these agents suppressed HIF transcripts with differential dynamics, these effects were not predictive of drug efficacy in other relevant assays. We provide evidence for EC154 targeting of HIF in CCRCC and for LBH589 acting as a suppressor of both HIF-1 and HIF-2 activity. We also demonstrate that 17-AAG and EC154, but not LBH589, can restore endothelial barrier function, highlighting a potentially new clinical application for Hsp90 inhibitors. Finally, given the discordance between HIF activity and protein expression, we conclude that HIF expression is not a reliable surrogate for HIF activity. Taken together, our findings emphasize the need to incorporate an integrated approach in evaluating Hsp90 inhibitors within the context of HIF suppression

  12. Metastasis to Paranasal Sinuses as the First Presenting Sign of Renal Cell Carcinoma

    OpenAIRE

    Hélio Assuncao Gouveia; José Anacleto Dutra Resende Júnior; Gustavo Ruschi Bechara; Thomás Accioly de Souza

    2012-01-01

    The clear cell carcinoma is a relatively rare tumor, represented approximately 85% by renal cell carcinoma (RCC), but has a characteristic of early metastatic, which sometimes spread to unusual places. Metastatic tumors in the paranasal sinuses are very rare. This case report a 65 years-old patient who presented sinusitis and epitaxis as a first sign of renal cell carcinoma with metastasis to the right maxillary sinus, which was opereted at Lagoa Hospital—RJ and strengthen the inclusion of th...

  13. Successful treatment of a brain-metastasized renal cell carcinoma

    OpenAIRE

    Johnston, Kim W.; Walid, M. Sami

    2009-01-01

    Renal cell carcinoma is an uncommon type of cancer that rarely metastasizes to the brain. The prognosis after discovering brain metastasis has traditionally been dismal. We are presenting a case of renal cell carcinoma with multiple brain metastases that was successfully treated with multimodal therapy including a new type of medication.

  14. Renal cell carcinoma-associated adult dermatomyositis treated laparoscopic nephrectomy

    Directory of Open Access Journals (Sweden)

    Elizabeth Nevins

    2013-01-01

    Full Text Available A 77-year-old female, who suffered from rheumatoid arthritis and hypothyroidism, developed severe muscle weakness. Clinical features, blood results and muscle biopsy suggested a possible diagnosis of dermatomyositis. A computed tomography of the chest, abdomen and pelvis showed a solid mass in the left kidney. She underwent a left laparoscopic nephrectomy and histology confirmed conventional (clear cell renal cell carcinoma. She recovered slowly and almost back to normal life after 6 months. Early appreciation of the typical skin rash may provide a clue to the diagnosis and screening for neoplasm may improve prognosis.

  15. Emerging surgical treatments for renal cell carcinoma.

    Science.gov (United States)

    Husain, Fatima Z; Badani, Ketan K; Sfakianos, John P; Mehrazin, Reza

    2016-04-01

    Treatment of renal cell carcinoma has evolved considerably over the last few years. While total nephrectomy is necessary at times, nephron-sparing surgery, with a goal of renal function preservation, should always be considered. Although open partial nephrectomy is considered the gold standard approach for nephron-sparing surgery, laparoscopic- or robotic-assisted techniques allow urologists to perform renal surgery less invasively, with excellent long-term oncological outcomes. Cryotherapy and radiofrequency ablation are less invasive management approaches for carefully selected patients with small renal masses. Active surveillance should be considered in elderly or patients who are unfit for surgery. Ultimately, the method chosen for management of a renal mass is an informed decision made by the physician and patient. PMID:26892144

  16. Sequential Therapy in Metastatic Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Bradford R Hirsch

    2016-04-01

    Full Text Available The treatment of metastatic renal cell carcinoma (mRCC has changed dramatically in the past decade. As the number of available agents, and related volume of research, has grown, it is increasingly complex to know how to optimally treat patients. The authors are practicing medical oncologists at the US Oncology Network, the largest community-based network of oncology providers in the country, and represent the leadership of the Network's Genitourinary Research Committee. We outline our thought process in approaching sequential therapy of mRCC and the use of real-world data to inform our approach. We also highlight the evolving literature that will impact practicing oncologists in the near future.

  17. Renal cell carcinoma: links and risks.

    Science.gov (United States)

    Kabaria, Reena; Klaassen, Zachary; Terris, Martha K

    2016-01-01

    This review provides an overview of the incidence of renal cell carcinoma (RCC) and a summary of the most commonly associated risk factors. A literature review was performed with a focus on recent studies with a high level of evidence (large prospective cohort studies and meta-analyses). The incidence rate of RCC varies globally, with the rate rising rapidly in more developed regions, demonstrating the effects of increased use of diagnostic imaging and prevalence of modifiable risk factors. Based on the current evidence, cigarette smoking, obesity, and hypertension are the most well-established risk factors for sporadic RCC worldwide. Acquired cystic kidney disease is also a significant risk factor, specifically in dialysis patients. There is increasing evidence for an inverse association between RCC risk and moderate alcohol consumption. Certain analgesics and occupational exposure have been linked to an increased risk of RCC, although data are limited. Diets rich in fruits and vegetables may provide a protective effect. PMID:27022296

  18. [Outlook: Future therapy of renal cell carcinoma].

    Science.gov (United States)

    Bergmann, Lothar; Miller, Kurt

    2010-01-01

    Targeted therapies have fundamentally altered the therapy of metastatic renal cell carcinoma (mRCC). Sunitinib today is an internationally recommended reference standard in first-line therapy; other drugs such as Temsirolimus, Everolimus, Bevacizumab (in combination with Interferon-alpha) and Sorafenib are part of the therapeutic arsenal. Practitioners thus have now more and better therapeutic options at hand, leading to a significantly improved prognosis for mRCC patients. Numerous ongoing research activities aim at the improvement of the benefits of the new compounds in the metastatic situation or application earlier in the course of the disease. Key aspects of future development in RCC are the optimization of the current therapy options by developing new targeted therapies, the search for the best combinations and sequences including the role of nephrectomy and the assessment in the adjuvant or neo-adjuvant setting. The following contribution provides an overview of ongoing studies, thus giving insight into the future therapy of RCC. PMID:20164673

  19. Outcome of Patients With Metastatic Sarcomatoid Renal Cell Carcinoma: Results From the International Metastatic Renal Cell Carcinoma Database Consortium

    DEFF Research Database (Denmark)

    Kyriakopoulos, Christos E; Chittoria, Namita; Choueiri, Toni K;

    2015-01-01

    BACKGROUND: Sarcomatoid renal cell carcinoma is associated with poor prognosis. Data regarding outcome in the targeted therapy era are lacking. PATIENTS AND METHODS: Clinical, prognostic, and treatment parameters in metastatic renal cell carcinoma patients with and without sarcomatoid histology...... of sRCC is needed to develop alternative therapeutics....

  20. Case Report: Multifocal biphasic squamoid alveolar renal cell carcinoma [version 1; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Jose Ignacio Lopez

    2016-04-01

    Full Text Available A multifocal biphasic squamoid alveolar renal cell carcinoma in a 68-year-old man is reported. Four different peripheral tumor nodules were identified on gross examination. A fifth central tumor corresponded to a conventional clear cell renal cell carcinoma. Biphasic squamoid alveolar renal cell carcinoma is a rare tumor that has been very recently characterized as a distinct histotype within the spectrum of papillary renal cell carcinoma. Immunostaining with cyclin D1 seems to be specific of this tumor subtype. This is the first reported case with multifocal presentation.

  1. Tubulocystic renal cell carcinoma: a new radiological entity

    International Nuclear Information System (INIS)

    Tubulocystic renal cell carcinoma (TC-RCC) is a recently identified renal malignancy. While approximately 100 cases of TC-RCC have been reported in the pathology literature, imaging features have not yet been clearly described. The purpose of this review is to describe the main radiologic features of this rare sub-type of RCC on ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), based jointly on the literature and findings from a multi-institutional retrospective HIPAA-compliant review of pathology and imaging databases. Using a combination of sonographic and CT/MRI features, diagnosis of TC-RCC appeared to be strongly suggested in many cases. (orig.)

  2. Tubulocystic renal cell carcinoma: a new radiological entity

    Energy Technology Data Exchange (ETDEWEB)

    Cornelis, F.; Grenier, N. [Pellegrin Hospital, Department of Radiology, Bordeaux (France); Helenon, O.; Correas, J.M. [Necker Hospital, Department of Radiology, Paris (France); Lemaitre, L. [Claude Huriez Hospital, Department of Radiology, Lille (France); Andre, M. [La-Conception Hospital, Department of Radiology, Marseille (France); Meuwly, J.Y. [Centre Hospitalier Universitaire Vaudois, Department of Radiology, Lausanne (Switzerland); Sengel, C. [Grenoble Hospital, Department of Radiology, Grenoble (France); Derchi, L. [Universita di Genova, Radiologia - DICMI, Genova (Italy); Yacoub, M. [Pellegrin Hospital, Department of Pathology, Bordeaux (France); Verkarre, V. [Necker Hospital, Department of Pathology, Paris (France)

    2016-04-15

    Tubulocystic renal cell carcinoma (TC-RCC) is a recently identified renal malignancy. While approximately 100 cases of TC-RCC have been reported in the pathology literature, imaging features have not yet been clearly described. The purpose of this review is to describe the main radiologic features of this rare sub-type of RCC on ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), based jointly on the literature and findings from a multi-institutional retrospective HIPAA-compliant review of pathology and imaging databases. Using a combination of sonographic and CT/MRI features, diagnosis of TC-RCC appeared to be strongly suggested in many cases. (orig.)

  3. Racial difference in histologic subtype of renal cell carcinoma

    International Nuclear Information System (INIS)

    In the United States, renal cell carcinoma (RCC) has rapidly increased in incidence for over two decades. The most common histologic subtypes of RCC, clear cell, papillary, and chromophobe have distinct genetic and clinical characteristics; however, epidemiologic features of these subtypes have not been well characterized, particularly regarding any associations between race, disease subtypes, and recent incidence trends. Using data from the Surveillance, Epidemiology, and End Results (SEER) Program, we examined differences in the age-adjusted incidence rates and trends of RCC subtypes, including analysis focusing on racial differences. Incidence rates increased over time (2001–2009) for all three subtypes. However, the proportion of white cases with clear cell histology was higher than among blacks (50% vs. 31%, respectively), whereas black cases were more likely than white cases to have papillary RCC (23% vs. 9%, respectively). Moreover, papillary RCC incidence increased more rapidly for blacks than whites (P < 0.01) over this period. We also observed that increased incidence of papillary histology among blacks is not limited to the smallest size strata. We observed racial differences in proportionate incidence of RCC subtypes, which appear to be increasing over time; this novel finding motivates further etiologic, clinical, molecular, and genetic studies. Using national data, we observed a higher proportion of black renal cell carcinoma (RCC) cases with papillary histology compared to Caucasian cases. We also observed time trends in black-white incidence differences in histologic RCC subtypes, with rapid increases in the disproportionate share of black cases with papillary histology

  4. Multilevel Genomics-Based Taxonomy of Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Fengju Chen

    2016-03-01

    Full Text Available On the basis of multidimensional and comprehensive molecular characterization (including DNA methalylation and copy number, RNA, and protein expression, we classified 894 renal cell carcinomas (RCCs of various histologic types into nine major genomic subtypes. Site of origin within the nephron was one major determinant in the classification, reflecting differences among clear cell, chromophobe, and papillary RCC. Widespread molecular changes associated with TFE3 gene fusion or chromatin modifier genes were present within a specific subtype and spanned multiple subtypes. Differences in patient survival and in alteration of specific pathways (including hypoxia, metabolism, MAP kinase, NRF2-ARE, Hippo, immune checkpoint, and PI3K/AKT/mTOR could further distinguish the subtypes. Immune checkpoint markers and molecular signatures of T cell infiltrates were both highest in the subtype associated with aggressive clear cell RCC. Differences between the genomic subtypes suggest that therapeutic strategies could be tailored to each RCC disease subset.

  5. Bone Metastasis from Renal Cell Carcinoma

    Science.gov (United States)

    Chen, Szu-Chia; Kuo, Po-Lin

    2016-01-01

    About one-third of patients with advanced renal cell carcinoma (RCC) have bone metastasis that are often osteolytic and cause substantial morbidity, such as pain, pathologic fracture, spinal cord compression and hypercalcemia. The presence of bone metastasis in RCC is also associated with poor prognosis. Bone-targeted treatment using bisphosphonate and denosumab can reduce skeletal complications in RCC, but does not cure the disease or improve survival. Elucidating the molecular mechanisms of tumor-induced changes in the bone microenvironment is needed to develop effective treatment. The “vicious cycle” hypothesis has been used to describe how tumor cells interact with the bone microenvironment to drive bone destruction and tumor growth. Tumor cells secrete factors like parathyroid hormone-related peptide, transforming growth factor-β and vascular endothelial growth factor, which stimulate osteoblasts and increase the production of the receptor activator of nuclear factor κB ligand (RANKL). In turn, the overexpression of RANKL leads to increased osteoclast formation, activation and survival, thereby enhancing bone resorption. This review presents a general survey on bone metastasis in RCC by natural history, interaction among the immune system, bone and tumor, molecular mechanisms, bone turnover markers, therapies and healthcare burden. PMID:27338367

  6. Role of everolimus in the treatment of renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Saby George

    2009-08-01

    Full Text Available Saby George1, Ronald M Bukowski21University of Texas Health Sciences Center, MC-8221, Division of Hematology and Oncology, San Antonio, Texas, USA; 2CCF Lerner College of Medicine Division of Hematology and Oncology, Cleveland, Ohio, USAAbstract: The therapeutic options in metastatic renal cell carcinoma have been recently expanded by the discovery of the VHL gene, the mutation of which is associated with development of clear cell carcinoma, and overexpression of the angiogenesis pathway, resulting in a very vascular tumor. This breakthrough in science led to the development of a variety of small molecules inhibiting the VEGF-dependent angiogenic pathway, such as sunitinib and sorafenib. These agents prolong overall and progression-free survival, respectively. The result was the development of robust front-line therapies which ultimately fail and are associated with disease progression. In this setting, there existed an unmet need for developing second-line therapies for patients with refractory metastatic renal cell carcinoma (MRCC. Everolimus (RAD 001 is an oral inhibitor of the mammalian target of rapamycin (mTOR pathway. The double-blind, randomized, placebo-controlled phase III trial of everolimus (RECORD-1 conducted in MRCC patients after progression on sunitinib or sorafenib, or both, demonstrated a progression-free survival benefit favoring the study drug (4.9 months vs 1.9 months, HR 0.33, 95% CI 0.25 to 0.43, P ≤ 0 0.001. Everolimus thus established itself as a standard of care in the second-line setting for patients with MRCC who have failed treatment with VEGF receptor inhibitors.Keywords: mTOR inhibitor, mammalian target of rapamycin inhibitor, signal transduction inhibitor, renal cell carcinoma, targeted therapy

  7. T1 relaxation in renal cell carcinoma with pathologic correlation

    International Nuclear Information System (INIS)

    Renal cell carcinoma, unlike most tumors, can have a shorter T1 on MR imaging than its host tissue. The author compared the signal intensity of renal tumor and normal renal tissue on T1 images obtained using contrast agents. A short T1 signal was seen in 16 of 23 cases of clear cells and/or hemorrhage. In six of eight cases with a long T1 signal, necrosis was found on gross pathologic examination. In four of five cases of isointense signal an unusual pathology was found; one of the five patients was in end-stage renal failure. Fat-containing clear cells and hemorrhage produce a short T1 signal, whereas necrosis produces a long T1 signal

  8. The Role of Everolimus in Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Malek Meskawi

    2015-12-01

    Full Text Available Everolimus (RAD001 is an orally administered agent that inhibits the mammalian target of rapamycin serine-threonine kinase. A phase III pivotal trial on everolimus, published in 2008, provided the first evidence for the efficacy of sequential therapy for patients with metastatic clear cell renal cell carcinoma (RCC. In this study, everolimus was used after failure of one or several previous lines of therapy, and it demonstrated a 3-month survival benefit relative to placebo. Currently, based on the level 1 evidence, everolimus represents the molecule of choice for third-line therapy after failure of previous two tyrosine kinase inhibitors (TKIs. However, second-line use after failure of one TKI is challenged by two new molecules (nivolumab and cabozantinib, which proved to have better efficacy with similar toxicity profile. In non-clear cell metastatic RCC, the current evidence recommends everolimus as a second-line therapy after failure of previous first-line sunitinib.

  9. Small renal cell carcinoma: CT and pathologic correlation

    International Nuclear Information System (INIS)

    Objective: To analyze the correlation of CT and pathological manifestation of small renal cell carcinoma (SRCC). Methods: Thirty-six SRCC were all diagnosed by surgical pathology. On CT, attenuation value and the amount of enhancement were observed; on pathology, tumor cell characteristics, cell arrangement, the stage and grade of the tumor et al were observed. Results: 31 tumors were iso- or hypo-attenuation on CT and clear cell tumors were dominant in 28 cases; 5 cases were hyper-attenuation and 2 of them were granular cell carcinoma. After the contrast enhancement, 31 tumors were enhanced more than 40 HU. 27 of them were solid which had abundant sinusoid vessels; Enhancement in 29 cases was heterogeneous, and on pathology, hemorrhage and necrosis were found in 27 of them. Conclusion: The CT findings of SRCC were correlated with tumor cell characteristic and architecture

  10. The relationship of mast cells and angiogenesis with prognosis in renal cell carcinoma

    International Nuclear Information System (INIS)

    Objective: To evaluate the effects of mast cell count and angiogenesis on the prognosis of renal cell carcinoma. Methods: The retrospective study was conducted at the Harran University, Sanliurfa, Turkey, and included 64 cases with diagnosis of renal cell carcinoma between 2002 and 2012. Immunohistochemical analysis was performed on paraffin sections using the standard streptavidin-biotin immunoperoxidase method. CD31 antibodies were used to identify microvessels in tumoural tissues. The microvessel density was calculated using a serological method. The mean vascular density was equivalent to the vascular surface area (in mm) per unit tissue volume (in mm) (MVD=mm). Mast cells tryptase antibody was used to evaluate the mast cell count in tumoural and non-tumoural tissues. The relationship between mast cell count and microvessel density was evaluated and compared with stage, grade, tumour diameter, and age. Results: The mast cell count in the tumoral tissue of renal cell carcinoma was significantly higher compared with non-neoplastic renal tissue (p0.05). The intratumoural mast cell count in clear cell renal carcinoma was significantly higher compared with non-clear variety (p=0.001). No significant relationship was found between microvessel density, age, stage, diameter, or grade of the tumour and tumoral mast cell count (p>0.05). Conclusion: No significant association was found between the number of mast cells in tumoral tissue and microvessel density. Further studies are needed to demonstrate the effect of mast cells on angiogenesis in renal cell carcinoma. (author)

  11. A Case of Metastatic Renal Cell Carcinoma to Thyroid Gland

    OpenAIRE

    Lee, Jae-Geun; Yang, Youngro; Kim, Kwang Sik; Hyun, Chang Lim; Lee, Ji Shin; Koh, Gwanpyo; Lee, Daeho

    2011-01-01

    Metastasis to the thyroid gland from distant cancer is rare, and, in some cases, is a diagnostic challenge. Here, we report a case of metastatic renal cell carcinoma of the thyroid gland. A 77-year-old man presented with a neck mass detected about 1 month previously. He had undergone a right nephrectomy owing to renal cell carcinoma 14 years previously. Fine needle aspiration cytology showed a few atypical follicular cells with nuclear atypia. Under a tentative diagnosis of papillary thyroid ...

  12. Presence of intratumoral neutrophils is an independent prognostic factor in localized renal cell carcinoma

    DEFF Research Database (Denmark)

    Jensen, Hanne Krogh; Donskov, Frede; Marcussen, Niels; Nordsmark, Marianne; Lundbeck, Finn; von der Maase, Hans

    2009-01-01

    PURPOSE: We have previously demonstrated a significant negative impact of intratumoral neutrophils in metastatic renal cell carcinoma. This study assessed intratumoral neutrophils in localized clear cell renal cell carcinoma (RCC). PATIENTS AND METHODS: The study comprised 121 consecutive patients....... CONCLUSION: The presence of intratumoral neutrophils is a new, strong, independent prognostic factor for short recurrence-free, cancer-specific, and overall survival in localized clear cell RCC....... who had a nephrectomy for localized RCC. Biomarkers (intratumoral CD8+, CD57+ immune cells, CD66b+ neutrophils, and carbonic anhydrase IX [CA IX]) were assessed by immunohistochemistry, and the relationship with clinical and histopathologic features and patient outcome was evaluated. RESULTS: The...

  13. Solitary pulmonary metastases from renal cell carcinoma. Comparison of high-resolution CT with pathological findings

    International Nuclear Information System (INIS)

    The aim of this study was to examine the radiographic features of solitary pulmonary metastases from renal cell carcinoma by comparing high-resolution CT (HRCT) findings with histopathological observations. Three thoracic radiologists retrospectively reviewed HRCT findings from eight patients who underwent surgery on the basis of the diagnosis of solitary pulmonary metastatic renal cell carcinoma. The histopathological diagnoses for six of these eight lesions were metastases from clear cell carcinoma of the kidney, one case was a metastasis from papillary renal cell carcinoma, and the remaining case was a metastasis from a poorly differentiated carcinoma including predominantly spindle cells, papillary cells, and clear cells. The HRCT findings of all cases of clear cell carcinoma showed solid nodular lesions without ground-glass attenuation (GGA). The HRCT findings for one case of papillary renal cell carcinoma showed a lobulated nodule with a small amount of GGA in an area in the periphery and an air bronchogram. The HRCT findings of the remaining case of poorly differentiated carcinoma showed an ill-defined nodule with a GGA area and pleural indentations. In brief, solitary pulmonary metastases from renal cell carcinoma may present as a smoothly marginated nodule, lobulated nodule, or a nodule with peripheral GGA. (author)

  14. Renal Preservation Therapy for Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Yichun Chiu

    2012-01-01

    Full Text Available Renal preservation therapy has been a promising concept for the treatment of localized renal cell carcinoma (RCC for 20 years. Nowadays partial nephrectomy (PN is well accepted to treat the localized RCC and the oncological control is proved to be the same as the radical nephrectomy (RN. Under the result of well oncological control, minimal invasive method gains more popularity than the open PN, like laparoscopic partial nephrectomy (LPN and robot assisted laparoscopic partial nephrectomy (RPN. On the other hand, thermoablative therapy and cryoablation also play an important role in the renal preservation therapy to improve the patient procedural tolerance. Novel modalities, but limited to small number of patients, include high-intensity ultrasound (HIFU, radiosurgery, microwave therapy (MWT, laser interstitial thermal therapy (LITT, and pulsed cavitational ultrasound (PCU. Although initial results are encouraging, their real clinical roles are still under evaluation. On the other hand, active surveillance (AS has also been advocated by some for patients who are unfit for surgery. It is reasonable to choose the best therapeutic method among varieties of treatment modalities according to patients' age, physical status, and financial aid to maximize the treatment effect among cancer control, patient morbidity, and preservation of renal function.

  15. Perfusion computed tomography in renal cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Chandan; J; Das; Usha; Thingujam; Ananya; Panda; Sanjay; Sharma; Arun; Kumar; Gupta

    2015-01-01

    Various imaging modalities are available for the diagnosis, staging and response evaluation of patients with renal cell carcinoma(RCC). While contrast enhanced computed tomography(CT) is used as the standard of imaging for size, morphological evaluation and response assessment in RCC, a new functional imaging technique like perfusion CT(p CT), goes down to the molecular level and provides new perspectives in imaging of RCC. p CT depicts regional tumor perfusion and vascular permeability which are indirect parameters of tumor angiogenesis and thereby provides vital information regarding tumor microenvironment. Also response evaluation using p CT may predate the size criteria used in Response Evaluation Criteria in Solid Tumors, as changes in the perfusion occurs earlier following tissue kinase inhibitors before any actual change in size. This may potentially help in predicting prognosis, better selection of therapy and more accurate and better response evaluation in patients with RCC. This article describes the techniques and role of p CT in staging and response assessment in patients with RCCs.

  16. Systemic adjuvant therapies in renal cell carcinoma.

    Science.gov (United States)

    Buti, Sebastiano; Bersanelli, Melissa; Donini, Maddalena; Ardizzoni, Andrea

    2012-10-01

    Renal cell carcinoma (RCC) is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to describe the results of past and ongoing phase III clinical trials in this field. We explored all the systemic treatments, including chemotherapy, immunotherapy and targeted drugs while alternative approaches have also been described. Appropriate selection of patients who would benefit from adjuvant therapies remains a crucial dilemma. Although the international guidelines do not actually recommend any adjuvant treatment after radical surgery for RCC, no conclusions have yet been drawn pending the results of the promising ongoing clinical trials with the target therapies. The significant changes that these new drugs have made on advanced disease outcome could represent the key to innovation in terms of preventing recurrence, delaying relapse and prolonging survival after radical surgery for RCC. PMID:25992216

  17. Systemic adjuvant therapies in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sebastiano Buti

    2012-10-01

    Full Text Available Renal cell carcinoma (RCC is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to describe the results of past and ongoing phase III clinical trials in this field. We explored all the systemic treatments, including chemotherapy, immunotherapy and targeted drugs while alternative approaches have also been described. Appropriate selection of patients who would benefit from adjuvant therapies remains a crucial dilemma. Although the international guidelines do not actually recommend any adjuvant treatment after radical surgery for RCC, no conclusions have yet been drawn pending the results of the promising ongoing clinical trials with the target therapies. The significant changes that these new drugs have made on advanced disease outcome could represent the key to innovation in terms of preventing recurrence, delaying relapse and prolonging survival after radical surgery for RCC.

  18. Perfusion computed tomography in renal cell carcinoma.

    Science.gov (United States)

    Das, Chandan J; Thingujam, Usha; Panda, Ananya; Sharma, Sanjay; Gupta, Arun Kumar

    2015-07-28

    Various imaging modalities are available for the diagnosis, staging and response evaluation of patients with renal cell carcinoma (RCC). While contrast enhanced computed tomography (CT) is used as the standard of imaging for size, morphological evaluation and response assessment in RCC, a new functional imaging technique like perfusion CT (pCT), goes down to the molecular level and provides new perspectives in imaging of RCC. pCT depicts regional tumor perfusion and vascular permeability which are indirect parameters of tumor angiogenesis and thereby provides vital information regarding tumor microenvironment. Also response evaluation using pCT may predate the size criteria used in Response Evaluation Criteria in Solid Tumors, as changes in the perfusion occurs earlier following tissue kinase inhibitors before any actual change in size. This may potentially help in predicting prognosis, better selection of therapy and more accurate and better response evaluation in patients with RCC. This article describes the techniques and role of pCT in staging and response assessment in patients with RCCs. PMID:26217456

  19. Complete remission with tyrosine kinase inhibitors in renal cell carcinoma

    OpenAIRE

    Albiges, Laurence; Oudard, Stéphane; Negrier, Sylvie; Caty, Armelle; Gravis, Gwenaëlle; Joly, Florence; Duclos, Brigitte; Geoffrois, Lionel; Rolland, Frédéric; Guillot, Aline; Laguerre, Brigitte; Legouffe, Eric; Kohser, Frédéric; Dietrich, Pierre-Yves; Theodore, Christine A

    2012-01-01

    Complete remission (CR) is uncommon during treatment for metastatic renal cell carcinoma (mRCC) with tyrosine kinase inhibitors (TKIs), but it may occur in some patients. It remains a matter of debate whether therapy should be continued after CR.

  20. Genetics Home Reference: hereditary leiomyomatosis and renal cell cancer

    Science.gov (United States)

    ... Central Sudarshan S, Pinto PA, Neckers L, Linehan WM. Mechanisms of disease: hereditary leiomyomatosis and renal cell cancer-- ... with a qualified healthcare professional . About Genetics Home Reference Site Map Contact Us Selection Criteria for Links ...

  1. Microarray profile of human kidney from diabetes, renal cell carcinoma and renal cell carcinoma with diabetes

    OpenAIRE

    Kosti, Adam; Harry Chen, Hung-I; Mohan, Sumathy; Liang, Sitai; Chen, Yidong; Habib, Samy L

    2015-01-01

    Recent study from our laboratory showed that patients with diabetes are at a higher risk of developing kidney cancer. In the current study, we have screened whole human DNA genome from healthy control, patients with diabetes or renal cell carcinoma (RCC) or RCC+diabetes. We found that 883 genes gain/163 genes loss of copy number in RCC+diabetes group, 669 genes gain/307 genes loss in RCC group and 458 genes gain/38 genes loss of copy number in diabetes group, after removing gain/loss genes ob...

  2. Translocation Renal Cell Carcinomas in Adults: A Single Institution Experience

    OpenAIRE

    Zhong, Minghao; De Angelo, Patricia; Osborne, Lisa; Mondolfi, Paniz; Geller, Matthew; Yang, Youfeng; Linehan, W. Marston; Merino, Maria J.; Cordon-Cardo, Carlos; Cai, Dongming

    2012-01-01

    Translocation renal cell carcinoma is a newly recognized subtype of renal cell carcinoma (RCC) with chromosomal translocations involving TFE3 (Xp11.2) or, less frequently, TFEB (6p21). Xp11 translocation RCC was originally described as a pediatric neoplasm representing 20–40% of pediatric RCCs with a much lower frequency in the adult population. TFEB translocation RCC is very rare, with approximately 10 cases reported in the literature. Here, we describe the clinicopathological features of ad...

  3. Leptomeningeal carcinomatosis associated with papillary renal cell carcinoma

    OpenAIRE

    Chilkulwar, Abhishek; Pottimutyapu, Ramya; Wu, Fawng; Padooru, Keerthi R; Pingali, Sai Ravi; Kassem, Mohammed

    2014-01-01

    Leptomeningeal carcinomatosis (LMC), or neoplastic meningitis, occurs in about 5–20% of patients with metastatic cancer, depending on the type of the primary malignancy and kind of treatment received. The association of LMC with renal cell carcinoma (RCC) is a rare entity, and only two cases of papillary renal cell cancer with leptomeningeal metastasis have been reported. Leptomeningeal spread usually confers a poor prognosis despite the use of modern treatment strategies as compared to patie...

  4. Comprehensive Molecular Characterization of Papillary Renal Cell Carcinoma

    Science.gov (United States)

    Linehan, W. Marston; Spellman, Paul T.; Ricketts, Christopher J.; Creighton, Chad J.; Fei, Suzanne S.; Davis, Caleb; Wheeler, David A.; Murray, Bradley A.; Schmidt, Laura; Vocke, Cathy D.; Peto, Myron; Al Mamun, Abu Amar M.; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W. Kimryn; Brooks, Angela N.; Hoadley, Katherine A.; Robertson, A. Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J.; Bootwalla, Moiz; Baylin, Stephen B.; Laird, Peter W.; Cherniack, Andrew D.; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B.; Akbani, Rehan; Leiserson, Mark D.M.; Raphael, Benjamin J.; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K.; Czerniak, Bogdan; Godwin, Andrew K.; Hakimi, A. Ari; Ho, Thai; Hsieh, James; Ittmann, Michael; Kim, William Y.; Krishnan, Bhavani; Merino, Maria J.; Mills Shaw, Kenna R.; Reuter, Victor E.; Reznik, Ed; Shelley, Carl Simon; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D.; Penny, Robert J.; Shelton, Candace; Shelton, W. Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T.; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A.; Felau, Ina; Hutter, Carolyn M.; Sheth, Margi; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S.N.; Carlsen, Rebecca; Carter, Scott L.; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R.; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, HarshaVardhan; Drummond, Jennifer; Gabriel, Stacey B.; Gibbs, Richard A.; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D. Neil; Holt, Robert A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Steven J.M.; Jones, Corbin D.; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A.; Moore, Richard A.; Morton, Donna; Mose, Lisle E.; Mungall, Andrew J.; Muzny, Donna; Parker, Joel S.; Perou, Charles M.; Roach, Jeffrey; Schein, Jacqueline E.; Schumacher, Steven E.; Shi, Yan; Simons, Janae V.; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G.; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D.; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N.; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J. Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L.; Boice, Lori; Bollag, Roni J.; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C.; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K.; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L.; Slaton, Joel; Stanton, Melissa; Thompson, R. Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M.; Winemiller, Cythnia; Zach, Leigh Anne; Zuna, Rosemary

    2016-01-01

    Background Papillary renal cell carcinoma, accounting for 15% of renal cell carcinoma, is a heterogeneous disease consisting of different types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal cell carcinoma; no effective forms of therapy for advanced disease exist. Methods We performed comprehensive molecular characterization utilizing whole-exome sequencing, copy number, mRNA, microRNA, methylation and proteomic analyses of 161 primary papillary renal cell carcinomas. Results Type 1 and Type 2 papillary renal cell carcinomas were found to be different types of renal cancer characterized by specific genetic alterations, with Type 2 further classified into three individual subgroups based on molecular differences that influenced patient survival. MET alterations were associated with Type 1 tumors, whereas Type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-ARE pathway. A CpG island methylator phenotype (CIMP) was found in a distinct subset of Type 2 papillary renal cell carcinoma characterized by poor survival and mutation of the fumarate hydratase (FH) gene. Conclusions Type 1 and Type 2 papillary renal cell carcinomas are clinically and biologically distinct. Alterations in the MET pathway are associated with Type 1 and activation of the NRF2-ARE pathway with Type 2; CDKN2A loss and CIMP in Type 2 convey a poor prognosis. Furthermore, Type 2 papillary renal cell carcinoma consists of at least 3 subtypes based upon molecular and phenotypic features. PMID:26536169

  5. Oral cavity metastasis of renal cell carcinoma: A case report

    OpenAIRE

    Will Thomas; Agarwal Neena; Petruzzelli Guy

    2008-01-01

    Abstract Introduction Despite being reported rarely, renal cell carcinoma is the third most frequent neoplasm to metastasize to the head and neck region preceded only by breast and lung cancer. Little information exists regarding the presentation and work-up of metastatic renal cell carcinoma in the oral cavity. Case presentation We report the case of a 63-year-old Caucasian man presenting with an oral cavity lesion that was painful and that had grown substantially over several months. Biopsy...

  6. Gallbladder metastasis from renal cell carcinoma mimicking acute cholecystitis

    Directory of Open Access Journals (Sweden)

    Sand M

    2009-02-01

    Full Text Available Abstract Renal cell carcinoma constitutes about 3% of adult malignancies. It has a high metastatic potential associated with synchronous or metachronous metastatic disease. Further, it is known to metastasize mainly to the lung, bone, brain, liver, or adrenal glands. In very rare cases it can metastasize to the gallbladder mimicking acute cholecystitis on clinical exam. In this case we present a patient who developed a gallbladder metastasis five years after a renal cell carcinoma mimicking acute cholecystitis.

  7. Renal cell cancer among African Americans: an epidemiologic review

    Directory of Open Access Journals (Sweden)

    Lipworth Loren

    2011-04-01

    Full Text Available Abstract Incidence rates for renal cell cancer, which accounts for 85% of kidney cancers, have been rising more rapidly among blacks than whites, almost entirely accounted for by an excess of localized disease. This excess dates back to the 1970s, despite less access among blacks to imaging procedures in the past. In contrast, mortality rates for this cancer have been virtually identical among blacks and whites since the early 1990s, despite the fact that nephrectomy rates, regardless of stage, are lower among blacks than among whites. These observations suggest that renal cell cancer may be a less aggressive tumor in blacks. We have reviewed the epidemiology of renal cell cancer, with emphasis on factors which may potentially play a role in the observed differences in incidence and mortality patterns of renal cell cancer among blacks and whites. To date, the factors most consistently, albeit modestly, associated with increased renal cell cancer risk in epidemiologic studies among whites - obesity, hypertension, cigarette smoking - likely account for less than half of these cancers, and there is virtually no epidemiologic evidence in the literature pertaining to their association with renal cell cancer among blacks. There is a long overdue need for detailed etiologic cohort and case-control studies of renal cell cancer among blacks, as they now represent the population at highest risk in the United States. In particular, investigation of the influence on renal cell cancer development of hypertension and chronic kidney disease, both of which occur substantially more frequently among blacks, is warranted, as well as investigations into the biology and natural history of this cancer among blacks.

  8. Familial renal cell carcinoma: clinical and molecular genetic aspects

    OpenAIRE

    Maher, E. R.; Yates, J. R. W.

    1991-01-01

    Renal cell carcinoma (RCC) accounts for 2% of all human cancer, but familial cases are infrequent. Riches (1963) and Griffin et al. (1984) in a population-based case-control study found a family history of renal cell carcinoma in 2.4% of affected patients compared to 1.4% of controls. Nevertheless the importance of inherited tumours in clinical practice and medical research is disproportionate to their frequency. In clinical practice recognition of familial RCC can provide opportunities to pr...

  9. Breast Metastasis from Renal Cell Carcinoma: A Case Report

    International Nuclear Information System (INIS)

    Metastatic breast cancer from renal cell carcinoma is extremely rare and has non-specific findings that include a well circumscribed lesion without calcification on mammography and a well circumscribed hypoechoic lesion without posterior acoustic shadowing on sonography. We report a case of metastatic breast cancer from renal cell carcinoma and describe the radiologic findings in a 63-year-old woman who has no history of primary neoplasm

  10. Transcriptome network analysis reveals candidate genes for renal cell carcinoma

    OpenAIRE

    Wei Zhai; Yun-Fei Xu; Min Liu; Jun-Hua Zheng

    2012-01-01

    Context: Renal cell carcinoma (RCC) is a kidney cancer that originates in renal parenchyma and it is the most common type of kidney cancer with approximately 80% lethal cases. Aims: To interpret the mechanism, explore the regulation of TF-target genes and TF-pathway, and identify the potential key genes of renal cell carcinoma. Settings and Design: After constructing a regulation network from differently expressed genes and transcription factors, pathway regulation network and gene onto...

