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Sample records for invasive cutaneous melanoma

  1. Data Set for Pathology Reporting of Cutaneous Invasive Melanoma

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    Judge, Meagan J.; Evans, Alan; Frishberg, David P.; Prieto, Victor G.; Thompson, John F.; Trotter, Martin J.; Walsh, Maureen Y.; Walsh, Noreen M.G.; Ellis, David W.

    2013-01-01

    An accurate and complete pathology report is critical for the optimal management of cutaneous melanoma patients. Protocols for the pathologic reporting of melanoma have been independently developed by the Royal College of Pathologists of Australasia (RCPA), Royal College of Pathologists (United Kingdom) (RCPath), and College of American Pathologists (CAP). In this study, data sets, checklists, and structured reporting protocols for pathologic examination and reporting of cutaneous melanoma were analyzed by an international panel of melanoma pathologists and clinicians with the aim of developing a common, internationally agreed upon, evidence-based data set. The International Collaboration on Cancer Reporting cutaneous melanoma expert review panel analyzed the existing RCPA, RCPath, and CAP data sets to develop a protocol containing “required” (mandatory/core) and “recommended” (nonmandatory/noncore) elements. Required elements were defined as those that had agreed evidentiary support at National Health and Medical Research Council level III-2 level of evidence or above and that were unanimously agreed upon by the review panel to be essential for the clinical management, staging, or assessment of the prognosis of melanoma or fundamental for pathologic diagnosis. Recommended elements were those considered to be clinically important and recommended for good practice but with lesser degrees of supportive evidence. Sixteen core/required data elements for cutaneous melanoma pathology reports were defined (with an additional 4 core/required elements for specimens received with lymph nodes). Eighteen additional data elements with a lesser level of evidentiary support were included in the recommended data set. Consensus response values (permitted responses) were formulated for each data item. Development and agreement of this evidence-based protocol at an international level was accomplished in a timely and efficient manner, and the processes described herein may

  2. Expression of IL-27 by tumor cells in invasive cutaneous and metastatic melanomas [corrected]..

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    Julie Gonin

    Full Text Available Interleukin (IL-27 is a cytokine of the IL-12 family that displays either immunostimulatory or immunosuppressive functions depending on the context. In various murine tumor models including melanoma models, ectopic expression of IL-27 has been shown to play an anti-tumoral role and to favor tumor regression. In this study, we investigated whether IL-27 might play a role in the development of melanoma in humans. We analyzed the in situ expression of IL-27 in melanocytic lesions (n = 82 representative of different stages of tumor progression. IL-27 expression was not observed in nevus (n = 8 nor in in situ melanoma (n = 9, but was detected in 28/46 (61% cases of invasive cutaneous melanoma, notably in advanced stages (19/23 cases of stages 3 and 4. In most cases, the main source of IL-27 was tumor cells. Of note, when IL-27 was detected in primary cutaneous melanomas, its expression was maintained in metastatic lesions. These in situ data suggested that the immunosuppressive functions of IL-27 may dominate in human melanoma. Consistent with this hypothesis, we found that IL-27 could induce suppressive molecules such as PD-L1, and to a lesser extent IL-10, in melanoma cells, and that the in situ expression of IL-27 in melanoma correlated with those of PD-L1 and IL-10.

  3. Human mitochondrial NAD(P)(+)-dependent malic enzyme participates in cutaneous melanoma progression and invasion.

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    Chang, Yung-Lung; Gao, Hong-Wei; Chiang, Chien-Ping; Wang, Wei-Ming; Huang, Shih-Ming; Ku, Chien-Fen; Liu, Guang-Yaw; Hung, Hui-Chih

    2015-03-01

    Cutaneous melanoma is the most life-threatening neoplasm of the skin, accounting for most of the skin cancer deaths. Accumulating evidence suggests that targeting metabolism is an appealing strategy for melanoma therapy. Mitochondrial NAD(P)(+)-dependent malic enzyme (ME2), an oxidative decarboxylase, was evaluated for its biological significance in cutaneous melanoma progression. ME2 mRNA and protein expression significantly increased during melanoma progression, as evidenced by Gene Expression Omnibus analysis and immunohistochemistry on clinically annotated tissue microarrays, respectively. In addition, ME2 knockdown attenuated melanoma cell proliferation in vitro. ME2 ablation resulted in reduced cellular ATP levels and elevated cellular reactive oxygen species production, which activated the AMP-activated protein kinase pathway and inhibited acetyl-CoA carboxylase. Furthermore, ME2 expression was associated with cell migration and invasion. ME2 knockdown decreased anchorage-independent growth in vitro and tumor cell growth in vivo. These results suggested that ME2 might be an important factor in melanoma progression and a novel biomarker of invasion.

  4. CD207+/langerin positive dendritic cells in invasive and in situ cutaneous malignant melanoma

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    Grzegorz Dyduch

    2017-05-01

    Full Text Available Introduction : Dendritic cells are crucial for cutaneous immune response. Their role in melanoma progression is however a matter of controversy. Material and methods : The number of dendritic cells within epidermis and in peri- and intratumoral location was analyzed using CD207 immunostain in 17 cases of in situ and 25 case of invasive melanoma. Results : Average peritumoral CD207+ cells count was 22.88 for all cases, 17.94 for in situ lesions and 26.24 for invasive cases. Average epidermal CD207+ cells count was 164.47 for all cases, 183.00 for in situ lesions and 150.78 – for invasive cases. In case of invasive melanomas, peritumoral CD207+ cells count was positively correlated with Breslow stage (R = 0.59 mitotic activity within the tumor (R = 0.62. Invasive cases with regression showed higher intratumoral and epidermal CD207+ cells count than the ones without (275.00 vs. 95.32 and 173.20 vs. 148.35 but lower peritumoral CD207+ cells count (17.60 vs. 27.26. Invasive cases with ulceration showed higher intratumoral and peritumoral CD207+ cells count than the ones without ulceration (220.08 vs. 55.67 and 44.17 vs. 9.69. Conclusions : CD207+ cells play a role in both progression and regression of melanoma but their exact role needs further studies.

  5. The relationship between MDM2 expression and tumor thickness and invasion in primary cutaneous malignant melanoma

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    Parvin Rajabi

    2012-01-01

    Full Text Available Background: Malignant melanoma is the most invasive cutaneous tumor which is associated with an incredibly high mortality rate. The most reliable histological factors associated with melanoma prognosis are tumor thickness- measured by the Breslow index- and invasion depth- measured by Clark level. Murine double minute 2 (MDM2 gene inhibits p53-dependent apoptosis. An increase in MDM2 expression has been found in many tumors. This study aimed to investigate MDM2 expression and its correlation with tumor thickness and invasion level in malignant melanoma. Materials and Methods: This study evaluated paraffin blocks from 43 randomly selected patients with primary cutaneous melanoma who referred to the main university pathology center in Isfahan, Iran. MDM2 expression rate was assessed via immunohistochemical techniques and hematoxylin and eosin staining to determine tumor thickness and invasion level. Correlations between MDM2 expression and tumor thickness and invasion were analyzed using Spearman′s correlation coefficient in SPSS 17 . Results: The mean age of patients was 61.2 ± 15 years. Men and women constituted 55.8% and 44.2% of the participants, respectively. The rate of MDM2 positivity was 28.9%. MDM2 expression was directly associated with tumor thickness (r = 0.425; p = 0.002 and weakly with invasion level (r = 0.343; p = 0.01. Conclusions: Despite the low MDM2 expression rate observed in this study, direct relationships between MDM2 positivity and tumor thickness and invasion level were identified. MDM2 expression can thus be suggested as a potential new predictive prognostic factor.

  6. Staging of cutaneous melanoma

    NARCIS (Netherlands)

    P. Mohr (P.); A.M.M. Eggermont (Alexander); A. Hauschild (Axel); A. Buzaid (A.)

    2009-01-01

    textabstractThe American Joint Committee on Cancer (AJCC) staging of cutaneous melanoma is a continuously evolving system. The identification of increasingly more accurate prognostic factors has led to major changes in melanoma staging over the years, and the current system described in this review

  7. Cutaneous manifestations associated with melanoma.

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    Vyas, Ritva; Selph, Jacqueline; Gerstenblith, Meg R

    2016-06-01

    Melanoma is a malignancy most commonly arising from the skin; therefore, primary melanoma characteristics are usually the first cutaneous manifestations of melanoma. Cutaneous metastases, which can occur locally or diffusely, are important to detect in a timely manner as treatments for advanced melanoma that impact survival are now available. Melanoma can be associated with local or diffuse pigmentation changes, including depigmentation associated with the leukodermas and hyperpigmentation associated with diffuse melanosis cutis. The leukodermas occur frequently, illustrate the immunogenic nature of melanoma, and may impact prognosis. Paraneoplastic syndromes in association with melanoma are rare, though can occur. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Incidence trends and clinical-pathological characteristics of invasive cutaneous melanoma from 1980 to 2010 in the Canton of Zurich, Switzerland.

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    Minini, Remo; Rohrmann, Sabine; Braun, Ralph; Korol, Dimitri; Dehler, Silvia

    2017-04-01

    The aims of this paper are to describe the incidence trends of invasive cutaneous melanoma in the Canton of Zurich and to evaluate clinical and pathological factors such as cancer subtype, localization, age and Breslow thickness. A retrospective analysis was carried out with data from the population-based Cancer Registry of Zurich and Zug located in Zurich. A total of 8469 cases in 8034 different patients of invasive cutaneous melanoma were registered for the period 1980-2010 in the Canton of Zurich. Incidence trends were age standardized to the European standard population. Joinpoint regression was used to compute changes in incidence and mortality rates, measured as the annual percent change (APC). The most common subtypes of cutaneous melanoma were superficial spreading melanoma (SSM, 41.1%), followed by nodular melanoma (16.5%), lentigo maligna melanoma (13.5%), acral-lentiginous melanoma (5.0%) and other types of melanoma (2.8%); 21.1% were melanoma not otherwise specified. The trunk was the most frequent location (30.8%), followed by the lower limb and hip (26.4%) and the upper limb and shoulder (22.8%). Statistically significantly increasing incidence trends were observed for both men (APC=3.0%) and women (APC=2.1%). Incidences of SSM and melanoma not otherwise specified were the histological subtypes for which a significant increase in incidence was observed (APC for the period 1980-2010=3.2% for both). In terms of Breslow thickness, thin melanomas (0.01-1.00 mm) showed an increasing incidence. The incidence of melanoma increased in both men and women between 1980 and 2010. In terms of the different subtypes and Breslow thickness, increasing incidences of the SSM and of thin melanomas (0.01-1.00 mm) were observed. These observations are in agreement with other studies from Southern and Western Switzerland as well as other European countries and the USA.

  9. Cutavirus in Cutaneous Malignant Melanoma

    DEFF Research Database (Denmark)

    Mollerup, Sarah; Fridholm, Helena; Vinner, Lasse

    2017-01-01

    A novel human protoparvovirus related to human bufavirus and preliminarily named cutavirus has been discovered. We detected cutavirus in a sample of cutaneous malignant melanoma by using viral enrichment and high-throughput sequencing. The role of cutaviruses in cutaneous cancers remains...

  10. Cutaneous melanoma in women

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    Mi Ryung Roh, MD

    2017-03-01

    Conclusions: The published findings on gender disparities in melanoma have yielded many advances in our understanding of this disease. Biological, environmental, and behavioral factors may explain the observed gender difference in melanoma incidence and outcome. Further research will enable us to learn more about melanoma pathogenesis, with the goal of offering better treatments and preventative advice to our patients.

  11. Cutaneous melanoma in women

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    Mi Ryung Roh, MD

    2015-02-01

    Conclusions: The published findings on gender disparities in melanoma have yielded many advances in our understanding of this disease. Biological, environmental, and behavioral factors may explain the observed gender difference in melanoma incidence and outcome. Further research will enable us to learn more about melanoma pathogenesis, with the goal of offering better treatments and preventative advice to our patients.

  12. Histological Types of Polypoid Cutaneous Melanoma II

    OpenAIRE

    Knežević, Fabijan; Duančić, Vjekoslav; Šitić, Sanda; Horvat-Knežević, Anica; Benković, Vesna; Ramić, Snježana; Kostović, Krešimir; Ramljak, Vesna; Velemir Vrdoljak, Danko; Stanec, Mladen; Božović, Angelina

    2007-01-01

    The aim of this study was to ascertain which histological types of melanoma can clinically and morphologically appear as polypoid melanomas. In 645 cases of primary cutaneous melanoma we have analyzed criteria for diagnosis of polypoid cutaneous melanoma and afterwards we have analyzed growth phase in each polypoid melanoma, histological type of atypical melanocytes, the number of epidermal ridges which are occupied by atypical melanocytes, and distribution according to age, sex a...

  13. Prognostic value of BRAF mutations in localized cutaneous melanoma.

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    Nagore, Eduardo; Requena, Celia; Traves, Víctor; Guillen, Carlos; Hayward, Nicholas K; Whiteman, David C; Hacker, Elke

    2014-05-01

    BRAF mutations are frequent in melanoma but their prognostic significance remains unclear. We sought to further evaluate the prognostic value of BRAF mutations in localized cutaneous melanoma. We undertook an observational retrospective study of 147 patients with localized invasive (stages I and II) cutaneous melanomas to determine the prognostic value of BRAF mutation status. After a median follow-up of 48 months, patients with localized melanomas with BRAF-mutant melanomas exhibited poorer disease-free survival than those with BRAF-wt genotype (hazard ratio 2.2, 95% confidence interval 1.1-4.3) even after adjustment for Breslow thickness, tumor ulceration, location, age, sex, and tumor mitotic rate. The retrospective design and the small number of events are limitations. Our findings suggest that reappraisal of clinical treatment approaches for patients with localized melanoma harboring tumors with BRAF mutation might be warranted. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  14. Clinicopathological and molecular aspects of cutaneous Melanoma

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    Bogenrieder, T.

    2009-01-01

    Clinicopathological and molecular aspects of cutaneous melanoma. Melanoma arises form the transformation of neural crest-derived melanocytes, the pigment cells of the skin, which reside in the basal layer of the epidermis. Melanoma is the deadliest form of skin cancer and one of the most aggressive

  15. Malignant cutaneous melanoma in patients from Las Tunas province

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    Alicia María Yabor Palomo

    2015-11-01

    Full Text Available Background: malignant melanoma is a highly aggressive skin neoplasia, whose incidence shows a constant and rapid increase.Objective: to characterize variables in patients diagnosed with cutaneous melanoma, whose biopsies were analyzed in the pathologic anatomy department of "Dr. Ernesto Guevara de la Serna" General Teaching Hospital from January, 2008 to December, 2014.Methods: a descriptive and cross-sectional study was performed in 31 patients treated in the place and period of time mentioned above. The official form of biopsy was used as a secondary source of collecting information and it was processed using descriptive statistics.Results: the 10,6 % of the biopsies analyzed corresponded with cutaneous melanoma, its frequency prevailed in 2011 and 2010, with a 25,8 % and 19,3 % respectively. It was evident a higher percentage in males (67,7 % and in the age group between 60 and 69 years old, with a 35,4 %. Caucasian patients were the most affected ones, with a 90,3 % and the predominant location was in the lower limbs in 45,1 % of the cases. The prevailing Clark invasion level was IV, evident by the 32,2 % of the sample, and the most frequent histological variety was the malignant nodular melanoma in 19 patients, for a 61,2 %.Conclusions: cutaneous melanoma prevailed in lower extremities in males and it had a belated diagnosis, since there was prevalence of IV Clark invasion level and nodular melanoma as the most frequent histological type.

  16. Prediction of sentinel lymph node positivity by growth rate of cutaneous melanoma.

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    Tejera-Vaquerizo, Antonio; Nagore, Eduardo; Herrera-Acosta, Enrique; Martorell-Calatayud, Antonio; Martín-Cuevas, Paula; Traves, Víctor; Herrera-Ceballos, Enrique

    2012-05-01

    To determine whether growth rate (GR) of cutaneous melanoma predicts the histological sentinel lymph node (SLN) positivity. Retrospective cohort study. Two tertiary melanoma referral centers. A total of 698 patients with invasive primary cutaneous melanoma in whom the SLN was identified between January 1, 2000, and June 30, 2010. Based on previous studies, a surrogate measure for GR in primary invasive melanoma was calculated as the ratio of Breslow thickness to time to melanoma development. The SLN was positive in 20.2% of patients. Multivariate logistic regression analysis revealed that GR, Breslow thickness, and the presence of microscopic satellitosis were independently associated with SLN positivity. The probability of SLN positivity was 8.2% for slow-growth melanomas (0.50 mm/mo). Growth rate was not an independent predictive factor for survival. Growth rate of primary cutaneous melanoma, together with Breslow thickness and the presence of microscopic satellitosis, predicts the histological SLN positivity.

  17. Selenium for the Prevention of Cutaneous Melanoma

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    Douglas Grossman

    2013-03-01

    Full Text Available The role of selenium (Se supplementation in cancer prevention is controversial; effects often depend on the nutritional status of the subject and on the chemical form in which Se is provided. We used a combination of in vitro and in vivo models to study two unique therapeutic windows for intervention in the process of cutaneous melanomagenisis, and to examine the utility of two different chemical forms of Se for prevention and treatment of melanoma. We studied the effects of Se in vitro on UV-induced oxidative stress in melanocytes, and on apoptosis and cell cycle progression in melanoma cells. In vivo, we used the HGF transgenic mouse model of UV-induced melanoma to demonstrate that topical treatment with l-selenomethionine results in a significant delay in the time required for UV-induced melanoma development, but also increases the rate of growth of those tumors once they appear. In a second mouse model, we found that oral administration of high dose methylseleninic acid significantly decreases the size of human melanoma xenografts. Our findings suggest that modestly elevation of selenium levels in the skin might risk acceleration of growth of incipient tumors. Additionally, certain Se compounds administered at very high doses could have utility for the treatment of fully-malignant tumors or prevention of recurrence.

  18. Stereological estimation of nuclear volume in benign melanocytic lesions and cutaneous malignant melanomas

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    Sørensen, Flemming Brandt

    1989-01-01

    V in melanocytic cutaneous tumors and to compare these with estimates of nuclear volume fraction and with traditional two-dimensional morphometric estimates of nuclear profile area, nuclear density, and mitotic index. Routinely processed, paraffin embedded tissue specimens from 47 malignant melanomas and 76...... noninvasive melanocytic cutaneous tumors were investigated retrospectively. vV clearly distinguished between noninvasive (average vV = 122 microns 3) and invasive lesions (average vV = 246 microns 3). Most of the patients with malignant melanomas showing an overlap of nuclear vV with benign lesions had...... estimator for distinguishing between melanocytic cutaneous tumors showing different biological behavior, well-suited for objective malignancy grading....

  19. Primary cutaneous melanoma: an 18-year study

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    Moris Anger

    2010-01-01

    Full Text Available BACKGROUND: Primary cutaneous melanoma still constitutes the main cause of skin cancer death in developed countries, and its incidence in recent years has been increasing in a steady, worrisome manner. OBJECTIVES: This study evaluated the clinical, epidemiological and demographic aspects of this disease, and correlated them with patient prognosis. METHODS: Using epidemiologic and clinical data, we analyzed 84 patients with mild to severe primary cutaneous melanoma treated between 1990 and 2007. Slides containing surgical specimens were analyzed, and new slides were made from archived paraffin sections when necessary. RESULTS: The melanoma incidence was higher in areas of sun exposure, with lesions commonly observed in the trunk for males, and lower limbs for females. In addition to Breslow's thickness and ulceration (p = 0.043 and p 1 mm and 4 mm and the mitotic index (0 when absent or 1 when >1 per mm² allowed the establishment of a prognostic score: if the sum was equal to or over three, nearly all (91.7% patients had systemic disease. The 5-year survival was approximately seventy percent. CONCLUSION: Because American Join Committee of Cancer Staging will update the classification of malignant tumors (TNM staging in the near future, and introduce mitosis as a prognostic factor, our results show the importance of such a feature. Additional studies are necessary to confirm the importance of a prognostic score as proposed herein.

  20. Sun behaviour after cutaneous malignant melanoma

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    Idorn, L W; Datta, P; Heydenreich, J

    2013-01-01

    Background  It has been reported that patients with cutaneous malignant melanoma (CMM) can lower their risk of a second primary melanoma by limiting recreational sun exposure. Previous studies based on questionnaires and objective surrogate measurements indicate that before their diagnosis......, patients with CMM are exposed to higher ultraviolet radiation (UVR) doses than controls, followed by a reduction after diagnosis. Objectives  In a prospective, observational case-control study, we aimed to assess sun exposure after diagnosis of CMM by objective measurements to substantiate advice about sun...... months and 6 years before the start of the study. During a summer season participants filled in sun exposure diaries daily and wore personal electronic UVR dosimeters in a wristwatch that continuously measured time-stamped UVR doses in standard erythema dose. Results  The UVR dose of recently diagnosed...

  1. Pitfalls in Cutaneous Melanoma Lymphatic Drainage.

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    Voinea, Silviu; Sandru, Angela; Gherghe, Mirela

    2016-01-01

    Sentinel node (SN) biopsy has become standard in staging of cutaneous melanoma. As skin lymphatic drainage is complex, preoperative empirical assessment of SN localization is virtually impossible. Therefore in order to identify all regional lymphatic basins corresponding to a specific primary tumor is mandatory to carry out preoperative lymphoscintigraphy. In this paper we present a clinical case that highlights the importance of identifying, biopsy and histological analysis of all SN in order to achieve a correct staging of the patient, followed by appropriate treatment according to the real clinical stage of the disease. Celsius.

  2. ZNF23 Suppresses Cutaneous Melanoma Cell Malignancy via Mitochondria-Dependent Pathway

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    Xin Zhang

    2017-08-01

    Full Text Available Background/Aims: Cutaneous melanoma is one of the leading causes of cancer deaths with an increasing incidence worldwide. A KRAB-containing zinc finger protein member, zinc finger 23 (ZNF23, was reduced in some types of tumors and inhibited cell growth by inducing cell cycle arrest. However, the role of ZNF23 expression is still poorly understood in melanoma. Methods: The level of ZNF23 expression was detected in cutaneous melanoma, adjacent normal skin tissues and cutaneous melanoma cell lines using immunohistochemistry and western blotting. The correlations between ZNF23 expression and other clinicopathologic parameters were analyzed in melanoma patients. Ectopic expression of ZNF23 plasmid was transfected into melanoma cells, SK-MEL-1 and SK-MEL-28. MTT, flow cytometry and transwell assay were used to measure cell proliferation, apoptosis, invasion and migration abilities, respectively. Mitochondrial functions and structures were detected by mitochondrial membrane potential assay and Transmission electron microscopy (TEM method in melanoma cells transfected with overexpressing ZNF23 plasmid or empty vector. Western blotting was performed to detect the levels of ZNF23, p53, p27, Bcl-2 and cleaved caspase-3 after overexpressing of ZNF23 in melanoma cells. Results: ZNF23 was elevated in adjacent normal skin tissues compared with melanoma tissues. Patients with low level of ZNF23 expression exhibited higher incidence of lymphoid metastasis, thicker size of tumors and worse outcome. By using Cox’s regression analysis, ZNF23 expression, tumor thickness and lymph node metastasis were the independent prognostic factors for overall survival (p < 0.05. Results from cellular experiments indicated that ectopic expression of ZNF23 induced cell apoptosis by activation of caspase-3, p27, p53 expression and down-regulation of Bcl-2 through mitochondria-dependent pathway. Conclusions: Decreased ZNF23 was contributed to melanoma progression and poor survival

  3. Infrared thermography of cutaneous melanoma metastases.

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    Shada, Amber L; Dengel, Lynn T; Petroni, Gina R; Smolkin, Mark E; Acton, Scott; Slingluff, Craig L

    2013-06-01

    Differentiating melanoma metastasis from benign cutaneous lesions currently requires biopsy or costly imaging, such as positron emission tomography scans. Melanoma metastases have been observed to be subjectively warmer than similarly appearing benign lesions. We hypothesized that infrared (IR) thermography would be sensitive and specific in differentiating palpable melanoma metastases from benign lesions. Seventy-four patients (36 females and 38 males) had 251 palpable lesions imaged for this pilot study. Diagnosis was determined using pathologic confirmation or clinical diagnosis. Lesions were divided into size strata for analysis: 0-5, >5-15, >15-30, and >30 mm. Images were scored on a scale from -1 (colder than the surrounding tissue) to +3 (significantly hotter than the surrounding tissue). Sensitivity and specificity were calculated for each stratum. Logistical challenges were scored. IR imaging was able to determine the malignancy of small (0-5 mm) lesions with a sensitivity of 39% and specificity of 100%. For lesions >5-15 mm, sensitivity was 58% and specificity 98%. For lesions >15-30 mm, sensitivity was 95% and specificity 100%, and for lesions >30 mm, sensitivity was 78% and specificity 89%. The positive predictive value was 88%-100% across all strata, and the negative predictive value was 95% for >15-30 mm lesions and 80% for >30 mm lesions. Malignant lesions >15 mm were differentiated from benign lesions with excellent sensitivity and specificity. IR imaging was well tolerated and feasible in a clinic setting. This pilot study shows promise in the use of thermography for the diagnosis of malignant melanoma with further potential as a noninvasive tool to follow tumor responses to systemic therapies. Copyright © 2013. Published by Elsevier Inc.