  11. Breast Metastasis from Renal Cell Carcinoma: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seon Jeong; Kim, Ji Young; Jeong, Myeong Ja; Kim, Jae Hyung; Kim, Soung Hee; Kim, Soo Hyun; Jun, Woo Sun; Kim, Hyun Jung; Han, Se Hwan [Sanggye Paik Hospital, Seoul (Korea, Republic of)

    2010-01-15

    Metastatic breast cancer from renal cell carcinoma is extremely rare and has non-specific findings that include a well circumscribed lesion without calcification on mammography and a well circumscribed hypoechoic lesion without posterior acoustic shadowing on sonography. We report a case of metastatic breast cancer from renal cell carcinoma and describe the radiologic findings in a 63-year-old woman who has no history of primary neoplasm.

  12. Renal cell carcinoma in patient with crossed fused renal ectopia

    OpenAIRE

    Ozgur Cakmak; Cemal Selcuk Isoglu; Ercument Aziz Peker; Huseyin Tarhan; Ulku Kucuk; Orcun Celik; Ferruh Zorlu; Yusuf Ozlem Ilbey

    2016-01-01

    Primary renal cell carcinomas have rarely been reported in patients with crossed fused renal ectopia. We presented a patient with right to left crossed fused kidney harbouring renal tumor. The most frequent tumor encountered in crossed fused renal ectopia is renal cell carcinoma. In this case, partial nephrectomy was performed which pave way to preservation of the uninvolved both renal units. Due to unpredictable anatomy, careful preoperative planning and meticulous delineation of renal vascu...

  13. Protein Expression Profiling in the Spectrum of Renal Cell Carcinomas

    Directory of Open Access Journals (Sweden)

    Vladimir A Valera, Elsa Li-Ning-T, Beatriz A Walter, David D. Roberts, W M Linehan, Maria J Merino

    2010-01-01

    Full Text Available In this study, we aimed to evaluate the protein expression profile of a spectrum of renal cell carcinomas (RCC to find potential biomarkers for disease onset and progression and therefore, prospective therapeutic targets. A 2D-gel based proteomic analysis was used to outline differences in protein levels among different subtypes of renal cell carcinomas, including clear cell carcinomas, papillary lesions, chromophobe tumors and renal oncocytomas. Spot pattern was compared to the corresponding normal kidney from the same patients and distinctive, differentially expressed proteins were characterized by mass spectrometry. Twenty-one protein spots were found differentially expressed between clear cell RCC and normal tissue and 38 spots were found expressed in chromophobe tumors. Eleven proteins were identified, with most differentially expressed -by fold change- between clear cell tumors and the corresponding normal tissue. Two of the identified proteins, Triosephosphate isomerase 1 (TPI-1 and Heat Shock protein 27 (Hsp27, were further validated in a separate set of tumors by immunohistochemistry and expression levels were correlated with clinicopathologic features of the patients. Hsp27 was highly expressed in 82% of the tumors used for validation, and all cases showed strong immunoreactivity for TPI-1. In both Hsp27 and TPI-1, protein expression positively correlated with histologic features of the disease. Our results suggest that the subjacent cytogenetic abnormalities seen in different histological types of RCC are followed by specific changes in protein expression. From these changes, Hsp27 and TPI-1 emerged as potential candidates for the differentiation and prognosis in RCC.

  14. Epidemiologic characteristics and risk factors for renal cell cancer

    Directory of Open Access Journals (Sweden)

    Loren Lipworth

    2009-04-01

    Full Text Available Loren Lipworth1,2, Robert E Tarone1,2, Lars Lund2,3, Joseph K McLaughlin1,21International Epidemiology Institute, Rockville, MD, USA; 2Department of Medicine (JKM, RET and Preventive Medicine (LL, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA; 3Department of Urology, Viborg Hospital, Viborg, DenmarkAbstract: Incidence rates of renal cell cancer, which accounts for 85% of kidney cancers, have been rising in the United States and in most European countries for several decades. Family history is associated with a two- to four-fold increase in risk, but the major forms of inherited predisposition together account for less than 4% of renal cell cancers. Cigarette smoking, obesity, and hypertension are the most consistently established risk factors. Analgesics have not been convincingly linked with renal cell cancer risk. A reduced risk of renal cell cancer among statin users has been hypothesized but has not been adequately studied. A possible protective effect of fruit and vegetable consumption is the only moderately consistently reported dietary finding, and, with the exception of a positive association with parity, evidence for a role of hormonal or reproductive factors in the etiology of renal cell cancer in humans is limited. A recent hypothesis that moderate levels of alcohol consumption may be protective for renal cell cancer is not strongly supported by epidemiologic results, which are inconsistent with respect to the categories of alcohol consumption and the amount of alcohol intake reportedly associated with decreased risk. For occupational factors, the weight of the evidence does not provide consistent support for the hypotheses that renal cell cancer may be caused by asbestos, gasoline, or trichloroethylene exposure. The established determinants of renal cell cancer, cigarette smoking, obesity, and hypertension, account for less than half of these cancers. Novel epidemiologic approaches

  15. Dicer expression in relation to tumorigenesis and metastasis of clear cell renal cell carcinoma%Dicer表达与肾透明细胞癌发生及转移的关系

    Institute of Scientific and Technical Information of China (English)

    范阳; 黄庆波; 高宇; 艾青; 倪栋; 陈伟浩; 马鑫; 张旭

    2013-01-01

    目的:探讨Dicer在肾透明细胞癌发生及转移中的作用.方法:选取正常肾小管上皮细胞株HKC、非转移性肾透明细胞癌细胞株769-P、转移性肾透明细胞癌细胞株Caki-1以及36例肾透明细胞癌手术标本(其中11例已发生远处转移)和相应癌旁正常肾组织,应用实时定量PCR和Western blot方法检测Dicer在肾透明细胞癌细胞株和组织中mRNA和蛋白的表达情况,并分析Dicer的mRNA水平与临床病理资料的关系.结果:和正常肾小管上皮细胞株HKC相比,Dicer的mRNA水平在肾透明细胞癌细胞株769-P和Caki-1中均降低(P<0.001),而转移性肾透明细胞癌细胞株Caki-1比非转移性肾透明细胞癌细胞株769-P表达水平更低(P<0.001);和癌旁正常肾组织相比,Dicer的mRNA水平在肾透明细胞癌手术标本中明显降低(P<0.001),且已发生远处转移的肾癌标本比末发生远处转移的肾癌标本表达水平更低(P=0.01);Dicer在细胞株和组织中的蛋白水平的变化与mRNA水平的变化一致(P <0.001);Dicer的mRNA水平在不同年龄、性别、组织学分级、肿瘤大小及T分期组间无统计学差异(P>0.05).结论:Dicer表达降低可能在肾透明细胞癌的肿瘤发生中发挥作用,且其表达的进一步下降可能与肾透明细胞癌的远处转移有关.%Objective:To explore the role of Direr in tumorigenesis and metastasis of clear cell renal cell carcinoma (ccRCC). Method:The expression of Dicer in mRNA and protein levels were detected in human kidney tubule epithelial cell line HKC. non-metastatic ccRCV cell line 769-P, metastatic ccRCC cell line Caki-1 . and 36 cases of ccRCC surgical specimens( including 11 cases with distant metastasis)and their corresponding adjacent normal renal tissues by real-time PCR and Western blot respectively, analyzing the relationship between the mRNA levels of Dicer and clinicopathological variables. Result:Compared to human kidney tubule epithelial cell line

  16. Single metastatic renal cell carcinoma in gallbladder: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Young; Cho, Bum Sang; Kang, Min Ho; Lee, Seung Young; Yi, Kyung Sik; Park, Kil Sun; Sung, Ro Hyun [Chungbuk National Univ. Hospital, Cheongju (Korea, Republic of)

    2012-07-15

    Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancy. 25% to 57% of RCC patients exhibit overt evidence of metastatic disease at initial presentation. Metastases to the gallbladder is uncommon and usually detected in only 0.4-0.6% of autopsies. We report the case of a 58 year old man who presented with a metastasis in the gallbladder from RCC. He had undergone went a right nephrectomy four years ago. There was no evidence of metastasis. A follow up abdomen CT scan taken three years after operation showed a polypoid lesion within the gallbladder. The size of the polypoid lesion had increased at the follow up CT and the enhancement pattern of lesion became similar to that of RCC. A Cholecystectomy was performed. Histopathological examination revealed the polyp was clear cell carcinoma of metastatic origin from kidney.

  17. Single metastatic renal cell carcinoma in gallbladder: A case report

    International Nuclear Information System (INIS)

    Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancy. 25% to 57% of RCC patients exhibit overt evidence of metastatic disease at initial presentation. Metastases to the gallbladder is uncommon and usually detected in only 0.4-0.6% of autopsies. We report the case of a 58 year old man who presented with a metastasis in the gallbladder from RCC. He had undergone went a right nephrectomy four years ago. There was no evidence of metastasis. A follow up abdomen CT scan taken three years after operation showed a polypoid lesion within the gallbladder. The size of the polypoid lesion had increased at the follow up CT and the enhancement pattern of lesion became similar to that of RCC. A Cholecystectomy was performed. Histopathological examination revealed the polyp was clear cell carcinoma of metastatic origin from kidney

  18. Microarray gene expression profiling and analysis in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sadhukhan Provash

    2004-06-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC is the most common cancer in adult kidney. The accuracy of current diagnosis and prognosis of the disease and the effectiveness of the treatment for the disease are limited by the poor understanding of the disease at the molecular level. To better understand the genetics and biology of RCC, we profiled the expression of 7,129 genes in both clear cell RCC tissue and cell lines using oligonucleotide arrays. Methods Total RNAs isolated from renal cell tumors, adjacent normal tissue and metastatic RCC cell lines were hybridized to affymatrix HuFL oligonucleotide arrays. Genes were categorized into different functional groups based on the description of the Gene Ontology Consortium and analyzed based on the gene expression levels. Gene expression profiles of the tissue and cell line samples were visualized and classified by singular value decomposition. Reverse transcription polymerase chain reaction was performed to confirm the expression alterations of selected genes in RCC. Results Selected genes were annotated based on biological processes and clustered into functional groups. The expression levels of genes in each group were also analyzed. Seventy-four commonly differentially expressed genes with more than five-fold changes in RCC tissues were identified. The expression alterations of selected genes from these seventy-four genes were further verified using reverse transcription polymerase chain reaction (RT-PCR. Detailed comparison of gene expression patterns in RCC tissue and RCC cell lines shows significant differences between the two types of samples, but many important expression patterns were preserved. Conclusions This is one of the initial studies that examine the functional ontology of a large number of genes in RCC. Extensive annotation, clustering and analysis of a large number of genes based on the gene functional ontology revealed many interesting gene expression patterns in RCC. Most

  19. Ipsilateral synchronous renal cell carcinoma and transitional cell carcinoma.

    OpenAIRE

    Lee, J. W.; Kim, M. J.; Song, J H; Kim, J H; Kim, J. M.

    1994-01-01

    The simultaneous occurrence of renal cell carcinoma(RCC) and transitional cell carcinoma(TCC) in the same kidney is unusual. We report a 53-year-old man with ipsilateral synchronous renal adenocarcinoma and renal pelvic transitional cell carcinoma with severe hypercalcemia and a huge staghorn calculus in the opposite kidney. The patient was admitted to the hospital because of left flank pain and intermittent fever which he had had for 2 months. Computerized tomography revealed a huge stone in...

  20. Multi-slice spiral CT and pathological correlation of renal cell carcinoma

    International Nuclear Information System (INIS)

    Objective: To analyze relationship between characteristics on multi-slice spiral CT (MSCT) and pathology of renal cell carcinoma. Methods: Multi-slice spiral CT and surgical pathological results on 32 cases of renal cell carcinoma were retrospectively analyzed. Results: Of the 32 cases, 28 were pathologically diagnosed as clear cell carcinoma, with tumor contrast enhancement similar to the normal cortex in the renal cortical phase (146-175HU), slight contrast washout in the renal parenchyma phase and significant contrast washout from the tumor in the pyelographic phase. Granular cell carcinoma in 4 patients showed no or mild contrast enhancement (38- 55HU) in all three phase. The overall diagnostic accordance rate was 100%, with preoperative staging accordance rate of 96.42%. Conclusion: The triple-phase contrast-enhanced MSCT is useful in predicting the tumor cell type and staging of renal cell carcinoma. (authors)

  1. Magnetic resonance imaging in the staging of renal cell carcinoma

    International Nuclear Information System (INIS)

    Eighteen patients with renal neoplasm underwent magnetic resonance imaging (MRI) using a 1.5 Tesla superconducting magnetic system and spin echo images were obtained by quick scan technique under holding breath. MR images were interpreted independently of the computerized tomography (CT) findings. The preoperative stagings of the 18 renal carcinomas, as judged by MRI, were compared with those obtained at laparotomy. The anatomic staging was correctly performed by MRI in 13 patients (72 %). In the patients who had intrarenal small tumor with normal renal contour, MRI demonstrated a solid mass clearly distinguishable from surrounding renal parenchyma using the paramagnetic contrast agent (gadolinium-DTPA). When compared with results of evaluation by CT in staging, MRI appeared to have several advantages in determination of whole mass; the detection of tumor thrombus into renal vein and inferior vena cava; and the evaluation of direct tumor invasion of adjacent organs. MRI should play an important role in the staging of renal cell carcinoma. (author)

  2. {sup 11}C-Acetate PET imaging for renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Oyama, Nobuyuki; Kusukawa, Naoya; Kaneda, Taisei; Miwa, Yoshiji; Akino, Hironobu; Yokoyama, Osamu [University of Fukui, Department of Urology, Fukui (Japan); Okazawa, Hidehiko; Fujibayashi, Yasuhisa [University of Fukui, Biomedical Imaging Research Center, Fukui (Japan); Yonekura, Yoshiharu [National Institute of Radiological Sciences, Chiba (Japan); Welch, Michael J. [Washington University School of Medicine, Mallinckrodt Institute of Radiology, Saint Louis, MO (United States)

    2009-03-15

    In this study, we investigated the effectiveness of positron emission tomography (PET) with {sup 11}C-acetate (AC) for evaluation of renal cell carcinoma. Enrolled in the study were 20 patients with suspected renal tumour, one of whom had three renal lesions. In all, 22 renal lesions were evaluated. Following administration of 350 MBq (10 mCi) of AC, whole-body PET images were obtained. Based on these PET findings, kidney lesions were scored as positive or negative. The PET results were correlated with the CT findings and histological diagnosis after surgery. In 18 patients, 20 tumours were diagnosed as renal cell carcinoma. Lesions in the remaining two patients were diagnosed as complicated cyst without malignant tissue. Of the 20 renal cell carcinomas. 14 (70%) showed positive AC PET findings; 6 were negative. The two patients with complicated cyst had negative AC PET findings. Of the 20 renal cell carcinomas, 19 were clear-cell carcinoma and 1 was a papillary cell carcinoma. This papillary cell carcinoma showed high AC uptake. AC demonstrates marked uptake in renal cell carcinoma. These preliminary data show that AC is a possible PET tracer for detection of renal cancer. (orig.)

  3. Renal Cell Carcinoma with Intraluminal Spread of the Entire Upper Urinary Tract

    OpenAIRE

    Shigenori Kakutani; Haruki Kume; Yoshikazu Hirano; Toshihiko Wakita; Yukio Homma

    2013-01-01

    We describe an unusual case of renal cell carcinoma (RCC) involving the entire upper urinary tract. A 51-year-old female was referred to us because of macroscopic hematuria. Computed tomography revealed a renal tumor filling renal pelvis and ureter, which turned to be a clear cell RCC after nephroureterectomy.

  4. Involvement of multiple loci on chromosome 3 in renal cell cancer development

    NARCIS (Netherlands)

    van den Berg, Anke; Buys, CHCM

    1997-01-01

    In renal cell carcinoma (RCC), mostly occurring as sporadic cases, the short arm of chromosome 3 is a frequent target of deletion events. Taking into account cytological classifications of RCC, the deletions appear to be characteristic of clear cell or nonpapillary RCC only. This subtype constitutes

  5. [Bilateral metastases of renal cell carcinoma to the ovaries--a case report].

    Science.gov (United States)

    Hołody-Zareba, Joanna; Kinalski, Piotr; Sulkowski, Stanisław; Kozłowski, Robert; Kinalski, Maciej

    2013-07-01

    Renal cell carcinoma accounts for 75% of renal neoplasms. Clear cell carcinoma is diagnosed in about 80% of the cases. Renal cell carcinoma most frequently metastasizes to the lungs (50-60%), lymph nodes (36%), bones (30-40%), liver (30-40%), and brain (5%). In other organs the metastasis changes are observed very rarely. Ovarian metastases are found in 0.5% of renal cancers. So far, only 23 cases of renal cell carcinoma metastases to the ovary have been reported in the literature. In 18 cases they were metastases of renal cell carcinoma of the clear cell type. The authors present a case of a 50-year-old woman with double-sided metastatic changes to the ovary from renal cell carcinoma. The patient was admitted to the Gynecological ward with preliminary diagnosis of ovarian tumors. Gynecological examination revealed double-sided ovarian tumors, 6-7cm in diameter. Computed tomography also showed a 155 x 80 mm hetrogenous, multiform tumor localized above the uterus. In addition, CT showed a 75 x 55 mm tumor in the lower pole, and a smaller one, 15 mm in diameter in the upper pole of the right kidney. Laboratory tests were normal. The antigen Ca 125 was 25 j/ml. Mammography cytology gastroscopy colonoscopy were normal. The consulting urologist proposed a two-stage treatment. In the first stage, the removal of the double-sided ovarian tumors was proposed, while in the second stage the right nephrectomy was suggested. Double-sided ovarian tumors were found and removed (in the wall of the cyst- yellow, solid masses) during the first operation. Intraoperative histological examination showed changes with unknown grade of malignancy in both ovaries (number of studies QN 291). The patient underwent total hysterectomy. On day 5 postoperatively the woman was discharged from the hospital in good condition with the recommendation to pick up the histological test result in two weeks time. The final histological examination showed metastatic changes of renal cell carcinoma of the

  6. Endoscopic Management of Unusual Metastasis of Renal Cell Carcinoma to the Sinonasal Area

    Directory of Open Access Journals (Sweden)

    Mosavi Bahar Seyed Habibollah

    2009-10-01

    Full Text Available Metastatic  tumors in the nose and paranasal sinuses are infrequent. The origin of this metastatic tumors are often renal cell carcinoma. We present one case of metastatic renal cell carcinoma  to the nose and paranasal sinuses ,4 years after initial nephrectomy and diagnosis of stage T1N0M0 clear cell carcinoma. The patient complained of nasal obstruction and recurrent epistaxis  who was treated with endoscopic sinus surgery and was successfully palliated after one year.

  7. Localized Pleural Metastases of Renal Cell Carcinoma After Nephrectomy: A Case Report and Literature Review.

    Science.gov (United States)

    Yasuda, Yuichiro; Tobino, Kazunori; Ko, Yuki; Asaji, Mina; Yamaji, Yoshikazu; Tsuruno, Kosuke; Mukasa, Yosuke; Ebi, Noriyuki

    2016-01-01

    We herein report the case of a 61-year-old Japanese male with localized pleural metastases of renal cell carcinoma. The patient was admitted to our hospital because of dyspnea on exertion and left-sided pleural effusion. He had undergone right radical nephrectomy 10 years previously. Contrast-enhanced whole-body computed tomography revealed scattered nodular thickening of the left pleura with contrast enhancement and left-sided pleural effusion. Thoracoscopy performed under local anesthesia was applied to obtain a biopsy of the pleural nodules, and the specimen was consequently diagnosed as exhibiting pleural metastasis of renal cell carcinoma, clear cell type. PMID:26705014

  8. Renal Clear Cell Carcinoma and Tonsil Metastasis

    OpenAIRE

    Dario Marcotullio; Giannicola Iannella; Gian Franco Macri; Caterina Marinelli; Melissa Zelli; Giuseppe Magliulo

    2013-01-01

    Renal cell carcinoma is the most common renal tumor in adults. Clear cell carcinoma represents 85% of all histological subtypes. In February 2012 a 72-year-old woman came to our department due to the appearance of massive hemoptysis and pharyngodinia. Previously, this patient was diagnosed with a renal cell carcinoma treated with left nephrectomy. We observed an exophytic, grayish, and ulcerated mass in the left tonsillar lodge and decided to subject the patient to an immediate tonsillectomy....

  9. Renal cell apoptosis in human lupus nephritis: a histological study

    DEFF Research Database (Denmark)

    Faurschou, M; Penkowa, Milena; Andersen, C B; Starklint, H; Jacobsen, S

    2009-01-01

    Nuclear autoantigens from apoptotic cells are believed to drive the immunological response in systemic lupus erythematosus (SLE). Conflicting data exist as to the possible renal origin of apoptotic cells in SLE patients with nephritis. We assessed the level of renal cell apoptosis in kidney biops...

  10. Radiosensitization by Inhibiting STAT1 in Renal Cell Carcinoma

    International Nuclear Information System (INIS)

    Purpose: Renal cell carcinoma (RCC) has been historically regarded as a radioresistant malignancy, but the molecular mechanism underlying its radioresistance is not understood. This study investigated the role of signal transducer and activator of transcription 1 (STAT1), a transcription factor downstream of the interferon-signaling pathway, in radioresistant RCC. Methods and Materials: The expressions of STAT1 and STAT3 in 164 human clear cell RCC samples, 47 papillary RCC samples, and 15 normal kidney tissue samples were examined by microarray expression profiling and immunohistochemistry. Western blotting was performed to evaluate the total and phosphorylated STAT1 expression in CRL-1932 (786-O) (human clear cell RCC), SKRC-39 (human papillary RCC), CCL-116 (human fibroblast), and CRL-1441 (G-401) (human Wilms tumor). STAT1 was reduced or inhibited by fludarabine and siRNA, respectively, and the effects on radiation-induced cell death were investigated using clonogenic assays. Results: STAT1 expression, but not STAT3 expression, was significantly greater in human RCC samples (p = 1.5 x 10-8 for clear cell; and p = 3.6 x 10-4 for papillary). Similarly, the expression of STAT1 was relatively greater in the two RCC cell lines. STAT1 expression was reduced by both fludarabine and siRNA, significantly increasing the radiosensitivity in both RCC cell lines. Conclusion: This is the first study reporting the overexpression of STAT1 in human clear cell and papillary RCC tissues. Radiosensitization in RCC cell lines was observed by a reduction or inhibition of STAT1 signaling, using fludarabine or siRNA. Our data suggest that STAT1 may play a key role in RCC radioresistance and manipulation of this pathway may enhance the efficacy of radiotherapy

  11. Bilateral multiloculated cystic renal cell carcinoma (Case report)

    OpenAIRE

    Gümürdülü, D; Uğuz, A; Gökdemir, A.; Soyupak, B.

    2014-01-01

    Aim: Multiloculated cystic renal cell carcinoma is a rare variant of renal cell carcinoma. Incidence and biological behaviour of the tumor are unknown and bilateral cases are very rare. Case report: Fifty four-years- old male patient was admitted to the Urology policlinic with a left flank pain which was present during one month. On ultra sonographic examination solid hypoecoic mass 37x 32 mm in size and extending to the adrenal area were found at the upperpole of right kidney. Another mass 3...

  12. Renal cell carcinoma arising in ipsilateral duplex system.

    Science.gov (United States)

    Mohan, Harsh; Kundu, Reetu; Dalal, Usha

    2014-09-01

    Congenital anomalies of the kidney and urinary tract are common and include a wide anatomic spectrum. Duplex systems are one of the more common renal anomalies, with the majority being asymptomatic. Little is known about the molecular pathogenesis of these anomalies; however, certain causative genes have been implicated. The finding of renal cell carcinoma arising in a kidney with the duplication of pelvicalyceal system and ureters, as in the present case, is uncommon. The association between a duplex system and renal cell carcinoma may be more than a coincidence, requiring a deeper insight and further elucidation. PMID:26328175

  13. Renal cell carcinoma metastasis to thyroid tumor: a case report and review of the literature

    OpenAIRE

    Medas, Fabio; Calò, Pietro Giorgio; Lai, Maria Letizia; Tuveri, Massimiliano; Pisano, Giuseppe; Nicolosi, Angelo

    2013-01-01

    Introduction Metastatic neoplasms to the thyroid gland are rare in clinical practice. Clear cell renal carcinoma is the most frequent site of origin of thyroid metastases and represents 12 to 34% of all secondary thyroid tumors. Tumor-to-tumor metastases, in which a thyroid neoplasm is the recipient of a metastasis, are exceedingly rare. We report a case of clear cell renal carcinoma metastatic to a follicular adenoma. This is the tenth case of renal cell carcinoma metastasis to thyroid tumor...

  14. Contemporary approach to diagnosis and classification of renal cell carcinoma with mixed histologic features

    OpenAIRE

    Monzon, Federico A; Eric Jonasch; Priya Rao; Kanishka Sircar; Pheroze Tamboli

    2013-01-01

    Renal cell carcinoma (RCC) is an important contributor to cancer-specific mortality worldwide. Targeted agents that inhibit key subtype-specific signaling pathways have improved survival times and have recently become part of the standard of care for this disease. Accurately diagnosing and classifying RCC on the basis of tumor histology is thus critical. RCC has been traditionally divided into clear-cell and non-clear-cell categories, with papillary RCC forming the most common subtype of non-...

  15. Metastatic Renal Cell Carcinoma to the Contralateral Ureter: A Rare Phenomenon

    OpenAIRE

    Ashley Dixon; Maria Tretiakova; John Gore; Voelzke, Bryan B.

    2015-01-01

    Metastatic renal cell carcinoma (RCC) to the contralateral ureter is a rare phenomenon. We report a metastatic RCC to the contralateral ureter 5 months after right radical nephrectomy for Fuhrman grade 3/4 clear cell adenocarcinoma with pathologic T3 staging. The distal ureter was excised followed by partial ileal ureteral substitution. Pathology confirmed metastatic clear cell RCC Fuhrman grade 2/4. Ileal ureteral substitution has been shown to provide good long-term functional outcomes and ...

  16. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma

    DEFF Research Database (Denmark)

    Choueiri, Toni K; Escudier, Bernard; Powles, Thomas;

    2015-01-01

    antiangiogenic drugs. This randomized, open-label, phase 3 trial evaluated the efficacy of cabozantinib, as compared with everolimus, in patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy. METHODS: We randomly assigned 658 patients to receive cabozantinib at a dose of 60 mg daily...

  17. Severe paraneoplastic hypereosinophilia in metastatic renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Todenhöfer Tilman

    2012-03-01

    Full Text Available Abstract Background Renal cell carcinoma can cause various paraneoplastic syndromes including metabolic and hematologic disturbances. Paraneoplastic hypereosinophilia has been reported in a variety of hematologic and solid tumors. We present the first case in the literature of severe paraneoplastic hypereosinophilia in a patient with renal cell carcinoma. Case presentation A 46 year-old patient patient with a history of significant weight loss, reduced general state of health and coughing underwent radical nephrectomy for metastasized renal cell carcinoma. Three weeks after surgery, the patient presented with excessive peripheral hypereosinophilia leading to profound neurological symptoms due to cerebral microinfarction. Systemic treatment with prednisolone, hydroxyurea, vincristine, cytarabine, temsirolimus and sunitinib led to reduction of peripheral eosinophils but could not prevent rapid disease progression of the patient. At time of severe leukocytosis, a considerable increase of cytokines associated with hypereosinophilia was measurable. Conclusions Paraneoplastic hypereosinophilia in patients with renal cell carcinoma might indicate poor prognosis and rapid disease progression. Myelosuppressive therapy is required in symptomatic patients.

  18. Alcoholic beverages and risk of renal cell cancer

    NARCIS (Netherlands)

    Greving, J. P.; Lee, J. E.; Wolk, A.; Lukkien, C.; Lindblad, P.; Bergstrom, A.

    2007-01-01

    Using a mailed questionnaire, we investigated the risk of renal cell cancer in relation to different types of alcoholic beverages, and to total ethanol in a large population- based case - control study among Swedish adults, including 855 cases and 1204 controls. Compared to non- drinkers, a total et

  19. A brief symptom index for advanced renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Cella David

    2006-09-01

    Full Text Available Abstract Background Our objective was to test a brief, symptom index for advanced renal cell carcinoma, a disease affecting over 38,000 Americans each year and often diagnosed in late stages. Methods We conducted secondary data analyses on patient-reported outcomes of 209 metastatic renal cell carcinoma patients participating in a Phase III clinical trial. Patient-reported outcomes, obtained from the FACT-Biological Response Modifier (FACT-BRM scale, were available at baseline, 2, and 8 weeks. We analyzed data from eight FACT-BRM items previously identified by clinical experts to represent the most important symptoms of advanced renal cell carcinoma. Items comprising this index assess nausea, pain, appetite, perceived sickness, fatigue and weakness, with higher scores indicating fewer symptoms. We determined reliability and validity of the index and estimated a minimally important difference. Results The index had excellent internal reliability at all three time points (alphas ≥ 0.83. Baseline scores were able to discriminate patients across Karnofsky performance status, number of metastatic sites, and risk group categories (ps Conclusion The 8-item index of patient-reported symptoms of renal cell carcinoma appears to be a psychometrically sound measure. It is a brief, reliable, and valid measure that can easily be adapted for use in clinical trials and observational studies.

  20. Feasibility of sentinel node detection in renal cell carcinoma: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Bex, Axel [Netherlands Cancer Institute, Department of Urology, Amsterdam (Netherlands); Netherlands Cancer Institute, Division of Surgical Oncology, Department of Urology, Amsterdam (Netherlands); Vermeeren, Lenka; Olmos, Renato A.V. [Netherlands Cancer Institute, Department of Nuclear Medicine, Amsterdam (Netherlands); Windt, Geraldine de; Horenblas, Simon [Netherlands Cancer Institute, Department of Urology, Amsterdam (Netherlands); Prevoo, Warner [Netherlands Cancer Institute, Department of Radiology, Amsterdam (Netherlands)

    2010-06-15

    Lymphatic drainage from renal cell carcinoma is unpredictable and the therapeutic benefit and extent of lymph node dissection are controversial. We evaluated the feasibility of intratumoural injection of a radiolabelled tracer to image and sample draining lymph nodes in clinically non-metastatic renal cell carcinoma. Eight patients with cT1-2 cN0 cM0 (<6 cm) renal cell carcinoma prospectively received percutaneous intratumoural injections of {sup 99m}Tc-nanocolloid under ultrasound guidance (0.4 ml, 225 MBq at one to four intratumoural locations depending on tumour size). Lymphoscintigraphy was performed 20 min, 2 h and 4 h after injection. After the delayed images a hybrid SPECT/CT was performed. SPECT was fused with CT to determine the anatomical localization of the sentinel node. Surgery with sampling was performed the following day using a gamma probe and a portable mini gamma camera. Eight patients, seven with right-sided renal cell carcinoma, were included with a mean age of 55 years (range: 45-77). The mean tumour size was 4 cm (range: 3.5-6 cm). Six patients had sentinel nodes on scintigraphy (two retrocaval, four interaortocaval, including one hilar) with one extraretroperitoneal location along the internal mammary chain. All nodes could be mapped and sampled. In two patients no drainage was visualized. Renal cell carcinomas were of clear cell subtype with no lymph node metastases. Sentinel node identification using preoperative and intraoperative imaging to locate and sample the sentinel node at surgery in renal cell carcinoma is feasible. Sentinel node biopsy may clarify the pattern of lymphatic drainage and extent of lymphatic spread which may have diagnostic and therapeutic implications. (orig.)

  1. Effect of chaetocin on renal cell carcinoma cells and cytokine-induced killer cells

    Directory of Open Access Journals (Sweden)

    Rombo, Roman

    2016-04-01

    Full Text Available We examined the cytotoxic effects of chaetocin on clear cell renal cell carcinoma (ccRCC cells and the possibility to combine the effects of chaetocin with the effects of cytokine-induced killer cells (CIK assayed by MTT assay and FACS analysis. Chaetocin is a thiodioxopiperazine produced by fungi belonging to the chaetomiaceae family. In 2007, it was first reported that chaetocin shows potent and selectiveanti-cancer activity by inducing reactive oxygen species. CIK cells are generated from CD3+/CD56- T lymphocytes with double negative phenotype that are isolated from human blood. The addition of distinct interleukins and antibodies results in the generation of CIK cells that are able to specifically target and destroy renal carcinoma cells. The results of this research state that the anti-ccRCC activity of chaetocin is weak and does not show a high grade of selectivity on clear cell renal cell carcinoma cells. Although the CIK cells show a high grade of selective anti-ccRCC activity, this effect could not be improved by the addition of chaetocin. So chaetocin seems to be no suitable agent for specific targeting ccRCC cells or for the combination therapy with CIK cells in renal cancer.

  2. Renal cell carcinoma treated with stereotactic radiotherapy with histological change confirmed on autopsy: a case report

    OpenAIRE

    Onishi, Hiroshi; Kawasaki, Tomonori; Zakoji, Hidenori; Yoshida, Takashi; Komiyama, Takafumi; Kuriyama, Kengo; Araya, Masayuki; Saito, Ryo; Aoki, Shinichi; Maehata, Yoshiyasu; Tominaga, Licht; Marino, Kan; Watanabe, Iori; Oguri, Mitsuhiko; Araki, Tsutomu

    2014-01-01

    Background Treatment of primary renal cell carcinoma using radiotherapy with curative intent is rare, because renal cell carcinoma is generally regarded as a radiation-resistant tumor. Recently, stereotactic body radiation therapy has been radically applied for cancers in various organs including renal cell carcinoma. However, there were few reports describing pathological changes of renal cell carcinoma post stereotactic body radiation therapy. This is the first report we are aware of docume...

  3. Thyroid Metastasis in Pyramidal Lobe from Renal Cell Carcinoma: A Case Report

    International Nuclear Information System (INIS)

    Thyroid metastasis is rare. The most common primary malignancy of thyroid metastasis worldwide is known to be renal cell carcinoma, but the most common primary malignancy in South Korea is breast cancer. Many studies have reported that primary renal cell carcinoma is almost unilateral and thyroid metastasis from renal cell carcinoma is a nearly ipsilateral, single lesion. We report a case of pyramidal lobe metastasis from renal cell carcinoma.

  4. Thyroid Metastasis in Pyramidal Lobe from Renal Cell Carcinoma: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Hyung Seok; Kim, Dong Wook; Kim, Sang Su [Dept. of Radiology, Busan Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of); Jung, Soo Jin [Dept. of Pathology, Busan Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of)

    2011-06-15

    Thyroid metastasis is rare. The most common primary malignancy of thyroid metastasis worldwide is known to be renal cell carcinoma, but the most common primary malignancy in South Korea is breast cancer. Many studies have reported that primary renal cell carcinoma is almost unilateral and thyroid metastasis from renal cell carcinoma is a nearly ipsilateral, single lesion. We report a case of pyramidal lobe metastasis from renal cell carcinoma.

  5. Automated grading of renal cell carcinoma using whole slide imaging

    Directory of Open Access Journals (Sweden)

    Fang-Cheng Yeh

    2014-01-01

    Full Text Available Introduction: Recent technology developments have demonstrated the benefit of using whole slide imaging (WSI in computer-aided diagnosis. In this paper, we explore the feasibility of using automatic WSI analysis to assist grading of clear cell renal cell carcinoma (RCC, which is a manual task traditionally performed by pathologists. Materials and Methods: Automatic WSI analysis was applied to 39 hematoxylin and eosin-stained digitized slides of clear cell RCC with varying grades. Kernel regression was used to estimate the spatial distribution of nuclear size across the entire slides. The analysis results were correlated with Fuhrman nuclear grades determined by pathologists. Results: The spatial distribution of nuclear size provided a panoramic view of the tissue sections. The distribution images facilitated locating regions of interest, such as high-grade regions and areas with necrosis. The statistical analysis showed that the maximum nuclear size was significantly different (P < 0.001 between low-grade (Grades I and II and high-grade tumors (Grades III and IV. The receiver operating characteristics analysis showed that the maximum nuclear size distinguished high-grade and low-grade tumors with a false positive rate of 0.2 and a true positive rate of 1.0. The area under the curve is 0.97. Conclusion: The automatic WSI analysis allows pathologists to see the spatial distribution of nuclei size inside the tumors. The maximum nuclear size can also be used to differentiate low-grade and high-grade clear cell RCC with good sensitivity and specificity. These data suggest that automatic WSI analysis may facilitate pathologic grading of renal tumors and reduce variability encountered with manual grading.

  6. Renal cell apoptosis in human lupus nephritis: a histological study

    DEFF Research Database (Denmark)

    Faurschou, M; Penkowa, Milena; Andersen, C B;

    2009-01-01

    Nuclear autoantigens from apoptotic cells are believed to drive the immunological response in systemic lupus erythematosus (SLE). Conflicting data exist as to the possible renal origin of apoptotic cells in SLE patients with nephritis. We assessed the level of renal cell apoptosis in kidney...... biopsies from 35 patients with lupus nephritis by means of terminal deoxynucleotidyl-transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labeling (TUNEL). Five samples of normal kidney tissue served as control specimens. We did not observe apoptotic glomerular cells in any of...... that apoptotic renal cells constitute a quantitatively important source of auto-antibody-inducing nuclear auto-antigens in human lupus nephritis....