  4. INFRARED THERMOGRAPHY OF CUTANEOUS MELANOMA METASTASES

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    Shada, Amber L.; Dengel, Lynn T.; Petroni, Gina R.; Smolkin, Mark E.; Acton, Scott; Slingluff, Craig L.

    2014-01-01

    Background Differentiating melanoma metastasis from benign cutaneous lesions currently requires biopsy or costly imaging, such as positron emission tomography scans. Melanoma metastases have been observed to be subjectively warmer than similarly appearing benign lesions. We hypothesized that infrared (IR) thermography would be sensitive and specific in differentiating palpable melanoma metastases from benign lesions. Materials and methods Seventy-four patients (36 females and 38 males) had 251 palpable lesions imaged for this pilot study. Diagnosis was determined using pathologic confirmation or clinical diagnosis. Lesions were divided into size strata for analysis: 0–5, >5–15, >15–30, and >30 mm. Images were scored on a scale from −1 (colder than the surrounding tissue) to +3 (significantly hotter than the surrounding tissue). Sensitivity and specificity were calculated for each stratum. Logistical challenges were scored. Results IR imaging was able to determine the malignancy of small (0–5 mm) lesions with a sensitivity of 39% and specificity of 100%. For lesions >5–15 mm, sensitivity was 58% and specificity 98%. For lesions >15–30 mm, sensitivity was 95% and specificity 100%, and for lesions >30 mm, sensitivity was 78% and specificity 89%. The positive predictive value was 88%–100% across all strata, and the negative predictive value was 95% for >15–30 mm lesions and 80% for >30 mm lesions. Conclusions Malignant lesions >15 mm were differentiated from benign lesions with excellent sensitivity and specificity. IR imaging was well tolerated and feasible in a clinic setting. This pilot study shows promise in the use of thermography for the diagnosis of malignant melanoma with further potential as a noninvasive tool to follow tumor responses to systemic therapies. PMID:23043862

  5. Defining the dermoscopic characteristics of fast-growing cutaneous melanomas.

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    Tejera-Vaquerizo, Antonio; Arias-Santiago, Salvador; Nagore, Eduardo; Martín-Cuevas, Paula; Orgaz-Molina, Javier; Traves, Victor; Herrera-Acosta, Enrique; Naranjo-Sintes, Ramón; Guillén, Carlos; Herrera-Ceballos, Enrique

    2015-06-01

    A high growth rate in melanomas has been associated with a more aggressive phenotype and worse survival. The aim of this study was to define the dermoscopic characteristics associated with this type of cutaneous melanoma. We carried out a retrospective study of 132 cutaneous melanomas, analyzing certain clinical characteristics and the most important dermoscopic variables related to the melanomas. Fast-growing melanomas were considered to be those with a growth rate of more than 0.5 mm per month. Fast-growing melanomas more often lacked an atypical network, were symmetrical, presented ulceration, and were hypopigmented. The dermoscopic vascular pattern often showed atypical irregular vessels and milky-red areas. The association of these two is a specific characteristic. Fast-growing melanomas have a characteristic phenotype and dermoscopy can be useful for their identification.

  6. BAP1 PLAYS A SURVIVAL ROLE IN CUTANEOUS MELANOMA

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    Kumar, Raj; Taylor, Michael; Miao, Benchun; Ji, Zhenyu; Njauw, Jenny Ching-Ni; Jönsson, Göran; Frederick, Dennie Tompers; Tsao, Hensin

    2014-01-01

    Although the pattern of BAP1 inactivation in ocular melanoma specimens and in the BAP1 cutaneous/ocular melanoma (CM/OM) predisposition syndrome suggests a tumor suppressor function, the specific role of this gene in the pathogenesis of cutaneous melanoma is not fully understood. We thus set out to characterize BAP1 in cutaneous melanoma and discovered an unexpected pro-survival effect of this protein. Tissue and cell lines analysis showed that BAP1 expression was maintained, rather than lost, in primary melanomas compared to nevi and normal skin. Genetic depletion of BAP1 in melanoma cells reduced proliferation and colony forming capability, induced apoptosis and inhibited melanoma tumor growth in vivo. On the molecular level, suppression of BAP1 led to a concomitant drop in the protein levels of survivin a member of anti-apoptotic proteins and a known mediator of melanoma survival. Restoration of survivin in melanoma cells partially rescued the growth-retarding effects of BAP1 loss. In contrast to melanoma cells, stable overexpression of BAP1 into immortalized but non-transformed melanocytes did suppress proliferation and reduce survivin. Taken together, these studies demonstrate that BAP1 may play a growth-sustaining role in melanoma cells, but that its impact on ubiquitination underpins a complex physiology which is context and cell dependent. PMID:25521456

  7. POLE mutations in families predisposed to cutaneous melanoma

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    Aoude, Lauren G; Heitzer, Ellen; Johansson, Peter

    2015-01-01

    Germline mutations in the exonuclease domain of POLE have been shown to predispose to colorectal cancers and adenomas. POLE is an enzyme involved in DNA repair and chromosomal DNA replication. In order to assess whether such mutations might also predispose to cutaneous melanoma, we interrogated...... whole-genome and exome data from probands of 34 melanoma families lacking pathogenic mutations in known high penetrance melanoma susceptibility genes: CDKN2A, CDK4, BAP1, TERT, POT1, ACD and TERF2IP. We found a novel germline mutation, POLE p.(Trp347Cys), in a 7-case cutaneous melanoma family....... Functional assays in S. pombe showed that this mutation led to an increased DNA mutation rate comparable to that seen with a Pol ε mutant with no exonuclease activity. We then performed targeted sequencing of POLE in 1243 cutaneous melanoma cases and found that a further ten probands had novel or rare...

  8. Lymphatic invasion and the Shields index in predicting melanoma metastases.

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    Špirić, Zorica; Erić, Mirela; Eri, Živka

    2017-11-01

    Findings of the prognostic significance of lymphatic invasion are contradictory. To determine an as efficient cutaneous melanoma metastasis predictor as possible, Shields et al. created a new prognostic index. This study aimed to examine whether the lymphatic invasion analysis and the Shields index calculation can be used in predicting lymph node status in patients with cutaneous melanoma. Lymphatic invasion of 100 melanoma specimens was detected by dual immunohistochemistry staining for the lymphatic endothelial marker D2-40 and melanoma cell S-100 protein. The Shields index was calculated as a logarithm by multiplying the melanoma thickness, square of peritumoural lymphatic vessel density and the number "2" for the present lymphatic invasion. No statistically significant difference was observed between lymph node metastatic and nonmetastatic melanomas regarding the lymphatic invasion. Metastatic melanomas showed a significantly higher Shields index value than nonmetastatic melanomas (p = 0.00). Area under the receiver operator characteristic (ROC) curve (AUC) proved that the Shields index (AUC = 0.86, 95% confidence interval (CI) 0.79-0.93, p = 0.00) was the most accurate predictor of lymph node status, followed by the melanoma thickness (AUC = 0.76, 95% CI 0.67-0.86, p = 0.00) and American Joint Committee on Cancer (AJCC) staging (AUC = 0.75, 95% CI 0.66-0.85, p = 0.00), while lymphatic invasion was not successful in predicting (AUC = 0.56, 95% CI 0.45-0.67, p = 0.31). The Shields index achieved 81.3% sensitivity and 75% specificity (cut-off mean value). Our findings show that D2-40/S-100 immunohistochemical analysis of lymphatic invasion cannot be used for predicting the lymph node status, while the Shields index calculation predicts disease outcome more accurately than the melanoma thickness and AJCC staging. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights

  9. CDKN2A (INK4A-ARF) mutation analysis to distinguish cutaneous melanoma metastasis from a second primary melanoma.

    NARCIS (Netherlands)

    Blokx, W.A.M.; Lesterhuis, W.J.; Andriessen, M.P.M.; Verdijk, M.A.J.; Punt, C.J.A.; Ligtenberg, M.J.L.

    2007-01-01

    The histologic differential diagnosis between a second primary cutaneous melanoma and cutaneous melanoma metastasis in a patient with a previous history of melanoma can be very difficult. This case report describes the first application of CDKN2A mutation analysis for discriminating a cutaneous

  10. CDKN2A (INK4A-ARF) mutation analysis to distinguish cutaneous melanoma metastasis from a second primary melanoma

    NARCIS (Netherlands)

    Blokx, Willeke A. M.; Lesterhuis, W. Joost; Andriessen, Monique P. M.; Verdijk, Marian A. J.; Punt, Cornelis J. A.; Ligtenberg, Marjolijn J. L.

    2007-01-01

    The histologic differential diagnosis between a second primary cutaneous melanoma and cutaneous melanoma metastasis in a patient with a previous history of melanoma can be very difficult. This case report describes the first application of CDKN2A mutation analysis for discriminating a cutaneous

  11. Cutaneous melanoma primary site is linked to nevus density.

    Science.gov (United States)

    Martin-Gorgojo, Alejandro; Llinares, Marta; Virós, Amaya; Requena, Celia; Garcia-Casado, Zaida; Traves, Víctor; Kumar, Rajiv; Nagore, Eduardo

    2017-11-17

    There are at least two pathways driving cutaneous melanoma; one is linked to an inherent melanoma susceptibility to nevi development and the second to environmental cumulative ultraviolet light exposure. In this study, we examined the relation between nevus density, accrued sun damage and the site of primary melanoma excision. In a series of 888 consecutive cutaneous melanoma patients, melanomas appearing in skin areas with a high relative nevus density were most prominent in men, with an elevated nevus count, at sites without solar elastosis, but with an epidemiological history of previous sunburn. The present study associates melanoma development to sites with high nevus density. Our study supports more careful surveillance of body areas with increased nevus density in patients with high total body number of nevi, especially when they report a history of sunburns at these sites.