  7. Renal cell carcinoma: histological classification and correlation with imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Muglia, Valdair F., E-mail: fmuglia@fmrp.usp.br [Universidade de Sao Paulo (CCIFM/FMRP/USP), Ribeirao Preto, SP (Brazil). Centro de Ciencias das Imagens e Fisica Medica. Faculdade de Medicina; Prando, Adilson [Universidade Estadual de Campinas (UNICAMP), SP (Brazil); Hospital Vera Cruz, Campinas, SP (Brazil). Dept. de Imaginologia

    2015-05-15

    Renal cell carcinoma (RCC) is the seventh most common histological type of cancer in the Western world and has shown a sustained increase in its prevalence. The histological classification of RCCs is of utmost importance, considering the significant prognostic and therapeutic implications of its histological subtypes. Imaging methods play an outstanding role in the diagnosis, staging and follow-up of RCC. Clear cell, papillary and chromophobe are the most common histological subtypes of RCC, and their preoperative radiological characterization, either followed or not by confirmatory percutaneous biopsy, may be particularly useful in cases of poor surgical condition, metastatic disease, central mass in a solitary kidney, and in patients eligible for molecular targeted therapy. New strategies recently developed for treating renal cancer, such as cryo and radiofrequency ablation, molecularly targeted therapy and active surveillance also require appropriate preoperative characterization of renal masses. Less common histological types, although sharing nonspecific imaging features, may be suspected on the basis of clinical and epidemiological data. The present study is aimed at reviewing the main clinical and imaging findings of histological RCC subtypes. (author)

  8. Renal cell carcinoma: histological classification and correlation with imaging findings

    International Nuclear Information System (INIS)

    Renal cell carcinoma (RCC) is the seventh most common histological type of cancer in the Western world and has shown a sustained increase in its prevalence. The histological classification of RCCs is of utmost importance, considering the significant prognostic and therapeutic implications of its histological subtypes. Imaging methods play an outstanding role in the diagnosis, staging and follow-up of RCC. Clear cell, papillary and chromophobe are the most common histological subtypes of RCC, and their preoperative radiological characterization, either followed or not by confirmatory percutaneous biopsy, may be particularly useful in cases of poor surgical condition, metastatic disease, central mass in a solitary kidney, and in patients eligible for molecular targeted therapy. New strategies recently developed for treating renal cancer, such as cryo and radiofrequency ablation, molecularly targeted therapy and active surveillance also require appropriate preoperative characterization of renal masses. Less common histological types, although sharing nonspecific imaging features, may be suspected on the basis of clinical and epidemiological data. The present study is aimed at reviewing the main clinical and imaging findings of histological RCC subtypes. (author)

  9. Increased intratumoral FOXP3-positive regulatory immune cells during interleukin-2 treatment in metastatic renal cell carcinoma

    DEFF Research Database (Denmark)

    Jensen, Hanne Krogh; Donskov, Frede; Nordsmark, Marianne; Marcussen, Niels; von der Maase, Hans

    2009-01-01

    PURPOSE: The administration of interleukin-2 (IL-2) may increase the frequency of peripherally circulating FOXP3-positive regulatory immune cells, thus potentially compromising this treatment option for patients with metastatic renal cell carcinoma. The impact of IL-2-based therapy on the...... accumulation of FOXP3-positive immune cells in the tumor microenvironment in metastatic renal cell carcinoma is unknown. EXPERIMENTAL DESIGN: Baseline (n = 58) and on-treatment (n = 42) tumor core biopsies were prospectively obtained from patients with clear cell metastatic renal cell carcinoma before and...... during IL-2-based immunotherapy. Immunohistochemical expression of FOXP3 was estimated by stereological counting technique and correlated with other immune cell subsets and overall survival. RESULTS: A significant increase in absolute intratumoral FOXP3-positive immune cells was observed comparing...

  10. Tumor-to-Tumor Metastasis to Chromophobe Renal Cell Carcinoma: A First Report

    OpenAIRE

    Hiromitsu Mimata; Fuminori Sato; Tomoko Kan; Toshitaka Shin

    2011-01-01

    Tumor-to-tumor metastasis is a rare phenomenon. From our review of the international literature, around 150 cases have been reported since it was first documented by Campbel in 1868. Renal clear cell carcinoma is well known to be the most common recipient of tumor-to-tumor metastasis in all tumors. However, renal chromophobe cell carcinoma has not been reported to be a recipient. Here, we report a first case of colorectal carcinoma metastatic to chromophobe renal cell carcinoma.

  11. Correlation Between Fuhrman Nuclear Grade and Stage with Survival in Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Evrim KUŞ

    2009-09-01

    Full Text Available Objective: Our aim was to find out the correlation between histopathological findings and survival of patients with renal cell carcinoma.Material and Method: We examined 114 cases diagnosed as renal cell carcinoma at the Pathology Department in 1997 - 2007. We explored the correlation of histological type, size, Fuhrman nuclear grade, renal capsule invasion, renal vein and lymphatic/vascular invasion, tumoral necrosis and stage with survival.Results: Histological subtypes were determined as clear cell in 101 cases (88,6% , papillary in 9 cases (7,9%, and chromophobe renal cell carcinoma in 4 cases (3,5%. Reliable follow-up data were available in 96 of 114 cases. 74 of them (77,1% were alive and 22 of them (22,9% had died related to renal cell carcinoma. The mean follow-up time was 21,5 months with a wide range between 2 days and 87 months. 5 year survival was 61,3 months, and its probability was 58,2%.Conclusion: We provide statistical results compatible with the recent literature in regard to high Fuhrman nuclear grade, advanced stage, necrosis, capsule invasion, microvascular invasion and lymph node invasion decreasing the survival time.

  12. Molecular Genetic Alterations in Renal Cell Carcinomas With Tubulocystic Pattern: Tubulocystic Renal Cell Carcinoma, Tubulocystic Renal Cell Carcinoma With Heterogenous Component and Familial Leiomyomatosis-associated Renal Cell Carcinoma. Clinicopathologic and Molecular Genetic Analysis of 15 Cases.

    Science.gov (United States)

    Ulamec, Monika; Skenderi, Faruk; Zhou, Ming; Krušlin, Božo; Martínek, Petr; Grossmann, Petr; Peckova, Kvetoslava; Alvarado-Cabrero, Isabel; Kalusova, Kristyna; Kokoskova, Bohuslava; Rotterova, Pavla; Hora, Milan; Daum, Ondrej; Dubova, Magdalena; Bauleth, Kevin; Slouka, David; Sperga, Maris; Davidson, Whitney; Rychly, Boris; Perez Montiel, Delia; Michal, Michal; Hes, Ondrej

    2016-08-01

    The characteristic morphologic spectrum of tubulocystic renal cell carcinoma (TC-RCC) may include areas resembling papillary RCC (PRCC). Our study includes 15 RCCs with tubulocystic pattern: 6 TC-RCCs, 1 RCC-high grade with tubulocystic architecture, 5 TC-RCCs with foci of PRCC, 2 with high-grade RCC (HGRCC) not otherwise specified, and 1 with a clear cell papillary RCC/renal angiomyoadenomatous tumor-like component. We analyzed aberrations of chromosomes 7, 17, and Y; mutations of VHL and FH genes; and loss of heterozygosity at chromosome 3p. Genetic analysis was performed separately in areas of classic TC-RCC and in those with other histologic patterns. The TC-RCC component demonstrated disomy of chromosome 7 in 9/15 cases, polysomy of chromosome 17 in 7/15 cases, and loss of Y in 1 case. In the PRCC component, 2/3 analyzable cases showed disomy of chromosome 7 and polysomy of chromosome 17 with normal Y. One case with focal HGRCC exhibited only disomy 7, whereas the case with clear cell papillary RCC/renal angiomyoadenomatous tumor-like pattern showed polysomies of 7 and 17, mutation of VHL, and loss of heterozygosity 3p. FH gene mutation was identified in a single case with an aggressive clinical course and predominant TC-RCC pattern. The following conclusions were drawn: (1) TC-RCC demonstrates variable status of chromosomes 7, 17, and Y even in cases with typical/uniform morphology. (2) The biological nature of PRCC/HGRCC-like areas within TC-RCC remains unclear. Our data suggest that heterogenous TC-RCCs may be associated with an adverse clinical outcome. (3) Hereditary leiomyomatosis-associated RCC can be morphologically indistinguishable from "high-grade" TC-RCC; therefore, in TC-RCC with high-grade features FH gene status should be tested. PMID:26447894

  13. Rate of renal cell carcinoma subtypes in different races

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    Alexander Sankin

    2011-02-01

    Full Text Available PURPOSE: We sought to identify racial differences among histological subtypes of renal cell carcinoma (RCC between black and non-black patients in an equal-access health care system. MATERIALS AND METHODS: We established a multi-institutional, prospective database of patients undergoing partial or radical nephrectomy between January 1, 2000 and Sept 31, 2009. For the purposes of this study, data captured included age at diagnosis, race, tumor size, presence of lymphovascular invasion, presence of capsular invasion, margin status, and tumor histology. RESULTS: 204 kidney tumors were identified (Table-1. Of these, 117 (57.4% were in black patients and 87 (42.6% were in non-black patients. Age at surgery ranged from 37 to 87 with a median of 62. Tumor size ranged from 1.0 to 22.0 cm with a median of 5.0 cm. Overall, tumors were composed of clear cell RCC in 97 cases (47.5%, papillary RCC in 65 cases (31.9%, chromophobe RCC in 13 cases (6.4%, collecting duct/medullary RCC in 2 cases (1.0%, RCC with multiple histological subtypes in 8 cases (3.9%, malignant tumors of other origin in 6 cases (2.9%, and benign histology in 13 cases (6.4%. Among black patients, papillary RCC was seen in 56 cases (47.9%, compared to 9 cases (10.3% among non-black patients (p < 0.001 (Table-2. Clear cell RCC was present in 38 (32.5% of black patients and in 59 (67.8% of non-blacks (p < 0.001. CONCLUSIONS: In our study, papillary RCC had a much higher occurrence among black patients compared to non-black patients. This is the first study to document such a great racial disparity among RCC subtypes.

  14. Sorafenib and sunitinib: novel targeted therapies for renal cell cancer.

    Science.gov (United States)

    Grandinetti, Cheryl A; Goldspiel, Barry R

    2007-08-01

    Renal cell cancer (RCC) is a relatively uncommon malignancy, with 51,190 cases expected to be diagnosed in 2007. Localized disease is curable by surgery; however, locally advanced or metastatic disease is not curable in most cases and, until recently, had a limited response to drug treatment. Historically, biologic response modifiers or immunomodulating agents were tested in clinical trials based on observations that some cases of RCC can spontaneously regress. High-dose aldesleukin is approved by the United States Food and Drug Administration as a treatment for advanced RCC; however, the drug is associated with a high frequency of severe adverse effects. Responses have been observed with low-dose aldesleukin and interferon alfa, but with little effect on overall survival. Sorafenib and sunitinib are novel therapies that target growth factor receptors known to be activated by the hypoxia-inducible factor and the Ras-Raf/MEK/ERK pathways. These pathways are important in the pathophysiology of RCC. Sorafenib and sunitinib have shown antitumor activity as first- and second-line therapy in patients with cytokine-refractory metastatic RCC who have clear-cell histology. Although complete responses are not common, both drugs promote disease stabilization and increase progression-free survival. This information suggests that disease stabilization may be an important determinant for response in RCC and possibly other cancers. Sorafenib and sunitinib are generally well tolerated and are considered first- and second-line treatment options for patients with advanced clear cell RCC. In addition, sorafenib and sunitinib have shown promising results in initial clinical trials evaluating antitumor activity in patients who are refractory to other antiangiogenic therapy. The most common toxicities with both sorafenib and sunitinib are hand-foot syndrome, rash, fatigue, hypertension, and diarrhea. Research is directed toward defining the optimal use of these new agents. PMID:17655513

  15. A case of bilateral renal cell carcinoma associated with long-term dialysis showing false-positive immunoreactivity for TFE3 as Xp11 translocation renal cell carcinoma.

    Science.gov (United States)

    Kurisaki-Arakawa, Aiko; Saito, Tsuyoshi; Takahashi, Michiko; Mitani, Keiko; Fukumura, Yuki; Nagashima, Yoji; Argani, Pedrum; Yao, Takashi

    2013-01-01

    Renal carcinomas associated with Xp11.2 translocations/transcription factor 3 (TFE3) gene fusion (Xp11 translocation RCC) are a rare subtype of renal cell carcinoma. A middle-aged Japanese man, who had a medical history of dialysis for more than 12 years, had bilateral renal cancers with a background of acquired cystic disease of the kidney and remarkable deposition of calcium oxalate in the tumorous area. The right renal tumor showed papillary architecture of clear cells with diffuse and strong immunoreactivity for TFE3 and focal and weak positivity for cathepsin K, suggesting a possibility of Xp11 translocation RCC. However, RT-PCR failed to detect any type of the reported fusion genes involving TFE3. Thus, the sample was sent for a TFE3 break-apart FISH assay in a renal tumor consultation service, which reported no evidence of TFE3 gene rearrangement. The right renal tumor was finally diagnosed as papillary renal cell carcinoma with cystic change. We report here a case of bilateral renal cell carcinoma in a patient undergoing long-term dialysis, which showed false-positive immunoreactivity for TFE3 immunostaining. Titration of TFE3 immunohistochemical staining (IHC) should be performed and cross-referenced with the FISH or RT-PCR results to avoid the misinterpretation of TFE3 IHC results. PMID:24228124

  16. Ruptured renal cell carcinoma in pregnancy: a rare case presentation

    Directory of Open Access Journals (Sweden)

    Prameela RC

    2016-05-01

    Full Text Available Malignancy in pregnancy is rare. Carcinomas in pregnancy are mostly kidney cell mass. Renal cell carcinoma (RCC is the commonest malignancy in pregnancy. Because of softness and increased vascularity, rupture of renal cell carcinoma is not uncommon. Here we are presenting a rare case of renal cell carcinoma in pregnancy with spontaneous rupture resulting in massive hemoperitoneum and serious outcome because of late presentation renal cell carcinoma seldom ruptures. A 26 year old woman G2P1L1 with term pregnancy was referred to hospital 80kms away from periphery with non-progression of labour. There was antenatal record suggesting hypertensive disorder of pregnancy in second trimester. On examination, patient was in hypovolemic shock with profuse distension of abdomen. Diagnosis of abruption grade 3 or rupture uterus was made and immediate laparotomy was done. On opening the abdomen, there was hemoperitoneum but uterus was intact. Emergency LSCS done extracted a stillborn baby. There were no retro placental clots also. There was lot of necrotic tissue in the abdomen and there was a tumour arising from lower pole of left kidney which had invaded the renal vessels and had ruptured. Peripartum hysterectomy and left nephrectomy was done. Women did not respond to treatment and died. The objective of presenting this case is the dilemmas faced by the obstetrician in case of shock in 2nd stage of labour. Simple diagnostic tool like renal ultrasound will help to detect at an early stage which could improve the outcome. All cases of hypertensive disorders of pregnancy should be investigated for secondary causes of hypertension. Abdominal USG must be done for all cases of hypertensive disorders of pregnancy in 2nd trimester. Prompt diagnosis and early treatment is the key in management of such condition in pregnancy. [Int J Reprod Contracept Obstet Gynecol 2016; 5(5.000: 1677-1679

  17. Inferior vena cava tumor thrombus after partial nephrectomy for renal cell carcinoma

    OpenAIRE

    Akatsuka, Jun; Suzuki, Yasutomo; Hamasaki, Tsutomu; Shindo, Takao; Yanagi, Masato; Kimura, Go; Yamamoto, Yoichiro; Kondo, Yukihiro

    2014-01-01

    Background Partial nephrectomy is now the gold standard treatment for small renal tumors. Local recurrence is a major problem after partial nephrectomy, and local recurrence in the remnant kidney after partial nephrectomy is common. Case presentation A 77-year-old man underwent right partial nephrectomy for a T1 right renal cell carcinoma. Microscopic examination revealed a clear cell renal carcinoma, grade 2, stage pT3a. Although the surgical margin was negative, the carcinoma invaded the pe...

  18. Targeted treatments in advanced renal cell carcinoma: focus on axitinib

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    Verzoni E

    2014-03-01

    Full Text Available Elena Verzoni, Paolo Grassi, Isabella Testa, Roberto Iacovelli, Pamela Biondani, Enrico Garanzini , Filippo De Braud, Giuseppe ProcopioDepartment of Medical Oncology 1, Fondazione IRCCS Istituto Nazionale Tumori, Milan, ItalyAbstract: Antiangiogenesis options have evolved rapidly in the last few years, with an increasing number of agents currently approved by the US Food and Drug Administration and European Medicines Agency. Angiogenesis inhibitors have been shown to be very effective for the treatment of metastatic renal cancer cell. Axitinib is a third-generation inhibitor of vascular endothelial growth factor receptor and is currently being developed for the treatment of various malignancies. The pharmacokinetic properties of axitinib may have a selective therapeutic effect, with minimal adverse reactions and enhanced safety. In a large Phase III study of previously treated patients with metastatic renal cell carcinoma, axitinib achieved a longer progression-free survival than sorafenib with an acceptable safety profile and good quality of life. This review focuses on the pharmacology, pharmacokinetics, and clinical activity of axitinib in the current treatment of renal cell carcinoma. The role of axitinib in the adjuvant and/or neoadjuvant setting needs to be evaluated in further clinical trials.Keywords: axitinib, renal cell carcinoma, vascular endothelial growth factor receptor, angiogenesis

  19. Simultaneous Development of Renal Cell Carcinoma and Multifocal Urothelial Carcinoma

    OpenAIRE

    Cheng-Keng Chuang; Heng-Chang Chuang; Kwai-Fong Ng

    2008-01-01

    Simultaneous occurrence of multifocal urothelial carcinoma (UC) and ipsilateral renalcell carcinoma (RCC) is rare. We report a 67-year-old woman with multifocal, infiltratingurothelial carcinoma and unilateral renal cell carcinoma. She was referred to our departmentbecause of painless gross hematuria. Cystoscopy, computed tomography and retrogradepyelography studies revealed bladder, bilateral renal and ureter UC. She was treated withtransurethral resection of the bladder tumor followed by bi...

  20. Obstructive jaundice due to ampullary metastasis of renal cell carcinoma

    OpenAIRE

    Karakatsanis, Andreas; Vezakis, Antonios; Fragulidis, Georgios; Staikou, Chryssa; Carvounis, Eleni E; Polydorou, Andreas

    2013-01-01

    Renal cell carcinoma is often characterized by the presence of metachronous metastases in unusual sites. The presence of isolated metastases is treated with surgical excision with good anticipated results. On the other hand, systemic chemotherapy is administered in the context of metastatic spread, usually sunitib or sorafenib. In such cases, however, the presence of symptomatic foci calls for minimal intervention. We present a case of a 77-year-old patient who presented with obstructive jaun...

  1. Nutlin-3 Enhances Sorafenib Efficacy in Renal Cell Carcinoma

    OpenAIRE

    Vatsyayan, Rit; Singhal, Jyotsana; Nagaprashantha, Lokesh Dalasanur; Awasthi, Sanjay; SINGHAL, SHARAD S.

    2011-01-01

    The renal cell carcinoma (RCC) is one of the top ten cancers in USA. The renal tumors are highly angiogenic and are resistant to conventional interventions, particularly radiotherapy. The advent of multispecific tyrosine kinase inhibitor sorafenib has improved the progression-free survival in RCC, but overall survival in recurrent and metastatic RCC is still a concern that has lead to characterization of combinatorial regimens. Hence, we studied the effect of combination of nutlin-3, an MDM2 ...

  2. An overview of renal cell cancer: Pathology and genetics

    OpenAIRE

    Moch, Holger

    2012-01-01

    Renal cell carcinoma is a group of malignancies arising from the epithelium of the renal tubules. The pattern of somatic mutations in kidney tumors has been extensively investigated. In the current 2004 WHO classification, the molecular background of a renal tumor has become, in addition to histopathology, a major criterion for tumor classification. The goal of this review is to discuss morphology and genetics of adult renal epithelial cancer included in the 2004 WHO classification and to men...

  3. Management of renal cell carcinoma presenting as inflammatory renal mass

    OpenAIRE

    Ehab Eltahawy; Mohamed Kamel; Mahmoud Ezzet

    2015-01-01

    Introduction: Renal cell carcinoma (RCC) can have a wide spectrum of clinical presentations. In the immunocompromised patient fever and an inflammatory renal mass can harbor RCC. Materials and Methods: We reviewed the charts of patients who were managed at our department during 1998-2008 as renal abscess or perinephric collection. Renal ultrasound and subsequently abdominal CT was done. Medical treatment in the form of antibiotics, control of diabetes and drainage was done. Percutaneous ...

  4. Renal cell carcinoma in dialysis patients. A single center experience

    International Nuclear Information System (INIS)

    Renal cell carcinoma (RCC) is a life-threatening complication of end-stage renal disease with an unclear pathogenesis. We evaluated RCC developing in patients undergoing dialysis. In 2624 patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis at our hospital between July 1993 and March 2004, we performed annual screening for RCC using abdominal computed tomography and ultrasonography. Patients diagnosed with RCC underwent radical nephrectomy as well as clinical and pathologic evaluation. RCC was detected in 44 patients (1.68%; 31 males and 13 females). The age of RCC patients was 55.5±11.1 years. Dialysis duration before RCC diagnosis was 11.2±7.2 years. Most RCC were early stage and low stage by TNM classification, 43 patients had N0M0 RCC, whereas one had N1M0. Tumor size was 2.9±1.9 cm. The predominant histological type of RCC was common or conventional cell-type carcinoma (clear cell carcinoma and granular cell carcinoma). Of patients, 5 (11.4%) had bilateral RCC, and satellite tumor lesions in RCC were detected in 13 (29.5%). In 36 patients (81.8%) RCC was accompanied by acquired cystic disease of the kidney. These patients had longer dialysis durations (P=0.01) and smaller tumors (P=0.048). RCC metastasized postoperatively in 4 patients (9.1%), while one (2.3%) died of cancer. Our dialysis patients showed a higher incidence of RCC than the general population. Prognosis was favorable because tumors were detected by screening when they were small. Therefore, periodical screening for RCC seems very important in dialysis patients. (author)

  5. Synchronous Bilateral Adrenal Metastases from Papillary Renal Cell Carcinoma

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    Kaan Gokcen

    2014-12-01

    Full Text Available We report a case of synchronous bilateral adrenal metastasis of renal cell carcinoma. The contralateral metastatic adrenal mass was treated by the laparoscopic transperitoneal approach. The renal mass and its huge ipsilateral metastatic adrenal gland were removed en bloc with open procedure. A 54-year-old man presented to our clinic with left-sid renal cell carcinoma synchronously bilateral adrenal metastases. The primary tumor was localized in the upper-mid pole of the kidney. The diagnosis was established preoperatively by computed tomography. The size of the contralateral adrenal mass was 65 x 45 mm, but the ipsilateral metastatic adrenal mass was huge (140 x 65 mm. After all analysis and other scannings for any metastasis, a contralateral lapararoscopic transperitoneal adrenalectomy and a left open nephroadrenalectomy were performed simultaneously. Synchronous bilateral adrenal metastases from primary renal cell carcinoma without another metastasis is very rare. The optimal surgical procedure should be selected according to the metastatic adrenal masses size and the patient%u2019s status.

  6. Feasibility of sentinel node detection in renal cell carcinoma: a pilot study

    International Nuclear Information System (INIS)

    Lymphatic drainage from renal cell carcinoma is unpredictable and the therapeutic benefit and extent of lymph node dissection are controversial. We evaluated the feasibility of intratumoural injection of a radiolabelled tracer to image and sample draining lymph nodes in clinically non-metastatic renal cell carcinoma. Eight patients with cT1-2 cN0 cM0 (99mTc-nanocolloid under ultrasound guidance (0.4 ml, 225 MBq at one to four intratumoural locations depending on tumour size). Lymphoscintigraphy was performed 20 min, 2 h and 4 h after injection. After the delayed images a hybrid SPECT/CT was performed. SPECT was fused with CT to determine the anatomical localization of the sentinel node. Surgery with sampling was performed the following day using a gamma probe and a portable mini gamma camera. Eight patients, seven with right-sided renal cell carcinoma, were included with a mean age of 55 years (range: 45-77). The mean tumour size was 4 cm (range: 3.5-6 cm). Six patients had sentinel nodes on scintigraphy (two retrocaval, four interaortocaval, including one hilar) with one extraretroperitoneal location along the internal mammary chain. All nodes could be mapped and sampled. In two patients no drainage was visualized. Renal cell carcinomas were of clear cell subtype with no lymph node metastases. Sentinel node identification using preoperative and intraoperative imaging to locate and sample the sentinel node at surgery in renal cell carcinoma is feasible. Sentinel node biopsy may clarify the pattern of lymphatic drainage and extent of lymphatic spread which may have diagnostic and therapeutic implications. (orig.)

  7. Class I histone deacetylases 1, 2 and 3 are highly expressed in renal cell cancer

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    Jung Klaus

    2008-12-01

    Full Text Available Abstract Background Enhanced activity of histone deacetylases (HDAC is associated with more aggressive tumour behaviour and tumour progression in various solid tumours. The over-expression of these proteins and their known functions in malignant neoplasms has led to the development of HDAC inhibitors (HDI as new anti-neoplastic drugs. However, little is known about HDAC expression in renal cell cancer. Methods We investigated the expression of HDAC 1, 2 and 3 in 106 renal cell carcinomas and corresponding normal renal tissue by immunohistochemistry on tissue micro arrays and correlated expression data with clinico-pathological parameters including patient survival. Results Almost 60% of renal cell carcinomas expressed the HDAC isoforms 1 and 2. In contrast, HDAC 3 was only detected in 13% of all renal tumours, with particular low expression rates in the clear cell subtype. HDAC 3 was significantly higher expressed in pT1/2 tumours in comparison to pT3/4 tumours. Expression of class I HDAC isoforms correlated with each other and with the proliferative activity of the tumours. We found no prognostic value of the expression of any of the HDAC isoforms in this tumour entity. Conclusion Class I HDAC isoforms 1 and 2 are highly expressed in renal cell cancer, while HDAC 3 shows low, histology dependent expression rates. These unexpected differences in the expression patterns suggests alternative regulatory mechanisms of class I HDACs in renal cell cancer and should be taken into account when trials with isoform selective HDI are being planned. Whether HDAC expression in renal cancers is predictive of responsiveness for HDI will have to be tested in further studies.

  8. Class I histone deacetylases 1, 2 and 3 are highly expressed in renal cell cancer

    International Nuclear Information System (INIS)

    Enhanced activity of histone deacetylases (HDAC) is associated with more aggressive tumour behaviour and tumour progression in various solid tumours. The over-expression of these proteins and their known functions in malignant neoplasms has led to the development of HDAC inhibitors (HDI) as new anti-neoplastic drugs. However, little is known about HDAC expression in renal cell cancer. We investigated the expression of HDAC 1, 2 and 3 in 106 renal cell carcinomas and corresponding normal renal tissue by immunohistochemistry on tissue micro arrays and correlated expression data with clinico-pathological parameters including patient survival. Almost 60% of renal cell carcinomas expressed the HDAC isoforms 1 and 2. In contrast, HDAC 3 was only detected in 13% of all renal tumours, with particular low expression rates in the clear cell subtype. HDAC 3 was significantly higher expressed in pT1/2 tumours in comparison to pT3/4 tumours. Expression of class I HDAC isoforms correlated with each other and with the proliferative activity of the tumours. We found no prognostic value of the expression of any of the HDAC isoforms in this tumour entity. Class I HDAC isoforms 1 and 2 are highly expressed in renal cell cancer, while HDAC 3 shows low, histology dependent expression rates. These unexpected differences in the expression patterns suggests alternative regulatory mechanisms of class I HDACs in renal cell cancer and should be taken into account when trials with isoform selective HDI are being planned. Whether HDAC expression in renal cancers is predictive of responsiveness for HDI will have to be tested in further studies

  9. Oncogenic micro-RNAs and Renal Cell Carcinoma

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    Cristina eGrange

    2014-03-01

    Full Text Available Tumor formation is a complex process that occurs in different steps and involves many cell types, including tumor cells, endothelial cells, and inflammatory cells, which interact to promote growth of the tumor mass and metastasization. Epigenetic alterations occurring in transformed cells result in de-regulation of miRNA expression (a class of small non-coding RNA that regulates multiple functions which contributes to tumorigenesis. The specific miRNAs, which have an aberrant expression in tumors, are defined as oncomiRNAs, and may be either over- or under-expressed, but down-regulation is most commonly observed.Renal cell carcinoma is a frequent form of urologic tumor, associated with an alteration of multiple signaling pathways. Many molecules involved in the progression of renal cell carcinomas, such as HIF, VEGF or mTOR, are possible targets of deregulated miRNAs. Within tumor mass, the cancer stem cell population is a fundamental component that promotes tumor growth. The cancer stem cell hypothesis postulates that cancer stem cells have the unique ability to self-renew and to maintain tumor growth and metastasis. Cancer stem cells present in renal cell carcinoma were shown to express the mesenchymal stem cell marker CD105 and to exhibit self-renewal and clonogenic properties, as well as the ability to generate serially transplantable tumors. The phenotype of cancer stem cell has been related to the potential to undergo the epithelial-mesenchymal transition, which has been linked to the expression pattern of tumorigenic miRNAs or down-regulation of anti-tumor miRNAs. In addition, the pattern of circulating miRNAs may allow discrimination between healthy and tumor patients. Therefore, a miRNA signature may be used as a tumor biomarker for cancer diagnosis, as well as to classify the risk of relapse and metastasis, and for a guide for therapy.

  10. Papillary renal cell carcinoma with metastatic laparoscopic port site and vaginal involvement: a case report

    Directory of Open Access Journals (Sweden)

    Fong Kah

    2011-04-01

    Full Text Available Abstract Introduction Laparoscopic port-site metastasis is a rare but well recognized outcome following surgery in urological cancers, with its etiology not clearly understood. Additionally, vaginal metastasis in clear cell renal cell carcinoma is rare, and has not been previously reported in the setting of papillary renal cell carcinoma. Case presentation We present the case of a 71-year-old Chinese woman with metastatic type II papillary renal cell carcinoma with histologically verified vaginal involvement and a concurrent laparoscopic port-site metastasis. This was also associated with a unique constellation of widely disseminated metastatic sites, which include a local relapse, the peritoneum and the urethra. Conclusion Laparoscopic port-site metastases are associated with the presence of advanced cancer with multiple sites of metastasis. We hypothesize from the findings of our report and background data that this phenomenon is more likely to be related to tumor factors rather than operative factors. We also present what is, to the best of our knowledge, the first reported case in the literature of vaginal and urethral metastasis and the second reported case of laparoscopic port-site recurrence.

  11. Clonal expansion of renal cell carcinoma-infiltrating T lymphocytes

    DEFF Research Database (Denmark)

    Sittig, Simone; Køllgaard, Tania; Grønbæk, Kirsten;

    2013-01-01

    T lymphocytes can mediate the destruction of cancer cells by virtue of their ability to recognize tumor-derived antigenic peptides that are presented on the cell surface in complex with HLA molecules and expand. Thus, the presence of clonally expanded T cells within neoplastic lesions is an...... indication of ongoing HLA-restricted T cell-mediated immune responses. Multiple tumors, including renal cell carcinomas (RCCs), are often infiltrated by significant amounts of T cells, the so-called tumor-infiltrating lymphocytes (TILs). In the present study, we analyzed RCC lesions (n = 13) for the presence...... of expanded T-cell clonotypes using T-cell receptor clonotype mapping. Surprisingly, we found that RCCs comprise relatively low numbers of distinct expanded T-cell clonotypes as compared with melanoma lesions. The numbers of different T-cell clonotypes detected among RCC-infiltrating lymphocytes were...

  12. Optimal management of metastatic renal cell carcinoma: current status.

    Science.gov (United States)

    Escudier, Bernard; Albiges, Laurence; Sonpavde, Guru

    2013-04-01

    The armamentarium for the systemic therapy of advanced renal cell carcinoma (RCC) has undergone dramatic changes over the past 6 years. While high-dose interleukin (IL)-2 remains an option for highly selected good and intermediate risk patients with clear-cell histology because of durable complete responses in a small fraction of patients, cytokine-based therapy including interferon (IFN) has been supplanted by vascular-endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors. Treatment decision is initially based on prognostication of the disease. As metastatic RCC (mRCC) is commonly an indolent disease, a period of observation should always been considered. For good and intermediate risk disease, pazopanib, sunitinib or the combination of bevacizumab plus IFN are considered. Notably, recent data suggest non-inferiority for the efficacy of pazopanib compared to sunitinib coupled with a better toxicity profile. A novel VEGF receptor inhibitor, tivozanib, is expected to be approved based on improvement in PFS when compared to sorafenib in the first-line setting. The use of temsirolimus for poor risk disease is supported by a phase III trial dedicated to this group of patients. The role of cytoreductive nephrectomy in the context of VEGF and mTOR inhibitors is being studied in randomized trials. Selected patients with solitary or oligometastatic disease may be eligible for metastatectomy. Following first-line VEGF inhibitors, second-line therapy with everolimus and axitinib have demonstrated benefits in progression-free survival (PFS). One phase III trial comparing sorafenib and temsirolimus in the post-sunitinib setting showed no difference in PFS, the primary endpoint, but did show a superior overall survival for sorafenib. Sorafenib, pazopanib and axitinib have all demonstrated clinical benefit following cytokines. Therapy following first-line mTOR inhibitors remains undefined, although VEGF inhibitors have demonstrated activity in

  13. Renal cell carcinoma with bilateral synchronous adrenal gland metastases: a case report

    OpenAIRE

    Koutalellis, Georgios E; Felekouras, Evangelos; Evangelou, Constantinos; Koritsiadis, Georgios; Chasiotis, Dimitrios; Anastasiou, Ioannis

    2009-01-01

    Introduction Renal cell carcinoma is characterized by its potential of metastasizing widely and to unusual sites, with the metastases occasionally preceding clinical recognition of the primary tumor. Synchronous bilateral adrenal metastases from renal cell carcinoma, without other metastases, are rare and, to our knowledge, only 17 cases have been published in the literature to date. In general, patients with synchronous bilateral adrenal metastases from renal cell carcinoma have a poor progn...

  14. Sarcomatoid Renal Cell Carcinoma Metastasis to the Penis

    OpenAIRE

    Liou, Victor D.; Darwish, Oussama M.; Henry, Mary M.; Jun, Ik C.; Siddiqui, Sameer A.

    2015-01-01

    Secondary cancers of the penis are extremely uncommon with less than 300 cases reported in the past 100 years. These cancers are most frequently a result of an aggressive or poorly managed primary prostate or bladder cancer and rarely a metastasis from a primary kidney tumor. Currently, there is no published literature which describes the spread of sarcomatoid renal cell carcinoma (SRCC) to the penis. In this report, we present a 55-year-old-man who presented with a large right-sided SRCC wh...

  15. Penoscrotal lymphedema associated with metastatic renal cell carcinoma.

    Science.gov (United States)

    Crawley, David; Haddock, Peter; Jackson, Max; Kamradt, Jeffrey; Kesler, Stuart

    2015-08-01

    A 64-year-old male presented with lower back pain, radiating in a sciatic-type distribution, swelling in his lower abdomen and right leg, and edema of the scrotum and penile shaft. A sonogram and CT imaging indicated an enhancing mass in the right kidney and a spinal metastasis. The right lower extremity and penoscrotal lymphedema was caused by lymphatic obstruction due to a sacral metastasis of renal cell carcinoma. He was treated with cytoreductive nephrectomy, radiation and a systemic tyrosine kinase inhibitor. Pelvic imaging is suggested to determine whether malignant lymphatic obstruction is present when presented with idiopathic penoscrotal edema. PMID:26267035

  16. Colon metastasis of chromophobe renal cell carcinoma with sarcomatoid change

    Institute of Scientific and Technical Information of China (English)

    ZHAO Wei-ping; YU Yan-lan; CHEN Zhi-qiang; HUANG Xue-feng; ZHANG Zhi-gen

    2012-01-01

    We present a rare case of colonic metastasis of renal cell carcinoma (RCC) and review the literature.A 54-year-old male was referred to our hospital with a history of bloody stools and fever.A dght kidney tumor measuring about 10 cm in diameter was found by abdominal computed tomography.Right radical nephrectomy and a right hemicolectomy with ileotransversostomy were performed.Pathological diagnosis was chromophobe RCC with sarcomotoid change involving the colon.Chromophobe RCC with sarcomotoid change is very rare.

  17. IMMUNOLOGICAL MONITORING OF BIOTHERAPY FOR DISSEMINATED RENAL-CELL CARCINOMA

    OpenAIRE

    O. E. Molchanov; M. I. Karelin

    2009-01-01

    Objective: to assess a role of immunomonitoring in patients with disseminated renal-cell carcinoma.  Subjects and methods. One hundred and seventy-five patients treated in 1998 to 2008 were followed up. The patients received various immunochemotherapy regimens including interleukin-2 (IL-2), interferon-α (IFN-α), Xeloda, cyclophosphamide. The immune status, including lymphocytes and their subpopulations, cytokine components (IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12; IFN-α, IFN-γ; tumor necr...

  18. Molecular features of renal cell carcinoma: early diagnostics and perspectives for therapy

    OpenAIRE

    O. V. Kovaleva; O. R. Nazarova; V. B. Matveev; A. N. Gratchev

    2015-01-01

    Kidney cancer (renal cell carcinoma) is one of the major problems of modern urological oncology. In Russia renal cell carcinoma accountsfor 4.3 % of all cancers. The global incidence of renal cell carcinoma has increased over the past two decades. Worldwide renal cell carcinoma accounts for 3.6 % of all cancers and is 10th frequent malignancy. For some malignancies, for instance tumours of prostate, there are markers known that allowed improved early diagnostics. Kidney cancer, however, remai...

  19. Acid, basic, and neutral peptidases present different profiles in chromophobe renal cell carcinoma and in oncocytoma.