  12. Sunbed use, Sunscreen use, Childhood Sun Exposure, and Cutaneous Melanoma

    NARCIS (Netherlands)

    P.J.M. Autier (Philippe)

    2011-01-01

    textabstractCancer registries established after World War II show that in most light‐skinned populations, the incidence of malignant cutaneous melanoma (hereafter termed melanoma) has steadily increased. In the 1970s and 1980s, laboratory and epidemiological studies documented the possibility

  13. Role of epithelial-mesenchymal transition involved molecules in the progression of cutaneous melanoma.

    Science.gov (United States)

    Murtas, Daniela; Maxia, Cristina; Diana, Andrea; Pilloni, Luca; Corda, Claudia; Minerba, Luigi; Tomei, Sara; Piras, Franca; Ferreli, Caterina; Perra, Maria Teresa

    2017-12-01

    Epithelial-mesenchymal transition (EMT) has been suggested to have a driving role in the acquisition of a metastatic potential by melanoma cells. Important hallmarks of EMT include both E-cadherin downregulation and increased expression of N-cadherin. This switch in distinct classes of adhesion molecules leads melanoma cells to lose contact with adjacent keratinocytes and interact instead with stromal fibroblasts and endothelial cells, thus promoting dermal and vascular melanoma invasion. Consequently, tumor cells migrate to distant host tissues and establish metastases. A key regulator in the induction of EMT in melanoma is the Notch1 signaling pathway that, when activated, is prompt to upregulate N-cadherin expression. By means of this strategy, melanoma cells gain enhanced survival, proliferation and invasion properties, driving the tumor toward a more aggressive phenotype. On the basis of these statements, the present study aimed to investigate the possible association between N-cadherin and Notch1 presence in primary cutaneous melanomas and lymph node metastases. Our results from immunohistochemical analysis confirmed a positive correlation between N-cadherin and Notch1 presence in the same tumor samples. Moreover, this study highlighted that a concomitant high expression of N-cadherin and Notch1, both in primary lesions and in lymph node metastases, predicts an adverse clinical outcome in melanoma patients. Therefore, N-cadherin and Notch1 co-presence can be monitored as a predictive factor in early- and advanced-stage melanomas and open additional therapeutic targets for the restraint of melanoma metastasis.

  14. Decreased expression of hyaluronan synthase 1 and 2 associates with poor prognosis in cutaneous melanoma.

    Science.gov (United States)

    Poukka, Mari; Bykachev, Andrey; Siiskonen, Hanna; Tyynelä-Korhonen, Kristiina; Auvinen, Päivi; Pasonen-Seppänen, Sanna; Sironen, Reijo

    2016-05-16

    Hyaluronan is a large extracellular matrix molecule involved in several biological processes such as proliferation, migration and invasion. In many cancers, hyaluronan synthesis is altered, which implicates disease progression and metastatic potential. We have previously shown that synthesis of hyaluronan and expression of its synthases 1-2 (HAS1-2) decrease in cutaneous melanoma, compared to benign melanocytic lesions. In the present study, we compared immunohistological staining results of HAS1 and HAS2 with clinical and histopathological parameters to investigate whether HAS1 or HAS2 has prognostic value in cutaneous melanoma. The specimens consisted of 129 tissue samples including superficial (Breslow ≤ 1 mm) and deep (Breslow > 4 mm) melanomas and lymph node metastases. The differences in immunostainings were analysed with non-parametric Mann-Whitney U test. Associations between immunohistological staining results and clinical parameters were determined with the χ(2) test. Survival between patient groups was compared by the Kaplan-Meier method using log rank test and Cox's regression model was used for multivariate analyses. The expression of HAS1 and HAS2 was decreased in deep melanomas and metastases compared to superficial melanomas. Decreased immunostaining of HAS2 in melanoma cells was significantly associated with several known unfavourable histopathologic prognostic markers like increased mitotic count, absence of tumor infiltrating lymphocytes and the nodular subtype. Furthermore, reduced HAS1 and HAS2 immunostaining in the melanoma cells was associated with increased recurrence of melanoma (p = 0.041 and p = 0.006, respectively) and shortened disease- specific survival (p = 0.013 and p = 0.001, respectively). This study indicates that reduced expression of HAS1 and HAS2 is associated with melanoma progression and suggests that HAS1 and HAS2 have a prognostic significance in cutaneous melanoma.

  15. Optic nerve invasion of uveal melanoma

    DEFF Research Database (Denmark)

    Lindegaard, Jens; Isager, Peter; Prause, Jan Ulrik

    2007-01-01

    The aim of the study was to identify the histopathological characteristics associated with the invasion of the optic nerve of uveal melanoma and to evaluate the association between invasion of the optic nerve and survival. In order to achieve this, all uveal melanomas with optic nerve invasion...... in Denmark between 1942 and 2001 were reviewed (n=157). Histopathological characteristics and depth of optic nerve invasion were recorded. The material was compared with a control material from the same period consisting of 85 cases randomly drawn from all choroidal/ciliary body melanomas without optic nerve...... invasion. Prelaminar/laminar optic nerve invasion was in multivariate analysis associated with focal retinal invasion, neovascularization of the chamber angle, and scleral invasion. Postlaminar invasion was further associated with non-spindle cell type and rupture of the inner limiting membrane...

  16. Sunbed use and cutaneous melanoma in Norway.

    Science.gov (United States)

    Moan, Johan E; Baturaite, Zivile; Grigalavicius, Mantas; Juzeniene, Asta

    2013-12-01

    Incidence rates of cutaneous melanoma (CM) in light skinned people in Norway are among the highest in the world. Sunbed use has increased in Norway since 1980. We will try to elucidate whether there is any correlation between the increase in sunbed use and the CM incidence rates, whether the increase in CM risk is similar for all age groups, and whether the possible difference between young and old persons can inform future healthcare strategies. The frequency of sunbed use by different age groups in the time period 1980-2011 and incidence rates (1980-2009) of CM at different age groups in Norway were studied. Time in minutes per day spent in front of screen of computers or TVs for boys and girls was also analysed. The number of sunbed sessions per year in Norway increased throughout the entire period. The number of men and women diagnosed with CM per year, all ages combined, also increased. Sunbed use increased at a similar rate for three age groups (0-19, 20-50, and >50 years old), while the age-adjusted CM incidence rate increased only for the oldest group. Time spent in front of the screen of computers or TVs increased from 1985 to 2005 and is still increasing. CM incidence is decreasing while sunbed use is increasing in younger age groups. The present data indicate that more work needs to be done before one can know whether the overall health effects of sunbed exposure are positive or negative.

  17. Worldwide Increasing Incidences of Cutaneous Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Dianne E. Godar

    2011-01-01

    Full Text Available The incidence of cutaneous malignant melanoma (CMM has been increasing at a steady rate in fair-skinned populations around the world for decades. Scientists are not certain why CMM has been steadily increasing, but strong, intermittent UVB (290–320 nm exposures, especially sunburn episodes, probably initiate, CMM, while UVA (321–400 nm passing through glass windows in offices and cars probably promotes it. The CMM incidence may be increasing at an exponential rate around the world, but it definitely decreases with increasing latitude up to ~50°N where it reverses and increases with the increasing latitude. The inversion in the incidence of CMM may occur because there is more UVA relative to UVB for most of the year at higher latitudes. If windows, allowing UVA to enter our indoor-working environment and cars, are at least partly responsible for the increasing incidence of CMM, then UV filters can be applied to reduce the rate of increase worldwide.

  18. Prognostic significance of ALCAM (CD166/MEMD) expression in cutaneous melanoma patients.

    Science.gov (United States)

    Donizy, Piotr; Zietek, Marcin; Halon, Agnieszka; Leskiewicz, Marek; Kozyra, Cyprian; Matkowski, Rafal

    2015-07-02

    ALCAM (activated leukocyte cell adhesion molecule, CD166, MEMD) is a transmembrane protein of immunoglobulin superfamily (Ig-SF) and plays an important role in human malignant melanoma progression and formation of locoregional and distant metastases. The study using melanoma cell lines showed that overexpression of ALCAM is directly related with the increase of cytoaggregation and the ability to form cell nests. The aim of the study was to assess the expression and intracellular localization of ALCAM in primary skin melanomas and metastatic lesions from regional lymph nodes. Also, prognostic significance of ALCAM expression in primary tumor cells and metastatic lesion cells was evaluated in the context of 5-year observation. Formalin-fixed paraffin-embedded tissue specimens from 104 primary cutaneous melanomas and 16 regional lymph nodes metastases were studied for the expression of ALCAM measured by immunohistochemistry. We demonstrate that high ALCAM expression in primary melanoma cells (IRS ≥8) is strongly correlated with unfavorable prognosis as compared with patients with lower ALCAM immunoreactivity in tumor compartment as regards cancer specific overall survival (CSOS) (P = 0.001) and disease free survival (DFS) (P melanoma invasion in the primary tumor according to Clark scale (P = 0.032). It was also found that decreased ALCAM expression (IRS melanoma cells of the primary tumor can be used as a marker of negative outcome and may indicate a more invasive phenotype of cancer cells, which would require a more intensive therapeutic strategy. Low expression of ALCAM in regional lymph node metastases is a feature associated with unfavorable prognosis in patients with cutaneous melanoma. Our study is the first one to evaluate the effect of increased ALCAM expression on long-term survival in melanoma patients.

  19. Presence of histological regression as a prognostic factor in cutaneous melanoma patients.

    Science.gov (United States)

    Tas, Faruk; Erturk, Kayhan

    2016-10-01

    Regression is caused by a host immunological response primarily characterized by lymphocytic infiltration directed against melanoma cells. The prognostic significance of regression remains controversial in cutaneous melanoma patients. The aim of this study was to determine the clinical significance of the histological regression status in patients with cutaneous melanoma. A total of 664 patients with a pathologically confirmed cutaneous melanoma were enrolled into this study and were investigated retrospectively. The median age of the patients was 51 years, ranging in age from 16 to 104 years. The majority of them had lesions without regression (n=495; 74.5%) and others had lesions with regression (n=169; 25.5%). Melanoma patients with regression were more frequently males (60.1 vs 51.7%; P=0.038) and had axial localized lesions (67.5 vs 53.7%; P=0.002), superficial spreading histologic subtype (73.2 vs 49.1%; P=0.000), thin Breslow depth (nodular pathology, advanced Clark invasion level (IV-V), thick Breslow depth (≥2 mm), high mitotic rate (>3/mm), ulceration, vertical growth phase, neurotropism, lymphovascular invasion, lymph node involvement, metastasis, and recurrence of disease, and male patients had poor prognostic variables for both relapse-free survival and overall survival. However, the presence of regression was not associated with relapse-free survival (P=0.093) nor overall survival (P=0.113) similar to other factors such as age, tumor localization, tumor-infiltrating lymphocytes, and association with a pre-existing melanocytic nevus. Similar insignificant P values were also observed in multivariate analyses (P=0.115 and 0.816, respectively). In conclusion, the presence of histological regression plays no prognostic role in nodal involvement nor survival in patients with cutaneous melanoma.

  20. Cutaneous melanomas in rabbits: rare but often fatal

    Directory of Open Access Journals (Sweden)

    Martin Hammer

    2011-10-01

    Full Text Available An adult male dwarf rabbit (Oryctolagus cuniculus was presented to the veterinarian due to hind limb lameness. The rabbit was in a reduced body condition. Clinical examination and cytology identified a cutaneous melanoma in the inguinal region. Whole body radiographs identified multifocal radio-opaque masses in both lungs which where assumed to be lung metastases. The animal was euthanized due to the poor prognosis. Necropsy confirmed a malignant, melanotic melanoma with pulmonary and hepatic metastases. Histopathologically, the primary tumor and the metastases were composed of epitheloid cells which showed infiltrative growth. The rabbit was diagnosed with metastatic, cutaneous, melanotic melanoma. Melanomas in rabbits can be recognized as highly malignant independent on their pigmentation status. Pulmonary tropism seems to be a distinct feature of this tumor type in rabbits and indicates that a comprehensive diagnostic workup is necessary to avoid anesthesia-related incidents.

  1. SOLAR RADIATION AS A RISK FACTOR FOR CUTANEOUS MELANOMA: REVIEW

    Directory of Open Access Journals (Sweden)

    Marianna Pesce

    2013-04-01

    Full Text Available Melanoma is a particularly aggressive type of skin cancer, and its incidence has been increasing steadily since the 1970s. In this article we have reviewed the main risk factors for this disease in particular: sun exposure, the use of tanning beds or sunlamps and skin phototype. We also mention the importance of primary prevention in subjects at risk to reduce the onset of cutaneous melanoma.