    Science.gov (United States)

    Blanco, Lorena; Larrinaga, Gorka; Pérez, Itxaro; López, José I; Gil, Javier; Agirregoitia, Ekaitz; Varona, Adolfo

    2008-04-01

    Renal cell carcinomas (RCCs) are neoplasias with high prevalence and mortality. We previously reported that several peptidases may be involved in the pathophysiology of clear cell renal cell carcinoma (CCRCC). Now, to gain insight into the reasons that lead the various RCC types to behave very differently with regard to aggressiveness and response to anticancer treatments, we analyzed subsets of chromophobe renal cell carcinoma (ChRCC), and renal oncocytoma (RO), a benign tumor; as well as different grades and stages of CCRCCs. Particulate APN, APB, and APA activities were decreased in both ChRCC and RO (tumor vs. nontumor tissues). Interestingly, activities were downregulated in a tumor-type specific way and the intensities of the decreases were stronger in the benign tumor than in the malignant type. Moreover, when two key histopathological parameters for tumor prognosis (high vs. low stage and grade) were analyzed, increases of activity were also observed in several of these cell surface peptidases (APN, APB). Some soluble activities (APB, Asp-AP) were also downregulated in the RCCs. With respect to genetic expression, PSA and APN were in a positive correlation related to their activities in both ChRCC and RO; but not APB, Asp-AP, APA, and PGI. These results may suggest an involvement of several peptidases in the pathophysiology of renal cancer, since they presented different patterns of activity and expression in tumors with different behaviors. PMID:18216146

  20. Everolimus – a new approach in the treatment of renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    G Anandappa

    2010-03-01

    Full Text Available G Anandappa, AE Hollingdale, TG EisenDepartment of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UKAbstract: With the increasing understanding of the biology of the disease and the development of targeted therapy, there has been a paradigm shift in the treatment of clear cell metastatic renal cell carcinoma (mRCC. Traditionally patients with metastatic RCC have been treated with immunotherapy which has limited efficacy. The multikinase inhibitors sunitinib, sorafenib and pazopanib, the VEGF antibody bevacizumab in combination with interferon and the mTOR inhibitor temsirolimus have all been shown to prolong progression-free survival in phase III studies. Here we review another mTOR inhibitor, everolimus (Afinitor®; Novartis, USA which was approved in March 2009 by the US FDA for treatment of targeted-therapy refractory metastatic renal cell cancer. The phase III study of everolimus (the RECORD study was terminated early after a significant difference in efficacy was noted in the treatment arm with everolimus (progression-free survival of 4.0 months in patients on the treatment arm vs 1.9 months in the placebo arm. The most common adverse events were stomatitis, pneumonitis, fatigue and infections. We review Phase I–III data with a particular emphasis on safety data and patient focused outcomes.Keywords: metastatic renal cell carcinoma, targeted therapy, mTOR, everolimus

  1. Use of FISH analysis for diagnosis of Renal Cell Carcinoma Subtypes

    International Nuclear Information System (INIS)

    Cytogenetic and molecular genetic techniques have been used in demonstrating the chromsomal abnormalities which characterize specific subtypes of renal cell carcinoma (RCC). The aim this study was to determine the efficiency of fluorescent in situ hybridization (FISH) technique in characterizing various subtypes of RCC based on the presence of specific chromosome abnormalities found in each RCC subtype. FISH was performed on touch imprint smears from eight renal cell carcinomas histologically confirmed by established criteria. In four tumors with histologic features of chromophobe renal cell carcinoma (ChRCC), interphase fish was performed using centrometric probes for chrosomes 1, 2, 6, 10, 12, 17 and 21. All four ChRCC tumors showed one FIISH signal corresponding to one copy number for each of these chromosomes. Two papillary RCCs included in this study showed trisomy 7 and 17, and loss of chromosome Y, using the corresponding chromosome centrometric probes. Similarly, we tested two clear cell RCCs for chromosome 3 short arm deletion with DNA probe 3p21.3. Both tumors showed loss of 3p21.3 signal. We conclude that interphase fish performed on touch imprint smears is a relatively simple, rapid and reliable method for detecting chromosome abnormalities which are specific for various subtypes of RCC. (author)

  2. Sarcomatoid differentiation in renal cell carcinoma: prognostic implications

    Directory of Open Access Journals (Sweden)

    Marcos F. Dall'Oglio

    2005-02-01

    Full Text Available INTRODUCTION: Renal cell carcinoma with sarcomatoid differentiation is a tumor with aggressive behavior that is poorly responsive to immunotherapy. The objective of this study is to report our experience in the treatment of 15 patients with this tumor. MATERIALS AND METHODS: We retrospectively analyzed 15 consecutive cases of renal cell carcinoma with sarcomatoid differentiation diagnosed between 1991 and 2003. The clinical presentation and the pathological stage were assessed, as were the tumor's pathological features, use of adjuvant immunotherapy and survival. The study's primary end-point was to assess survival of these individuals. RESULTS: The sample included 8 women and 7 men with mean age of 63 years (44 - 80; follow-up ranged from 1 to 100 months (mean 34. Upon presentation, 87% were symptomatic and 4 individuals had metastatic disease. Mean tumor size was 9.5 cm (4 - 24 with the following pathological stages: 7% pT1, 7% pT2, 33% pT3, and 53% pT4. The pathological features showed high-grade tumors with tumoral necrosis in 87% of the lesions and 80% of intratumoral microvascular invasion. Disease-free and cancer-specific survival rates were 40 and 46% respectively, with 2 cases responding to adjuvant immunotherapy. CONCLUSIONS: Patients with sarcomatoid tumors of the kidney have a low life expectancy, and sometimes surgical resection associated with immunotherapy can lead to a long-lasting therapeutic response.

  3. Epidemiology, molecular epidemiology, and risk factors for renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Chiara Paglino

    2011-12-01

    Full Text Available Despite only accounting for approximately 2% of all new primary cancer cases, renal cell carcinoma (RCC incidence has dramatically increased over time. Incidence rates vary greatly according to geographic areas, so that it is extremely likely that exogenous risk factors could play an important role in the development of this cancer. Several risk factors have been linked with RCC, including cigarette smoking, obesity, hypertension (and antihypertensive drugs, chronic kidney diseases (also dialysis and transplantation, as well as the use of certain analgesics. Furthermore, although RCC has not generally been considered an occupational cancer, several types of occupationally-derived exposures have been implicated in its pathogenesis. These include exposure to asbestos, chlorinated solvents, gasoline, diesel exhaust fumes, polycyclic aromatic hydrocarbons, printing inks and dyes, cadmium and lead. Finally, families with a predisposition to the development of renal neoplasms were identified and the genes involved discovered and characterized. Therefore, there are now four well-characterized, genetically determined syndromes associated with an increased incidence of kidney tumors, i.e., Von Hippel Lindau (VHL, Hereditary Papillary Renal Carcinoma (HPRC, Birt-Hogg-Dubé Syndrome (BHD, and Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC. This review will address present knowledge about the epidemiology, molecular epidemiology and risk factors of RCC.

  4. MRI of renal cell carcinoma in hemodialyzed kidneys

    International Nuclear Information System (INIS)

    We evaluated MRI findings of 7 cases of renal cell carcinomas developed in patients with long-term hemodialysis. There were 4 men and 3 women with their ages from 46 to 82 years (mean; 59). They had undergone hemodialysis from 4 years and 10 months, to 20 years (mean; 11 years and 10 months). On T1-weighted images the tumors showed a high intensity to renal parenchyma in 6 of 7 cases. On T2-weighted images they showed either an iso or high intensity except one case with a low intensity. On dynamic studies with Gd-DTPA 6 of 7 cases showed an early enhancement with a distinct delineation of the tumor. Acquired cystic disease of the kidneys was present in 6 of 7 cases. There was no side effect due to Gd-DTPA. We conclude that a dynamic MRI study with Gd-DTPA is useful for the diagnosis of renal cell carcinoma in hemodialyzed kidney. (J.P.N.)

  5. MRI of renal cell carcinoma in hemodialyzed kidneys

    Energy Technology Data Exchange (ETDEWEB)

    Kawasaki, Yoshimichi; Nakamura, Katsumi; Egashira, Kanji; Nakata, Hajime; Kaizu, Kazo; Okamura, Tomohiko; Sugita, Atsuo [University of Occupational and Environmental Health, Kitakyushu, Fukuoka (Japan)

    1995-12-01

    We evaluated MRI findings of 7 cases of renal cell carcinomas developed in patients with long-term hemodialysis. There were 4 men and 3 women with their ages from 46 to 82 years (mean; 59). They had undergone hemodialysis from 4 years and 10 months, to 20 years (mean; 11 years and 10 months). On T1-weighted images the tumors showed a high intensity to renal parenchyma in 6 of 7 cases. On T2-weighted images they showed either an iso or high intensity except one case with a low intensity. On dynamic studies with Gd-DTPA 6 of 7 cases showed an early enhancement with a distinct delineation of the tumor. Acquired cystic disease of the kidneys was present in 6 of 7 cases. There was no side effect due to Gd-DTPA. We conclude that a dynamic MRI study with Gd-DTPA is useful for the diagnosis of renal cell carcinoma in hemodialyzed kidney. (J.P.N.).

  6. [Renal cell carcinoma metastasizing to choroid plexus of lateral ventricle; a case report].

    Science.gov (United States)

    Mizuno, M; Asakura, K; Nakajima, S; Sampei, T; Sayama, I; Kawamura, S; Yasui, N; Fukazawa, H

    1992-04-01

    A rare case of renal cell carcinoma metastasizing to the choroid plexus of the lateral ventricle is reported. A 59-year-old woman was admitted to our institution on November 26, 1987 complaining of left-half headache for one month. She had a past history of right nephrectomy due to renal cell carcinoma 4 years before admission, and of right radical mastectomy due to breast cancer 10 years before admission. She had no abnormal neurological findings and laboratory results were normal. CT scan revealed a well-circumscribed, apparently homogeneously enhancing mass in the left lateral ventricle with mild ventricular dilatation. Left vertebral angiogram showed a tumor stain fed by the left posterior choroidal artery. The most likely diagnosis was thought to be metastasis of renal cell carcinoma. The patient underwent the operation for tumor removal via the posterior interhemispheric transcallosal approach 14 days after admission. A histological examination of the tumor determined the diagnosis of clear-cell type renal cell carcinoma. The operation was uneventful and the patient was discharged 20 days after operation without neurological deficit. But she had recent-memory disturbance, low activity, and gait disturbance in May 1989. CT scan revealed ventricular dilatation and tumor recurrence at the same site. She also suffered from diabetes due to the regrowth and invasion of primary tumor to the pancreas. She was discharged free of neurological defects after ventriculo-peritoneal shunt. In December 1989, she gradually deteriorated due to the regrowth of the intraventricular metastatic lesion, and now she is bedridden. Choroid plexus metastasis is quite rare, and, to our knowledge, only three cases have been described. PMID:1570073

  7. Circulating Tumor Cell Composition in Renal Cell Carcinoma

    Science.gov (United States)

    Bublitz, Kira; Lazaridis, Lazaros; Goergens, André; Giebel, Bernd; Schuler, Martin; Hoffmann, Andreas-Claudius

    2016-01-01

    Purpose Due to their minimal-invasive yet potentially current character circulating tumor cells (CTC) might be useful as a “liquid biopsy” in solid tumors. However, successful application in metastatic renal cell carcinoma (mRCC) has been very limited so far. High plasticity and heterogeneity of CTC morphology challenges currently available enrichment and detection techniques with EpCAM as the usual surface marker being underrepresented in mRCC. We recently described a method that enables us to identify and characterize non-hematopoietic cells in the peripheral blood stream with varying characteristics and define CTC subgroups that distinctly associate to clinical parameters. With this pilot study we wanted to scrutinize feasibility of this approach and its potential usage in clinical studies. Experimental Design Peripheral blood was drawn from 14 consecutive mRCC patients at the West German Cancer Center and CTC profiles were analyzed by Multi-Parameter Immunofluorescence Microscopy (MPIM). Additionally angiogenesis-related genes were measured by quantitative RT-PCR analysis. Results We detected CTC with epithelial, mesenchymal, stem cell-like or mixed-cell characteristics at different time-points during anti-angiogenic therapy. The presence and quantity of N-cadherin-positive or CD133-positive CTC was associated with inferior PFS. There was an inverse correlation between high expression of HIF1A, VEGFA, VEGFR and FGFR and the presence of N-cadherin-positive and CD133-positive CTC. Conclusions Patients with mRCC exhibit distinct CTC profiles that may implicate differences in therapeutic outcome. Prospective evaluation of phenotypic and genetic CTC profiling as prognostic and predictive biomarker in mRCC is warranted. PMID:27101285

  8. Rationale for targeted therapies and potential role of pazopanib in advanced renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Peter E Clark

    2010-06-01

    Full Text Available Peter E ClarkVanderbilt University Medical Center, Nashville, Tennessee, USAAbstract: Advanced renal cell carcinoma (RCC remains a challenging, major health problem. Recent advances in understanding the fundamental biology underlying one form of RCC, ie, clear cell (or conventional RCC, have opened the door to a series of targeted agents, such as the tyrosine kinase inhibitors (TKIs, which have become the standard of care in managing advanced clear cell RCC. Among the newest of these agents to receive Food and Drug Administration approval in this disease is pazopanib. This review will summarize what is known about the fundamental biology that underlies clear cell RCC, the data surrounding the previously approved targeted agents for this disease, including not only the TKIs but also the mTOR inhibitors and the vascular endothelial growth factor-specific agent, bevacizumab, and the newest TKI, pazopanib. It will also explore the potential role for pazopanib relative to the other available agents and where it may fit into the armamentarium for treatment of advanced/metastatic RCC.Keywords: pazopanib, targeted therapy, tyrosine kinase inhibitor, clear cell renal cell carcinoma

  9. Renal cell carcinoma with metastasis to the submandibular and parotid glands A case report

    NARCIS (Netherlands)

    Smits, J.G.; Slootweg, P.J.

    1984-01-01

    Differential diagnosis between acinic cell carcinoma and renal cell carcinoma is an oft-quoted problem. A case is presented of a 60-year-old woman with metastatic lesions from a renal cell carcinoma to the parotid as well as the submandibular gland. Appropriate diagnosis was delayed due to lack of c

  10. Whole-body MRI in follow-up of patients with renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Platzek, Ivan; Zastrow, Stefan; Deppe, Pierre-Emanuel; Laniado, Michael; Stroszczynski, Christian (Dept. of Radiology, Dresden Univ. of Technology, Dresden (Germany)), e-mail: ivan.platzek@uniklinikum-dresden.de; Grimm, Marc-Oliver; Wirth, Manfred (Dept. of Urology, Dresden Univ. of Technology, Dresden (Germany))

    2010-06-15

    Background: Recent technological advances have made whole-body MRI feasible within a reasonable time-frame. The clinical utility of whole-body MRI in patients with renal cell carcinoma has not been evaluated yet. Purpose: To compare the diagnostic accuracy of whole-body MRI and computed tomography (CT) in follow-up of patients with renal cell carcinoma. Material and Methods: In 28 patients with primary renal cell carcinoma a multislice CT scan of the thorax, abdomen, and pelvis, and a whole-body MRI were carried out as part of the postoperative follow-up. A combination of subsequent imaging studies and histology served as standard of reference. Results: MRI demonstrated a significantly better diagnostic accuracy regarding musculoskeletal metastases compared with CT (97.7% vs 82%, P<0.001). In contrast, CT was superior in the detection of pulmonary metastases (88.5% vs 71.9%, P<0.001). Both methods had similar diagnostic performance regarding lymph node metastases (CT, accuracy 82.4%; MRI, accuracy 83.4%, P=0.25). The concordance of both modalities regarding N and M stage was excellent (Cohen's kappa 1.00). In two patients cerebral metastases were revealed by MRI, which led to a change in therapy. Conclusion: At this stage, whole-body MRI cannot be considered an adequate replacement for CT in the follow-up of patients with renal cell carcinoma. Further significant improvement of lung MR protocols is necessary, as CT's sensitivity for pulmonary nodules is clearly superior. In contrast, the main advantage of whole-body MRI is its high diagnostic accuracy for musculoskeletal metastases

  11. Whole-body MRI in follow-up of patients with renal cell carcinoma

    International Nuclear Information System (INIS)

    Background: Recent technological advances have made whole-body MRI feasible within a reasonable time-frame. The clinical utility of whole-body MRI in patients with renal cell carcinoma has not been evaluated yet. Purpose: To compare the diagnostic accuracy of whole-body MRI and computed tomography (CT) in follow-up of patients with renal cell carcinoma. Material and Methods: In 28 patients with primary renal cell carcinoma a multislice CT scan of the thorax, abdomen, and pelvis, and a whole-body MRI were carried out as part of the postoperative follow-up. A combination of subsequent imaging studies and histology served as standard of reference. Results: MRI demonstrated a significantly better diagnostic accuracy regarding musculoskeletal metastases compared with CT (97.7% vs 82%, P<0.001). In contrast, CT was superior in the detection of pulmonary metastases (88.5% vs 71.9%, P<0.001). Both methods had similar diagnostic performance regarding lymph node metastases (CT, accuracy 82.4%; MRI, accuracy 83.4%, P=0.25). The concordance of both modalities regarding N and M stage was excellent (Cohen's kappa 1.00). In two patients cerebral metastases were revealed by MRI, which led to a change in therapy. Conclusion: At this stage, whole-body MRI cannot be considered an adequate replacement for CT in the follow-up of patients with renal cell carcinoma. Further significant improvement of lung MR protocols is necessary, as CT's sensitivity for pulmonary nodules is clearly superior. In contrast, the main advantage of whole-body MRI is its high diagnostic accuracy for musculoskeletal metastases

  12. Review of the Interaction Between Body Composition and Clinical Outcomes in Metastatic Renal Cell Cancer Treated With Targeted Therapies

    OpenAIRE

    Steven M Yip; Heng, Daniel Y. C.; Tang, Patricia A.

    2016-01-01

    Treatment of metastatic renal cell cancer (mRCC) currently focuses on inhibition of the vascular endothelial growth factor pathway and the mammalian target of rapamycin (mTOR) pathway. Obesity confers a higher risk of RCC. However, the influence of obesity on clinical outcomes in mRCC in the era of targeted therapy is less clear. This review focuses on the impact of body composition on targeted therapy outcomes in mRCC. The International Metastatic Renal Cell Carcinoma Database Consortium dat...

  13. Coexistence of subacute thyroiditis and renal cell carcinoma: a paraneoplastic syndrome

    OpenAIRE

    Algün, Ekrem; ALICI, Süleyman; Topal, Cevat; Ugras, Serdar; Erkoç, Reha; Sakarya, M.Emin; Özbey, Nese

    2003-01-01

    RENAL CELL CARCINOMA IS CHARACTERIZED by varied manifestations, which include unusual metastatic sites and paraneoplastic and vascular syndromes. We describe the case of a 57-year-old man who presented with high fever, weight loss, palpitations and a tender goitre. We suggest that, in this patient, subacute thyroiditis manifested as a paraneoplastic syndrome of renal cell carcinoma.

  14. The dreadful and the deadly erection—Malignant priapism from renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Cheng-Ling Lee

    2014-12-01

    Full Text Available Penile metastasis of renal cell carcinoma is a rare occurrence. We report a case in a 44-year-old man who presented with malignant priapism as the first sign of recurrence of renal cell carcinoma. Although invasive procedures have a limited role in survival benefits, we performed a total penectomy to alleviate pain and provide a better quality of life.

  15. Papillary renal cell carcinoma with lipocyte-like cells: A rare morphological variant or an indication of aggressiveness?

    Directory of Open Access Journals (Sweden)

    Sari Aysegul

    2010-07-01

    Full Text Available Papillary renal cell carcinoma (PRCC is the second most common carcinoma of the kidney, which is classified into two types. Type 1 displays single layer of cells with scanty pale cytoplasm and type 2 has pseudostratified high-grade nuclei with eosinophilic cytoplasm. Recently, apart from these two types, oncocytic PRCC and clear-cell PRCC have been described. To the best of our knowledge, lipocyte-like cells have not yet been reported to accompany any subtypes of renal cell carcinoma. Herein, we report a case of PRCC with lipocyte-like cells and sarcomatoid features. Lipocyte-like cells might represent a special type of PRCC or this feature may be an indication of poor prognosis regarding its association with sarcomatoid change.

  16. Cytodiagnosis of cutaneous metastasis from renal cell carcinoma: A case report with review of literature

    Directory of Open Access Journals (Sweden)

    Vishal Dhingra

    2011-01-01

    Full Text Available Cytodiagnosis of cutaneous metastasis of renal cell carcinoma (RCC in the absence of history of primary tumor is difficult as it can be confused with other clear cell tumors. We report here a case of cytodiagnosis of cutaneous metastasis of RCC in a patient who had nephrectomy done 9 years back at some other centre, but did not have any records with him. Clinicians should be aware of the possibility of primary internal organ malignancy in patients presenting with cutaneous lesions and therefore conduct a careful examination and get necessary investigations. Prompt diagnosis and treatment will have its bearing on the eventual outcome.

  17. Bilateral renal cell carcinoma in a horseshoe kidney: preoperative assessment with MRI and digital subtraction angiography

    International Nuclear Information System (INIS)

    Renal cell carcinoma in a horseshoe kidney is an unusual entity. To our knowledge, only 123 cases have been published to date. We report the first bilateral case of two clear-cell carcinomas in an asymmetrically fused kidney. Optimum preservation of renal function after radical tumor removal requires accurate preoperative imaging. Since the vascular supply in fusion anomalies is extremely variable, angiography is mandatory. Magnetic resonance imaging was most suitable to predict the tumor extent and localization, because it simultaneously gave the most comprehensive anatomical overview of the malformation. (orig.)

  18. A case of metastatic renal cell carcinoma treated effectively by gemcitabine and sunitinib

    OpenAIRE

    Morizane, Shuichi; Iwamoto, Hideto; Yao, Akihisa; Isoyama, Tadahiro; Sejima, Takehiro; Takenaka, Atsushi

    2012-01-01

    A 60-year-old man with renal cell carcinoma developed lung metastases after treatment with left radical nephrectomy (pT3bN0M0, clear cell renal carcinoma, Fuhrman G3 >2). The patient received treatment with gemcitabine and interferon-α and achieved complete response after seven cycles of therapy. However, eight months later, local recurrence was discovered in the renal fossa. We changed the therapeutic strategy to sunitinib, a multi-target tyrosine kinase inhibitor. The patient achieved a com...

  19. Sarcomatoid Renal Cell Carcinoma Metastasis to the Penis

    Directory of Open Access Journals (Sweden)

    Victor D. Liou

    2015-01-01

    Full Text Available Secondary cancers of the penis are extremely uncommon with less than 300 cases reported in the past 100 years. These cancers are most frequently a result of an aggressive or poorly managed primary prostate or bladder cancer and rarely a metastasis from a primary kidney tumor. Currently, there is no published literature which describes the spread of sarcomatoid renal cell carcinoma (SRCC to the penis. In this report, we present a 55-year-old-man who presented with a large right-sided SRCC which metastasized to the base of his penis within 1 month of symptom onset. We also discuss the possible route of metastasis based on primary tumor size and location within the retroperitoneum.

  20. Treatment of elderly patients with metastatic renal cell carcinoma.

    Science.gov (United States)

    Zanardi, Elisa; Grassi, Paolo; Cavo, Alessia; Verzoni, Elena; Maggi, Claudia; De Braud, Filippo; Boccardo, Francesco; Procopio, Giuseppe

    2016-01-01

    The risk of developing renal cell carcinoma (RCC) increases with age, and given the constant gain in life expectancy of the general population, both localized RCC and metastatic RCC (mRCC) are more frequently observed in the elderly population. The elderly are a heterogeneous group of patients often characterized by the presence of comorbidities, different compliance to treatment and polypharmacy. Here we review the available data with the aim to analyze the safety and efficacy of new targeted therapies (TTs) in elderly mRCC patients. TTs seem to be effective in both older and younger patients, but elderly patients appear to show reduced tolerance to treatments compared to younger patients. Prospective trials are needed to better understand how to manage mRCC in elderly patients. PMID:26654225

  1. Tivozanib in the treatment of renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Hepgur M

    2013-06-01

    Full Text Available Mehmet Hepgur, Sarmad Sadeghi, Tanya B Dorff, David I Quinn Division of Medical Oncology, University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA, USA Abstract: Renal cell carcinoma (RCC is an aggressive malignancy compared to other urological malignancies and has been associated with poor responses to conventional cytotoxic chemotherapy. Interferon-a and interleukin-2 were previously utilized in a limited number of patients with good performance status due to toxicity and safety issues. Over the last decade, through advances in the understanding of the biology and pathology of RCC, the important role of vascular endothelial growth factor (VEGF in RCC has been identified. Data from randomized trials have led to the approval of first-generation tyrosine kinase inhibitors (TKIs sorafenib, sunitinib, and pazopanib; however, these agents inhibit a wide variety of kinase targets and are associated with a range of adverse effects. More recently, a new generation TKI, axitinib, has been approved by the US Food and Drug Administration. Tivozanib is a novel TKI, which is a potent inhibitor of VEGF-1, VEGF-2, VEGF-3, c-kit, and PDGR kinases, with a more restricted target spectrum. Phase II and III studies have demonstrated significant activity and a favorable safety profile as an initial targeted treatment for advanced RCC. This review examines the emerging data with tivozanib for the treatment of advanced RCC. Preclinical investigations as well as Phase I, II, and III data are examined; data on the comparative benefits of tivozanib are reviewed. Finally, we discuss the future potential of tivozanib in combination, biomarkers associated with tivozanib response, and acquisition of resistance and nonkidney cancer indications. Keywords: targeted therapy, renal cell cancer, tyrosine kinase inhibitor, tivozanib

  2. Utility of PET-FDG in renal cell carcinoma: evaluation in our habitat

    International Nuclear Information System (INIS)

    The great utility of FDG-PET in most oncologic diseases is well known. One of the limitations of the FDG-PET is for the evaluation of renal carcinoma. For better evaluation of the usefulness of FDG-PET in renal cell carcinoma, we reviewed several studies about the subject and compared the results with our own FDG-PET study on patients with renal carcinoma. Results of most studies are clearly influenced by the reason for which the FDG-PET study was requested: initial diagnosis, staging or re-staging. Our results demonstrate that optimizing patient preparation and using flexible study protocols, better results than reported can be achieved

  3. Oligoarray comparative genomic hybridization of renal cell tumors that developed in patients with acquired cystic renal disease.

    Science.gov (United States)

    Kuntz, Eva; Yusenko, Maria V; Nagy, Anetta; Kovacs, Gyula

    2010-09-01

    Renal cell carcinoma occurs at higher frequency in acquired cystic renal disease than in the general population. We have analyzed 4 tumors obtained from the kidneys of 2 patients with acquired cystic renal disease, including 2 conventional renal cell carcinomas and 2 acquired cystic renal disease-associated tumors, for genetic alterations. DNA changes were established by applying the 44K Agilent Oligonucleotide Array-Based CGH (Agilent Technologies, Waldbronn, Germany), and mutation of VHL gene was detected by direct sequencing of the tumor genome. DNA losses and mutation of the VHL gene, which are characteristic for conventional renal cell carcinomas, were seen in 2 of the tumors. The acquired cystic renal disease-associated eosinophilic-vacuolated cell tumor showed gain of chromosomes 3 and 16. No DNA alterations occurred in the papillary clear cell tumor. We suggest that not only the morphology but also the genetics of renal cell tumors associated with acquired cystic renal disease may differ from those occurring in the general population. PMID:20646738

  4. Collision tumor of kidney: A case of renal cell carcinoma with metastases of prostatic adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Monika Vyas

    2013-01-01

    Full Text Available Simultaneous occurrence of prostatic adenocarcinoma and renal cell carcinoma is well documented in the literature. However, metastatic prostatic adenocarcinoma in a kidney harboring a renal cell carcinoma (RCC is quite rare. Although renal cell carcinoma is the most common tumor that can harbor metastasis, metastatic prostatic adenocarcinoma in a kidney harboring a RCC is quite rare. There are four cases in the literature showing metastasis of prostatic adenocarcinoma to RCC. However, as per our knowledge, this is the first case of a collision between RCC and metastatic prostatic adenocarcinoma.

  5. An obscure cause of gastrointestinal bleeding: Renal cell carcinoma metastasis to the small bowel

    OpenAIRE

    Robyn L. Gorski; Salah Abdel Jalil; Manver Razick; Ala' Abdel Jalil

    2015-01-01

    Renal cell carcinoma metastasis to the small intestine is a rare condition. It usually results in gastrointestinal bleeding and it could happen many years after the diagnosis with renal cell cancer. Treatment includes surgery as well as targeted agents such as tyrosine kinases. We report here the case of an 82-year-old man with a past medical history of high-grade renal cell carcinoma and right nephrectomy 6 years earlier, who presented with recurrent episodes of syncope and black stools. He ...

  6. Sunitinib activates Axl signaling in renal cell cancer.

    Science.gov (United States)

    van der Mijn, Johannes C; Broxterman, Henk J; Knol, Jaco C; Piersma, Sander R; De Haas, Richard R; Dekker, Henk; Pham, Thang V; Van Beusechem, Victor W; Halmos, Balazs; Mier, James W; Jiménez, Connie R; Verheul, Henk M W

    2016-06-15

    Mass spectrometry-based phosphoproteomics provides a unique unbiased approach to evaluate signaling network in cancer cells. The tyrosine kinase inhibitor sunitinib is registered as treatment for patients with renal cell cancer (RCC). We investigated the effect of sunitinib on tyrosine phosphorylation in RCC tumor cells to get more insight in its mechanism of action and thereby to find potential leads for combination treatment strategies. Sunitinib inhibitory concentrations of proliferation (IC50) of 786-O, 769-p and A498 RCC cells were determined by MTT-assays. Global tyrosine phosphorylation was measured by LC-MS/MS after immunoprecipitation with the antiphosphotyrosine antibody p-TYR-100. Phosphoproteomic profiling of 786-O cells yielded 1519 phosphopeptides, corresponding to 675 unique proteins including 57 different phosphorylated protein kinases. Compared to control, incubation with sunitinib at its IC50 of 2 µM resulted in downregulation of 86 phosphopeptides including CDK5, DYRK3, DYRK4, G6PD, PKM and LDH-A, while 94 phosphopeptides including Axl, FAK, EPHA2 and p38α were upregulated. Axl- (y702), FAK- (y576) and p38α (y182) upregulation was confirmed by Western Blot in 786-O and A498 cells. Subsequent proliferation assays revealed that inhibition of Axl with a small molecule inhibitor (R428) sensitized 786-O RCC cells and immortalized endothelial cells to sunitinib up to 3 fold. In conclusion, incubation with sunitinib of RCC cells causes significant upregulation of multiple phosphopeptides including Axl. Simultaneous inhibition of Axl improves the antitumor activity of sunitinib. We envision that evaluation of phosphoproteomic changes by TKI treatment enables identification of new targets for combination treatment strategies. PMID:26815723

  7. Molecular genetics and immunohistochemistry characterization of uncommon and recently described renal cell carcinomas.

    Science.gov (United States)

    Rao, Qiu; Xia, Qiu-Yuan; Cheng, Liang; Zhou, Xiao-Jun

    2016-02-01

    Renal cell carcinoma (RCC) compromises multiple types and has been emerging dramatically over the recent several decades. Advances and consensus have been achieved targeting common RCCs, such as clear cell carcinoma, papillary RCC and chromophobe RCC. Nevertheless, little is known on the characteristics of several newly-identified RCCs, including clear cell (tubulo) papillary RCC, Xp11 translocation RCC, t(6;11) RCC, succinate dehydrogenase (SDH)-deficient RCC, acquired cystic disease-associated RCC, hereditary leiomyomatosis RCC syndrome-associated RCC, ALK translocation RCC, thyroid-like follicular RCC, tubulocystic RCC and hybrid oncocytic/chromophobe tumors (HOCT). In current review, we will collect available literature of these newly-described RCCs, analyze their clinical pathologic characteristics, discuss their morphologic and immunohistologic features, and finally summarize their molecular and genetic evidences. We expect this review would be beneficial for the understanding of RCCs, and eventually promote clinical management strategies. PMID:27041925

  8. Familial Non-VHL Clear Cell Renal Cell Carcinoma

    Science.gov (United States)

    ... syndromes. For more information, talk with an assisted reproduction specialist at a fertility clinic. How common is ... of the internal organs, computed tomography (CT or CAT) scan , which creates a three-dimensional picture of ...

  9. Review of renal cell carcinoma with rhabdoid features with focus on clinical and pathobiological aspects.

    Science.gov (United States)

    Kuroda, Naoto; Karashima, Takashi; Inoue, Keiji; Kasajima, Atsuko; Ohe, Chisato; Kawakami, Fumi; Mikami, Shuji; Matsuura, Keiko; Moriyama, Masatsugu; Nagashima, Yoji; Petersson, Fredirk; Lopez, Jose I; Cohen, Ronald J; Michal, Michal; Hes, Ondrej

    2015-03-01

    Rhabdoid morphology in renal cell carcinoma (RCC) may, like sarcomatoid change, be perceived as a type of dedifferentiation, and is a poor prognostic factor. Histologically, rhabdoid neoplastic cells are round to polygonal cells with globular eosinophilic cytoplasmic inclusions and eccentric vesicular nuclei and enlarged nucleoli. All types of RCC, including clear cell, papillary, chromophobe, collecting duct carcinoma, renal medullary carcinoma, acquired cystic disease-associated RCC, ALK-positive renal cancer and unclassified RCC, may display a variably prominent rhabdoid phenotype. Immunohistochemically, the cytoplasm of rhabdoid cells shows positivity for vimentin and/or cytokeratin. Ultrastructurally, cytoplasmic whorls/aggregates of intermediate filaments correspond to light microscopically observed inclusions. Genetically, a previous report suggests that combined loss of BAP1 and PBRM1 may be associated with rhabdoid morphology. As with sarcomatoid change, pathologists should describe, estimate and state the proportion of tumor cells with a rhabdoid phenotype in the routine pathology report of RCC. PMID:26017874

  10. Targeted therapy for renal cell carcinoma: The next lap.

    Science.gov (United States)

    Kanesvaran, Ravindran; Tan, Min-Han

    2014-01-01

    Advances in rationally targeted therapeutics over the last decade have transformed the clinical care of advanced kidney cancer. While oncologists consolidate the gains of the wave of new agents, comprising a panoply of anti-vascular endothelial growth factor multi-targeted tyrosine kinase inhibitors and inhibitors of the mammalian target of rapamycin (mTOR), there is an increasing sense that a plateau has been reached in the short term. It is sobering that all currently approved targeted therapies have not yielded durable remissions and remain palliative in intent. In the context of recent insights in kidney cancer biology, we review promising ongoing and future approaches for kidney cancer therapeutics aimed toward forging new paths in the systemic management of renal cell carcinoma. Broadly, candidate agents for such innovative strategies include immune check-point inhibitors, anti-cancer stem cell agents, next-generation anti-vascular endothelial growth factor receptor and anti-mTOR agents as well as more investigational agents in the preclinical and early clinical development settings. PMID:24737951

  11. Temsirolimus in the treatment of advanced renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Bernard J. Escudier

    2011-12-01

    Full Text Available Temsirolimus is a novel inhibitor of mammalian target of rapamycin (mTOR, which is a central regulator of the response of tumour cells to growth and survival signals. When heavily pretreated patients with advanced solid tumours received intravenous (IV temsirolimus over a broad dose range, antitumour activity was observed in various tumour types, including advanced renal cell carcinoma (RCC. A study of singleagent temsirolimus in patients with cytokine-refractory metastatic RCC subsequently demonstrated antitumour activity and encouraging progression- free survival and overall survival. Temsirolimus was generally well tolerated over the 3 dose levels tested (25 mg, 75 mg or 250 mg weekly as a 30-minute IV infusion. The most frequent grade 3 or 4 treatment-related adverse events reported (n=110 were hyperglycemia (17%, hypophosphatemia (13%, anemia (9%, and hypertriglyceridemia (6%. Results from a randomized phase III study that enrolled previously untreated patients with advanced RCC and poor-prognostic features have recently demonstrated a significant increase in overall survival (p=0.0089 for patients who received temsirolimus 25 mg IV, 30-minute infusion once weekly compared with those who received interferon-alpha up to 18 million units subcutaneously thrice weekly. On the basis of improved survival, temsirolimus can be considered a first-line treatment for patients with advanced RCC.

  12. Targeted therapy for renal cell carcinoma: The next lap

    Directory of Open Access Journals (Sweden)

    Ravindran Kanesvaran

    2014-01-01

    Full Text Available Advances in rationally targeted therapeutics over the last decade have transformed the clinical care of advanced kidney cancer. While oncologists consolidate the gains of the wave of new agents, comprising a panoply of anti-vascular endothelial growth factor multi-targeted tyrosine kinase inhibitors and inhibitors of the mammalian target of rapamycin (mTOR, there is an increasing sense that a plateau has been reached in the short term. It is sobering that all currently approved targeted therapies have not yielded durable remissions and remain palliative in intent. In the context of recent insights in kidney cancer biology, we review promising ongoing and future approaches for kidney cancer therapeutics aimed toward forging new paths in the systemic management of renal cell carcinoma. Broadly, candidate agents for such innovative strategies include immune check-point inhibitors, anti-cancer stem cell agents, next-generation anti-vascular endothelial growth factor receptor and anti-mTOR agents as well as more investigational agents in the preclinical and early clinical development settings.

  13. Identification and Characterization of Renal Cell Carcinoma Gene Markers

    Directory of Open Access Journals (Sweden)

    Louis S. Liou

    2007-01-01

    Full Text Available Microarray gene expression profiling has been used to distinguish histological subtypes of renal cell carcinoma (RCC, and consequently to identify specific tumor markers. The analytical procedures currently in use find sets of genes whose average differential expression across the two categories differ significantly. In general each of the markers thus identifi ed does not distinguish tumor from normal with 100% accuracy, although the group as a whole might be able to do so. For the purpose of developing a widely used economically viable diagnostic signature, however, large groups of genes are not likely to be useful. Here we use two different methods, one a support vector machine variant, and the other an exhaustive search, to reanalyze data previously generated in our Lab (Lenburg et al. 2003. We identify 158 genes, each having an expression level that is higher (lower in every tumor sample than in any normal sample, and each having a minimum differential expression across the two categorie at a signifi cance of 0.01. The set is highly enriched in cancer related genes (p = 1.6 × 10 – 12, containing 43 genes previously associated with either RCC or other types of cancer. Many of the biomarkers appear to be associated with the central alterations known to be required for cancer transformation. These include the oncogenes JAZF1, AXL, ABL2; tumor suppressors RASD1, PTPRO, TFAP2A, CDKN1C; and genes involved in proteolysis or cell-adhesion such as WASF2, and PAPPA.

  14. Extracerebral metastases determine the outcome of patients with brain metastases from renal cell carcinoma

    International Nuclear Information System (INIS)

    In the era of cytokines, patients with brain metastases (BM) from renal cell carcinoma had a significantly shorter survival than patients without. Targeted agents (TA) have improved the outcome of patients with metastatic renal cell carcinoma (mRCC) however, their impact on patients with BM is less clear. The aim of this analysis was to compare the outcome of patients with and without BM in the era of targeted agents. Data from 114 consecutive patients who had access to targeted agent were analyzed for response rates (ORR), progression free survival (PFS) and overall survival (OS). All patients diagnosed with BM underwent local, BM-specific treatment before initiation of medical treatment. Data of 114 consecutive patients who had access to at least one type of targeted agents were analyzed. Twelve out of 114 renal cell carcinoma (RCC) patients (10.5%) were diagnosed with BM. Systemic treatment consisted of sunitinib, sorafenib, temsirolimus or bevacizumab. The median PFS was 8.7 months (95% CI 5.1 - 12.3) and 11.4 months (95% CI 8.7 - 14.1) for BM-patients and non-BM-patients, respectively (p = 0.232). The median overall survival for patients with and without BM was 13.4 (95% CI 1- 43.9) and 33.3 months (95% CI 18.6 - 47.0) (p = 0.358), respectively. No patient died from cerebral disease progression. ECOG Performance status and the time from primary tumor to metastases (TDM) were independent risk factors for short survival (HR 2.74, p = 0.001; HR: 0.552, p = 0.034). Although extracerebral metastases determine the outcome of patients with BM, the benefit from targeted agents still appears to be limited when compared to patients without BM

  15. Diagnostic utility of cytokeratins 7, 10 and 20 in renal cell carcinoma and oncocytoma

    OpenAIRE

    BALTACI, Sümer; Tulunay, Özden; KİREMİTÇİ, Saba; Orhan GÖĞÜŞ

    2008-01-01

    Renal cell carcinoma is the most frequent renal epithelial tumor having various subtypes differing in their prognosis and therapeutic response. In most cases it is possible to distinguish subtypes on the basis of histology alone, however, there are diagnostic difficulties for the tumors having granular/eosinophilic cells which create morphologic similarities not only between the subtypes of renal cell carcinoma, but also, between a benign tumor and renal oncocytoma. To achieve correct diagnos...

  16. 3D Texture Analysis in Renal Cell Carcinoma Tissue Image Grading

    OpenAIRE

    Tae-Yun Kim; Nam-Hoon Cho; Goo-Bo Jeong; Ewert Bengtsson; Heung-Kook Choi

    2014-01-01

    One of the most significant processes in cancer cell and tissue image analysis is the efficient extraction of features for grading purposes. This research applied two types of three-dimensional texture analysis methods to the extraction of feature values from renal cell carcinoma tissue images, and then evaluated the validity of the methods statistically through grade classification. First, we used a confocal laser scanning microscope to obtain image slices of four grades of renal cell carcin...

  17. Spontaneous regression of bone metastasis from renal cell carcinoma; A case report

    International Nuclear Information System (INIS)

    Spontaneous regression of metastatic renal cell carcinoma is rarely observed. Metastatic renal cell carcinoma was identified in a 70-year-old male using computed tomography-guided percutaneous needle biopsy. Two months after the diagnosis, a partial resection of the sternal bone was performed. Pathological examination revealed granulated tissue with bleeding and necrosis but no carcinogenic cells. We report a pathologically identified case in which a sternal bone metastasis that was noticed two years after radical nephrectomy regressed completely and spontaneously

  18. Pattern of failure following surgical resection of renal cell carcinoma

    International Nuclear Information System (INIS)

    Purpose/objective: To identify the pattern of failure in patients with resected renal cell carcinoma (RCC). Materials and Methods: The records of 116 patients with unilateral non-metastatic RCC, who were treated with definitive surgery and referred to the Ottawa Regional Cancer Centre between 1977 and 1988, were reviewed. Distribution by stage included: T1 = 3 patients, T2 = 42 patients, T3 =71 patients. The median follow-up was 44 months, with a range of 4-267 months. Results: Loco-regional failure (LRF) developed in 8 patients, yielding a 7-year actuarial incidence of 8% for LRF, as first event. Nine patients developed local or regional recurrence + distant failure, and 58 patients had distant metastases only. Seven-year actuarial incidence of distant failure was 55%. The overall 7-year actuarial survival rate was 40%, and cause-specific survival was 45%. Conclusion: LRF was rare following nephrectomy. This data does not support the role of adjuvant radiation therapy in this disease

  19. Immunotherapy in Metastatic Renal Cell Carcinoma: A Comprehensive Review

    Directory of Open Access Journals (Sweden)

    Rachna Raman

    2015-01-01

    Full Text Available Localized renal cell carcinoma (RCC is often curable by surgery alone. However, metastatic RCC is generally incurable. In the 1990s, immunotherapy in the form of cytokines was the mainstay of treatment for metastatic RCC. However, responses were seen in only a minority of highly selected patients with substantial treatment-related toxicities. The advent of targeted agents such as vascular endothelial growth factor tyrosine kinase inhibitors VEGF-TKIs and mammalian target of rapamycin (mTOR inhibitors led to a change in this paradigm due to improved response rates and progression-free survival, a better safety profile, and the convenience of oral administration. However, most patients ultimately progress with about 12% being alive at 5 years. In contrast, durable responses lasting 10 years or more are noted in a minority of those treated with cytokines. More recently, an improved overall survival with newer forms of immunotherapy in other malignancies (such as melanoma and prostate cancer has led to a resurgence of interest in immune therapies in metastatic RCC. In this review we discuss the rationale for immunotherapy and recent developments in immunotherapeutic strategies for treating metastatic RCC.

  20. The present approach to treatment of renal cell carcinoma

    International Nuclear Information System (INIS)

    Until the turn of the millennium, metastatic renal cell carcinoma (mRCC) was regarded as one of the most refractory cancers; highly resistant to both radiation and systemic therapy, and only small group of patients responded to immune modulation. Involved targeted therapies, which influence specific signal transduction pathways of tumor formation and progression, opened new options of treatment to give patients a new hope. After the first experiences with the new biologic agents we can claim, that these patients have improved a quality of life, provided stabilization of disease and prolong life of patients, but the cure is not available. However, there are so many studies with target therapies in RCC, but the most correct algorithm of treatment does not exist. Targeted therapies rarely achieve remission, prevailing a stabilisation of disease so patients have to undergo chronic treatment. In choice of optimal treatment is necessary to regard for quality of life, so usually the winner is the drug with the lowest toxic potential. (author)

  1. Detection, staging and clinical implications of renal cell carcinoma

    International Nuclear Information System (INIS)

    To compare the epidemiologic, clinical and pathologic characteristics of symptomatic and incidental renal cell carcinoma (RCC)in Jordan.Results were compared with published Western figure. Records of 119 patients with renal tumors diagnosed during the period January1992 to December 2001at Jordan University of Science and Technology, Irbid, Jordan were reviewed. Age,gender, radiologic and biologic workup, treatment,features of tumor were reviewed. The mean patient age was 54 and the male to female ratio was 3.4:1. 26% of tumors were discoverd accidentlly.The incidental detction group had significantly small size of tumor.,lower stage and lower histological grading.In symptomatic group woman have significantly lower mean size of tumor than men. A radical nephrectomy was performed in 92% of the cases, and in 8% of the cases, conservative mangement was adopted. The present study showed that the incidence rate of RCC in Jordan is less than Western countries. Significant number of RCC were detected incidently with lower pathological stage and grade. Subsequently these clinically and histologically less aggressive lesions lead to better survival. These data efforts should be directed to the devlopment of screening protocol to detect these lesions early. (author)

  2. Current Status of Minimally Invasive Surgery for Renal Cell Carcinoma.

    Science.gov (United States)

    Smith, Zachary L

    2016-06-01

    Over the last three decades, the incidence of renal cell carcinoma (RCC) has continuously risen, generally attributed to the increased use of cross-sectional imaging across all medical disciplines. Fortunately, despite this rising incidence, the estimated 5-year relative survival rate has improved. This survival improvement likely parallels the stage migration of the last two decades toward an increased incidence of small renal masses (SRMs). However, this survival improvement may be secondary to improved surgical techniques and medical therapies for these malignancies. The increased incidence of SRMs has led to an expected evolution in the treatment of RCC. Minimally invasive surgical applications for the treatment of RCC have gained widespread popularity, and now these approaches to renal malignancies have surpassed open techniques in frequency of utilization. Laparoscopic and robotic-assisted techniques have now been applied to both radical and partial nephrectomy procedures of varying complexity. Additionally, percutaneous ablative procedures have been applied to the treatment of some SRMs, increasing the urologist's armamentarium further. Below, we provide a review of these minimally invasive surgical (MIS) procedures for the treatment of RCC. PMID:27021911

  3. Functional significance of erythropoietin in renal cell carcinoma

    International Nuclear Information System (INIS)

    One of the molecules regulated by the transcription factor, hypoxia inducible factor (HIF), is the hypoxia-responsive hematopoietic factor, erythropoietin (EPO). This may have relevance to the development of renal cell carcinoma (RCC), where mutations of the von Hippel-Lindau (VHL) gene are major risk factors for the development of familial and sporadic RCC. VHL mutations up-regulate and stabilize HIF, which in turn activates many downstream molecules, including EPO, that are known to promote angiogenesis, drug resistance, proliferation and progression of solid tumours. HIFs typically respond to hypoxic cellular environment. While the hypoxic microenvironment plays a critical role in the development and progression of tumours in general, it is of special significance in the case of RCC because of the link between VHL, HIF and EPO. EPO and its receptor, EPOR, are expressed in many cancers, including RCC. This limits the use of recombinant human EPO (rhEPO) to treat anaemia in cancer patients, because the rhEPO may be stimulatory to the cancer. EPO may also stimulate epithelial-mesenchymal transition (EMT) in RCC, and pathological EMT has a key role in cancer progression. In this mini review, we summarize the current knowledge of the role of EPO in RCC. The available data, either for or against the use of EPO in RCC patients, are equivocal and insufficient to draw a definitive conclusion

  4. Impact of lymphadenectomy in management of renal cell carcinoma

    International Nuclear Information System (INIS)

    Purpose: To evaluate the impact of regional lymphadenectomy as part of a management plan on morbidity, morbidity and survival in renal cell carcinoma (RCC). Patients and methods: A retrospective study reviewing 158 cases diagnosed as RCC at the National Cancer Institute, Cairo university, Egypt, during the time period from 2000 to 2007. Histopathological data and significant operative and postoperative events were retrieved to compare three lymphadenectomy groups; Group A, where more than 5 nodes were dissected, Group B where 5 or less nodes were dissected and Group C where no nodal dissection was done. Results: More positive lymph nodes were seen in group A (37.8%) compared to group B (9.6%) (p= 0.002). Lymph node positivity was significantly associated with higher grade (p= 0.005), but not with larger tumor size (p= 0.221). There was no significant difference in overall survival between the three lymphadenectomy groups (p= 0.163). Overall survival was not significantly affected by lymph node status (p= 0.585). Conclusion: Regional lymphadenectomy in RCC has no impact on the mortality or morbidity.

  5. Role of the ubiquitin proteasome system in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Corn Paul G

    2007-11-01

    Full Text Available Abstract Renal cell carcinoma (RCC accounts for approximately 2.6% of all cancers in the United States. While early stage disease is curable by surgery, the median survival of metastatic disease is only 13 months. In the last decade, there has been considerable progress in understanding the genetics of RCC. The VHL tumor suppressor gene is inactivated in the majority of RCC cases. The VHL protein (pVHL acts as an E3 ligase that targets HIF-1, the hypoxia inducible transcription factor, for degradation by the ubiquitin proteasome system (UPS. In RCC cases with mutant pVHL, HIF-1 is stabilized and aberrantly expressed in normoxia, leading to the activation of pro-survival genes such as vascular endothelial growth factor (VEGF. This review will focus on the defect in the UPS that underlies RCC and describe the development of novel therapies that target the UPS. Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com.

  6. Ultra-deep T cell receptor sequencing reveals the complexity and intratumour heterogeneity of T cell clones in renal cell carcinomas

    OpenAIRE

    Gerlinger, Marco; Quezada, Sergio A; Peggs, Karl S.; Furness, Andrew JS; Fisher, Rosalie; Marafioti, Teresa; Shende, Vishvesh H.; McGranahan, Nicholas; Rowan, Andrew J.; Hazell, Steven; Hamm, David; Robins, Harlan S; Pickering, Lisa; Gore, Martin; Nicol, David L.

    2013-01-01

    The recognition of cancer cells by T cells can impact upon prognosis and be exploited for immunotherapeutic approaches. This recognition depends on the specific interaction between antigens displayed on the surface of cancer cells and the T cell receptor (TCR), which is generated by somatic rearrangements of TCR α- and β-chains (TCRb). Our aim was to assess whether ultra-deep sequencing of the rearranged TCRb in DNA extracted from unfractionated clear cell renal cell carcinoma (ccRCC) samples...

  7. Cystic local recurrence of renal cell carcinoma after laparoscopic radical nephrectomy in a hemodialysis patient.

    Science.gov (United States)

    Ito, Kazuyo; Takagi, Toshio; Kondo, Tsunenori; Yoshida, Kazuhiko; Iizuka, Junpei; Kobayashi, Hirohito; Tomita, Eri; Hashimoto, Yasunobu; Tanabe, Kazunari

    2014-03-01

    Although local recurrence of renal cell carcinoma after laparoscopic radical nephrectomy is sometimes reported, cystic local recurrence of renal cell carcinoma has rarely been reported. We report the case of a 59-year-old man with hemodialysis who developed cystic local recurrence of renal cell carcinoma accompanied by acquired cystic disease of the kidney in the retroperitoneal space after laparoscopic radical nephrectomy. A cystic tumor of 5.1 cm in diameter occurred in the left retroperitoneal space 15 months after left laparoscopic radical nephrectomy, and enlarged to 7.2 cm in diameter with enhanced mass along the wall of the cyst 36 months after surgery. The cystic tumor was removed and showed local recurrence of renal cell carcinoma on pathological examination. PMID:23909823

  8. Clinical Practice Guidelines for the Treatment of Metastatic Renal Cell Carcinoma: Today and Tomorrow

    OpenAIRE

    Molina, Ana M.; Motzer, Robert J.

    2011-01-01

    Recent updates to the guidelines put forth by the National Comprehensive Cancer Network and the European Association of Urology for the treatment of metastatic renal cell carcinoma are discussed and future areas of research to be explored are outlined.

  9. Simultaneous Renal Cell Carcinoma and Giant Retroperitoneal Liposarcoma Involving Small Intestine.

    Science.gov (United States)

    Reznichenko, Aleksandr A

    2016-01-01

    Background. The concomitant occurrence of a renal cell carcinoma and retroperitoneal sarcoma is extremely rare with only few cases being reported. Methods. We present a case of simultaneous renal cell carcinoma and exceptionally large size retroperitoneal sarcoma involving small intestine. Surgical resection of retroperitoneal sarcoma and simultaneous right nephrectomy were performed. Results. Patient developed recurrent and metastatic disease and underwent debulking surgery following by chemotherapy. Despite aggressive behavior of the retroperitoneal sarcomas, patient is currently (7 years after simultaneous resection and nephrectomy) recurrence-free. Conclusions. Complete surgical resection is the mainstay of therapy for both renal cell carcinoma and retroperitoneal sarcoma. We present a case of simultaneous renal cell carcinoma and exceptionally large size retroperitoneal sarcoma. Debulking surgery and chemotherapy were helpful in our case. PMID:27595033

  10. Synchronous sigmoid and caecal cancers together with a primary renal cell carcinoma.

    LENUS (Irish Health Repository)

    Bhargava, A

    2012-06-01

    Multiple primary neoplasms, a common clinical entity, can be classified as synchronous or metachronous. Renal cell carcinoma, in particular, is associated with a high rate of multiple primary neoplasms.

  11. Everolimus – a new approach in the treatment of renal cell carcinoma

    International Nuclear Information System (INIS)

    With the increasing understanding of the biology of the disease and the development of targeted therapy, there has been a paradigm shift in the treatment of clear cell metastatic renal cell carcinoma (mRCC). Traditionally patients with metastatic RCC have been treated with immunotherapy which has limited efficacy. The multikinase inhibitors sunitinib, sorafenib and pazopanib, the VEGF antibody bevacizumab in combination with interferon and the mTOR inhibitor temsirolimus have all been shown to prolong progression-free survival in phase III studies. Here we review another mTOR inhibitor, everolimus (Afinitor®; Novartis, USA) which was approved in March 2009 by the US FDA for treatment of targeted-therapy refractory metastatic renal cell cancer. The phase III study of everolimus (the RECORD study) was terminated early after a significant difference in efficacy was noted in the treatment arm with everolimus (progression-free survival of 4.0 months in patients on the treatment arm vs 1.9 months in the placebo arm). The most common adverse events were stomatitis, pneumonitis, fatigue and infections. We review Phase I–III data with a particular emphasis on safety data and patient focused outcomes

  12. Photon-deficient Mass on FDG-PET Scan in Renal Cell Carcinoma: A Case Report

    OpenAIRE

    George Shih; Wei-Jen Shih; Bonnie Mitchell; Milan, Primo P

    2008-01-01

    F-18 Fluorodeoxyglucose Positron Emission Tomography imaging (F-18 FDG PET) detects malignancies depending on the uptake profile of glycolysis of tumors; however, the role of FDG PET is limited in the evaluation of primary renal malignancy because of low FDG uptake by renal cell carcinoma and also because normal urinary excretion of FDG seen in the images. A patient with renal cell carcinoma whose FDG PET imaging study incidentally shows a photon-deficient mass in the upper pole of the right ...

  13. Mass spectrometric characterization of urinary fibrinogen-derived peptides in prostate cancer and renal cell carcinoma

    OpenAIRE

    Mesihää, M. (Markus)

    2015-01-01

    In previous studies we have found that urinary fibrinogen-derived peptides are potential tumor markers for renal cell carcinoma. These peptides occur at low concentrations in urine. Identification of a low-abundant tumor marker requires optimal sample preparation and a highly sensitive analyzer. In this work different chromatographic and mass spectrometric methods were compared and evaluated for tumor marker discovery. We used urine samples from patients with renal cell carcinoma and pro...

  14. Renal cell carcinoma metastasis to the parathyroid gland: A very rare occurrence

    OpenAIRE

    Ofo, Enyinnaya; Mandavia, Rishi; Jeannon, Jean-Pierre; Odell, Edward; Simo, Ricard

    2014-01-01

    INTRODUCTION Metastases to the parathyroid gland are very uncommon. Although renal cell carcinoma metastasis to the head and neck region is well recognised, with a predilection for unpredictable metastasis to unusual sites such as the thyroid gland, nose, paranasal sinuses, and cranial bones, there are no reports of parathyroid gland involvement. PRESENTATION OF CASE We describe an unusual case of renal cell carcinoma metastasis to a parathyroid gland in a 69-year-old male who had been treate...

  15. Metastatic Renal Cell Carcinoma Presenting as Nasal Mass: Case Report and Review of Literature.

    Science.gov (United States)

    Mahajan, Ritesh; Mayappa, Nagaraj; Prashanth, V

    2016-09-01

    Sinonasal neoplasms are rare and exceptional site for metastatic tumours and comprising CT scan revealed a tumour in the right nasal cavity and maxillary sinus. The presence of primary renal cell carcinoma was recognized only after surgical removal of metastatic tumour. Very few reports have been presented in literature of metastatic renal cell carcinoma in the sinonasal region. We present this case to document its occurrence; highlight the rarity, presentation and difficulties in diagnosis and treatment along with review of literature. PMID:27508143

  16. Papillary renal cell carcinoma. A morphologic and cytogenetic study of 11 cases.

    OpenAIRE

    Kovacs, G

    1989-01-01

    Most renal cell carcinomas are characterized by constant loss of the 3p13-pter chromosome segment and a frequent gain of the 5q22-qter segment. A comparative histologic and cytogenetic investigation of large series of renal cell carcinomas now shows that purely papillary tumors differ from the more common nonpapillary form not only in their morphologic characteristic, but also in karyotype changes observed. All of the 11 papillary tumors of this study failed to show any rearrangement of the c...

  17. Tongue metastasis as an initial presentation of renal cell carcinoma: a case report and literature review

    OpenAIRE

    Azam Faisal; Abubakerr Muneer; Gollins Simon

    2008-01-01

    Abstract Introduction Primary tumour of the kidney metastasizing to the tongue is very unusual and only anecdotal cases have been reported. An exhaustive literature review covering the period from 1911 onwards disclosed 28 cases. Out of those, only 3 cases presented initially with tongue metastases before the diagnosis of primary renal cell carcinoma. The prognosis for patients with lingual metastasis of renal cell carcinoma is poor. Treatment of tongue metastasis is usually palliative and ai...

  18. A Commentary on “Risk Factors for Renal Cell Cancer in a Japanese Population”

    OpenAIRE

    Cidon, Esther Uña

    2009-01-01

    The well-written and researched article reported in Clinical Medicine: Oncology by Dr. Washio and Dr. Mori entitled “Risk factors for renal cell cancer in a Japanese population”1 makes evident the differences in incidence and mortality rates from renal cell carcinoma (RCC) between different populations and highlights the relevance of carrying out epidemiological studies, investigating additional risk factors which may explain the differences.

  19. Hyponatremia as a prognostic and predictive factor in metastatic renal cell carcinoma

    DEFF Research Database (Denmark)

    Jeppesen, A N; Jensen, H K; Donskov, F; Marcussen, Niels; von der Maase, H

    2010-01-01

    Low serum sodium has recently been associated with poor survival in localised renal cell carcinoma (RCC). We now show the prognostic effect of serum sodium in patients with metastatic RCC (mRCC).......Low serum sodium has recently been associated with poor survival in localised renal cell carcinoma (RCC). We now show the prognostic effect of serum sodium in patients with metastatic RCC (mRCC)....

  20. Metastasis from renal cell carcinoma to thyroid presenting as rapidly growing neck mass

    OpenAIRE

    Afshin Mohammadi; Seyed Babak Mosavi Toomatari; Mohammad Ghasemi-Rad

    2014-01-01

    INTRODUCTION: Renal cell carcinoma (RCC) is commonly known as the “internist's tumor” because of its unpredictable behavior. Metastasis to the thyroid gland is rarely found in clinical practice. PRESENTATION OF CASE: We report a rare case of non-thyroid malignancies NTM from renal cell carcinoma 1.5 years after radical nephrectomy in a 58-year-old man with a rapidly growing neck mass. DISCUSSION: Malignant melanoma, breast carcinoma, lung, and skin cancer are the most common sources of ...

  1. Isolated Late Metastasis of a Renal Cell Cancer Treated by Radical Distal Pancreatectomy

    OpenAIRE

    J. P. Barras; Baer, H.; Stenzl, A.; Czerniak, A

    1996-01-01

    A 53–year-old man underwent right nephrectomy for a locally advanced renal cell carcinoma with concomitant resection of a solitary metastasis in the right lung. Ten years later, he presented with haematochezia caused by a tumour in the tail of pancreas, invading the transverse colon and the greater curvature of the stomach. The tumour was radically resected, and histological examination revealed a solitary metastasis of the previous renal cell carcinoma. This case illustrates a rare indicatio...

  2. Radionuclide imaging of primary renal-cell carcinoma by I-131-labeled antitumor antibody

    International Nuclear Information System (INIS)

    A goat antibody against human renal-cell carcinoma reacted on immunofluorescence with renal-cell carcinomas from 20 patients, but not with normal adult human tissues, including kidney. After i.v. administration the I-131-linked antibody showed preferential tumor localization in six of seven patients with primary renal carcinoma. Labeled antitumor antibodies may have the specificity for tumor imaging that current radiopharmaceuticals lack

  3. Validity of positron emission tomography (PET) using 2-deoxy-2-(/sup 18/F)fluoro-D-glucose (FDG) in patients with renal cell carcinoma (preliminari report)

    Energy Technology Data Exchange (ETDEWEB)

    Kawamura, Juichi; Hida, Shuichi; Yoshida, Osamu; Yonekura, Yoshiharu; Senda, Michio; Yamamoto, Kazutaka; Saji, Hideo; Fujita, Toru; Konishi, Junji.

    1988-10-01

    Positron emission tomography (PET) using 2-deoxy-2-(/sup 18/F)fluoro-D-glucose (FDG) was carried out in 6 patients with renal tumors (5 renal cell carcinomas including one patient in whom the primary renal lesion was nephrectomized and 1 angiomyolipoma) and FDG accumulation was evaluated in the tumor lesion as a ''hot spot''. In dynamic images after 16 min. FDG accumulated in the tumor portion in 3 out of 4 patients with renal cell carcinoma. However, there was no accumulation in one renal cell carcinoma in which marked necrosis was histologically found. FDG accumulation was not evident in the tumorous lesion of angiomyolipoma. FDG accumulation was also noticed in the metastatic lesion of renal cell carcinoma in the liver or retroperitoneal lymph node. A gradual increase of FDG activity in the lesion of renal cell carcinoma was clearly demonstrated in the time-radioactivity curve, while activities rapidly decreased in renal cortex and pelvis, and liver. In the healthy portion of the kidney, FDG is filtered from the glomerulus and is not reabsorbed from the tubulus and is excreted in the collecting system. On the contrary, FDG, catalyzed by hexokinase, is phospholylated to FDG-6-phosphate which accumulates in the tumor tissue. PET using FDG can provide a new insight for understanding biological activity of renal cell carcinoma from the point of glucose metabolism in tumor tissue.

  4. Validity of positron emission tomography (PET) using 2-deoxy-2-[18F]fluoro-D-glucose (FDG) in patients with renal cell carcinoma (preliminari report)

    International Nuclear Information System (INIS)

    Positron emission tomography (PET) using 2-deoxy-2-[18F]fluoro-D-glucose (FDG) was carried out in 6 patients with renal tumors (5 renal cell carcinomas including one patient in whom the primary renal lesion was nephrectomized and 1 angiomyolipoma) and FDG accumulation was evaluated in the tumor lesion as a ''hot spot''. In dynamic images after 16 min. FDG accumulated in the tumor portion in 3 out of 4 patients with renal cell carcinoma. However, there was no accumulation in one renal cell carcinoma in which marked necrosis was histologically found. FDG accumulation was not evident in the tumorous lesion of angiomyolipoma. FDG accumulation was also noticed in the metastatic lesion of renal cell carcinoma in the liver or retroperitoneal lymph node. A gradual increase of FDG activity in the lesion of renal cell carcinoma was clearly demonstrated in the time-radioactivity curve, while activities rapidly decreased in renal cortex and pelvis, and liver. In the healthy portion of the kidney, FDG is filtered from the glomerulus and is not reabsorbed from the tubulus and is excreted in the collecting system. On the contrary, FDG, catalyzed by hexokinase, is phospholylated to FDG-6-phosphate which accumulates in the tumor tissue. PET using FDG can provide a new insight for understanding biological activity of renal cell carcinoma from the point of glucose metabolism in tumor tissue. (author)

  5. An obscure cause of gastrointestinal bleeding: Renal cell carcinoma metastasis to the small bowel

    Directory of Open Access Journals (Sweden)

    Robyn L. Gorski

    2015-01-01

    Full Text Available Renal cell carcinoma metastasis to the small intestine is a rare condition. It usually results in gastrointestinal bleeding and it could happen many years after the diagnosis with renal cell cancer. Treatment includes surgery as well as targeted agents such as tyrosine kinases. We report here the case of an 82-year-old man with a past medical history of high-grade renal cell carcinoma and right nephrectomy 6 years earlier, who presented with recurrent episodes of syncope and black stools. He underwent esophagogastroduodenoscopy (EGD and colonoscopy without evident source of bleeding. Video capsule endoscopy (VCE showed three bleeding lesions in the jejunum and ileum. Push enteroscopy revealed a proximal jejunum bleeding mass that was suspicious for malignancy. Histopathology demonstrated poorly differentiated carcinoma. Given the patient’s history of high-grade renal cell carcinoma, and similarity of histologic changes to the old renal cell cancer specimen, metastatic renal cell carcinoma was felt to be the responsible etiology.

  6. Targeted therapies in the management of renal cell carcinoma: role of bevacizumab

    Directory of Open Access Journals (Sweden)

    Bernard Escudier

    2008-09-01

    Full Text Available Bernard Escudier1, Jan Cosaert2, Sangeeta Jethwa21Unité Immunothérapie, Institut Gustave Roussy, Villejuif, France; 2F. Hoffmann-La Roche Ltd, Basel, SwitzerlandAbstract: Bevacizumab (10 mg/kg every 2 weeks, in combination with interferon alpha-2a (IFN, is an effective option for first-line therapy for advanced and/or metastatic renal cell carcinoma (RCC. Two phase III trials clearly show significant improvements in progression-free survival and response rate in patients with treatment-naïve metastatic RCC receiving bevacizumab combined with IFN compared with IFN. The dose of IFN, which was initiated at 9 MIU 3 times a week in these trials, can be reduced to effectively manage IFN-related side effects without compromising the efficacy of bevacizumab plus IFN. Bevacizumab has good tolerability with manageable side effects, both alone and in combination with other agents; the tolerability profile of bevacizumab in combination with IFN is consistent with the well-characterized and well-established profiles of these therapies. The tolerability of bevacizumab combined with IFN and the flexibility to manage IFN-related side effects are important considerations when selecting first-line therapy. With a number of options now available for RCC therapy, optimizing their use is a key consideration in improving patient benefit.Keywords: bevacizumab (Avastin®, interferon alpha, efficacy, tolerability, renal cell carcinoma (RCC, low-dose interferon

  7. Fractionated stereotactic radiotherapy of brain metastases from renal cell carcinoma

    International Nuclear Information System (INIS)

    Purpose: To retrospectively evaluate the effectiveness of fractionated stereotactic radiotherapy (FSRT) for brain metastases from renal cell carcinoma (RCC). Methods and Materials: From May 1983 to September 1998, 35 patients with brain metastases from RCC underwent radiotherapy at the National Cancer Center Hospital, Tokyo; 10 patients treated initially with FSRT (FSRT group); 11 with surgery followed by conventional radiotherapy (S/CR group); and 14 with conventional radiotherapy (CR group). Survival and local control rates were determined for patients who had an ECOG performance status of 0-2. Results: Overall median survival rate was 18 months, and actuarial 1- and 2-year survival rates were 57.6% and 31.0%, respectively. Median survival rates were 25.6 months for the FSRT group, 18.7 months for the S/CR group, and 4.3 months for the CR group. Significant prognostic factors associated with survival were age less than 60 years and good performance status. In patients treated with FSRT, imaging studies revealed that 21 of 24 tumors (88%) were locally controlled during a median follow-up time of 5.2 months (range 0.5-68). Actuarial 1- and 2-year local control rates were 89.6% and 55.2%, respectively. No patient suffered from acute or late complications during and following FSRT. Conclusions: FSRT offers better tumor control and prolonged survival over the S/CR or CR groups, and should be considered as primary treatment for brain metastases from RCC. Patients under 60-years-old and those with a good performance status at the beginning of radiotherapy had a better prognosis.

  8. Clinicopathological characteristics of renal cell carcinoma in a dialysis patient

    International Nuclear Information System (INIS)

    In order to clarify the clinicopathological features of renal cell carcinoma (RCC) occurring in chronic hemodialysis patients, we analyzed patient demographics, hemodialysis duration, pathological characteristics of the tumors and prognosis of these patients. We retrospectively reviewed the record of 16 patients who had undergone radical nephrectomy for RCC at Kawashima Hospital between November 1994 and December 2007. They ranged in age from 32 to 82 years old (mean age, 55.0), and comprised 14 males and 2 females. All the patients were clinical stage I. As for the underlying disease which caused renal failure, chronic glomerulonephritis was noted in 12 patients and diabetes mellitus was noted in 1 patient. The causes in 3 patients were unknown. The duration of hemodialysis ranged from 1 to 226 months, (90 months on average). As for the main diagnostic methods, CT was performed in 14 cases. Two patients demonstrated macroscopic hematuria Acquired cystic disease of the kidney (ACDK) was present in 10 patients (68.8%). Patients were divided two groups; patients who had undergone open surgery (group 1, N=7) and patients who had undergone retroperitoneoscopic surgery (group 2, N=9). The following factors were analyzed: operation time, bleeding volume, postoperative complications, hospitalization. Nephrectomy was performed for the right kidney in 8 patients, and for the left kidney in 8 patients. Operation time ranged from 90 to 150 minutes (average, 111 min), in group 1, and from 80 to 284 minutes (average, 146 min), in group 2. Bleeding volume ranged from 10 to 170 ml (average, 72 ml), in group 1, and from 10 to 50 ml (average, 15 ml), in group 2. Complications of nephrectomy were observed in 6 patients, but all were minor problems. As for hospitalization, in group 1 it was 20 days and in group 2 it was 12 days. Fifteen patients survived and are tumor free. One patient died of causes unrelated to RCC. (author)

  9. Gene Expression Profiling Predicts Survival in Conventional Renal Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    2005-12-01

    Full Text Available BACKGROUND: Conventional renal cell carcinoma (cRCC accounts for most of the deaths due to kidney cancer. Tumor stage, grade, and patient performance status are used currently to predict survival after surgery. Our goal was to identify gene expression features, using comprehensive gene expression profiling, that correlate with survival. METHODS AND FINDINGS: Gene expression profiles were determined in 177 primary cRCCs using DNA microarrays. Unsupervised hierarchical clustering analysis segregated cRCC into five gene expression subgroups. Expression subgroup was correlated with survival in long-term follow-up and was independent of grade, stage, and performance status. The tumors were then divided evenly into training and test sets that were balanced for grade, stage, performance status, and length of follow-up. A semisupervised learning algorithm (supervised principal components analysis was applied to identify transcripts whose expression was associated with survival in the training set, and the performance of this gene expression-based survival predictor was assessed using the test set. With this method, we identified 259 genes that accurately predicted disease-specific survival among patients in the independent validation group (p < 0.001. In multivariate analysis, the gene expression predictor was a strong predictor of survival independent of tumor stage, grade, and performance status (p < 0.001. CONCLUSIONS: cRCC displays molecular heterogeneity and can be separated into gene expression subgroups that correlate with survival after surgery. We have identified a set of 259 genes that predict survival after surgery independent of clinical prognostic factors.

  10. F-18 FDG PET in Detecting Renal Cell Carcinoma

    International Nuclear Information System (INIS)

    Purpose: To assess the role of F-18 FDG imaging with a dual head coincidence mode gamma camera (Co-PET) in the detection of renal cell carcinoma (RCC) in patients with renal masses. Material and Methods: An F-18 FDG Co-PET study was performed in 19 patients (7 F, 12 M; mean age 58.15±2.5 years, age range 45-79 years) with suspected primary renal tumors based on conventional imaging techniques, including computed tomography (CT) and ultrasonography (US) before nephrectomy or surgical resection of the mass. Results: Histologically documented RCC was present in 15 patients. Of the 19 patients with suspected primary renal tumors, F-18 FDG Co-PET was true-positive in 13, false-negative in 2, true-negative in 3, and false-positive in 1 patient. Twangiomyolipomas and one renal mass due to infarction and hemorrhage showed a true-negative Co-PET result. The patient with false-positive FDG Co-PET study was diagnosed as xantogranulomatous pyelonephritis. Overall sensitivity, specificity, and accuracy of FDG Co-PET for RCC were 86% (13/15), 75% (3/4), and 84% (16/19), respectively. Positive predictive value for RCC was 92% and negative predictive value 60%. Conclusion: These findings suggest that F-18 FDG Co-PET may have a role in the diagnostic evaluation of patients with RCC and primary staging of disease. Positive F-18 FDG study may be predictive of the presence of RCC. However, a negative study does not exclude the RCC

  11. Pairwise comparison of {sup 89}Zr- and {sup 124}I-labeled cG250 based on positron emission tomography imaging and nonlinear immunokinetic modeling: in vivo carbonic anhydrase IX receptor binding and internalization in mouse xenografts of clear-cell renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Cheal, Sarah M.; Punzalan, Blesida; Doran, Michael G.; Osborne, Joseph R. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Evans, Michael J. [Memorial Sloan-Kettering Cancer Center, Human Oncology and Pathogenesis Program, New York, NY (United States); Lewis, Jason S. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Program in Molecular Pharmacology and Chemistry, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Radiochemistry and Imaging Sciences Service, New York, NY (United States); Zanzonico, Pat [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Molecular Pharmacology and Therapy Service, New York, NY (United States); Memorial-Sloan Kettering Cancer Center, New York, NY (United States); Larson, Steven M. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Program in Molecular Pharmacology and Chemistry, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Molecular Pharmacology and Therapy Service, New York, NY (United States)

    2014-05-15

    The PET tracer, {sup 124}I-cG250, directed against carbonic anhydrase IX (CAIX) shows promise for presurgical diagnosis of clear-cell renal cell carcinoma (ccRCC) (Divgi et al. in Lancet Oncol 8:304-310, 2007; Divgi et al. in J Clin Oncol 31:187-194, 2013). The radiometal {sup 89}Zr, however, may offer advantages as a surrogate PET nuclide over {sup 124}I in terms of greater tumor uptake and retention (Rice et al. in Semin Nucl Med 41:265-282, 2011). We have developed a nonlinear immunokinetic model to facilitate a quantitative comparison of absolute uptake and antibody turnover between {sup 124}I-cG250 and {sup 89}Zr-cG250 using a human ccRCC xenograft tumor model in mice. We believe that this unique model better relates quantitative imaging data to the salient biological features of tumor antibody-antigen binding and turnover. We conducted experiments with {sup 89}Zr-cG250 and {sup 124}I-cG250 using a human ccRCC cell line (SK-RC-38) to characterize the binding affinity and internalization kinetics of the two tracers in vitro. Serial PET imaging was performed in mice bearing subcutaneous ccRCC tumors to simultaneously detect and quantify time-dependent tumor uptake in vivo. Using the known specific activities of the two tracers, the equilibrium rates of antibody internalization and turnover in the tumors were derived from the PET images using nonlinear compartmental modeling. The two tracers demonstrated virtually identical tumor cell binding and internalization but showed markedly different retentions in vitro. Superior PET images were obtained using {sup 89}Zr-cG250, owing to the more prolonged trapping of the radiolabel in the tumor and simultaneous washout from normal tissues. Estimates of cG250/CAIX complex turnover were 1.35 - 5.51 x 10{sup 12} molecules per hour per gram of tumor (20 % of receptors internalized per hour), and the ratio of {sup 124}I/{sup 89}Zr atoms released per unit time by tumor was 17.5. Pairwise evaluation of {sup 89}Zr-cG250 and {sup

  12. Therapeutic dendritic cell vaccination of patients with metastatic renal cell carcinoma - A clinical, phase 1/2 trial

    DEFF Research Database (Denmark)

    Berntsen, A.; Trepiakas, R.; Wenandy, L.;

    2008-01-01

    with a DC- based vaccine in patients with metastatic renal cell carcinoma. Twenty-seven patients with progressive cytokine-refractory metastatic renal cell carcinoma were vaccinated with DCs loaded with either a cocktail of survivin and telomerase peptides or tumor lysate depending on their HLA-A2...