  2. Cutaneous malignant melanoma arising in an acquired naevus of Ota.

    Science.gov (United States)

    Patterson, Clare R S; Acland, Katharine; Khooshabeh, Ramona

    2009-11-01

    Naevus of Ota is a dermal melanocytosis most commonly found in black or Asian skin and is usually a benign malformation, but with a low risk of melanoma. We describe a 32-year-old Caucasian man with an acquired naevus of Ota with subtle pigmentation, in which a melanocytic papule developed. The lesion, deceptively, had no clinically suspicious features, but investigation revealed an aggressive cutaneous malignant melanoma, extensive orbital ring melanocytosis and metastatic brain and subsequent liver disease.

  3. BAP1 has a survival role in cutaneous melanoma.

    Science.gov (United States)

    Kumar, Raj; Taylor, Michael; Miao, Benchun; Ji, Zhenyu; Njauw, Jenny C-N; Jönsson, Göran; Frederick, Dennie T; Tsao, Hensin

    2015-04-01

    Although the pattern of BAP1 inactivation in ocular melanoma specimens and in the BAP1 cutaneous melanoma (CM)/ocular melanoma predisposition syndrome suggests a tumor suppressor function, the specific role of this gene in the pathogenesis of CM is not fully understood. We thus set out to characterize BAP1 in CM and discovered an unexpected pro-survival effect of this protein. Tissue and cell lines analysis showed that BAP1 expression was maintained, rather than lost, in primary melanomas compared with nevi and normal skin. Genetic depletion of BAP1 in melanoma cells reduced proliferation and colony-forming capability, induced apoptosis, and inhibited melanoma tumor growth in vivo. On the molecular level, suppression of BAP1 led to a concomitant drop in the protein levels of survivin, a member of anti-apoptotic proteins and a known mediator of melanoma survival. Restoration of survivin in melanoma cells partially rescued the growth-retarding effects of BAP1 loss. In contrast to melanoma cells, stable overexpression of BAP1 into immortalized but non-transformed melanocytes did suppress proliferation and reduce survivin. Taken together, these studies demonstrate that BAP1 may have a growth-sustaining role in melanoma cells, but that its impact on ubiquitination underpins a complex physiology, which is context and cell dependent.

  4. Serum level of vitamin D3 in cutaneous melanoma

    Science.gov (United States)

    de Oliveira, Renato Santos; de Oliveira, Daniel Arcuschin; Martinho, Vitor Augusto Melão; Antoneli, Célia Beatriz Gianotti; Marcussi, Ludmilla Altino de Lima; Ferreira, Carlos Eduardo dos Santos

    2014-01-01

    Objective To compare the level of vitamin D3 in cutaneous melanoma patients, with or without disease activity, with reference values and with patients from a general hospital. Methods The serum levels of vitamin D3 were measured in cutaneous melanoma patients, aged 20 to 88 years, both genders, from January 2010 to December 2013. The samples from the general group were processed at Hospital Israelita Albert Einstein (control group). Data analysis was performed using the Statistics software. Results A total of 100 patients were studied, 54 of them men, with mean age of 54.67 years, and 95 Caucasian. Out of these 100 patients, 17 had active disease. The average levels of vitamin D3 in the melanoma patients were lower than the level considered sufficient, but above the average of the control group. Both groups (with or without active disease) of patients showed a similar distribution of vitamin D3 deficiency. Conclusion Vitamin D3 levels in melanoma patients were higher than those of general patients and lower than the reference level. If the reference values are appropriate, a large part of the population had insufficient levels of vitamin D, including those with melanoma, or else, this standard needs to be reevaluated. No difference in vitamin D3 levels was found among melanoma patients with or without active disease. More comprehensive research is needed to assess the relation between vitamin D and melanoma. PMID:25628199

  5. Genomic analysis and clinical management of adolescent cutaneous melanoma.

    Science.gov (United States)

    Rabbie, Roy; Rashid, Mamunur; Arance, Ana M; Sánchez, Marcelo; Tell-Marti, Gemma; Potrony, Miriam; Conill, Carles; van Doorn, Remco; Dentro, Stefan; Gruis, Nelleke A; Corrie, Pippa; Iyer, Vivek; Robles-Espinoza, Carla Daniela; Puig-Butille, Joan A; Puig, Susana; Adams, David J

    2017-05-01

    Melanoma in young children is rare; however, its incidence in adolescents and young adults is rising. We describe the clinical course of a 15-year-old female diagnosed with AJCC stage IB non-ulcerated primary melanoma, who died from metastatic disease 4 years after diagnosis despite three lines of modern systemic therapy. We also present the complete genomic profile of her tumour and compare this to a further series of 13 adolescent melanomas and 275 adult cutaneous melanomas. A somatic BRAF V 600E mutation and a high mutational load equivalent to that found in adult melanoma and composed primarily of C>T mutations were observed. A germline genomic analysis alongside a series of 23 children and adolescents with melanoma revealed no mutations in known germline melanoma-predisposing genes. Adolescent melanomas appear to have genomes that are as complex as those arising in adulthood and their clinical course can, as with adults, be unpredictable. © 2017 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.

  6. Clinicopathological characteristics and mutation profiling in primary cutaneous melanoma.

    Science.gov (United States)

    Yaman, Banu; Akalin, Taner; Kandiloğlu, Gülşen

    2015-05-01

    The incidence of mutations in malignant melanoma varies remarkably according to the subtype of melanoma, and this in itself is affected by racial and geographical factors. Studies screening melanoma case series for different types of mutations are relatively rare. The authors analyzed the frequency of various somatic point mutations of 10 genes in 106 primary cutaneous melanoma cases. The mutations (BRAF, NRAS, KIT, CDKN2A, KRAS, HRAS, PIK3CA, STK11, GNAQ, CTNNB1) were evaluated with real-time PCR-based PCR-Array through allele-specific amplification, and the results were correlated with various clinicopathological characteristics. Mutations were found in 64.2% of the melanomas overall. BRAF (42.5%), NRAS (15.1%), and CDKN2A (13.2%) were the 3 most common mutations. BRAF and NRAS mutations were more frequent in nodular and superficial spreading melanomas (P < 0.001). Associations with BRAF mutation were as follows: male gender [odds ratio (OR) = 2.4], younger age (OR = 2.7), superficial spreading (OR = 15.6) and nodular melanoma (OR = 9.5), trunk localization (OR = 6.3), and intermittent sun exposure (OR = 4.6). A considerable percentage of V600K (44.4%) mutations were found among the BRAF mutations, whereas KIT mutations (3.8%) were less frequent. Multiple mutations were detected in 13.2% of the melanomas. The most common co-occurrences were in the BRAF, NRAS, and CDKN2A genes. The authors analyzed 10 somatic mutations in the main subtypes of primary cutaneous melanomas from the western region of Turkey. Mutations were found in 64.2% of the melanomas overall. The most common mutations were in the BRAF and NRAS genes. In addition to other less common mutations, a notable number of multiple mutations were encountered. The multiplicity and concurrence of mutations in this study may provide further study areas for personalized targeted therapy.

  7. Prognosis of thin cutaneous head and neck melanoma (

    DEFF Research Database (Denmark)

    Andersson, A P; Dahlstrøm, Karin Kjærgaard; Drzewiecki, K T

    1996-01-01

    Thin malignant melanomas, i.e. tumours less than 1 mm, are generally considered to have a good prognosis. The records of 148 patients with thin invasive melanomas located to the head and neck region were reviewed. All patients were followed for the excision of the primary tumour until death, or t...

  8. Socioeconomic status and cutaneous malignant melanoma in Northern Europe

    DEFF Research Database (Denmark)

    Idorn, L W; Wulf, H C

    2014-01-01

    Socioeconomic status (SES) is associated with cutaneous malignant melanoma (CMM), also in Northern Europe despite equal access to health care. SES per se is not responsible for this association which must be ascribed to important risk factors for CMM such as intermittent UVR exposure, and screening...

  9. Some interesting prognostic factors related to cutaneous malignant melanoma

    International Nuclear Information System (INIS)

    Figueroa, Alejandro Yuri Joan; Diaz Anaya, Amnia; Montero Leon, Jorge Felipe; Jimenez Mendes, Lourdes

    2009-01-01

    The aim of present research was to determine the independent prognostic value and the 3 and 5 years survival of more significant clinicopathological prognostic factors and in each stage, according to pathological staging system of tumor-nodule-metastasis (TNM) in patients with cutaneous malignant melanoma (CMM)

  10. Pattern of cutaneous malignant melanoma in Zaria, Nigeria ...

    African Journals Online (AJOL)

    The histopathological patterns of distribution, presence of dark brown melanin pigments, nucleolar appearance and Clark's histological grading were studied. The data was analysed and tabulated into frequency tables. Results: Fifty four cases of cutaneous malignant melanoma were reviewed. The over all male: female sex ...

  11. Cutaneous malignant melanoma metastatic to the eye, lids, and orbit.

    Science.gov (United States)

    Rosenberg, Caroline; Finger, Paul T

    2008-01-01

    The incidence of malignant cutaneous melanoma is increasing faster than any other cancer. Thus, it will become an increasingly common source of metastatic disease to the eye, lids, and orbit. Herein, we have performed a systematic review of previously published cases including patient characteristics, clinical presentation, diagnostic techniques, current treatments, and outcomes. At the time of ocular diagnosis, nearly all reported patients had a known history of cutaneous melanoma and synchronous non-ocular metastases. Several aspects help in differentiating the tumors from primary uveal melanomas such as the presence of symptoms, rapidly growing multifocal tumors, vitreous seeding, and histopathological findings. Intraocular metastases (uvea, vitreous, retina, and anterior-segment) are more common and occur in younger patients than extraocular metastases (eyelids, orbit, and extraocular muscles). Palliative radiation therapy is often used for intraocular disease. Orbital metastases from cutaneous melanoma commonly involve the extraocular muscles resulting in diplopia and exophthalmos. The mainstays of extraocular treatment are surgical resection and radiation therapy. Unfortunately, there are few good options for systemic treatment of diffusely metastatic melanoma. Therefore, patients with ocular metastasis should be managed to prevent loss of vision or loss of the eye, and to maximize their quality of life.

  12. Tumor-infiltrating CD8+ lymphocytes effect on clinical outcome of muco-cutaneous melanoma

    Directory of Open Access Journals (Sweden)

    Mahtab Rahbar

    2015-01-01

    Full Text Available Background: Recent data have changed our views of prognostic factors in cutaneous melanoma, while some newer methods have yielded better prognostic information. Tumor-infiltrating lymphocytes are believed to represent the immune reaction/response to melanoma cells which is often found in melanocytic cancer. Aim and Objective: We carried out an analysis, aiming to establish pooled estimates for clinical outcomes based on the presence of CD8+ T cell in melanocytic cancer. Materials and Methods: We have included 42 patients with primary cutaneous melanocytic cancer without preoperative treatments in our study. We next analyzed the proliferative activity of CD8+ T cells that infiltrated in tumor cell nests. The intratumoral and adjacent to invasive margin of tumor CD+ T-cell infiltration were analyzed which could also reflect antitumor immunity. Results: The total number of CD8+ cells especially adjacent to invasive margin of tumor was positively correlated with anatomical tumor thickness (P < .001 and not correlated with patient′s age and sex. The stage of tumor which is related to vascular-neural invasion, regional lymph nodes involvement and tumor thickness shows positive correlation with CD8+ infiltration in tumor (P < .004, P < .005, P < .001, respectively. Acral melanoma shows more CD8 lymphocytes infiltration and also recurrence rate of tumor (P < .005. Conclusion: We believe that CD8+ T-cell infiltration in primary cutaneous melanocytic cancer represents the immune reaction/response to melanoma which could be an important new therapy for melanoma although more research is needed on this treatment modality.

  13. Progression of cutaneous melanoma: implications for treatment

    Science.gov (United States)

    Leong, Stanley P. L.; Mihm, Martin C.; Murphy, George F.; Hoon, Dave S. B.; Kashani-Sabet, Mohammed; Agarwala, Sanjiv S.; Zager, Jonathan S.; Hauschild, Axel; Sondak, Vernon K.; Guild, Valerie; Kirkwood, John M.