  13. Metastatic Renal Cell Carcinoma in the Sinonasal Region: A Case Report

    Directory of Open Access Journals (Sweden)

    Masood Asghari

    2015-12-01

    Full Text Available Metastatic tumors in the nose and paranasal sinuses are rare. In the present paper, a 68 year old man with metastatic renal cell carcinoma to the left frontoethmoidal region 4 years after initial nephrectomy is presented ..Pathologic diagnosis of the case was Clear Cell Carcinoma. The patient complained of mild nasal obstruction and intermittent  epistaxis, but the significant symptom was  bulging  in medial canthus from 20 days before. Clinical and endoscopic examinations of the left nasal cavity revealed a vascular mass in the axillary of the middle turbinate and anterior ethmoidal sinuses extending to the left orbital cavity .  The patient was treated with partial endoscopic sinus resection and chemoradiotherapy. He had a complete clinical response without any significant complications and recurrence of the tumor after 6 months follow up using interanasal endoscopic examination.

  14. Twelve-year survival after multiple recurrences and repeated metastasectomies for renal cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Wang Jue

    2011-11-01

    Full Text Available Abstract Background Metastatic renal cell carcinoma (RCC presents a therapeutic challenge for clinicians because of the unpredictable clinical course, resistance to chemotherapy or radiotherapy and the limited response to immunotherapy. Patients and Methods We report a case of a 62-year-old woman who underwent nephrectomy for T4N0 RCC, clear cell type, Fuhrman grade 3/4 in 1999. The patinet subsequently had multiple tumor recurrences. Results The patient underwent eight metastasectomies, including multiple partial left nephrectomies, right adrenalectomy, a complete left nephrectomy, and distal pancreatectomy. She remains well and tumor free 12 years after initial diagnosis. Conclusion Repeated resections after initial metastasectomy can be carried out safely and provide long-term survival in selected patients with recurrent metastasis from RCC. The findings from our case indicate that close follow-up for the early detection of recurrence and complete resection of metastases can improve the results after repeated resection.

  15. Renal Cell Carcinoma of Contralateral Kidney with Secondaries in Gallbladder Eight Years After Nephrectomy

    Directory of Open Access Journals (Sweden)

    Kechrid Mohamed

    2000-01-01

    Full Text Available A 55-year-old female underwent right nephrectomy for renal cell carcinoma (RCC. The histopathology showed clear cell carcinoma. There was no evidence of metastasis. After remaining asymptomatic for eight years, she developed pain in the right loin. Abdominal ultrasound, computerized tomography (CT Scan and magnetic resonance imaging (MRI were suggestive of a tumor mass in the right renal area, multiple tumor masses in the left kidney and a mass in the gallbladder. Cholecystectomy, left radical nephrectomy and right adrenal mass with excision of adjacent lymph nodes were performed. The histopathology from all sites was suggestive of RCC. She was maintained on hemodialysis. Two and half years later she died after surgical exploration for spinal cord decompression due to metastasis to the dorsal spine.

  16. Palliative thyroidectomy in the setting of a metastatic renal cell carcinoma

    International Nuclear Information System (INIS)

    A secondary neoplasm of the thyroid gland is a distinctly uncommon cause of thyroid enlargement. These tumors mimic primary thyroid gland tumors and often lead to diagnostic difficulties. We report an interesting case of secondary thyroid tumor coexisting with a micropapillary carcinoma in an elderly male patient following a radical nephrectomy done 15 years prior for a renal cell carcinoma (RCC). Interestingly, the previously described coincidental association of thyroid and pancreatic metastases in a metastatic RCC was also noted in our patient as was demonstrated in the positron emission tomography-computed tomography which was done as part of the metastatic workup. This association needs to be further explored as also the role of palliative thyroidectomy in the setting of a metastatic RCC. The possibility of metastatic RCC should be kept as a differential during the course of the evaluation of clear cell renal tumor of the thyroid gland

  17. IMMUNOLOGICAL MONITORING OF BIOTHERAPY FOR DISSEMINATED RENAL-CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    O. E. Molchanov

    2009-01-01

    Full Text Available Objective: to assess a role of immunomonitoring in patients with disseminated renal-cell carcinoma.  Subjects and methods. One hundred and seventy-five patients treated in 1998 to 2008 were followed up. The patients received various immunochemotherapy regimens including interleukin-2 (IL-2, interferon-α (IFN-α, Xeloda, cyclophosphamide. The immune status, including lymphocytes and their subpopulations, cytokine components (IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12; IFN-α, IFN-γ; tumor necrosis factor-α (TNF-α, immunoglobulins (IgA, IgG, IgM, complement components (C1q, C3, C3a, C4, C5a, was evaluated before treatment and at therapy-free intervals. Results.  The time course of changes in cytokines (IL-6, IL-8, IL-10; TNF-α and IFN-γ and some lymphocyte subpopulations (CD4+CD8+, CD3-CD16+CD56+, CD3+CD16+CD56+, CD4+CD25+Foxp3 greatly differs in patients who belong to different prognostic groups according to the Memorial Sloan-Kettering Cancer Center (MSKCC inclusion criteria. Multivariate analysis has shown that the levels of IL-6 (spontaneous and induced production, IL-8 (spontaneous and induced production, TNF-α (spontaneous production, IFN-γ (induced production, NK T cells (CD3+CD16+CD56+, regulatory T cells (CD4+CD25+Foxp3 affect survival. Integration of the above indices into the MSKCC scale revealed that the groups were prognostically heterogeneous. The median survival in patients with good prognosis was 36.2 months (50.3, 38.3, and 24.5 months in those with 0—1, 2—3, and more than 3 immunological factors, respectively and in those with relatively good and poor prognosis it was 15.3 (29.1, 15.3, and 18.1 months and 8.5 (12.1, 9.3, and 6.3 months months, respectively.Conclusion. The cytokine status reflects the aggressiveness of a tumor process. The cytokine level changes may be used to predict the out- come of the disease.  

  18. IMMUNOLOGICAL MONITORING OF BIOTHERAPY FOR DISSEMINATED RENAL-CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    O. E. Molchanov

    2014-08-01

    Full Text Available Objective: to assess a role of immunomonitoring in patients with disseminated renal-cell carcinoma.  Subjects and methods. One hundred and seventy-five patients treated in 1998 to 2008 were followed up. The patients received various immunochemotherapy regimens including interleukin-2 (IL-2, interferon-α (IFN-α, Xeloda, cyclophosphamide. The immune status, including lymphocytes and their subpopulations, cytokine components (IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12; IFN-α, IFN-γ; tumor necrosis factor-α (TNF-α, immunoglobulins (IgA, IgG, IgM, complement components (C1q, C3, C3a, C4, C5a, was evaluated before treatment and at therapy-free intervals. Results.  The time course of changes in cytokines (IL-6, IL-8, IL-10; TNF-α and IFN-γ and some lymphocyte subpopulations (CD4+CD8+, CD3-CD16+CD56+, CD3+CD16+CD56+, CD4+CD25+Foxp3 greatly differs in patients who belong to different prognostic groups according to the Memorial Sloan-Kettering Cancer Center (MSKCC inclusion criteria. Multivariate analysis has shown that the levels of IL-6 (spontaneous and induced production, IL-8 (spontaneous and induced production, TNF-α (spontaneous production, IFN-γ (induced production, NK T cells (CD3+CD16+CD56+, regulatory T cells (CD4+CD25+Foxp3 affect survival. Integration of the above indices into the MSKCC scale revealed that the groups were prognostically heterogeneous. The median survival in patients with good prognosis was 36.2 months (50.3, 38.3, and 24.5 months in those with 0—1, 2—3, and more than 3 immunological factors, respectively and in those with relatively good and poor prognosis it was 15.3 (29.1, 15.3, and 18.1 months and 8.5 (12.1, 9.3, and 6.3 months months, respectively.Conclusion. The cytokine status reflects the aggressiveness of a tumor process. The cytokine level changes may be used to predict the out- come of the disease.  

  19. Molecular features of renal cell carcinoma: early diagnostics and perspectives for therapy

    Directory of Open Access Journals (Sweden)

    O. V. Kovaleva

    2015-06-01

    Full Text Available Kidney cancer (renal cell carcinoma is one of the major problems of modern urological oncology. In Russia renal cell carcinoma accountsfor 4.3 % of all cancers. The global incidence of renal cell carcinoma has increased over the past two decades. Worldwide renal cell carcinoma accounts for 3.6 % of all cancers and is 10th frequent malignancy. For some malignancies, for instance tumours of prostate, there are markers known that allowed improved early diagnostics. Kidney cancer, however, remains to be hard to diagnose and to treat, since the symptoms can be detected on advanced stages of the disease. In Russia 75.4 % of renal cell carcinoma cases detected at the stage of local and locally advanced disease. Though there are various target drugs on the market aimed to treat this disease, the results of renal cell carcinoma treatment did not reach any substantial success. Most of existing target drugs for kidney cancer treatment include inhibitors of a single signalingpathway regulated by VHL1, which expression is lost in the vast majority of renal-cell carcinomas. Till now existing drugs did not reach sufficient efficacy. Therefore, it is highly important to search for new signaling pathways, regulating such cellular processes as proliferation, migration and apoptosis. Further, prognostic markers and therapy targets identified so far are not sufficient and poorly specific. Therefore identification and validation of new markers, and especially new specific targets for the treatment of kindey oncopathologies is highly important and timely task.

  20. Current treatment approach to non-clear cell renal carcinoma

    OpenAIRE

    I. V. Tsimafeyeu

    2015-01-01

    Non-clear cell renal cell carcinoma has various histologic subtypes. Tumor biology plays significant role in the disease development. However, despite the one surgical approach both to clear cell and non-clear cell renal carcinoma, patients’ outcomes within one stage of the disease may vary. Furthermore, tumor sensitivity and its response to therapy are highly dependent on the same histologic subtype.The article gives detailed data on the current treatment of papillary, chromophobe and other ...

  1. Expression of Fas and Fas-L in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Govedarović Vitomir

    2006-01-01

    Full Text Available Introduction: The previous investigations revealed that Fas-L expression on tumor cells can be one of the reasons of tumor growth, or tumor regression, with or without activation of the immune response. Objective: The objective of our study was to investigate the expression of Fas and Fas-L in situ in normal human renal tissue as well as in different types of renal cell carcinoma (RCC according to tumor grading. Method: Expression of Fas and Fas-L was examined in 25 RCCs classified according to nuclear grades: G1-G3 and to cell type: 17 clear cells, 3 chromophilics (2 eosinophilics, 1 basophilic, 2 chromophobes and 3 spindle cells. Ten normal human kidneys were analyzed, too. Indirect immunoperoxidase technique was applied. Spread and intensity of staining of Fas and Fas-L molecules expression were scored semiquantitatively. Results: Distribution of Fas expression in these RCC was typically diffuse. However, Fas-L was almost completely absent in clear cell RCC. In 3 clear cell RCC, some tumor stromal cells exhibited strong expression of Fas-L. On the contrary, chromophilic, chromophobe and spindle cell RCCs grading from G2- G3, manifested variable combinations of Fas and Fas-L expression. Conclusion: The most of clear cell type low grade RCCs manifested intensive and extensive expression of Fas and completely absence of Fas-L. However, RCCs of high grade malignancy belonging to the clear cell, eosinophilic, chromophobe or spindle cell types can have various combinations of Fas and Fas-L expression. It may probably lead to development of different mechanisms of avoidance of immune response to RCC.

  2. Neoadjuvant targeted therapy in patients with renal cell carcinoma

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    B. Ya. Alekseev

    2015-06-01

    Full Text Available Cytoreductive nephrectomy as an independent option in patients with metastatic renal cell carcinoma (mRCC cannot be considered as the only effective method, with rare exception, of a few patients with solitary metastases. Cytoreductive nephrectomy is now part of a multimodal approach encompassing surgical treatment and systemic drug therapy. Many retrospective and two prospective studies have demonstrated that it is expedient to perform cytoreductive nephrectomy. Immunotherapy should not be used as preoperatively in the era of cytokine therapy for mRCC due to that fact that it has no impact on primary tumor. In the current targeted therapy era, many investigators have concentrated attentionon the role of neoadjuvant targeted therapy for the treatment of patients with both localized and locally advanced mRCC. The potential benefits of neoadjuvant therapy for localized and locally advanced RCC include to make surgery easier and to increase the possibility of organsparing treatment, by decreasing the stage of primary tumor and the size of tumors. The possible potential advantages of neoadjuvant targeted therapy in patients with mRCC include prompt initiation of necessary systemic therapy; identification of patients with primary refractory tumors; and a preoperative reduction in the stage of primary tumor. Numerous retrospective and some prospective phase II studies have shown that neoadjuvant targeted therapy in patients with localized and locally advanced RCC is possible and tolerable and surgical treatment after neoadjuvant targeted therapy is safe and executable with a low incidence of complications. If neoadjuvant therapy is to be performed, it should be done within 2–4 months before surgery. Sorafenib and sunitinib are now most tested and suitable for neoadjuvant targeted therapy. Sorafenib is a more preferred drug due to its shorter half-life and accordingly to the possibility of discontinuing the drug immediately prior to

  3. Famitinib in metastatic renal cell carcinoma: a single center study

    Institute of Scientific and Technical Information of China (English)

    ZHANG Wen; ZHOU Ai-ping; QIN Qiong; CHANG Chun-xiao; JIANG Hao-yuan; MA Jian-hui; WANG Jin-wan

    2013-01-01

    Background Famitinib is a novel and potent multitargeting receptor tyrosine kinase inhibitor.The phase I clinical study showed that famitinib was well tolerated and had a broad anti-tumor spectrum.The purpose of this study was to examine the efficacy and safety of famitinib for the treatment of metastatic renal cell carcinoma (mRCC).Methods The data of famitinib in treating patients with mRCC from the single-center phases Ⅰ and Ⅱ clinical trials were analyzed.Famitinib was administered orally at the dose of 13-30 mg once daily until tumor progression,occurrence of intolerable adverse reactions or withdrawal of the informed consent.Results A total of 24 patients with mRCC were treated including 17 patients at a dose of 25 mg once daily,4 patients at a dose of 27 mg and 1 patient each at a dose of 13 mg,20 mg and 30 mg,respectively.Twelve (50.0%) patients achieved partial response (PR) and 9 patients achieved stable disease (SD).Progressive disease was found in 3 (12.5%) patients.The disease control rate was 87.5%.The median follow-up time was 17.6 months; the median progression free survival (PFS) was 10.7 (95% Cl7.0-14.4) months; and the estimated median overall survival (OS) time was 33.0 (95% Cl8.7-57.3) months.The adverse drug reactions mainly included hypertension (54.1%),hand-foot skin reactions (45.8%),diarrhea (33.3%),mucositis (29.2%),neutropenia (45.8%),thrombocytopenia (29.2%),hyperlipidemia (41.7%) and proteinuria (41.7%).The incidence rate of grades 3 and 4 adverse events was low,mainly including hypertension 12.5%,hand-foot skin reactions 4.2%,neutropenia 4.2%,thrombocytopenia 4.2%,hyperlipidemia 4.2% and proteinuria 12.5%.Conclusions Famitinib has significant anti-tumor activity in mRCC.The common adverse reactions are generally manageable.

  4. CT staging of renal cell carcinoma: Emphasis on perinephric tumor extension

    International Nuclear Information System (INIS)

    A total of 47 preoperative CT scans in patients with renal cell carcinoma were retrospectively reviewed and compared with surgical findings to assess the accuracy of CT for determining the perinephric tumor extension. CT criteria for perinephric extension were hazy ill-defined tumor margin, perirenal nodule and fascial thickening. Regardless of the tumor stage, the accuracy of CT in detecting perinephric extension was 76.6% (36/47), with a sensitivity of 88.9% (16/18) and specificity of 68.9% (20/29). The cause of understaging (n=2) was microscopic infiltration of the perinephric space. The causes of overstaging were tumor infiltration to the renal capsule (n=5), partial adhesion with the perinephric fat (n=3) and renal vein thrombosis (n=1). A smooth clear tumor margin is highly reliable sign for stage I but infiltrative findings onto renal capsule and perirenal fat could be considered stage I

  5. Sunitinib Does Not Accelerate Tumor Growth in Patients with Metastatic Renal Cell Carcinoma

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    Krastan B. Blagoev

    2013-02-01

    Full Text Available Preclinical studies have suggested that sunitinib accelerates metastases in animals, ascribing this to inhibition of the vascular endothelial growth factor receptor or the tumor’s adaptation. To address whether sunitinib accelerates tumors in humans, we analyzed data from the pivotal randomized phase III trial comparing sunitinib and interferon alfa in patients with metastatic renal cell carcinoma. The evidence clearly shows that sunitinib was not harmful, did not accelerate tumor growth, and did not shorten survival. Specifically, neither longer sunitinib treatment nor a greater effect of sunitinib on tumors reduced survival. Sunitinib did reduce the tumor’s growth rate while administered, thereby improving survival, without appearing to alter tumor biology after discontinuation. Concerns arising from animal models do not apply to patients receiving sunitinib and likely will not apply to similar agents.

  6. Autophagy Inhibition to Augment mTOR Inhibition: A Phase I/II Trial of RAD001 and Hydroxychloroquine in Patients With Previously Treated Renal Cell Carcinoma

    Science.gov (United States)

    2015-12-07

    Histological Evidence of Metastatic Clear Cell Renal Cell Carcinoma; That Has Been Previously Treated With 1-3 Prior Regimens. Phase 1 Only, Any Number of Prior Regimens; With Evidence of Progressive Disease on or Within 6 Months; of Discontinuing Sunitinib, Sorafenib or Pazopanib. Previous; Therapy With Bevacizumab, IL2, or Interferon Are Permitted.

  7. The clinicalapplication of interleukin-2therapy in patients withmetastatic renal cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Li-Wen Zhou

    2015-01-01

    Objective: To analyze the clinical application of interleukin-2 therapy in patients with metastatic renal cell carcinoma.Methods:From January 2010 to July 2014 of 108 patients with metastatic renal cell carcinoma patients in our hospital as research subjects were randomly divided into the experimental group and the control group. The experimental group received IL-2 combined with Nexavar therapy, and the control group only received Nexavar treatment, clinical efficacy and incidence of adverse reactions between the two groups of patients were compared.Results:Compared with the control group, clinical efficacy in the experimental group was significantly higher, the difference was statistically significant. The incidence of adverse events was higher in patients than that in the experimental group, the difference was statistically significant, but IL-2 had no new adverse reactions and side effects.Conclusions:Interleukin-2 combined with Nexavar treatment of metastatic renal cell carcinoma can improve the clinical efficacy of metastatic renal cell carcinoma in patients, and ease the patient's condition from worsening and promote the quality of life. However, adverse reactions caused by drugs were inevitable; we should pay attention to treatment and prevention of adverse reactions in order to improve the quality of life of patients with metastatic renal cell carcinoma.

  8. 肾透明细胞癌组织肾母细胞瘤过表达基因表达临床意义的探讨%Expression of NOV and its clinical significance in clear cell renal cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    牛志宏; 毕东滨; 吕家驹

    2012-01-01

    OBJECTIVE:To investigate the relationship between the expression of NOV and the stage,grade,proliferation index and prognosis of clear cell renal cell carcinoma(RCC). METHODS: Fifty-four samples of clear cell RCC tissues were collected. NOV expression and Ki-67 index were examined by immunohistochemical staining. RESULTS: The immunostaining intensity of NOV was significantly lower in tumor compared to normal kidney tissue and strong NOV expressions were demonstrated in all 22 normal kidney tissues. In contrast only 24(44. 4%) tumors were found to be weakly positive and 8(14. 8%) tumors were found to be moderately positive. The positive rate of NOV was also lower in tumor (59. 3%) compared to normal kidney tissue(100%). The Ki-67 index was significantly higher in NOV negative tumor [(4. 2 ± 2. 1)%] than that in NOV positive tumor [(2. 6±1. 5)%,P<0. 053. NOV expression could not be correlated with stage,grade,and size of tumors. The NOV positive group showed significantly higher 5 year cancer specific survival rate compared to NOV negative group (82. 6% vs 50. 3% ,P<0. 05). CONCLUSION; The results of this study suggest that NOV could play inhibitory role in clear cell RCC.%目的:探讨肾母细胞瘤过表达基因(NOV)对肾透明细胞癌分级、分期、大小、增殖状态和预后的影响.方法:应用免疫组化法检测54例肾透明细胞癌组织NOV蛋白的表达,分析其与肾透明细胞癌分期、分级、大小、Ki-67指数的相关性,并比较NOV阳性组和阴性组的生存率差异.结果:NOV在肾脏透明细胞癌组织中的染色强度明显低于癌旁正常肾组织,22例(100%)癌旁正常肾组织均呈强阳性染色,54例肾癌组织中24例(44.4%)为弱阳性染色,8例(14.8%)为中等阳性染色 ;癌组织总阳性率(59.3%)亦显著低于癌旁正常肾组织(100%),P<0.05.NOV阳性组的Ki-67指数(2.6±1.5)%,明显低于NOV阴性组的(4.2±2.1)%,P<0.05.NOV表达与肿瘤分期及大小无相关性,P>0

  9. Contemporary approach to diagnosis and classification of renal cell carcinoma with mixed histologic features

    Institute of Scientific and Technical Information of China (English)

    Kanishka Sircar; Priya Rao; Eric Jonasch; Federico A.Monzon; Pheroze Tamboli

    2013-01-01

    Renal cell carcinoma (RCC) is an important contributor to cancer-specific mortality worldwide.Targeted agents that inhibit key subtype-specific signaling pathways have improved survival times and have recently become part of the standard of care for this disease.Accurately diagnosing and classifying RCC on the basis of tumor histology is thus critical.RCC has been traditionally divided into clear-cell and non-clearcell categories,with papillary RCC forming the most common subtype of non-clear-cell RCC.Renal neoplasms with overlapping histologies,such as tumors with mixed clear-cell and papillary features and hybrid renal oncocytic tumors,are increasingly seen in contemporary practice and present a diagnostic challenge with important therapeutic implications.In this review,we discuss the histologic,immunohistochemical,cytogenetic,and clinicopathologic aspects of these differential diagnoses and illustrate how the classification of RCC has evolved to integrate both the tumor's microscopic appearance and its molecular fingerprint.

  10. A case of treatment in a patient with synchronous bilateral renal cell carcinoma and simultaneous metastatic involvement of both adrenal glands: Clinical observation

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    V. R. Latypov

    2014-11-01

    Full Text Available Synchronous bilateral renal cell carcinoma occurs in 1.4 % of cases. The probability of bilateral adrenal metastases from renal cell carcinoma is less than 0.5 %. The clinical observation presents a case of synchronous bilateral renal cell carcinoma and simultaneous metastatic involvement of both adrenal glands. A 55‑year-old male patient was adm tted with the signs of hematuria and anemia to the Unit of Urology, Clinic of General Surgery, Siberian State Medical University. He was found to have synchronous bilateral renal cell carcinoma and simultaneous bilateral adrenal involvement. Sequential surgical treatment – radical nephrectomy (with adrenal gland removal on the right side and, after 3 months, adrenalectomy and kidney resection on the left side were performed. All the organs removed displayed tumors that proved to be renal cell carcinomas (a clear cell variant. There were lymph node metastases in the right-sided renal portal. Postoperatively, the investigators performed hormone replacement therapy for adrenal insufficiency, an immunotherapy cycle, three cycles of targeted therapy withsorafenib and sunitinib (at an interval of 0.5–2 years, and insulin therapy for new-onset diabetes mellitus. The duration of a follow-up was 6.2 years. When describing the case, the patient was alive and showed a generalized tumorous process with extensive tumor involvement of the solitary kidney. Sunitinib therapy was used.

  11. Therapeutic Strategies for Patients With Metastatic Renal Cell Carcinoma in Whom First-Line Vascular Endothelial Growth Factor Receptor-Directed Therapies Fail.

    Science.gov (United States)

    Malouf, Gabriel G; Flippot, Ronan; Khayat, David

    2016-05-01

    Metastases are present in one third of renal cell carcinomas at diagnosis. The overall survival duration in metastatic renal cell carcinoma is approximately 22 months, which underlines the need for more effective systemic treatments. Therapies on the basis of antiangiogenic agents and inhibitors of the mammalian target of rapamycin have been approved for treatment of metastatic renal cell carcinoma, but only benefits for progression-free survival were demonstrated in the second-line setting. Fortunately, promising treatments are emerging, from new antiangiogenic agents to immune checkpoint inhibitors. For the first time, both an immune checkpoint inhibitor (nivolumab) and a dual inhibitor of the tyrosine kinases c-Met and vascular endothelial growth factor receptor-2 (cabozantinib) have demonstrated improvements in overall survival in the second-line setting. Finding the best sequence for these novel agents will be crucial to improving outcomes in patients with metastatic renal cell carcinoma. This article comprises both a systematic review of the literature and recommendations for second-line therapeutic strategies for patients with metastatic clear cell renal cell carcinoma in whom inhibitors of vascular endothelial growth factor have failed. PMID:27170687

  12. Renal cell carcinoma metastases to the pancreas - Value of arterial phase imaging at MDCT

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    Corwin, Michael T. [Univ. of California, Davis Medical Center, Dept. of Radiology, Sacramento (United States)], e-mail: Michael.corwin@ucdmc.ucdavis.edu; Lamba, Ramit; McGahan, John P. [Univ. of California, Davis Medical Center, Dept. of Radiology, Sacramento (United States); Wilson, Machelle [Univ. of California, Davis, Dept. of Public Health Sciences (United States)

    2013-04-15

    Background: The pancreas is an increasingly recognized site of renal cell carcinoma metastases. It is important to determine the optimal MDCT protocol to best detect RCC metastases to the pancreas. Purpose: To compare the rate of detection of renal cell carcinoma metastases to the pancreas between arterial and portal venous phase MDCT. Material and Methods: A retrospective review of CTs of the abdomen yielded six patients with metastatic RCC to the pancreas. Five of six patients had pathologically proven clear cell RCC. Two blinded reviewers independently reported the number of pancreatic lesions seen in arterial and venous phases. Each lesion was graded as definite or possible. The number of lesions was determined by consensus review of both phases. Attenuation values were obtained for metastatic lesions and adjacent normal pancreas in both phases. Results: There were a total of 24 metastatic lesions to the pancreas. Reviewer 1 identified 20/24 (83.3%) lesions on the arterial phase images and 13/24 (54.2%) lesions on the venous phase. Seventeen of 20 (85.0%) arterial lesions were deemed definite and 9/13 (69.2%) venous lesions were definite. Reviewer 2 identified 19/24 (79.2%) lesions on the arterial phase and 14/24 (58.3%) on the venous phase. Seventeen of 19 (89.5%) arterial lesions were definite and 7/14 (50%) venous lesions were definite. Mean attenuation differential between lesion and pancreas was 114 HU and 39 HU for arterial and venous phases, respectively (P<0.0001). Conclusion: Detection of RCC metastases to the pancreas at MDCT is improved using arterial phase imaging compared to portal venous phase imaging.

  13. Renal cell carcinoma metastases to the pancreas - Value of arterial phase imaging at MDCT

    International Nuclear Information System (INIS)

    Background: The pancreas is an increasingly recognized site of renal cell carcinoma metastases. It is important to determine the optimal MDCT protocol to best detect RCC metastases to the pancreas. Purpose: To compare the rate of detection of renal cell carcinoma metastases to the pancreas between arterial and portal venous phase MDCT. Material and Methods: A retrospective review of CTs of the abdomen yielded six patients with metastatic RCC to the pancreas. Five of six patients had pathologically proven clear cell RCC. Two blinded reviewers independently reported the number of pancreatic lesions seen in arterial and venous phases. Each lesion was graded as definite or possible. The number of lesions was determined by consensus review of both phases. Attenuation values were obtained for metastatic lesions and adjacent normal pancreas in both phases. Results: There were a total of 24 metastatic lesions to the pancreas. Reviewer 1 identified 20/24 (83.3%) lesions on the arterial phase images and 13/24 (54.2%) lesions on the venous phase. Seventeen of 20 (85.0%) arterial lesions were deemed definite and 9/13 (69.2%) venous lesions were definite. Reviewer 2 identified 19/24 (79.2%) lesions on the arterial phase and 14/24 (58.3%) on the venous phase. Seventeen of 19 (89.5%) arterial lesions were definite and 7/14 (50%) venous lesions were definite. Mean attenuation differential between lesion and pancreas was 114 HU and 39 HU for arterial and venous phases, respectively (P<0.0001). Conclusion: Detection of RCC metastases to the pancreas at MDCT is improved using arterial phase imaging compared to portal venous phase imaging

  14. 组氨酸三聚体核苷结合蛋白1在肾透明细胞癌中的表达及意义%Expression of histidine triad nucleotide-binding protein 1 in clear cell renal cell carcinoma and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    杨斌; 邢金春; 李伟; 张开颜; 吴准; 陈志阳; 杨盛华

    2011-01-01

    Objective: To determine the expressions of histidine triad nucleotide-binding protein 1 (HINT1) mRNA and protein in clear cell renal cell carcinoma (ccRCC) and their relationships with clinicopatholgical features. Methods: Real-time fluorescence quantitative reverse transcription PCR (RFQ-RT-PCR) was used to detect the expressions of HINT1 mRNA in 36 cases of fresh ccRCC and 37 cases of normal kidney tissues (29 paired cases), as well as their relationships with clinicopathological features were analyzed. Immunohistochemistry was used to detect the distribution and expression of HINT1 protein in 30 cases of paraffin embedded fresh ccRCC tissues and 12 cases of paraffin-embedded adjacent normal kidney tissues, as well as their relationships with clinicopathological features were analyzed. Results: The expression levels of HINT1 mRNA in 29 cases of paired ccRCC and normal kidney tissues were 0.209±0.033 and 0.733±0.136, respectively (P<0.001). The expression levels of HINT1 mRNA in 36 cases of ccRCC and 37 cases of normal kidney tissues were 0.245±0.035 and 0.694± 0.108, respectively (P<0.001). The positive expression rate of HINT1 protein in the adjacent normal kidney tissues was 100% (12/12), diffusely distributing in the nucleus and cytoplasm. HINT1 protein immunostaining in proximal convoluted tubule was stronger than that in distal convoluted tubule, while it was partially weaker in glomerular basement membrane and Bowman's capsule. The HINT1 protein expression was negative in renal interstitium. HINT1 protein expression distributing in nucleus and cytoplasm was 60% (18/30) positive in ccRCC, while it was negative in intercellular substance (P<0.01). The tendency of HINT1 mRNA expression in ccRCC and normal kidney tissues and their relationships with the clinicopathological features were the same as those of HINT1 protein. The expressions of HINT1 mRNA and protein in stages T1-2 of ccRCC were higher than those in stages T3-4 (P<0.05), and the

  15. The Study of Laparoscopic Nephrectomy Effectiveness in Patients with Renal Cell Carcinoma

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    Kochoyan T.M.

    2011-06-01

    Full Text Available The aim of the study is to assess the effectiveness of short-term and long-term results in patients with renal cell carcinoma being operated on using open surgery and laparoscopy. Materials and Methods. There were studied 214 patients with renal cell carcinoma with radical nephrectomy. 164 patients underwent laparoscopy, and 50 patients were operated on using open surgery technique. Conclusion. The comparative analysis of short-term and long-term results of renal cell carcinoma surgical treatment and long-term survival of patients depending on the approach — by an open surgery and by an endoscopic technique — showed the laparoscopic approach to be absolutely acceptable and oncologically adequate.

  16. Signs of hypervascularization at magnetic resonance imaging in bone metastases from renal cell carcinoma

    International Nuclear Information System (INIS)

    Objective: To evaluate the frequency of hypervascularization by visualizing vascular structures inside or around bone metastases from renal cell carcinoma. Materials and methods: Magnetic resonance imaging studies of 13 untreated patients with diagnosis of renal cell carcinoma and 15 metastatic bone lesions were retrospectively evaluated. Results: Signs of hypervascularization were found in 12 of the 15 bone lesions (80%), 6 of them localized in the lumbar spine, 3 in the hip, 3 in the thoracic spine, 1 in the ulna and 1 in the tibia. Conclusion: The high frequency of hypervascularization of bone metastases from renal cell carcinoma found in the present study may suggest that the renal etiology is a useful parameter in the evaluation of a usual clinical presentation of a single bone lesion with unknown primary neoplasm. (author)

  17. CT differentiation of renal tumor invading parenchyma and pelvis: renal cell carcinoma vs transitional cell carcinoma

    International Nuclear Information System (INIS)

    The differentiation between renal cell carcinoma(RCC) and transitional cell carcinoma(TCC) is important due to the different methods of treatment and prognosis. But occasionally it is difficult to draw a distinction between the two diseases when renal parenchyma and renal collecting systems are invaded simultaneously. We reviewed CT scans of 37 cases of renal cell carcinoma and 12 cases of transitional cell carcinoma which showed involvement of renal parenchyma and renal sinus fat on CT. Retrospective analysis was performed by 3 abdominal radiologists. Check points were renal contour bulging or reinform shape, location of mass center, intact parenchyma overlying the tumor, cystic change, calcification, LN metastasis, vessel invasion, and perirenal extention. There were renal contour bulging due to the tumor mass in 33 out of 37 cases of renal cell carcinoma, where a and nine of 12 cases of transitional cell carcinoma maintained the reinform appearance. This is significant statiscal difference between the two(P<0.005). Center of all TCCs were located in the renal sinus, and 24 out of 35 cases of RCC were located in the cortex(P<0.005). Thirty-six out of 37 cases of RCC lost the overlying parenchyma, where as 4 out of 9 cases of well enhanced TCC had intact overlying parenchyma(P<0.005) RCC showed uptic change within the tumor mags in 31 cases which was significanity higher than the 4 cases in TCC(P<0.05). CT findings of renal cell carcinoma are contour bulging, peripheral location, obliteration of parenchyma, and cystic change. Findings of transitional cell carcinoma are reinform appearance, central location within the kidney, intact overlying parenchyma, and rare cystic change

  18. RASSF1A protein expression and correlation with clinicopathological parameters in renal cell carcinoma

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    Machtens Stefan

    2008-09-01

    Full Text Available Abstract Background Epigenetic silencing of RAS association family 1A (RASSF1A tumor suppressor gene occurs in various histological subtypes of renal cell carcinoma (RCC but RASSF1A protein expression in clear cell RCC as well as a possible correlation with clinicopathological parameters of patients has not been analyzed at yet. Methods 318 primary clear cell carcinomas were analyzed using tissue microarray analysis and immunohistochemistry. Survival analysis was carried out for 187 patients considering a follow-up period of 2–240 month. Results Expression of RASSF1A was found to be significantly decreased in tumoral cells when compared to normal tubular epithelial cells. RASSF1A immunopositivity was significantly associated with pT stage, group stage and histological grade of tumors and showed a tendency for impaired survival in Kaplan-Meier analysis. Conclusion While most tumors demonstrate a loss of RASSF1A protein, a subset of tumors was identified to exhibit substantial RASSF1A protein expression and show increased tumor progression. Thus RCC tumorigenesis without depletion of RASSF1A may be associated with an adverse clinical outcome.

  19. Xp11 Translocation Renal Cell Carcinoma: Unusual Variant Masquerading as Upper Tract Urothelial Cell Carcinoma

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    Arash Akhavein

    2014-05-01

    Full Text Available Xp11 translocation renal cell carcinoma (TRCC is a rare subtype of renal cell carcinoma characterized by chromosomal translocations involving the TFE3 gene located at the Xp11.2 locus. Initial cases were more common in children, but cases in older adults have begun to accrue and suggest a relatively more aggressive course. We report a case of Xp11 TRCC in a 63-year-old female patient with initial presentation mimicking upper urinary tract urothelial cell carcinoma, with biopsy proving TRCC. She underwent a radical nephrectomy and paracaval lymph node dissection and is followed up with the intent to initiate vascular endothelial growth factor–targeted therapy in case of recurrence.