    2015-01-01

    The survival rates of melanoma, like any type of cancer, become worse with advancing stage. Spectrum theory is most consistent with the progression of melanoma from the primary site to the in-transit locations, regional or sentinel lymph nodes and beyond to the distant sites. Therefore, early diagnosis and surgical treatment before its spread is the most effective treatment. Recently, new approaches have revolutionized the diagnosis and treatment of melanoma. Genomic profiling and sequencing will form the basis for molecular taxonomy for more accurate subgrouping of melanoma patients in the future. New insights of molecular mechanisms of metastasis are summarized in this review article. Sentinel lymph node biopsy has become a standard of care for staging primary melanoma without the need for a more morbid complete regional lymph node dissection. With recent developments in molecular biology and genomics, novel molecular targeted therapy is being developed through clinical trials. PMID:22892755

  14. A retrospective multicenter evaluation of cutaneous melanomas in Turkey.

    Science.gov (United States)

    Gamsizkan, Mehmet; Yilmaz, Ismail; Buyukbabani, Nesimi; Demirkesen, Cuyan; Demiriz, Murat; Cetin, Emel Dikicioglu; Ince, Umit; Akalin, Taner; Demirkan, Nese Calli; Lebe, Banu; Erdem, Ozlem; Gokoz, Ozay; Sakiz, Damlanur; Demireli, Peyker Temiz; Astarci, Hesna Muzeyyen; Adim, Saduman Balaban; Zemheri, Itir Ebru; Acikalin, Arbil; Yaman, Banu; Aydin, Ovgu; Bassorgun, Cumhur Ibrahim

    2014-01-01

    We defined melanoma distribution in a large series of Turkish patients and evaluated the prognostic parameters of melanomas. A total of 1574 patients' data was retrospectively collected at 18 centers in Turkey. Demographic characteristics were questioned and noted. Prognostic parametres were evaluated based on sentinel lymph node involvement. Mean age was 56.7 (4-99) years. While 844 (53.6%) cases were male, 730 (46.4%) cases were female. One thousand four hundred forty-seven (92%) cases were invasive melanoma and 127 (8%) cases were in-situ melanoma. The most common histopathological form was the superficial spreading melanoma (SSM) which was found in 549 patients (37.9%). It was followed by nodular melanoma in 379 (26.2%), acral lentiginous melanoma (ALM) in 191 (13.2%) and lentigo maligna melanoma in 132 (9.1%), respectively. On univariate analysis, lymphovascular invasion (pmelanoma lesions' thickness were greater than 2 mm, corresponding Clark IV. Vascular invasion and tumor thickness are the most important factors for sentinel lymph node involvement.

  15. Chronology of metastasis in cutaneous melanoma: growth rate model.

    Science.gov (United States)

    Tejera-Vaquerizo, Antonio; Nagore, Eduardo; Meléndez, Juan J; López-Navarro, Norberto; Martorell-Calatayud, Antonio; Herrera-Acosta, Enrique; Traves, Victor; Guillén, Carlos; Herrera-Ceballos, Enrique

    2012-04-01

    In humans, it is not possible to obtain experimental evidence of when a cancer begins to metastasize. The purpose of this study was to estimate the time of onset of metastatic dissemination in cutaneous melanoma using a model based on its growth rate (GR). The critical time of onset of metastatic dissemination below which no cases of fatal melanomas were seen may be described with a potential function in which this time is inversely proportional to the GR. The critical time of development beyond which a melanoma may metastasize presents great variation. This time was just 1 month for those melanomas with a fast GR, whereas it was over 5 years for those with a very slow GR. Quantitatively, the fastest-growing melanomas began metastasizing with a greater thickness than the slowest-growing melanomas. A correlation exists between the critical time of onset of metastatic potential and the GR of the melanoma. These results may well have relevance to the understanding of mechanisms of tumor dissemination and for the design of future studies on melanomas, irrespective of whether they are basic studies on biomolecular mechamisms or clinical studies.

  16. Risk factors and outcomes of cutaneous melanoma in women less than 50 years of age.

    Science.gov (United States)

    Tellez, Alejandra; Rueda, Steven; Conic, Ruzica Z; Powers, Kristin; Galdyn, Izabela; Mesinkovska, Natasha Atanaskova; Gastman, Brian

    2016-04-01

    Melanoma is the fifth most common cancer in the United States, with recent reports indicating increasing incidence among young women. This study sought to investigate histopathology, staging, risk factors, and outcomes of cutaneous melanoma in women younger than 50 years. All female patients aged up to 49 years with biopsy-proven diagnosis of melanoma between 1988 and 2012 were included. Patients with a follow-up of less than 2 years were excluded. A total of 462 patients were identified, with mean age of 34.7 years. Invasive melanoma was less common in women 19 years of age or younger (P melanoma had a significantly worse prognosis in comparison with a control group of nonpregnant patients, with a 9-fold increase in recurrence (P melanoma for women younger than 50 years suggests that regular skin checks and self-examinations are warranted. In addition, in women given the diagnosis of melanoma during or within 1 year after childbirth, regular follow-up and monitoring for recurrence are recommended. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  17. Age-related characteristics of cutaneous melanoma in a Spanish Mediterranean population.

    Science.gov (United States)

    Montero, Iria; Requena, Celia; Traves, Victor; García-Casado, Zaida; Kumar, Rajiv; Nagore, Eduardo

    2015-07-01

    Melanoma is considered a heterogeneous tumor with genetic and environmental factors involved in its pathogenesis. The impact of these factors varies depending on age. The aim of this study was to characterize the epidemiological, phenotypic, and histological features of patients with melanoma according to three age groups: ≤40, 41-65, and >65 years. A total of 1122 consecutive patients with invasive melanoma definitively treated in our institution since January 2000 were selected from our melanoma database. Epidemiological, phenotypic, and histological data were retrieved and analyzed as a function of age. Female patients predominated in the younger age group. The location of cutaneous malignant melanoma differed with age. In the younger and middle age groups, tumors presented mainly on the trunk, while in the older group they were mainly found on the head/neck. Signs of actinic damage such as actinic keratoses, solar lentigines, or other skin tumors increased with age, while genetic factors such as family history of melanoma or a high number of common melanocytic nevi were more frequent in the younger group. Our results suggest that melanoma development in younger patients is the result of genetic factors, particularly related to multiple nevi, whereas in older patients environmental factors such as severe chronic sun exposure play a major role. © 2015 The International Society of Dermatology.

  18. Psychoeducational intervention for patients with cutaneous malignant melanoma

    DEFF Research Database (Denmark)

    Boesen, Ellen H; Ross, Lone; Frederiksen, Kirsten

    2005-01-01

    PURPOSE: In 1993, a randomized intervention study among patients with malignant melanoma showed a significant decrease in psychological distress and increased coping capacity 6 months after the intervention and enhanced survival 6 years later. We applied a similar intervention with a few modifica...... that a psychoeducational group intervention for such patients can decrease psychological distress and enhance effective coping. However, this effect is short term and the clinical relevance is not obvious.......PURPOSE: In 1993, a randomized intervention study among patients with malignant melanoma showed a significant decrease in psychological distress and increased coping capacity 6 months after the intervention and enhanced survival 6 years later. We applied a similar intervention with a few...... modifications in a randomized controlled trial among Danish patients with malignant melanoma and evaluated results on immediate and long-term effects on psychological distress and coping capacity. PATIENTS AND METHODS: A total of 262 patients with primary cutaneous malignant melanoma were randomly assigned...

  19. Increased NY-ESO-1 expression and reduced infiltrating CD3+ T cells in cutaneous melanoma.

    Science.gov (United States)

    Giavina-Bianchi, Mara; Giavina-Bianchi, Pedro; Sotto, Mirian Nacagami; Muzikansky, Alona; Kalil, Jorge; Festa-Neto, Cyro; Duncan, Lyn M

    2015-01-01

    NY-ESO-1 is a cancer-testis antigen aberrantly expressed in melanomas, which may serve as a robust and specific target in immunotherapy. NY-ESO-1 antigen expression, tumor features, and the immune profile of tumor infiltrating lymphocytes were assessed in primary cutaneous melanoma. NY-ESO-1 protein was detected in 20% of invasive melanomas (16/79), rarely in in situ melanoma (1/10) and not in benign nevi (0/20). Marked intratumoral heterogeneity of NY-ESO-1 protein expression was observed. NY-ESO-1 expression was associated with increased primary tumor thickness (P = 0.007) and inversely correlated with superficial spreading melanoma (P ESO-1 expression was also associated with reduced numbers and density of CD3+ tumor infiltrating lymphocytes (P = 0.017). When NY-ESO-1 protein was expressed, CD3+ T cells were less diffusely infiltrating the tumor and were more often arranged in small clusters (P = 0.010) or as isolated cells (P = 0.002) than in large clusters of more than five lymphocytes. No correlation of NY-ESO-1 expression with gender, age, tumor site, ulceration, lymph node sentinel status, or survival was observed. NY-ESO-1 expression in melanoma was associated with tumor progression, including increased tumor thickness, and with reduced tumor infiltrating lymphocytes.

  20. The chick embryo as an experimental system for melanoma cell invasion.

    Directory of Open Access Journals (Sweden)

    Christian Busch

    Full Text Available BACKGROUND: A primary cutaneous melanoma will not kill the patient, but its metastases. Since in vitro studies on melanoma cells in 2-D cultures do often not reflect reality, 3-D models might come closer to the physiological situation in the patient during cancer initiation and progression. METHODOLOGY/PRINCIPAL FINDINGS: Here, we describe the chick embryo model for in vivo studies of melanoma cell migration and invasion. After transplantation of neural crest-derived melanoma cells into the neural tube, the melanoma cells resume neural crest cell migration along the medial and lateral pathways and finally undergo apoptosis in the target areas. Upon transplantation into ectopic areas such as the hindbrain or the optic cup malignant invasion and local tissue destruction occurs. In contrast, melanocytes are not able to spontaneously resume neural crest cell migration. However, malignant invasion can be induced in melanocytes by pre-treatment with the TGF-beta family members bone morphegenetic protein-2 or nodal. Transplantation of MCF7 breast cancer cells yields a different growth pattern in the rhombencephalon than melanoma cells. CONCLUSIONS/SIGNIFICANCE: The chick embryo model is a feasible, cost-effective in vivo system to study invasion by cancer cells in an embryonic environment. It may be useful to study invasive behavior induced by embryonic oncogenes and for targeted manipulation of melanoma or breast cancer cells aiming at ablation of invasive properties.

  1. Sun exposure before and after a diagnosis of cutaneous malignant melanoma

    DEFF Research Database (Denmark)

    Idorn, L W; Philipsen, P A; Wulf, H C

    2011-01-01

    Previous studies on ultraviolet radiation (UVR) exposure before and after a diagnosis of cutaneous malignant melanoma (CMM) have been based primarily on questionnaires. Objective measures are needed....

  2. Study of melanoma invasion by FTIR spectroscopy

    Science.gov (United States)

    Yang, Y.; Sulé-Suso, J.; Sockalingum, G. D.

    2008-02-01

    Compared to other forms of skin cancer, a malignant melanoma has a high risk of spreading to other parts of the body. Melanoma invasion is a complex process involving changes in cell-extracellular matrix (ECM) interaction and cell-cell interactions. To fully understand the factors which control the invasion process, a human skin model system was reconstructed. HBL (a commercially available cell line) melanoma cells were seeded on a skin model with and without the presence of keratinocytes and/or fibroblasts. After 14 days culture, the skin specimens were fixed, parafin embedded and cut into 7 µm sections. The de-parafinised sections were investigated by synchrotron Fourier transformed infrared (FTIR) microspectroscopy to study skin cell invasion behaviour. The advantage of using FTIR is its ability to obtain the fingerprint information of the invading cells in terms of protein secondary structure in comparison to non-invading cells and the concentration of the enzyme (matrix-metalloproteinase) which digests protein matrix, near the invading cells. With aid of the spectral mapping images, it is possible to pinpoint the cells in non-invasion and invasion area and analyse the respective spectra. It has been observed that the protein bands in cells and matrix shifted between non-invasive and invasive cells in the reconstructed skin model. We hypothesise that by careful analysis of the FTIR data and validation by other models, FTIR studies can reveal information on which type of cells and proteins are involved in melanoma invasion. Thus, it is possible to trace the cell invasion path by mapping the spectra along the interface of cell layer and matrix body by FTIR spectroscopy.