  20. Genomic profiling of renal cell carcinoma in patients with end-stage renal disease.

    Science.gov (United States)

    Inoue, Toru; Matsuura, Keiko; Yoshimoto, Taichiro; Nguyen, Lam Tung; Tsukamoto, Yoshiyuki; Nakada, Chisato; Hijiya, Naoki; Narimatsu, Takahiro; Nomura, Takeo; Sato, Fuminori; Nagashima, Yoji; Kashima, Kenji; Hatakeyama, Shingo; Ohyama, Chikara; Numakura, Kazuyuki; Habuchi, Tomonori; Nakagawa, Masayuki; Seto, Masao; Mimata, Hiromitsu; Moriyama, Masatsugu

    2012-03-01

    The purpose of the present study was to determine the genomic profile of renal cell carcinoma (RCC) in end-stage renal disease (ESRD) by analyzing genomic copy number aberrations. Seventy-nine tumor samples from 63 patients with RCC-ESRD were analyzed by array comparative genomic hybridization using the Agilent Whole Human Genome 4 × 44K Oligo Micro Array (Agilent Technologies Inc., Palo Alto, CA, USA). Unsupervised hierarchical clustering analysis revealed that the 63 cases could be divided into two groups, Clusters A and B. Cluster A was comprised mainly of clear cell RCC (CCRCC), whereas Cluster B was comprised mainly of papillary RCC (PRCC), acquired cystic disease (ACD)-associated RCC, and clear cell papillary RCC. Analysis of the averaged frequencies revealed that the genomic profiles of Clusters A and B resembled those of sporadic CCRCC and sporadic PRCC, respectively. Although it has been proposed on the basis of histopathology that ACD-associated RCC, clear cell papillary RCC and PRCC-ESRD are distinct subtypes, the present data reveal that the genomic profiles of these types, categorized as Cluster B, resemble one another. Furthermore, the genomic profiles of PRCC, ACD-associated RCC and clear cell papillary RCC admixed in one tissue tended to resemble one another. On the basis of genomic profiling of RCC-ESRD, we conclude that the molecular pathogenesis of CCRCC-ESRD resembles that of sporadic CCRCC. Although various histologic subtypes of non-clear cell RCC-ESRD have been proposed, their genomic profiles resemble those of sporadic PRCC, suggesting that the molecular pathogenesis of non-CCRCC-ESRD may be related to that of sporadic PRCC. PMID:22145865

  1. Transport of circulating serum cholesterol by human renal cell carcinoma

    International Nuclear Information System (INIS)

    Clear cell renal cancer contains a large quantity of cholesterol ester (300-mg./gm. protein). To determine whether abnormalities in cholesterol transport could account for this sterol accumulation, the uptake, release, and imaging capabilities of intravenously injected 131I-6-iodomethyl-29-norcholesterol, a cholesterol analogue, were studied preoperatively in five patients with clear cell renal cancer. At surgery, samples of the liver, tumor, adrenal, and non-tumor kidney were obtained for analysis. 131I-sterol uptake by the tumor, when normalized for cholesterol content, was less than for adrenal, liver or kidney. In contrast, release of preloaded 131I-sterol from the human tumors was consistently slower than for normal kidney. The reduced release of free cholesterol from renal cancer cells may, in part, be responsible for the accumulation of cholesterol in human renal cancer

  2. Adjuvant therapy for locally advanced renal cell cancer: A systematic review with meta-analysis

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    Lima Carmen SP

    2011-03-01

    Full Text Available Abstract Background Many adjuvant trials have been undertaken in an attempt to reduce the risk of recurrence among patients who undergo surgical resection for locally advanced renal cancer. However, no clear benefit has been identified to date. This systematic review was conducted to examine the exact role of adjuvant therapy in renal cancer setting. Methods Randomized controlled trials were searched comparing adjuvant therapy (chemotherapy, vaccine, immunotherapy, biochemotherapy versus no active treatment after surgery among renal cell cancer patients. Outcomes were overall survival (OS, disease-free survival (DFS, and severe toxicities. Risk ratios (RR, hazard ratios (HR and 95% confidence intervals were calculated using a fixed-effects meta-analysis. Heterogeneity was measured by I2. Different strategies of adjuvant treatment were evaluated separately. Results Ten studies (2,609 patients were included. Adjuvant therapy provided no benefits in terms of OS (HR 1.07; 95%CI 0.89 to 1.28; P = 0.48 I2 = 0% or DFS (HR 1.03; 95%CI 0.87 to 1.21; P = 0.77 I2 = 15% when compared to no treatment. No subgroup analysis (immunotherapy, vaccines, biochemotherapy and hormone therapy had relevant results. Toxicity evaluation depicted a significantly higher frequency of serious adverse events in the adjuvant group. Conclusions This analysis provided no support for the hypothesis that the agents studied provide any clinical benefit for renal cancer patients although they increase the risk of toxic effects. Randomized trials are underway to test targeted therapies, which might open a new therapeutic frontier. Until these trials yield results, no adjuvant therapy can be recommended for patients who undergo surgical resection for renal cell cancer.

  3. Ischiogluteal bursitis mimicking soft-tissue metastasis from a renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Voelk, M.; Gmeinwieser, J.; Manke, C.; Strotzer, M. [Department of Radiology, University Hospital, Regensburg (Germany); Hanika, H. [Department of Urology, St. Josef Hospital, Regensburg (Germany)

    1998-09-01

    We report a case of ischiogluteal bursitis mimicking a soft-tissue metastasis from a renal cell carcinoma. A 66-year-old woman suffered from pain over the left buttock 6 months after she was operated on for renal cell carcinoma of the left kidney. CT of the abdomen and pelvis revealed a tumor-like lesion adjacent to the left os ischii, which was suspected to be a soft-tissue metastasis. Percutaneous biopsy revealed no evidence of malignancy, but the histopathological diagnosis of chronic bursitis. (orig.) With 2 figs., 8 refs.

  4. Post-renal Transplantation de novo Renal Cell Carcinoma in a Middle-aged Man

    OpenAIRE

    Pandya, V. K.; Sutariya, H. C.

    2016-01-01

    Renal cell carcinoma is usually seen in the native kidney but may be seen in the renal allograft. We report a rare case of renal cell carcinoma in a 56-year-old renal allograft recipient who was transplanted for end-stage renal disease induced by analgesic nephropathy. This complication developed after 13 years of renal transplantation. Patient was investigated for hematuria and abdominal pain with a normal renal function. Computed tomography depicted a mass sized 9.0×7.3×6.8 cm that involved...

  5. Isolated Late Metastasis of a Renal Cell Cancer Treated by Radical Distal Pancreatectomy

    Directory of Open Access Journals (Sweden)

    J. P. Barras

    1996-01-01

    Full Text Available A 53–year-old man underwent right nephrectomy for a locally advanced renal cell carcinoma with concomitant resection of a solitary metastasis in the right lung. Ten years later, he presented with haematochezia caused by a tumour in the tail of pancreas, invading the transverse colon and the greater curvature of the stomach. The tumour was radically resected, and histological examination revealed a solitary metastasis of the previous renal cell carcinoma. This case illustrates a rare indication for pancreatic resection because of pancreatic metastasis.

  6. Report of a Rare Case of Papillary Thyroid Carcinoma Associated with Renal Cell Carcinoma

    OpenAIRE

    Sh. Borzouei; S. Mahmoodi; A.H. Moaddab; A.R. Salim Bahrami

    2012-01-01

    Introduction: Papillary thyroid cancer (PTC) is the most common well-differentiated cancer of the thyroid. Only in few cases of PTC entity of renal cell carcinoma has been observed in patients affected with PTC. Case Report: In this study we report a case of sporadic PTC and renal cell carcinoma in a 63 year-old woman. Conclusion: After surgery the patient was hospitalized for 1 month in ICU section. 3 months after being discharged from the hospital, she was still in a good condition and is u...

  7. A gallbladder tumor revealing metastatic clear cell renal carcinoma: report of case and review of literature

    OpenAIRE

    Ghaouti Merieme; Znati Kaoutar; Jahid Ahmed; Zouaidia Fouad; Bernoussi Zakiya; Fakir Youssef El; Mahassini Najat

    2013-01-01

    Abstract Metastatic renal cell carcinoma in the gallbladder is extremely rare, with reported frequencies of less than 0.6% in large autopsy reviews. Only 40 cases were reported in the literature. We report a first case of gallbladder polypoid tumor revealing metastatic clear cell renal cell carcinoma, which demonstrates the importance of radiological tests, histology and immunohistochemistry when making a definitive diagnosis. These examinations also allow differentiating metastatic clear cel...

  8. In search of suitable reference genes for gene expression studies of human renal cell carcinoma by real-time PCR

    Directory of Open Access Journals (Sweden)

    Kristiansen Glen

    2007-06-01

    Full Text Available Abstract Background Housekeeping genes are commonly used as endogenous reference genes for the relative quantification of target genes in gene expression studies. No conclusive systematic study comparing the suitability of different candidate reference genes in clear cell renal cell carcinoma has been published to date. To remedy this situation, 10 housekeeping genes for normalizing purposes of RT-PCR measurements already recommended in various studies were examined with regard to their usefulness as reference genes. Results The expression of the potential reference genes was examined in matched malignant and non-malignant tissue specimens from 25 patients with clear cell renal cell carcinoma. Quality assessment of isolated RNA performed with a 2100 Agilent Bioanalyzer showed a mean RNA integrity number of 8.7 for all samples. The between-run variations related to the crossing points of PCR reactions of a control material ranged from 0.17% to 0.38%. The expression of all genes did not depend on age, sex, and tumour stage. Except the genes TATA box binding protein (TBP and peptidylprolyl isomerase A (PPIA, all genes showed significant differences in expression between malignant and non-malignant pairs. The expression stability of the candidate reference genes was additionally controlled using the software programs geNorm and NormFinder. TBP and PPIA were validated as suitable reference genes by normalizing the target gene ADAM9 using these two most stably expressed genes in comparison with up- and down-regulated housekeeping genes of the panel. Conclusion Our study demonstrated the suitability of the two housekeeping genes PPIA and TBP as endogenous reference genes when comparing malignant tissue samples with adjacent normal tissue samples from clear cell renal cell carcinoma. Both genes are recommended as reference genes for relative gene quantification in gene profiling studies either as single gene or preferably in combination.

  9. Solitary colonic metastasis from renal cell carcinoma presenting as a surgical emergency nine years post-nephrectomy

    Directory of Open Access Journals (Sweden)

    Thrumurthy Sri G

    2010-06-01

    Full Text Available Abstract Late colonic metastasis following curative surgery for renal cell carcinoma has rarely been described. We present the first reported case of solitary colonic renal cell carcinoma metastasis presenting as an intra-abdominal bleed, nine years post-nephrectomy.

  10. Clinical role of early dynamic FDG-PET/CT for the evaluation of renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, Reiko; Abe, Koichiro; Sakai, Shuji [Tokyo Women' s Medical University, Department of Diagnostic Imaging and Nuclear Medicine, Tokyo (Japan); Kondo, Tsunenori; Tanabe, Kazunari [Tokyo Women' s Medical University, Department of Urology, Tokyo (Japan)

    2016-06-15

    We studied the usefulness of early dynamic (ED) and whole-body (WB) FDG-PET/CT for the evaluation of renal cell carcinoma (RCC). One hundred patients with 107 tumours underwent kidney ED and WB FDG-PET/CT. We visually and semiquantitatively evaluated the FDG accumulation in RCCs in the ED and WB phases, and compared the accumulation values with regard to histological type (clear cell carcinoma [CCC] vs. non-clear cell carcinoma [N-CCC]), the TNM stage (high stage [3-4] vs. low stage [1-2]), the Fuhrman grade (high grade [3-4] vs. low grade [1-2]) and presence versus absence of venous (V) and lymphatic (Ly) invasion. In the ED phase, visual evaluation revealed no significant differences in FDG accumulation in terms of each item. However, the maximum standardized uptake value and tumour-to-normal tissue ratios were significantly higher in the CCCs compared to the N-CCCs (p < 0.001). In the WB phase, in contrast, significantly higher FDG accumulation (p < 0.001) was found in RCCs with a higher TNM stage, higher Furman grade, and the presence of V and Ly invasion in both the visual and the semiquantitative evaluations. ED and WB FDG-PET/CT is a useful tool for the evaluation of RCCs. (orig.)

  11. CRISPR-Mediated VHL Knockout Generates an Improved Model for Metastatic Renal Cell Carcinoma.

    Science.gov (United States)

    Schokrpur, Shiruyeh; Hu, Junhui; Moughon, Diana L; Liu, Peijun; Lin, Lucia C; Hermann, Kip; Mangul, Serghei; Guan, Wei; Pellegrini, Matteo; Xu, Hua; Wu, Lily

    2016-01-01

    Metastatic renal cell carcinoma (mRCC) is nearly incurable and accounts for most of the mortality associated with RCC. Von Hippel Lindau (VHL) is a tumour suppressor that is lost in the majority of clear cell RCC (ccRCC) cases. Its role in regulating hypoxia-inducible factors-1α (HIF-1α) and -2α (HIF-2α) is well-studied. Recent work has demonstrated that VHL knock down induces an epithelial-mesenchymal transition (EMT) phenotype. In this study we showed that a CRISPR/Cas9-mediated knock out of VHL in the RENCA model leads to morphologic and molecular changes indicative of EMT, which in turn drives increased metastasis to the lungs. RENCA cells deficient in HIF-1α failed to undergo EMT changes upon VHL knockout. RNA-seq revealed several HIF-1α-regulated genes that are upregulated in our VHL knockout cells and whose overexpression signifies an aggressive form of ccRCC in the cancer genome atlas (TCGA) database. Independent validation in a new clinical dataset confirms the upregulation of these genes in ccRCC samples compared to adjacent normal tissue. Our findings indicate that loss of VHL could be driving tumour cell dissemination through stabilization of HIF-1α in RCC. A better understanding of the mechanisms involved in this phenomenon can guide the search for more effective treatments to combat mRCC. PMID:27358011

  12. Distinct Cytoplasmic Expression of KL-6 Mucin in Chromophobe Renal Cell Carcinoma: A Comparative Immunohistochemical Study with Other Renal Epithelial Cell Tumors

    OpenAIRE

    Fukushima, Mana; Higuchi, Kayoko; Shimojo, Hisashi; Uehara, Takeshi; Ota, Hiroyoshi

    2012-01-01

    The presence of cytoplasmic sialyl glycoproteins is a conspicuous feature in chromophobe renal cell carcinoma (RCC). We compared the immunohistochemical expression of sialyl glycoproteins in chromophobe RCC with that in other types of renal tumors. Formalin-fixed, paraffin-embedded tissues of surgically resected renal tumors (chromophobe RCC, 14 cases [10 cases of classic type and 4 cases of eosinophilic variant]; oncocytoma, 7 cases; and clear cell RCC, 9 cases) and kidneys from immature inf...

  13. Prolonged survival after sequential multimodal treatment in metastatic renal cell carcinoma: two case reports and a review of the literature

    Directory of Open Access Journals (Sweden)

    Syrios John

    2012-09-01

    Full Text Available Abstract Introduction In this case series and short review of the literature, we underline the impact of nephrectomy combined with sequential therapy based on cytokines, antiangiogenic factors, and mammalian target of rapamycin inhibitors along with metastasectomy on overall survival and quality of life in patients with metastatic clear cell renal carcinoma. Case presentation In the first of two cases reported here, a 53-year-old Caucasian man underwent a radical left nephrectomy for renal cell cancer and relapsed with a bone metastasis in his right humerus. He was treated with closed nailing and cytokine-based chemotherapy. For 5 years, the disease was stable and he had great improvement in quality of life. Subsequently, the disease relapsed in his lymph nodes, lung, and thorax soft tissue. He was then treated with antiangiogenic factors and mammalian target of rapamycin inhibitors. The disease progressed until September 2009, when he died of allergic shock during a blood transfusion, 9 years after the initial diagnosis of renal cell cancer. In the second case, a 54-year-old Caucasian man underwent a radical left nephrectomy for renal cell cancer. A year later, the disease progressed to his neck lymph nodes, and cytokine-based chemotherapy was initiated. While he was on cytokines, a solitary pulmonary nodule appeared and he underwent a metastasectomy. Nine months later, magnetic resonance imaging of his brain revealed a focal right occipitoparietal lesion, which was resected. After two years of active surveillance, the disease relapsed as a pulmonary metastasis and he was treated with an antiangiogenic factor. Further progressions presenting as enlarged axillary lymph nodes, chest soft tissue lesions, and thoracic spine bone metastases were sequentially observed. He then received a first-generation mammalian target of rapamycin inhibitor, an antiangiogenic factor, and later a second-generation mammalian target of rapamycin inhibitor and

  14. [Secondary TFE3-associated renal cell carcinoma in a child treated for Ewing sarcoma].

    Science.gov (United States)

    Fedhila Ben Ayed, F; Rhayem, S; Doghri, R; Ben Hassine, L; Khemiri, M; Mrad, K; Bellagha, I; Barsaoui, S

    2016-02-01

    Renal cell carcinoma is a rare pediatric malignant tumor of the kidney. Unlike Wilms tumor, the efficacy of chemotherapy and radiation therapy in pediatric renal cell carcinoma remains uncertain. Surgery is the best treatment and prognosis is favorable when the tumor is localized and completely eradicated. We report an exceptional observation in a 7-year-old girl with renal cell carcinoma who had been treated 20 months previously for Ewing sarcoma with chemotherapy and radiotherapy. The renal tumor was revealed by abdominal pain without hematuria. She underwent a radical nephrectomy, and histopathology concluded in renal carcinoma associated with translocation Xp 11.2 grade 3 of Furhrman pT3a N1. No adjuvant therapy was given. After 3 years of follow-up, there is no evidence of local or metastatic recurrence. This observation is significant given the very young age of this patient, the occurrence after Ewing sarcoma with a short disease-free interval. It seems that translocation renal cell carcinoma is associated with previous exposure to chemotherapy, particularly topoisomerase II inhibitors or alkylating agents. PMID:26702489

  15. EORTC-GU group expert opinion on metastatic renal cell cancer

    NARCIS (Netherlands)

    T.M. Reijke; J. Bellmunt; H. van Poppel; S. Marreaud; M. Aapro

    2009-01-01

    There is no consensus on the detailed surveillance of renal cell cancer (RCC) patients after radical resection of the kidney. Where relapse is unlikely, one reasonable option would be to confine investigations to chest X-ray and abdominal ultrasound-carried out at 3-month intervals during the first

  16. Expression of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Qiao Zhen-kui

    2013-01-01

    Full Text Available Abstract Background Matrix metalloproteinases (MMPs are one of the major classes of proteolytic enzymes involved in tumor invasion and metastasis and are inhibited by naturally occurring tissue inhibitors of metalloproteinases (TIMPs. {AU Query: Please verify that corrections made to previous sentence did not alter intended meaning}. In this study, we examined the expression of MMP-2, MMP-9, membrane-type 1 (MT1-MMP, TIMP-1, and TIMP-2 in renal tissue samples of renal cell cancer and examined the correlation between their expression and clinicopathological parameters. Methods Renal tissue samples from 76 patients with renal cell carcinoma were available for this study. To determine the expression of MMP-2, MMP-9, MT1-MMP, TIMP-1, and TIMP-2, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR was carried out on tumor and normal tissues. Results Mean MMP-2, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 mRNA expression in the renal cell carcinomas was significantly higher than in the normal renal tissue (P Conclusions Mean MMP-2, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 mRNA expression in the renal cell carcinomas was significantly higher than in the normal renal tissue.

  17. Robot-Assisted Retroperitoneoscopic Surgery for Synchronous Contralateral Ureteral Metastasis of Renal-Cell Carcinoma

    Science.gov (United States)

    Lai, Wei-Hong; Chiu, Allen Wen-Shien; Lu, Chih-Cheng; Huang, Steven Kuan-Hua

    2015-01-01

    Abstract Renal-cell carcinoma (RCC) with synchronous metastasis to contralateral ureter is extremely rare with only four cases reported in the literature. We report a case of synchronous metastatic RCC to the contralateral ureter with effective robot-assisted retroperitoneoscopic nephron-sparing surgery that leads to favorable oncologic and functional outcome.

  18. A Rare Case of a Renal Cell Carcinoma Confined to the Isthmus of a Horseshoe Kidney

    Directory of Open Access Journals (Sweden)

    Michael Kongnyuy

    2015-01-01

    Full Text Available Horseshoe kidney (HSK is the most common renal anomaly. Reports of the incidence of renal cell carcinoma (RCC in HSK are conflicting. Very few cases of isthmus-located RCC have been reported in the literature. We report a unique case of an isthmus-located RCC. Proper vascular and tumor imaging prior to surgery is key to successful tumor removal.

  19. Vegetable and fruit consumption and risk of renal cell carcinoma: Results from the Netherlands cohort study

    NARCIS (Netherlands)

    Dijk, B.A.C. van; Schouten, L.J.; Kiemeney, L.A.L.M.; Goldbohm, R.A.; Brandt, P.A. van den

    2005-01-01

    Vegetable and fruit consumption is generally inversely associated with various cancer types, including renal cell carcinoma (RCC). The Netherlands cohort study on diet and cancer (NLCS) consists of 120,852 men and women, aged 55-69 years, who filled out a self-administered questionnaire that include

  20. Vegetable and fruit consumption and risk of renal cell carcinoma: results from the Netherlands cohort study.

    NARCIS (Netherlands)

    Dijk, B.A. van; Schouten, L.J.; Kiemeney, L.A.L.M.; Goldbohm, R.A.; Brandt, P.A. van den

    2005-01-01

    Vegetable and fruit consumption is generally inversely associated with various cancer types, including renal cell carcinoma (RCC). The Netherlands cohort study on diet and cancer (NLCS) consists of 120,852 men and women, aged 55-69 years, who filled out a self-administered questionnaire that include

  1. Outpatient-based subcutaneous interleukin-2 monotherapy in advanced renal cell carcinoma : An update

    NARCIS (Netherlands)

    Nieken, J; Sleijfer, DT; deLeij, L; Mulder, NH

    1996-01-01

    To minimize interleukin-2-related toxicity while retaining its efficacy, a treatment schedule utilizing subcutaneous IL-2 was evaluated in a phase II setting. Eighty unselected consecutive patients with metastatic or recurrent renal cell carcinoma (RCC), mean age 58 years (range, 21 to 76), received

  2. Amplification of epidermal growth factor receptor gene in renal cell carcinoma

    DEFF Research Database (Denmark)

    Harper, Peter; El-Hariry, Iman; Powles, Thomas; Lau, Mike R; Sternberg, Cora N; Ravaud, Alain; von der Maase, Hans; Zantl, Niko; Harper, Peter Mathias; Rolland, Frédéric; Audhuy, Bruno; Barthel, Friederike; Machiels, Jean-Pascal; Patel, Pina; Kreuser, Ernst-Dietrick; Hawkins, Robert E

    2010-01-01

    Expression of epidermal growth factor receptor (EGFR) may be of prognostic value in renal cell cancer (RCC). Gene amplification of EGFR was investigated in a cohort of 315 patients with advanced RCC from a previously reported randomised study. Using fluorescent in situ hybridisation, only 2...

  3. Overall survival after immunotherapy, tyrosine kinase inhibitors and surgery in treatment of metastatic renal cell cancer

    DEFF Research Database (Denmark)

    de Lichtenberg, Trine Honnens; Hermann, Gregers G.; Rorth, Mikael;

    2014-01-01

    Abstract Objective. The aim of this study was to evaluate overall survival (OS) after treatment of metastatic renal cell carcinoma (mRCC) following the introduction of tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors. Material and methods. One-hundred and fort...

  4. FDG-PET as a predictive biomarker for therapy with everolimus in metastatic renal cell cancer

    International Nuclear Information System (INIS)

    The mTOR (mammalian target of rapamycin) inhibitor, everolimus, affects tumor growth by targeting cellular metabolic proliferation pathways and delays renal cell carcinoma (RCC) progression. Preclinical evidence suggests that baseline elevated tumor glucose metabolism as quantified by FDG-PET ([18F] fluorodeoxy-glucose positron emission tomography) may predict antitumor activity. Metastatic RCC (mRCC) patients refractory to vascular endothelial growth factor (VEGF) pathway inhibition were treated with standard dose everolimus. FDG-PET scans were obtained at baseline and 2 weeks; serial computed tomography (CT) scans were obtained at baseline and every 8 weeks. Maximum standardized uptake value (SUVmax) of the most FDG avid lesion, average SUVmax of all measured lesions and their corresponding 2-week relative changes were examined for association with 8-week change in tumor size. A total of 63 patients were enrolled; 50 were evaluable for the primary endpoint of which 48 had both PET scans. Patient characteristics included the following: 36 (72%) clear cell histology and median age 59 (range: 37–80). Median pre- and 2-week treatment average SUVmax were 6.6 (1–17.9) and 4.2 (1–13.9), respectively. Response evaluation criteria in solid tumors (RECIST)-based measurements demonstrated an average change in tumor burden of 0.2% (−32.7% to 35.9%) at 8 weeks. Relative change in average SUVmax was the best predictor of change in tumor burden (all evaluable P = 0.01; clear cell subtype P = 0.02), with modest correlation. Baseline average SUVmax was correlated with overall survival and progression-free survival (PFS) (P = 0.023; 0.020), but not with change in tumor burden. Everolimus therapy decreased SUVs on follow-up PET scans in mRCC patients, but changes were only modestly correlated with changes in tumor size. Thus, clinical use of FDG-PET-based biomarkers is challenged by high variability. In this phase II trial, FDG-PET was explored as a predictive biomarker for

  5. Computed tomography of renal cell carcinoma in patients with terminal renal impairment

    International Nuclear Information System (INIS)

    Purpose: An increased incidence of renal tumors has been observed in patients with end-stage-renal-disease (ESRD). The very strong association with acquired renal cystic disease (ACRD) and increased incidence of the renal tumors (conventional renal cell carcinoma (CRCC), papillary renal cell carcinoma (PRCC) or papillary renal cell adenoma (PRCA)) was reported. This study discusses the role of computed tomography (CT) in detecting renal tumors in patients with renal impairment: pre-dialysis, those receiving dialysis or with renal allograft transplants. Materials and methods: Ten patients (nine male, one female) with renal cell tumors were enrolled into a retrospective study; two were new dialysis patients, three on long-term dialysis, and five were renal transplant recipients with history of dialysis. All patients underwent helical CT, a total of 11 procedures were performed. Sixteen-row detector system was used five times, and a 64-row detector system for the six examinations. All patients underwent nephrectomy of kidney with suspected tumor, 15 nephrectomies were performed, and 1 kidney was assessed during autopsy. CT findings were compared with macroscopic and microscopic assessments of the kidney specimen in 16 cases. Results: Very advanced renal parenchyma atrophy with small cysts corresponding to ESRD was found in nine patients, chronic pyelonephritis in remained one. A spontaneously ruptured tumor was detected incidentally in one case, patient died 2 years later. In the present study, 6.25% (1/16) were multiple PRCA, 12.5% (2/16) were solitary PRCC, 12.5% tumors (2/16) were solitary conventional renal cell carcinomas (CRCC's), 12.5% tumors (2/16) were multiple conventional renal cell carcinomas (CRCC's), 25% (4/16) were CRCC's combined with multiple papillary renal cell carcinomas with adenomas (PRCC's and PRCA's), and 25% (4/16) of the tumors were multiple PRCC's combined with PRCA's without coexisting CRCC's. Bilateral renal tumors were found in our study

  6. Computed tomography of renal cell carcinoma in patients with terminal renal impairment

    Energy Technology Data Exchange (ETDEWEB)

    Ferda, Jiri [Department of Radiology, Charles University Hospital Plzen, Alej Svobody 80, CZ-306 40 Plzen (Czech Republic)], E-mail: ferda@fnplzen.cz; Hora, Milan [Department of Urology, Charles University Hospital Plzen, Dr. Edvarda Benese 13, CZ-306 40 Plzen (Czech Republic); Hes, Ondrej [Institut of Pathology, Charles University Hospital Plzen, Alej Svobody 80, CZ-306 40 Plzen (Czech Republic); Reischig, Tomas [Department of Internal Medicine, Nephrology Unit, Charles University Hospital Plzen, Alej Svobody 80, CZ-306 40 Plzen (Czech Republic); Kreuzberg, Boris; Mirka, Hynek; Ferdova, Eva; Ohlidalova, Kristyna; Baxa, Jan [Department of Radiology, Charles University Hospital Plzen, Alej Svobody 80, CZ-306 40 Plzen (Czech Republic); Urge, Tomas [Department of Urology, Charles University Hospital Plzen, Dr. Edvarda Benese 13, CZ-306 40 Plzen (Czech Republic)

    2007-08-15

    Purpose: An increased incidence of renal tumors has been observed in patients with end-stage-renal-disease (ESRD). The very strong association with acquired renal cystic disease (ACRD) and increased incidence of the renal tumors (conventional renal cell carcinoma (CRCC), papillary renal cell carcinoma (PRCC) or papillary renal cell adenoma (PRCA)) was reported. This study discusses the role of computed tomography (CT) in detecting renal tumors in patients with renal impairment: pre-dialysis, those receiving dialysis or with renal allograft transplants. Materials and methods: Ten patients (nine male, one female) with renal cell tumors were enrolled into a retrospective study; two were new dialysis patients, three on long-term dialysis, and five were renal transplant recipients with history of dialysis. All patients underwent helical CT, a total of 11 procedures were performed. Sixteen-row detector system was used five times, and a 64-row detector system for the six examinations. All patients underwent nephrectomy of kidney with suspected tumor, 15 nephrectomies were performed, and 1 kidney was assessed during autopsy. CT findings were compared with macroscopic and microscopic assessments of the kidney specimen in 16 cases. Results: Very advanced renal parenchyma atrophy with small cysts corresponding to ESRD was found in nine patients, chronic pyelonephritis in remained one. A spontaneously ruptured tumor was detected incidentally in one case, patient died 2 years later. In the present study, 6.25% (1/16) were multiple PRCA, 12.5% (2/16) were solitary PRCC, 12.5% tumors (2/16) were solitary conventional renal cell carcinomas (CRCC's), 12.5% tumors (2/16) were multiple conventional renal cell carcinomas (CRCC's), 25% (4/16) were CRCC's combined with multiple papillary renal cell carcinomas with adenomas (PRCC's and PRCA's), and 25% (4/16) of the tumors were multiple PRCC's combined with PRCA's without coexisting CRCC

  7. ROLE OF THE MORPHOMETRIC PARAMETERS OF INTRATUMORAL MICROVESSELS AND THE PROLIFERATIVE ACTIVITY OF TUMOR CELLS IN RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    N. A. Gorban

    2014-08-01

    Full Text Available Tumor cell proliferation and angiogenesis are essential factors for tumor growth, progression, and metastasis.Objective: to assess the relationship between the values of proliferative activity and the morphometric parameters of intratumoral microvessels in metastatic and localized carcinomas of the kidney.Materials and methods. Surgical specimens taken from 54 patients (32 men and 22 women aged 26 to 69 years (mean age 55 ± 1.5 years with the verified diagnosis of clear-cell renal cell carcinoma (RCC were studied.Conclusion. Proliferative activity and angioarchitectonics are an important biological characteristic of a tumor of unequal clinical value in RCC. Metastatic carcinoma has a higher proliferative activity and a low tumor vascularization than those of localized carcinoma.

  8. [1-{sup 11}C]Acetate uptake is not increased in renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kotzerke, J.; Beuthien-Baumann, B. [Technische Universitaet Dresden und PET Zentrum Rossendorf, Klinik und Poliklinik fuer Nuklearmedizin, Dresden (Germany); Linne, C.; Wirth, M. [Technische Universitaet Dresden, Klinik und Poliklinik fuer Urologie, Dresden (Germany); Meinhardt, M.; Baretton, G. [Technische Universitaet Dresden, Institut fuer Pathologie, Dresden (Germany); Steinbach, J. [PET Zentrum Rossendorf, Forschungszentrum Rossendorf, Institut fuer Bioanorganische und Radiopharmazeutische Chemie, Dresden (Germany); Abolmaali, N. [Technische Universitaet Dresden, OncoRay, Medizinische Fakultaet Carl Gustav Carus, Dresden (Germany)

    2007-06-15

    The purpose of this study was to investigate the potential of [1-{sup 11}C]acetate (AC) as a metabolic tracer for renal cell cancer in human subjects. Twenty-one patients with suspected kidney tumours were investigated with AC and dynamic PET. AC uptake was scored on a five-step scale. Tumour localisation was known from CT/MRI. Histology was available in 18/21 patients. The results in these 18 patients are reported. AC uptake by the tumour was less than (n = 11), equal to (n = 5) or higher than (n = 2) uptake in the surrounding renal parenchyma. Histological tumour types showed a typical distribution, with a predominance of clear cell carcinomas (n = 14) and only a small number of papillary cell carcinomas (n = 2) and oncocytomas (n = 2). Only the benign oncocytomas were highly positive with AC. In most kidney tumours the AC accumulation was not higher than in normal kidney parenchyma. Therefore, AC PET cannot be recommend for the characterisation of a renal mass. (orig.)

  9. [1-11C]Acetate uptake is not increased in renal cell carcinoma

    International Nuclear Information System (INIS)

    The purpose of this study was to investigate the potential of [1-11C]acetate (AC) as a metabolic tracer for renal cell cancer in human subjects. Twenty-one patients with suspected kidney tumours were investigated with AC and dynamic PET. AC uptake was scored on a five-step scale. Tumour localisation was known from CT/MRI. Histology was available in 18/21 patients. The results in these 18 patients are reported. AC uptake by the tumour was less than (n = 11), equal to (n = 5) or higher than (n = 2) uptake in the surrounding renal parenchyma. Histological tumour types showed a typical distribution, with a predominance of clear cell carcinomas (n = 14) and only a small number of papillary cell carcinomas (n = 2) and oncocytomas (n = 2). Only the benign oncocytomas were highly positive with AC. In most kidney tumours the AC accumulation was not higher than in normal kidney parenchyma. Therefore, AC PET cannot be recommend for the characterisation of a renal mass. (orig.)

  10. [Molecular biological foundation of targeted therapy for metastatic renal cell carcinoma].

    Science.gov (United States)

    Chong, Lai; Xiaodong, Teng

    2016-05-25

    The incidence of renal cell carcinoma (RCC) is increasing. Radical cure by surgery can only be achieved in patients with early stage tumors. How to precisely use antineoplastic agents after surgery is an important problem to be solved. Most metastatic RCCs are pathologically identified as clear cell RCC (ccRCC), thus to develop agents targeting ccRCC is critical. Most clinically available targeted therapies are based on targeting some spots in specific pathways; or based on targeting new anti-tumor mechanisms, such as programmed death-1(PD-1), antibody-drug conjugates (ADC) and stem cells. There is still no targeted therapy having definite effect to most RCC patients. Only von Hippel-Lindau (VHL) pathway so far has been confirmed to be related to ccRCC development and progression; the inactivation of VHL gene causes many significant downstream gene changes. The key proteins involved in VHL pathway may be potential therapeutic targets for ccRCC. In this article, we review the current progress of targeted therapy for RCC, focus on the molecular characteristics of ccRCC, its relation to VHL pathway, the potential therapeutic targets and future clinical application for metastatic ccRCC. PMID:27045248

  11. Study of the diagnosis and treatment of renal cell carcinoma using monoclonal antibodies

    International Nuclear Information System (INIS)

    Among the potential applications of monoclonal antibodies (Mabs) in the diagnosis and treatment of human cancer is the use in the specific detection of cancer sites and the selective destruction of cancer cells. Fetal kidney was used as an immunogen to develop Mab A6H, which is highly reactive to 16/16 renal cell carcinoma (RCC) cell lines and to 16/19 human RCC specimens. RCC xenografts as small as 40 mg have been imaged clearly in radioimmunoscintigraphy studies using A6H labeled with iodine-131. In Mab-targeted radiotherapy studies, 2 doses of 100-150 uCi 131I-labeled A6H or an 131 I-labeled A6H-C5H cocktail caused tumor regression or tumor growth arrest in >80% of treated mice, while no such effect was observed in mice treated with 131I-labeled control Mab or unlabeled A6H. Internal radiation dosimetry, which was calculated by computer analysis of sequential radioimmunoscintigraphy, showed that A6H delivered approximately 35 rad/uCi of the injected dose to RCC xenografts. When the radiation dose to the tumor was 3000 rad resulted in tumor regression or growth arrest in >85% of mice. A clinical trial using 131I-labeled A6H in the diagnosis and treatment of RCC is now underway at our institution

  12. Renal cell carcinoma in India demonstrates early age of onset & a late stage of presentation

    Directory of Open Access Journals (Sweden)

    Shalini Agnihotri

    2014-01-01

    Full Text Available Background & objectives: Clinical spectrum of most of the diseases in developing countries is different from the west. Similarly whether renal cell carcinomas (RCC in a developing country like India is seen in the same spectrum in relation to the age at presentation as in the west is not described in the literature. This study was carried out to investigate the spectrum of RCC in India with regards to age of onset, stage at presentation and survival. Methods: Patients with renal tumour, treated between January 2000 to December 2012 in a tertiary care hospital in north India, were analyzed for age at presentation, clinical features and histopathological characteristics. Clinical diagnosis was made by contrast enhanced computerized tomography (CECT scans and/or magnetic resonance imaging (MRI. Renal masses diagnosed as angiomyolipoma, infective masses and hydatid cysts were excluded from the analysis. Impact of various age groups on gender, tumour size, TNM stage, Fuhrman grade, histopathological subtypes, lymph node, inferior vena cava (IVC involvement and survival was analyzed. Patients were grouped in five age groups i.e. ≤39, 40-49, 50-59, 60-69 and more than 70 yr of age. Results: Of the total 617 patients with 617 renal tumours (2 patients had bilateral tumours but only the larger tumour was considered clinically suspected as RCC, 586 had epithelial cell tumour and the remaining 31 had non epithelial cell tumour. The mean tumour size was 8.08±3.5 cm (median 7, range 1-25 cm. Tumour of less than 4 cm size was present in only 10.4 per cent patients. The mean age at diagnosis was 55.15±13.34 (median 56, range 14-91 yr years. A total of 30.03 per cent of renal tumours presented in patients younger than 50 yr of age. Though there was no difference in stage, Fuhrman′s grade, IVC involvement and lymph nodal spread among various age groups, younger patients had higher proportion of non clear cell RCC and only 48.59 per cent of them presented

  13. Piperlongumine and its analogs down-regulate expression of c-Met in renal cell carcinoma

    OpenAIRE

    Golovine, Konstantin; Makhov, Peter; Naito, Sei; Raiyani, Henish; Tomaszewski, Jeffrey; Mehrazin, Reza; Tulin, Alexei; Kutikov, Alexander; Uzzo, Robert G.; Kolenko, Vladimir M.

    2015-01-01

    The c-Met protein, a transmembrane receptor tyrosine kinase, is the product of a proto-oncogene. Its only known ligand, hepatocyte growth factor (HGF), regulates cell growth, motility, migration, invasion, proliferation, and angiogenesis. The aberrant expression of c-Met is often associated with poor prognosis in multiple cancers, including renal cell carcinoma (RCC). Silencing or inactivation of c-Met leads to decreased viability of cancer cells, thereby making ablation of c-Met signaling an...