  3. Cutaneous melanoma in Iceland: changing Breslow's tumour thickness.

    Science.gov (United States)

    Stefansson, H; Tryggvadottir, L; Olafsdottir, E J; Mooney, E; Olafsson, J H; Sigurgeirsson, B; Jonasson, J G

    2015-02-01

    The incidence of cutaneous melanoma increased dramatically in Iceland during the last two decades of the 20th century. The aim of this study was to investigate the trend in Breslow's tumour thickness during the years 1980-2009. The population-based Icelandic Cancer Registry provided information on all cutaneous melanomas diagnosed in the country during the study period, a total of 854 cases. Incidence rates were stratified according to gender, age at diagnosis, year of diagnosis and Breslow's tumour thickness. When stratified by gender and age, the incidence of thin (≤1.0 mm) melanomas increased dramatically in all subgroups. The increase in thin (≤1.0 mm) melanomas was more apparent in women or 2.6 per 100,000 in 1980-1989 to 13.3 in 2000-2009 and especially in young (4 mm) did not increase. The median Breslow's thickness declined from 2.15 mm in 1980-1989 to 0.9 mm in 2000-2009 in males and from 1.0 to 0.6 mm in females for the same period (P Iceland should be directed at older individuals, and that older men may need special attention regarding suspicious nevi. © 2014 European Academy of Dermatology and Venereology.

  4. Activated Notch1 expression is associated with angiogenesis in cutaneous melanoma.

    Science.gov (United States)

    Murtas, Daniela; Piras, Franca; Minerba, Luigi; Maxia, Cristina; Ferreli, Caterina; Demurtas, Paolo; Lai, Simone; Mura, Ester; Corrias, Michela; Sirigu, Paola; Perra, Maria Teresa

    2015-08-01

    An early event in melanocytic tumor growth is the upregulation of Notch signaling. When an active form of Notch1 is overexpressed in primary human melanocytes, it increases cell growth, survival and invasive properties, promoting melanoma progression. Recent evidence suggested that tumor initiation and growth are driven by a subset of tumor-initiating cells termed cancer stem cells. Notch1 plays a predominant role in the maintenance of melanoblasts, including melanocyte stem cells, by preventing initiation of apoptosis. Moreover, the importance of Notch1 in the regulation of tumor angiogenesis is supported by growing evidence in various cancers. Nestin has been widely used as a marker for melanocyte stem cells as well as an angiogenic marker to evaluate neovascularity of endothelial cells in tumors. To gain an insight into the impact of Notch1 activation on the maintenance of melanocyte stem cells and angiogenesis in melanoma, the expression levels of activated Notch1 and nestin were analyzed by immunohistochemistry in 114 primary cutaneous melanomas and 35 lymph node metastases. Activated Notch1 and nestin expression was also evaluated in four dysplastic melanocytic nevi. This study provides evidence that activated Notch1 is overexpressed in cutaneous melanoma, in tumor cells as well as in microvessel endothelium, and that it can promote tumor angiogenesis. Indeed, the overexpression of activated Notch1 in both tumor and vascular endothelial cells was significantly associated with microvascular density in melanoma samples. Thus, activated Notch1 inhibitors may provide a therapeutic strategy in the treatment of melanoma by blocking tumor-associated vascularization.

  5. MC1R variants predisposing to concomitant primary cutaneous melanoma in a monozygotic twin pair

    Directory of Open Access Journals (Sweden)

    Pellegrini Cristina

    2012-09-01

    Full Text Available Abstract Background Concomitant primary cutaneous melanoma in monozygotic twins has been reported in only two pairs but in neither of them genetic analysis was performed. Two high-penetrance susceptibility genes, CDKN2A and CDK4 and one low-penetrance gene, MC1R, are well-defined genetic risk factors for melanoma. MITF has been recently identified as a novel intermediate risk melanoma-predisposing gene. Case presentation We describe the extraordinary occurrence of a primary cutaneous invasive melanoma in two 44-year-old identical, female twins, on the same body site within 30 days of each other and report for the first time the genetic analysis of melanoma susceptibility genes in both twins. Data on characteristics of the twins were collected through a standardized questionnaire and skin examination. Exons 1α, 1β, 2 and 3 of CDKN2A, exon 2 of CDK4, the entire open reading frame of MC1R and the recently described MITF c.952 G > A (p.Glu318Lys variant were investigated by direct sequencing. Sequencing analysis of the high-penetrance susceptibility genes showed no changes in CDKN2A and in exon 2 of the CDK4 gene. Both patients were heterozygous for the same CDKN2A UTR c.*29C > G variant. Interestingly, the same two heterozygous variants of the MC1R were identified in both twins: the c.451C > T (p.Arg151Cys and the c.456C > A (p.Tyr152* variants. Neither patient showed the c.952 G > A (p.Glu318Lys substitution in the MITF gene. Conclusions Identification of two high-risk MC1R variants in our identical twins in the absence of CDKN2A and CDK4 mutations highlights the contribution of low penetrance genes, such as MC1R, in melanoma susceptibility.

  6. Capmatinib, Ceritinib, Regorafenib, or Entrectinib in Treating Patients With BRAF/NRAS Wild-Type Stage III-IV Melanoma

    Science.gov (United States)

    2017-12-20

    ALK Fusion Protein Expression; BRAF wt Allele; Invasive Skin Melanoma; MET Fusion Gene Positive; NRAS wt Allele; NTRK1 Fusion Positive; NTRK2 Fusion Positive; NTRK3 Fusion Positive; RET Fusion Positive; ROS1 Fusion Positive; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7

  7. [Update on surgical treatment of primary and metastatic cutaneous melanoma].

    Science.gov (United States)

    Zuluaga-Sepúlveda, María Alejandra; Arellano-Mendoza, Ivonne; Ocampo-Candiani, Jorge

    2016-01-01

    Melanoma is a common cutaneous tumour. It is of great importance due to its increasing incidence and aggressive behaviour, with metastasis to lymph nodes and internal organs. When suspecting melanoma, excisional biopsy should be performed to obtain complete histological information in order to determine the adverse factors such as ulceration, mitosis rate, and Breslow depth, which influence preoperative staging and provide data for sentinel lymph biopsy decision making. The indicated management for melanoma is wide local excision, observing recommended and well-established excision margins, depending on Breslow depth and anatomical location of the tumour. Therapeutic lymphadenectomy is recommended for patients with clinically or radiologically positive lymph nodes. This article reviews surgical treatment of melanoma, adverse histological factors, sentinel lymph node biopsy, and radical lymphadenectomy. Details are presented on special situations in which management of melanoma is different due to the anatomical location (plantar, subungual, lentigo maligna), or pregnancy. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  8. Treatment of cutaneous melanoma: current approaches and future prospects

    Directory of Open Access Journals (Sweden)

    Alain P Algazi

    2010-08-01

    Full Text Available Alain P Algazi1, Christopher W Soon2, Adil I Daud11Department of Medicine, Division of Hematology and Oncology, 2Department of Dermatology, University of California, San Francisco San Francisco, CA, USAAbstract: Melanoma is the most aggressive and deadly type of skin cancer. Surgical resection with or without lymph node sampling is the standard of care for primary cutaneous melanoma. Adjuvant therapy decisions may be informed by careful consideration of prognostic factors. High-dose adjuvant interferon alpha-2b increases disease-free survival and may modestly improve overall survival. Less toxic alternatives for adjuvant therapy are currently under study. External beam radiation therapy is an option for nodal beds where the risk of local recurrence is very high. In-transit melanoma metastases may be treated locally with surgery, immunotherapy, radiation, or heated limb perfusion. For metastatic melanoma, the options include chemotherapy or immunotherapy; targeted anti-BRAF and anti-KIT therapy is under active investigation. Standard chemotherapy yields objective tumor responses in approximately 10%–20% of patients, and sustained remissions are uncommon. Immunotherapy with high-dose interleukin-2 yields objective tumor responses in a minority of patients; however, some of these responses may be durable. Identification of activating mutations of BRAF, NRAS, c-KIT, and GNAQ in distinct clinical subtypes of melanoma suggest that these are molecularly distinct. Emerging data from clinical trials suggest that substantial improvements in the standard of care for melanoma may be possible.Keywords: melanoma, resection, immune modulation, small molecule kinase inhibitors, chemotherapy, clinical trials

  9. Surgery for abdominal metastases of cutaneous melanoma.

    Science.gov (United States)

    Gutman, H; Hess, K R; Kokotsakis, J A; Ross, M I; Guinee, V F; Balch, C M

    2001-06-01

    The objective of this study was to support our hypothesis that surgical resection of abdominal metastases of melanoma, regardless of symptomatology, could provide prolonged palliation and improved survival. We performed a retrospective chart review at M.D. Anderson Cancer Center. A series of 251 melanoma patients (stages I, II, or III at registration) who developed intraabdominal metastases during follow-up were studied. Altogether, 96 patients underwent 119 laparotomies; 51 underwent endoscopic or percutaneous procedures; and 116 patients were treated medically. Surgery was associated with a median survival of 11 months, significantly longer than that with other treatment (p < 0.001). Tumor was extirpated during 37% of the first laparotomies, and in an additional 33% very good palliation was achieved with incomplete resection. Tumor extirpation was associated with 10-month symptom-free survival (SFS), significantly longer than that with any other approach (p < 0.0001). In the nonsurgically treated patients, good palliation was achieved in 8% to 17% of patients with no complete response. The median SFS after surgery was 5 months, but 23% of patients were symptom-free more than 12 months; 87 patients with minimal symptoms; and 72 severely symptomatic patients underwent surgery. Complete resection was feasible in 42% and 34%, respectively. Surgery was associated with 12 months median survival in both groups. There was a significant survival benefit from surgery in patients with gastrointestinal (GI) tract metastases in contrast to those who had non-GI metastases. For the 96 surgically treated patients, a time interval of more than 4 years between diagnosis of the primary lesion and the abdominal recurrence predicted decreased risk of death (p = 0.038). The 30-day postoperative complication and mortality rates were 19.0% and 3.3%, respectively. Complete surgical resection of melanoma metastases in the abdomen is associated with median and symptom-free survival

  10. Cutaneous malignant melanoma show geographic and socioeconomic disparities in stage at diagnosis and excess mortality

    DEFF Research Database (Denmark)

    Strömberg, Ulf; Peterson, Stefan; Holmberg, Erik

    2016-01-01

    -specific incidence of CMM. The incidence of stage I-II tumors was higher in the western health care region, whereas the incidence of stage III-IV CMMs was higher in the southern region. The divergent incidence patterns per stage at diagnosis were consistent across population strata based on educational level......Background Preventive measures are needed to counteract the increasing burden of cutaneous malignant melanoma (CMM). As a basis for rational melanoma prevention, we investigated geographic differences and impact from socioeconomic factors related to incidence, clinical stage at diagnosis...... and outcome. Material and methods All patients with primary invasive CMM diagnosed in 2004-2013 in the southern and the western Swedish health care regions with a population of 2.9 million adults were eligible for the study. Population-based data were obtained from the national Cancer Register...

  11. FDG PET in early stage cutaneous malignant melanoma

    International Nuclear Information System (INIS)

    McIvor, Jody; Siew, Teck; McCarthy, Michael

    2014-01-01

    Fluorodeoxyglucose positron emission tomography (FDG PET) is not recommended in early stage melanoma; however, a significant number of cases are referred to our institution for FDG PET. We refer to early stage disease as American Joint Committee on Cancer (AJCC) stage I and II, which includes all cases without metastases. A retrospective review was undertaken to determine the clinical utility of FDG PET in this patient group. A retrospective study of FDG scans on all patients presenting to the WA PET Centre with early stage melanoma over a 5½ year period was undertaken. The positivity rate of the initial study for detection of malignant melanoma was determined. In patients with an initially negative FDG PET, the time from initial diagnosis to a positive surveillance study was determined. Both the initial positivity rate and time to a positive study were correlated with Breslow staging. Three hundred twenty-two patients were included in the study, of which 74 had initial positive FDG PET scans (23%). Adequate follow-up was available in 51 patients with the PET result confirmed as true positive in 37 (positive predictive value 73%). One hundred eight of 248 patients initially negative had follow-up scans during the follow-up period, of which 48 became positive. The 73% of recurrences were over 12 months post-diagnosis. No correlation with Breslow thickness was demonstrated. Despite FDG PET not being recommended for early cutaneous malignant melanoma, 27% of melanoma cases referred for FDG PET during the study period were AJCC stage I or II. Our results suggest FDG PET in early stage melanoma demonstrates occult disease in 17% of cases.