  14. AIF Downregulation and Its Interaction with STK3 in Renal Cell Carcinoma

    OpenAIRE

    Xu, Shengqiang; Wu, Hongjin; Nie, Huan; Yue, Lei; Jiang, Huadong; Xiao, Sheng; Li, Yu

    2014-01-01

    Apoptosis-inducing factor (AIF) plays a crucial role in caspase-independent programmed cell death by triggering chromatin condensation and DNA fragmentation. Therefore, it might be involved in cell homeostasis and tumor development. In this study, we report significant AIF downregulation in the majority of renal cell carcinomas (RCC). In a group of RCC specimens, 84% (43 out of 51) had AIF downregulation by immunohistochemistry stain. Additional 10 kidney tumors, including an oxyphilic adenom...

  15. Overexpressed CacyBP/SIP leads to the suppression of growth in renal cell carcinoma

    International Nuclear Information System (INIS)

    Calcyclin-binding protein/Siah-1-interacting protein (CacyBP/SIP), a target protein of S100, has been identified as a component of a novel ubiquitinylation complex leading to β-catenin degradation, which was found to be related to the malignant phenotypes of gastric cancer. However, the roles of CacyBP/SIP in renal cell carcinoma still remain unclear. In the present study, we had analyzed the expression of the CacyBP/SIP protein in human renal cancer cells and clinical tissue samples. The possible roles of CacyBP/SIP in regulating the malignant phenotype of renal cancer cells were also investigated. The results demonstrated that the expression of CacyBP/SIP was markedly down-regulated in renal cell carcinoma tissues and cell lines. Ectopic overexpression of CacyBP/SIP in A498 cells inhibited the proliferation of this cell and delayed cell cycle progression significantly, which might be related to the down-regulation of Cyclin D1 through reducing β-catenin protein. CacyBP/SIP also suppressed colony formation in soft agar and its tumorigenicity in nude mice. Taken together, our work showed that CacyBP/SIP, as a novel down-regulated gene in renal cell carcinoma, suppressed proliferation and tumorigenesis of renal cancer cells

  16. Effects of Hydroxyapatite Nanoparticles on Apoptosis and Invasion of Human Renal Cell Carcinoma 786-0 Cells

    Institute of Scientific and Technical Information of China (English)

    WANG Zhi-xin; KONG Xiang-bo; ZHAO Xu; ZHANG Ling; HOU Yi; HAN Wei; WANG Kai-chen; GUO Bao-feng; LIU Ying; CHANG Xi-hua; WANG Wei-hua; NA Wan-li

    2011-01-01

    Renal cell carcinoma is the most common cancer of the kidney, and resistant to traditional therapies. The aim of this study is to investigate the effects of hydroxyapatite nanoparticles on human renal cell carcinoma 786-0 cells. Cell proliferation was assessed with an 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide(MTT)staining kit. The apoptosis assay was assessed with an FITC Annexin V Apoptosis Detection Kit. Caspase-3 and caspase-12 were detected by immunocytochemical staining and semi-quantitative RT-PCR. Cell wound healing assay was used to ensure cell motility. Matrigel invasion assay was analysed via transwell chambers. Our results showed that hydroxyapatite nanoparticles significantly reduced cell proliferation, invasion and induced apoptosis of 786-0 cells. The inhibiting action may have relation with up-regulated caspase-12, leading the cells to apoptosis. This study suggests that hydroxyapatite nanoparticles may be an effective and delivery system for renal cell carcinoma therapy.

  17. Review of renal cell carcinoma and its common subtypes in radiology.

    Science.gov (United States)

    Low, Gavin; Huang, Guan; Fu, Winnie; Moloo, Zaahir; Girgis, Safwat

    2016-05-28

    Representing 2%-3% of adult cancers, renal cell carcinoma (RCC) accounts for 90% of renal malignancies and is the most lethal neoplasm of the urologic system. Over the last 65 years, the incidence of RCC has increased at a rate of 2% per year. The increased incidence is at least partly due to improved tumor detection secondary to greater availability of high-resolution cross-sectional imaging modalities over the last few decades. Most RCCs are asymptomatic at discovery and are detected as unexpected findings on imaging performed for unrelated clinical indications. The 2004 World Health Organization Classification of adult renal tumors stratifies RCC into several distinct histologic subtypes of which clear cell, papillary and chromophobe tumors account for 70%, 10%-15%, and 5%, respectively. Knowledge of the RCC subtype is important because the various subtypes are associated with different biologic behavior, prognosis and treatment options. Furthermore, the common RCC subtypes can often be discriminated non-invasively based on gross morphologic imaging appearances, signal intensity on T2-weighted magnetic resonance images, and the degree of tumor enhancement on dynamic contrast-enhanced computed tomography or magnetic resonance imaging examinations. In this article, we review the incidence and survival data, risk factors, clinical and biochemical findings, imaging findings, staging, differential diagnosis, management options and post-treatment follow-up of RCC, with attention focused on the common subtypes. PMID:27247714

  18. Advances of multidetector computed tomography in the characterization and staging of renal cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Athina; C; Tsili; Maria; I; Argyropoulou

    2015-01-01

    Renal cell carcinoma(RCC) accounts for approximately 90%-95% of kidney tumors. With the widespread use of cross-sectional imaging modalities, more than half of RCCs are detected incidentally, often diagnosed at an early stage. This may allow the planning of more conservative treatment strategies. Computed tomography(CT) is considered the examination of choice for thedetection and staging of RCC. Multidetector CT(MDCT) with the improvement of spatial resolution and the ability to obtain multiphase imaging, multiplanar and threedimensional reconstructions in any desired plane brought about further improvement in the evaluation of RCC. Differentiation of RCC from benign renal tumors based on MDCT features is improved. Tumor enhancement characteristics on MDCT have been found closely to correlate with the histologic subtype of RCC, the nuclear grade and the cytogenetic characteristics of clear cell RCC. Important information, including tumor size, localization, and organ involvement, presence and extent of venous thrombus, possible invasion of adjacent organs or lymph nodes, and presence of distant metastases are provided by MDCT examination. The preoperative evaluation of patients with RCC was improved by depicting the presence or absence of renal pseudocapsule and by assessing the possible neoplastic infiltration of the perirenal fat tissue and/or renal sinus fat compartment.

  19. [Solitary Bladder Metastasis of Chromophobe Renal Cell Carcinoma: Report of a Case].

    Science.gov (United States)

    Nitta, Satoshi; Suetomi, Takahiro; Kojou, Kousuke; Tanaka, Ken; Kurobe, Masahiro; Yoshino, Takayuki; Yamazaki, Kazumitu; Kimura, Tomokazu; Kandori, Shuya; Kawahara, Takashi; Kawai, Kouji; Miyazaki, Jun; Yano, Youko; Yamada, Kenji; Noguchi, Masayuki; Nishiyama, Hiroyuki

    2016-02-01

    Bladder metastasis of renal cell carcinoma (RCC) is relatively rare, and only 43 cases have been reported in the Japanese literature. In most cases, the histology of the primary site was clear cell type. Here, we report a case of bladder metastasis of chromophobe RCC. A 74-year-old man presented with asymptomatic gross hematuria. He had a history of chromophobe RCC treated with radical nephrectomy 11 years previously. Since cystoscopy revealed a papillary pedunculated tumor, he underwent transurethral resection of the bladder tumor (TUR-Bt). The pathological diagnosis was chromophobe RCC because the histological findings were similar to those of nephrectomized specimens. Four years after TUR-Bt, the patient received bacillus Calmette-Guérin (BCG) therapy under the diagnosis of carcinoma in situ of urothelial cancer of the bladder but not chromophobe RCC. There was no recurrence of chromophobe RCC within 5 years follow-up after TUR-Bt. To the best of our knowledge, there has been only one other case report of bladder metastasis of chromophobe RCC in the Japanese literature. PMID:27018407

  20. Analysis of Renal Cell Carcinoma as a First Step for Developing Mass Spectrometry-Based Diagnostics

    Science.gov (United States)

    Yoshimura, Kentaro; Chen, Lee Chuin; Mandal, Mridul Kanti; Nakazawa, Tadao; Yu, Zhan; Uchiyama, Takahito; Hori, Hirokazu; Tanabe, Kunio; Kubota, Takeo; Fujii, Hideki; Katoh, Ryohei; Hiraoka, Kenzo; Takeda, Sen

    2012-10-01

    Immediate diagnosis of human specimen is an essential prerequisites in medical routines. This study aimed to establish a novel cancer diagnostics system based on probe electrospray ionization-mass spectrometry (PESI-MS) combined with statistical data processing. PESI-MS uses a very fine acupuncture needle as a probe for sampling as well as for ionization. To demonstrate the applicability of PESI-MS for cancer diagnosis, we analyzed nine cases of clear cell renal cell carcinoma (ccRCC) by PESI-MS and processed the data by principal components analysis (PCA). Our system successfully delineated the differences in lipid composition between non-cancerous and cancerous regions. In this case, triacylglycerol (TAG) was reproducibly detected in the cancerous tissue of nine different individuals, the result being consistent with well-known profiles of ccRCC. Moreover, this system enabled us to detect the boundaries of cancerous regions based on the expression of TAG. These results strongly suggest that PESI-MS will be applicable to cancer diagnosis, especially when the number of data is augmented.

  1. State-of-the-science: An update on renal cell carcinoma

    Science.gov (United States)

    Jonasch, Eric; Futreal, Andrew; Davis, Ian; Bailey, Sean; Kim, William Y.; Brugarolas, James; Giaccia, Amato; Kurban, Ghada; Pause, Armin; Frydman, Judith; Zurita, Amado; Rini, Brian I.; Sharma, Pam; Atkins, Michael; Walker, Cheryl; Rathmell, W. Kimryn

    2012-01-01

    Renal cell carcinomas (RCC) are emerging as a complex set of diseases with major socioeconomic impact and a continued rise in incidence throughout the world. As the field of urologic oncology faces these trends, several major genomic and mechanistic discoveries have altered our core understanding of this multitude of cancers, including several new rare subtypes of renal cancers. This review will examine these new findings, and place them in the context of the well-established association of clear cell RCC (ccRCC) with mutations in the von Hippel-Lindau (VHL) gene and resultant aberrant hypoxia inducible factor (HIF) signaling. The impact of novel ccRCC-associated genetic lesions on chromatin remodeling and epigenetic regulation is explored. The effects of VHL mutation on primary ciliary function, extracellular matrix homeostasis, and tumor metabolism are discussed. VHL proteostasis is reviewed, with the goal of harnessing the proteostatic machinery to refunctionalize mutant VHL. Translational efforts using molecular tools to understand discriminating features of ccRCC tumors and develop improved prognostic and predictive algorithms are presented and new therapeutics arising from the earliest molecular discoveries in ccRCC are summarized. By creating an integrated review of the key genomic and molecular biological disease characteristics of ccRCC and placing these data in the context of the evolving therapeutic landscape, we intend to facilitate interaction between basic, translational and clinical researchers involved in the treatment of this devastating disease, and accelerate progress towards its ultimate eradication. PMID:22638109

  2. Sunitinib treatment in patients with advanced renal cell cancer: the Brazilian National Cancer Institute (INCA) experience

    Science.gov (United States)

    Coelho, Rafael Corrêa; Reinert, Tomás; Campos, Franz; Peixoto, Fábio Affonso; de Andrade, Carlos Augusto; Castro, Thalita; Herchenhorn, Daniel

    2016-01-01

    ABSTRACT Purpose: The aim of this study was to assess the impact of sunitinib treatment in a non-screened group of patients with metastatic renal cell cancer (mRCC) treated by the Brazilian Unified Health System (SUS) at a single reference institution. Material and Methods: Retrospective cohort study, which evaluated patients with mRCC who received sunitinib between May 2010 and December 2013. Results: Fifty-eight patients were eligible. Most patients were male 41 (71%), with a median age of 58 years. Nephrectomy was performed in 41 (71%) patients with a median interval of 16 months between the surgery and initiation of sunitinib. The most prevalent histological subtype was clear cell carcinoma, present in 52 (91.2%) patients. In 50 patients (86%), sunitinib was the first line of systemic treatment. The main adverse effects were fatigue (57%), hypothyroidism (43%), mucositis (33%) and diarrhea (29%). Grade 3 and 4 adverse effects were infrequent: fatigue (12%), hypertension (12%), thrombocytopenia (7%), neutropenia (5%) and hand-foot syndrome (5%). Forty percent of patients achieved a partial response and 35% stable disease, with a disease control rate of 75%. Median progression free survival was 7.6 months and median overall survival was 14.1 months. Conclusion: Sunitinib treatment was active in the majority of patients, especially those with low and intermediate risk by MSKCC score, with manageable toxicity. Survival rates were inferior in this non-screened population with mRCC treated in the SUS. PMID:27564279

  3. The biology of interleukin-2 efficacy in the treatment of patients with renal cell carcinoma.

    Science.gov (United States)

    Romo de Vivar Chavez, Antonio; de Vera, Michael E; Liang, Xiaoyan; Lotze, Michael T

    2009-01-01

    Renal cell carcinoma (RCC) is the eighth most common malignancy in adults in the United States. More than 50% of individuals present with metastatic disease and conventional chemotherapeutic strategies have been associated with poor response rates. Immunotherapy with Interleukin (IL)-2, however, induces durable remission, achieving >10 year recurrence free survival in 5-10% of patients with advanced RCC. First described as a T cell growth factor, IL-2 has a wide spectrum of effects in the immune system. Some of the possible mechanisms by which IL-2 carries out its anticancer effects include the augmentation of cytotoxic immune cell functions and reversal of T cell anergy, enabling delivery of immune cells and possibly serum components into tumor. IL-2 indirectly limits tumor escape mechanisms such as defective tumor cell expression of Class I or Class II molecules or expansion of regulatory T cells. Indirect effects on the tumor microenvironment are also likely and associated with rather dramatic T cell infiltration during the global delayed type hypersensitivity response that is associated with systemic IL-2 administration. The IL-2 signaling pathway, its effects on immune cells, and its role in various independent mechanisms of tumor surveillance likely play a role but little substantive data defining a clear phenotype or genotype of IL-2 responders distinguishing them from nonresponders has emerged in the last 25 years since IL-2 therapy was initiated. At best, we can only speculate that the disturbed homeostatic host/tumor interaction is reset in a small subset of patients allowing an antitumor response to recover or ensue. PMID:19148593

  4. Knockdown of COUP-TFII inhibits cell proliferation and induces apoptosis through upregulating BRCA1 in renal cell carcinoma cells.

    Science.gov (United States)

    Zheng, Jia; Qin, Weijun; Jiao, Dian; Ren, Jing; Wei, Ming; Shi, Shengjia; Xi, Wenjin; Wang, He; Yang, An-Gang; Huan, Yi; Wen, Weihong

    2016-10-01

    COUP-TFII belongs to the nuclear receptor family, which is highly expressed in many kinds of tumors. Previous studies have shown that COUP-TFII can promote tumor progression through regulating tumor angiogenesis and cell proliferation and migration of certain cancer cells. However, the function of COUP-TFII in renal cell carcinoma (RCC) is not clear. Here, we showed that clinical RCC tumor tissues showed much higher COUP-TFII expression level than adjacent normal tissues. When COUP-TFII was knocked down in RCC 769-P and 786-O cells by siRNA or shRNA-expressing lentivirus, the cell proliferation was markedly inhibited, and apoptosis increased. Moreover, the tumor growth of COUP-TFII knockdown 769-P and 786-O xenografts in nude mice was also obviously inhibited. Using qRT-PCR and Western blot, we showed that the expression of the tumor suppressor gene BRCA1 was upregulated in COUP-TFII knockdown cells. Simultaneously knockdown of BRCA1 and COUP-TFII partially rescued the inhibited cell proliferation and increased apoptosis in COUP-TFII single knockdown cells. These results indicate that COUP-TFII may play an oncogenic role in RCC, and COUP-TFII may promote tumor progression through inhibiting BRCA1. PMID:27193872

  5. Immunohistochemical Study of c-KIT (CD117) Expression in Renal Cell Carcinoma

    International Nuclear Information System (INIS)

    Certain subtypes of Renal cell carcinomas (RCCs) are diagnostically challenging owing to their overlapping histopathological features. Recently, c-KIT (CD117) has come into focus as a potential diagnostic marker of some renal tumors. c-KIT also provides a potentially suitable for targeted tumor therapy. The present study was designed to investigate the expression of c-KIT in RCCs in order to evaluate its diagnostic usefulness as a phenotypic marker and to establish the basis for a new possible therapeutic modality. Material and Methods: The present work was conducted on 49 patients with RCC: Clear cell RCC (CRCC): 30 cases (61.22%); chromophobe RCC (ChRCC): 9 cases (18.37%); papillary RCC (PRCC), type I: 5 cases (10.20%); and carcinoma of the collecting ducts of Bellini (CdRCC): 5 cases (10.20%). The expression of c-KIT was assessed using immunohistochemistry. The diagnostic performance of c-KIT expression was evaluated using ROC curve analysis. Results: Overall, 11 (22.5%) cases of RCC showed c-KIT expression: 2 (6.7%) CRCC, 7 (77.8%) ChRCC, and 2 (40.0%) CdRCC. Among the study group, ChRCC had the highest frequency (p=.001) and staining score (p=.001) for c-KIT. In addition, only ChRCC showed membranous pattern of c-KIT staining, while other tumors showed cytoplasmic staining (p=.013). c-KIT showed a sensitivity of 77.78% and a specificity of 95% for the diagnosis of ChRCC. The relation between c-KIT expression and clinico pathological parameters was not significant. High grade tumors had a statistically significant higher total score of c-KIT expression (p=.023). Conclusions: c-KIT is frequently and significantly expressed in chromophobe RCC suggesting that it might play a role in its pathogenesis. Immunohistochemical detection of c-KIT expression could be used to aid histological diagnosis of chromophobe RCC with a high sensitivity and specificity. The substantial c-Kit immunoreactivity in chromophobe RCC may be of clinical importance especially in the field of

  6. (1) H NMR metabolomics analysis of renal cell carcinoma cells: Effect of VHL inactivation on metabolism.

    Science.gov (United States)

    Cuperlovic-Culf, Miroslava; Cormier, Kevin; Touaibia, Mohamed; Reyjal, Julie; Robichaud, Sarah; Belbraouet, Mehdi; Turcotte, Sandra

    2016-05-15

    Von Hippel-Lindau (VHL) is an onco-suppressor involved in oxygen and energy-dependent promotion of protein ubiquitination and proteosomal degradation. Loss of function mutations of VHL (VHL-cells) result in organ specific cancers with the best studied example in renal cell carcinomas. VHL has a well-established role in deactivation of hypoxia-inducible factor (HIF-1) and in regulation of PI3K/AKT/mTOR activity. Cell culture metabolomics analysis was utilized to determined effect of VHL and HIF-1α or HIF-2α on metabolism of renal cell carcinomas (RCC). RCC cells were stably transfected with VHL or shRNA designed to silence HIF-1α or HIF-2α genes. Obtained metabolic data was analysed qualitatively, searching for overall effects on metabolism as well as quantitatively, using methods developed in our group in order to determine specific metabolic changes. Analysis of the effect of VHL and HIF silencing on cellular metabolic footprints and fingerprints provided information about the metabolic pathways affected by VHL through HIF function as well as independently of HIF. Through correlation network analysis as well as statistical analysis of significant metabolic changes we have determined effects of VHL and HIF on energy production, amino acid metabolism, choline metabolism as well as cell regulation and signaling. VHL was shown to influence cellular metabolism through its effect on HIF proteins as well as by affecting activity of other factors. PMID:26620126

  7. Middle segment-preserving pancreatectomy for recurrent metastasis of renal cell carcinoma after pancreatoduodenectomy: a case report.

    Science.gov (United States)

    Takeshi, Aiyama; Mitsuhiro, Inagaki; Hiromitsu, Akabane; Naoyuki, Yanagida; Taiichiro, Shibaki; Hiroki, Shomura; Takeaki, Kudo; Tatsuya, Shonaka; Futoshi, Oikawa; Hiroharu, Sakurai; Shiro, Nakano

    2014-01-01

    Many cases of surgical resection of metastatic pancreatic tumors originating from renal cell carcinoma have been reported; however, cases of reresection of recurrent pancreatic metastasis of renal cell carcinoma in the remnant pancreas are rare. We performed a second resection for recurrent pancreatic metastasis of renal cell carcinoma six years after pancreatoduodenectomy with pancreaticogastrostomy reconstruction. By performing middle segment-preserving pancreatectomy, we were able to successfully spare the exocrine and endocrine pancreatic function compared to that observed after total pancreatectomy, with no signs of recurrence for two years after the surgery. PMID:25061531

  8. Middle Segment-Preserving Pancreatectomy for Recurrent Metastasis of Renal Cell Carcinoma after Pancreatoduodenectomy: A Case Report

    Science.gov (United States)

    Takeshi, Aiyama; Mitsuhiro, Inagaki; Hiromitsu, Akabane; Naoyuki, Yanagida; Taiichiro, Shibaki; Hiroki, Shomura; Takeaki, Kudo; Tatsuya, Shonaka; Futoshi, Oikawa; Hiroharu, Sakurai; Shiro, Nakano

    2014-01-01

    Many cases of surgical resection of metastatic pancreatic tumors originating from renal cell carcinoma have been reported; however, cases of reresection of recurrent pancreatic metastasis of renal cell carcinoma in the remnant pancreas are rare. We performed a second resection for recurrent pancreatic metastasis of renal cell carcinoma six years after pancreatoduodenectomy with pancreaticogastrostomy reconstruction. By performing middle segment-preserving pancreatectomy, we were able to successfully spare the exocrine and endocrine pancreatic function compared to that observed after total pancreatectomy, with no signs of recurrence for two years after the surgery. PMID:25061531

  9. 血管内皮生长抑制因子在散发性肾透明细胞癌细胞中的表达及意义%Expression and role of vascular endothelial growth inhibitor in sporadic clear cell renal cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    吴栗洋; 程浩; 邓小虎; 善辉; 王伟; 杨勇; 张小东; 张宁

    2013-01-01

    Objective To evaluate the expression of vascular endothelial growth inhibitor (VEGI) in sporadic clear cell renal cell carcinoma (CCRCC) and explore its relationships between VEGI expression,pathologic grade and tumor staging.Methods Western blot and immunohistochemical staining were used to detect the expression of VEGI in CCRCC cell line (786-O cells),CCRCC and paired normal kidney tissues.A total of 50 CCRCC cases were recruited.There were 37 males and 13 females with an average age of 53 ±12 years.The tumor sizes were <7 cm (n=33) and ≥7 cm (n =17).Their pathologic grades were G1 (n=14),G2 (n=22) and G3 (n=14) and pathologic stages pT1 (n=32),10 pT2 (n=10) and pT3 (n =8).Results VEGI protein was predominantly located in cytoplasm.Compared with normal kidney tissues(mean optic density (MOD) of VEGI staining:0.40 ± 0.16),it was lower in CCRCC tissues (MOD:0.11 ± 0.06,P < 0.01).In addition,the positive rate of VEGI expression,the expression intensity and the MOD of VEGI protein were negatively correlated with the pathologic grade of CCRCC (r =-0.640,P <0.01 ; r =-0.831,P < 0.01 ; r =-0.781,P < 0.01 respectively).The MOD of VEGI expression in ≥7 cm tumors (MOD,0.08 ±0.04) was significantly lower than that in <7 cm tumors (MOD:0.12 ±0.06,P < 0.05).However,there was no correlations between the VEGI protein level and age,gender and pathologic stage of patients (P > 0.05).Conclusion VEGI protein is predominantly located in cytoplasm.Compared with CCRCC tissues,VEGI protein level is higher in normal ones.In consideration of negative correlations between VEGI expression,pathologic grade and tumor size,it is implied that VEGI may play a negative regulatory role in the occurrence and development of CCRCC.%目的 了解血管内皮生长抑制因子(VEGI)在散发性肾透明细胞癌(CCRCC)中的表达情况,分析其与CCRCC病理分级和分期等的关系.方法 应用Western印迹及免疫组化技术分析肾透明细胞癌细胞(786-O细胞)

  10. Functional epigenomics approach to identify methylated candidate tumour suppressor genes in renal cell carcinoma

    OpenAIRE

    Morris, M.

    2008-01-01

    Promoter region hypermethylation and transcriptional silencing is a frequent cause of tumour suppressor gene (TSG) inactivation in many human cancers. Previously, to identify candidate epigenetically inactivated TSGs in renal cell carcinoma (RCC), we monitored changes in gene expression in four RCC cell lines after treatment with the demethylating agent 5-azacytidine. This enabled us to identify HAI-2/SPINT2 as a novel epigenetically inactivated candidate RCC TSG. To identify further candidat...

  11. Helical CT scan: application in the diagnosis of small renal cell carcinoma

    International Nuclear Information System (INIS)

    Objective: To evaluate helical CT scan in the diagnosis of small renal cell carcinoma (RCC). Methods: Helical CT features and pathologic findings of 15 patients with small RCC are analyzed. Results: Of 13 cases of small solid RCC, 9 showed marked tumor enhancement in cortical phase, in another 4 cases the enhancement was slight to moderate. Two cases of small cystic RCC, presented enhancement of wall with nodules and the partition in cortical phase. Enhancement faded away in the following parenchymal phase and pyelographic phase. All cases had hypervascular appearance pathologically. Two cases of small cystic RCC showed clear cystic degeneration, but the solid portion was rich in vascularity. Conclusion: The multi-phasic helical CT scan is superior to the conventional CT in the diagnosis of small RCC. In most cases, tumor enhancement was strong in cortical phase but weak in parenchymal phase, they demonstrated some degree of fast wash-out phenomenon, which is a characteristic pattern of enhancement. And the authors believe this has diagnostic significance. Therefore, the acquisition of a cortical phase scan should be part of the routine helical CT protocol of small RCC

  12. Abscess formation mimicking disease progression, in a patient with metastatic renal cell carcinoma during sunitinib treatment

    Directory of Open Access Journals (Sweden)

    Gennatas Constantine

    2010-05-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC represents approximately 3% of all adult cancers and is more common in males. Systemic treatment for RCC has improved following the introduction of tyrosine kinase inhibitors, such as sunitinib. The molecular targets of sunitinib are receptor tyrosine kinases (RTKs. Moreover, sunitinib has an additional anti-angiogenic effect through its inhibition of the vascular endothelial growth factor receptor activation. Case presentation We present a case of intra-abdominal abscess formation mimicking disease progression, in a patient with metastatic renal cell carcinoma during sunitinib treatment. Conclusion In the advancing era of molecular therapy of solid tumours, sunitinib has demonstrated significant efficacy in the post-cytokine setting treatment of metastatic renal cancer. Concurrently, however, increasing evidence has emerged to indicate that this class of drugs exert profound immunomodulatory effects on T cells and play major roles in immune tumor surveillance.

  13. BSND and ATP6V1G3: Novel Immunohistochemical Markers for Chromophobe Renal Cell Carcinoma

    Science.gov (United States)

    Shinmura, Kazuya; Igarashi, Hisaki; Kato, Hisami; Koda, Kenji; Ogawa, Hiroshi; Takahashi, Seishiro; Otsuki, Yoshiro; Yoneda, Tatsuaki; Kawanishi, Yuichi; Funai, Kazuhito; Takayama, Tatsuya; Ozono, Seiichiro; Sugimura, Haruhiko

    2015-01-01

    Abstract Differentiating between chromophobe renal cell carcinoma (RCC) and other RCC subtypes can be problematic using routine light microscopy. This study aimed to identify novel immunohistochemical markers useful for a differential diagnosis between chromophobe RCC and other RCC subtypes. We selected 3 genes (including BSND and ATP6V1G3) that showed specific transcriptional expression in chromophobe RCC using expression data (n = 783) from The Cancer Genome Atlas (TCGA) database. A subsequent immunohistochemical examination of 186 RCCs obtained in our patient series resulted in a strong diffuse positivity of BSND and ATP6V1G3 proteins (both of which are involved in the regulation of membrane transport) in all the chromophobe RCC specimens (23/23 cases, 100%) but not in the clear cell RCC specimens (0/153 cases, 0%) or the papillary RCC specimens (0/10 cases, 0%). BSND and ATP6V1G3 protein expressions were also detected in renal oncocytoma (13/14 cases, 92.9%) and in the distal nephron, including the collecting duct, in the normal kidney. A computational analysis of TCGA data suggested that DNA methylation was involved in the differential expression pattern of both genes among RCC subtypes. Finally, an immunohistochemical analysis showed lung carcinomas were negative (0/85 cases, 0%) for the expression of both proteins. These results suggest that BSND and ATP6V1G3 are excellent novel immunohistochemical markers for differentiating between chromophobe RCC and other subtypes of RCC, including clear cell and papillary RCCs.

  14. Isolated omental metastasis of renal cell carcinoma after extraperitoneal open partial nephrectomy: A case report

    Science.gov (United States)

    Acar, Ömer; Mut, Tuna; Sağlıcan, Yeşim; Sag, Alan Alper; Falay, Okan; Selcukbiricik, Fatih; Tabak, Levent; Esen, Tarık

    2016-01-01

    Introduction Metachronous metastatic spread of clinically localized renal cell carcinoma (RCC) affects almost 1/3 of the patients. They occur most frequently in lung, liver, bone and brain. Isolated omental metastasis of RCC has not been reported so far. Case presentation A 62-year-old patient previously diagnosed and treated due to pulmonary sarcoidosis has developed an omental metastatic lesion 13 years after having undergone open extraperitoneal partial nephrectomy for T1 clear-cell RCC. Constitutional symptoms and imaging findings that were attributed to the presence of a sarcomatoid paraneoplastic syndrome triggered by the development this metastatic focus complicated the diagnostic work-up. Biopsy of the [18F]-fluorodeoxyglucose (+) lesions confirmed the diagnosis of metastatic RCC and the patient was managed by the resection of the omental mass via near-total omentectomy followed by targeted therapy with a tyrosine kinase inhibitor. Discussion Late recurrence of RCC has been reported to occur in 10–20% of the patients within 20 years. Therefore lifelong follow up of RCC has been advocated by some authors. Diffuse peritoneal metastases have been reported in certain RCC subtypes with adverse histopathological features. However, isolated omental metastasis without any sign of peritoneal involvement is an extremely rare condition. Conclusion To our knowledge, this is the first reported case of metachronously developed, isolated omental metastasis of an initially T1 clear-cell RCC. Constitutional symptoms, despite a long interval since nephrectomy, should raise the possibility of a paraneoplastic syndrome being associated with metastatic RCC. Morphological and molecular imaging studies together with histopathological documentation will be diagnostic. PMID:26874583

  15. BSND and ATP6V1G3: Novel Immunohistochemical Markers for Chromophobe Renal Cell Carcinoma.

    Science.gov (United States)

    Shinmura, Kazuya; Igarashi, Hisaki; Kato, Hisami; Koda, Kenji; Ogawa, Hiroshi; Takahashi, Seishiro; Otsuki, Yoshiro; Yoneda, Tatsuaki; Kawanishi, Yuichi; Funai, Kazuhito; Takayama, Tatsuya; Ozono, Seiichiro; Sugimura, Haruhiko

    2015-06-01

    Differentiating between chromophobe renal cell carcinoma (RCC) and other RCC subtypes can be problematic using routine light microscopy. This study aimed to identify novel immunohistochemical markers useful for a differential diagnosis between chromophobe RCC and other RCC subtypes. We selected 3 genes (including BSND and ATP6V1G3) that showed specific transcriptional expression in chromophobe RCC using expression data (n = 783) from The Cancer Genome Atlas (TCGA) database. A subsequent immunohistochemical examination of 186 RCCs obtained in our patient series resulted in a strong diffuse positivity of BSND and ATP6V1G3 proteins (both of which are involved in the regulation of membrane transport) in all the chromophobe RCC specimens (23/23 cases, 100%) but not in the clear cell RCC specimens (0/153 cases, 0%) or the papillary RCC specimens (0/10 cases, 0%). BSND and ATP6V1G3 protein expressions were also detected in renal oncocytoma (13/14 cases, 92.9%) and in the distal nephron, including the collecting duct, in the normal kidney. A computational analysis of TCGA data suggested that DNA methylation was involved in the differential expression pattern of both genes among RCC subtypes. Finally, an immunohistochemical analysis showed lung carcinomas were negative (0/85 cases, 0%) for the expression of both proteins. These results suggest that BSND and ATP6V1G3 are excellent novel immunohistochemical markers for differentiating between chromophobe RCC and other subtypes of RCC, including clear cell and papillary RCCs. PMID:26091477

  16. Characterizing the Impact of Lymph Node Metastases on the Survival Outcome for Metastatic Renal Cell Carcinoma Patients Treated with Targeted Therapies

    DEFF Research Database (Denmark)

    Kroeger, Nils; Pantuck, Allan J; Wells, J Connor; Lawrence, Nicola; Broom, Reuben; Kim, Jenny J; Srinivas, Sandy; Yim, Jessica; Bjarnason, Georg A; Templeton, Arnoud; Knox, Jennifer; Bernstein, Ezra; Smoragiewicz, Martin; Lee, Jae; Rini, Brian I; Vaishampayan, Ulka N; Wood, Lori A; Beuselinck, Benoit; Donskov, Frede; Choueiri, Toni K; Heng, Daniel Y

    2015-01-01

    BACKGROUND: It is unknown whether lymph node metastases (LNM) and their localization negatively affect clinical outcome in metastatic renal cell carcinoma (mRCC) patients. OBJECTIVE: To evaluate the clinicopathological features, survival outcome, and treatment response in mRCC patients with LNM...... supradiaphragmatic (SPD) LNM, subdiaphragmatic (SBD) LNM, and patients with LNM in both locations (SPD+/SBD+) without histologic considerations, and then separately in clear cell RCC (ccRCC) and non-clear cell RCC (nccRCC) patients, respectively. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was...... with shorter survival outcome when metastatic renal cell carcinoma (mRCC) patients are treated with targeted therapies. Clinical trials should evaluate whether surgical removal of regional lymph nodes at the time of nephrectomy may improve outcomes in high-risk RCC patients....

  17. Epigenetic change in kidney tumor: downregulation of histone acetyltransferase MYST1 in human renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Wang Yong

    2013-02-01

    Full Text Available Abstract Background MYST1 (also known as hMOF, a member of the MYST family of histone acetyltransferases (HATs as an epigenetic mark of active genes, is mainly responsible for histone H4K16 acetylation in the cells. Recent studies have shown that the abnormal gene expression of hMOF is involved in certain primary cancers. Here we examined the involvement of hMOF expression and histone H4K16 acetylation in primary renal cell carcinoma (RCC. Simultaneously, we investigated the correlation between the expression of hMOF and clear cell RCC (ccRCC biomarker carbohydrase IX (CA9 in RCC. Materials and methods The frozen RCC tissues and RCC cell lines as materials, the reverse transcription polymerase chain reaction (RT-PCR, western blotting and immunohistochemical staining approaches were used. Results RT-PCR results indicate that hMOF gene expression levels frequently downregulated in 90.5% of patients (19/21 with RCC. The reduction of hMOF protein in both RCC tissues and RCC cell lines is tightly correlated with acetylation of histone H4K16. In addition, overexpression of CA9 was detected in 100% of ccRCC patients (21/21. However, transient transfection of hMOF in ccRCC 786–0 cells did not affect both the gene and protein expression of CA9. Conclusion hMOF as an acetyltransferase of H4K16 might be involved in the pathogenesis of kidney cancer, and this epigenetic changes might be a new CA9-independent RCC diagnostic maker.

  18. Paraffin-embedded tissue is less accurate than frozen section analysis for determining VHL mutational status in sporadic renal cell carcinoma.

    OpenAIRE

    Verhoest, Grégory; Patard, Jean-Jacques; Fergelot, Patricia; Jouan, Florence; Zerrouki, Salim; Dréano, Stéphane; Mottier, Stéphanie; Rioux-Leclercq, Nathalie; Denis, Marc,

    2012-01-01

    International audience INTRODUCTION: Literature controversies exist regarding the prognostic value of VHL mutations. The objective was to compare paraffin-embedded and frozen section specimens for VHL mutations detection and to evaluate the reliability of DNA analysis in formalin-fixed tissues. METHODS: Seventy-six patients with clear cell renal cell carcinoma (RCC) previously assessed for VHL status from frozen samples were included. Seventy-three tumor samples were known to be mutated fo...

  19. Targeted therapy for metastatic renal cell carcinoma: Current treatment and future directions

    Directory of Open Access Journals (Sweden)

    Noura Majid

    2013-01-01

    Full Text Available Renal cell carcinoma (RCC is the most common renal tumor and accounts for 3% of all adult cancers. The treatment of metastatic renal cell carcinoma (mRCC has recently evolved from being a predominantly cytokine-based treatment to the use of targeted agents, which include Sorafenib, Sunitinib, Bevacizumab, Temsirolimus, Everolimus, Pazopanib, Axitinib, and most recently Tivozanib. Despite these advances mRCC remains a major health problem. Additional studies are needed to optimize the use of these agents in both advanced and early stage disease, either in combination or sequentially. In addition the development of biomarkers should be a priority in order to guide rational tailored development of emerging agents. This literature review was conducted using PubMed, Medline, and Cochrane databases for articles published until January 2013. Abstracts from relevant meeting of the American Society of Clinical Oncology and the European society of medical oncology were also included.

  20. Neoadjuvant treatment in advanced renal cell carcinoma: current situation and future perspectives.

    Science.gov (United States)

    Timsit, Marc-Olivier; Albiges, Laurence; Méjean, Arnaud; Escudier, Bernard

    2012-12-01

    Neoadjuvant approaches in renal cell carcinoma are currently under investigation, following the demonstration of targeted therapy efficacy in the metastatic setting. It raises the issues of downsizing locally advanced or nonresectable tumor and offering organ-sparing surgery, safety and its potential role in early micrometastatic disease. Relevant studies of the neoadjuvant setting in renal cell carcinoma with targeted therapies were identified from the literature, clinical trial databases and conference abstracts. To date, a neoadjuvant approach appears feasible in terms of safety. Currently available drugs do not achieve major tumor downsizing with primary tumor diameters response rate of 10%. Neoadjuvants should only be considered in clinical trials or as a litmus test in locally advanced patients. PMID:23253222