  12. Mohs Micrographic Surgery Using MART-1 Immunostain in the Treatment of Invasive Melanoma and Melanoma In Situ.

    Science.gov (United States)

    Valentín-Nogueras, Sheila M; Brodland, David G; Zitelli, John A; González-Sepúlveda, Lorena; Nazario, Cruz M

    2016-06-01

    Mohs micrographic surgery (MMS) with melanoma antigen recognized by T-cell (MART-1) immunostaining is an effective treatment of cutaneous melanoma. To determine the efficacy of MMS with MART-1 immunostain in the management of invasive and in situ melanoma. A retrospective cohort study evaluated 2,114 melanomas in 1,982 patients excised using MMS and MART-1 immunostain. The margins required for excision were calculated based on Breslow thickness, location, and size. Survival and local recurrence rates were calculated and compared with those of historical controls. The mean follow-up period was 3.73 years. Local recurrence was identified in 0.49% (7/1,419) of primary melanomas. Approximately 82% of melanomas were excised with ≤6-mm margins. The surgical margin was significantly related to tumor location and size but not to Breslow thickness. The five-year Kaplan-Meier local recurrence and disease-specific survival rates were 0.59 ± 0.30 and 98.53 ± 0.42, respectively. Mohs micrographic surgery with MART-1 immunostain achieved lower local recurrence rates and equivalent or higher Kaplan-Meier survival rates than conventional wide local excision. Mohs micrographic surgery with MART-1 immunostain is an effective treatment of melanoma as evidenced by low local recurrence rates. It offers the advantage of more tissue-conserving margins than those recommended for conventional excision.

  13. Cytokines and Growth Factors Expressed by Human Cutaneous Melanoma

    Directory of Open Access Journals (Sweden)

    Elias G. Elias

    2010-05-01

    Full Text Available Cytokines and growth factors have biologic effects that could stimulate tumor growth, invasion and angiogenesis. The incidence of 24 factors was investigated in 25 cultured human melanoma cell lines and in 62 fixed tissues at different stages of the disease. Over 80% of the human melanoma cell lines expressed TGF-β, IL-8, IL-6, VEGF, PDGF-AA and OPN. Significantly higher TGF-β, IGF-1 and IL-15 were determined in primary lesions compared to distant metastases by immunohistochemistry. Illustrating the complexity of the milieu of the tumor microenvironment, some of these factors may have to be considered in targeted therapy.

  14. Asymptomatic brain metastases in patients with cutaneous metastatic malignant melanoma

    DEFF Research Database (Denmark)

    Zukauskaite, Ruta; Schmidt, Henrik; Asmussen, Jon Thor

    2013-01-01

    The aim of the study was to identify the frequency of asymptomatic brain metastases detected by computed tomography (CT) scans in patients with metastatic cutaneous melanoma referred to first-line systemic treatment. Between 1995 and 2009, 697 Danish patients were screened with a contrast......-enhanced CT scan of the brain before the start of interleukin-2 (IL-2)-based immunotherapy. Among the 697 patients, 80 had asymptomatic brain metastases (12%). Patients' characteristics did not differ significantly between groups with and without brain metastases. Patients received systemic treatment (IL-2...

  15. Successful BNCT for patients with cutaneous and mucosal melanomas. Report of 4 cases

    International Nuclear Information System (INIS)

    Morita, Norimasa; Hiratsuka, Junichi; Kuwabara, Chiaki; Aihara, Teruhito; Harada, Tamotsu; Imajo, Yoshinari; Ono, Koji; Fukuda, Hiroshi; Kumada, Hiroaki

    2006-01-01

    Since 2003 we have conducted BNCT clinical trials on melanomas at the Kyoto University Research Reactor (KUR) and Japan Research Reactor No.4 (JRR-4). We report 4 patients given BNCT for malignant melanomas: 2 with superficial spreading types on the heel, 1 with mucosal melanoma in the nasal cavity, and 1 with a melanoma on the vulva and in the vagina. The two cutaneous melanomas and the nasal cavity mucosal melanoma showed a complete response (CR) by 6 months after BNCT. The residual melanoma showed a partial response (PR) by 3 months after treatment and no regrowth since then. Although two patients experienced normal-tissue damage that exceeded the tolerance level, all the participants were cured within a few months of treatment. BNCT was shown to be a promising treatment for mucosal, as well as for cutaneous, melanomas. (author)

  16. Serial or Parallel Metastasis of Cutaneous Melanoma? A Study of the German Central Malignant Melanoma Registry.

    Science.gov (United States)

    Gassenmaier, Maximilian; Eigentler, Thomas Kurt; Keim, Ulrike; Goebeler, Matthias; Fiedler, Eckhard; Schuler, Gerold; Leiter, Ulrike; Weide, Benjamin; Grischke, Eva-Maria; Martus, Peter; Garbe, Claus

    2017-12-01

    For more than a century the Halstedian hypothesis of contiguous metastasis from the primary tumor through the lymphatics to distant sites shaped lymph node surgery for melanoma. We challenge this dogma of serial metastatic dissemination. A single-center series of 2,299 patients with cutaneous metastatic melanoma was investigated to analyze overall survival and distant metastasis-free survival of stage IV patients with or without primary lymphatic metastasis. Results were then compared with those of 2,134 patients from three independent centers of the German Central Malignant Melanoma Registry. A multivariate binary logistic regression model was used to identify risk factors for the initial metastatic pathway. Distant metastasis-free survival (hazard ratio = 1.02; 95% confidence interval = 0.91-1.14; P = 0.76) and overall survival (HR = 1.09; 95% CI = 0.96-1.23; P = 0.177) did not differ between stage IV patients with primary hematogenous or primary lymphatic metastasis. Melanoma localization was the only significant risk factor for the initial metastatic pathway. These findings indicate that regional and distant metastases originate from the primary tumor itself in a rather parallel than serial fashion and could explain the lack of survival benefit associated with immediate complete lymph node dissection in sentinel lymph node-positive melanoma patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Solar considerations in the development of cutaneous melanoma.

    Science.gov (United States)

    Loggie, B W; Eddy, J A

    1988-12-01

    On the basis of these considerations, the possible action spectrum for melanoma can be narrowed considerably, but not confined to any one solar emission band. The physical factors discussed eliminate all but UV, visible, and NIR radiation as possible solar agents. Ionizing radiation fits neither the epidemiologic data nor first-order physical considerations. Wavelengths longer than the NIR wavelengths, although they could conceivably account for the occurrence of melanoma under clothed parts of the body, carry so little energy that they are probably unimportant. Epidemiologic evidence regarding the effects of skin pigment favors UV or visible radiation. A distinction between these two components is not obvious; UV-C and UV-B photons carry greater energy and are more likely to induce biochemical cutaneous effects, but the total flux in the UV-A and visible radiations is far greater. That UV-B radiation may play a role in melanoma is supported; at the same time, one cannot exclude the possibility that the action spectrum for melanoma is, instead, the UV-A, the visible, or even the NIR portion of the sunlight spectrum. The strong differential effect of altitude on the transmission of light of different wavelengths might serve as an important discriminating variable. If solar UV radiation is implicated in the development of melanoma, then altitude should emerge as a significant factor in epidemiologic studies. If visible or IR radiation is the active agent, then differences on the basis of altitude should be small or negligible. Intrinsic solar variations that follow the annual sunspot number appear inadequate in either the UV or the visible band to account directly for the apparent 11-year modulation of melanoma incidence found in some registries. Secondary atmospheric effects brought about by the action of solar UV changes on the ozone layer may be adequate to explain a weak 11-year modulation in melanoma incidence, although continuous measurements of UV-B flux made

  18. An update on cutaneous melanoma in Turkey: evaluation of 19-year data in a single tertiary centre and review of the literature.

    Science.gov (United States)

    Baykal, C; Atci, T; Polat Ekinci, A; Buyukbabani, N

    2017-02-01

    Information on frequency of melanoma and its clinicopathological subtypes derived from dermatology clinics in Turkey is limited. As data about melanoma show clear differences due to geographic and ethnic distribution, we scrutinized the rich data of our dermatology centre in Istanbul. Consecutive patients diagnosed with melanoma in a tertiary dermatology clinic during the last 19 years were retrospectively investigated about the clinical presentation of the skin lesions during admission, frequency of subtypes and localization of the tumour. There were 227 patients with melanoma showing five different clinical presentations: 200 of them had totally 207 primary cutaneous melanoma (PCM) lesions, nine had PCM lesions associated with metastatic skin lesions, three presented with local recurrence, eight with only skin metastases and seven with regressed skin melanoma following systemic melanoma metastases. Histologically, 23.19% of the PCM lesions were intraepidermal (in situ) and Breslow thickness was less than 1 mm in 30.9% of the patients with invasive melanoma. The most common subtype was superficial spreading melanoma (SSM) (37.19%), followed by lentigo malignant melanoma (LMM) (31.4%), acral lentiginous melanoma (ALM) (19.32%) and nodular melanoma (NM) (6.76%). Head and neck region was the most common (34.78%) localization of PCM lesions. Different clinical presentations, including various types of cutaneous melanoma metastases, were seen. However, a great proportion of our patients were relatively early diagnosed, either having an in situ or an invasive PCM with a Breslow thickness ≤1 mm. Even though SSM was the most common subtype of PCM in our series, its rate was lower compared to many European countries. Furthermore, the rate of NM subtype was also low, while LMM and ALM rates were higher in comparison to studies originating from European countries. This striking discrepancy requires further studies to explain the probable causes. © 2016 European Academy of

  19. Paraneoplastic vitelliform retinopathy associated with cutaneous or uveal melanoma and metastases.

    NARCIS (Netherlands)

    Sotodeh, M.; Paridaens, D.; Keunen, J.E.E.; Schooneveld, M. van; Adamus, G.; Baarsma, S.

    2005-01-01

    PURPOSE: To report unusual vitelliform fundus findings in three cases of paraneoplastic retinopathy associated with metastasised cutaneous or uveal melanoma and in one case, a unique immunoreactivity response. PATIENTS AND METHODS: Observational case series. The histories of three patients with

  20. Routine X-ray of the chest is not justified in staging of cutaneous melanoma patients

    DEFF Research Database (Denmark)

    Gjorup, Caroline Asirvatham; Hendel, Helle Westergren; Pilegaard, Rita Kaae

    2016-01-01

    INTRODUCTION: The incidence of cutaneous melanoma is increasing in Denmark and worldwide. However, the prevalence of distant metastases at the time of diagnosis has decreased to 1%. We therefore questioned the value of routine preoperative chest X-ray (CXR) for staging asymptomatic melanoma...... patients and hypothesised that routine CXR is not justified. METHODS: A retrospective study was conducted on patients undergoing wide local excision and sentinel lymph node biopsy for cutaneous melanoma in the period from 2010 to 2014. RESULTS: A total of 603 patients were included. The mean time of follow...... value was 8%, and the negative predictive value was 100%. CONCLUSION: Our results suggest that CXR cannot be justified in the initial staging of cutaneous melanoma patients. The guideline for the treatment of melanoma in Denmark is under revision: The use of CXR has been omitted. FUNDING: This study...

  1. Quem descobre o melanoma cutâneo Who discovers the cutaneous melanoma

    Directory of Open Access Journals (Sweden)

    Marcus Maia

    2006-06-01

    Full Text Available FUNDAMENTO: No Brasil não se sabe quem descobre os casos de melanoma cutâneo. A compreensão dos "modelos de descoberta" poderia servir de base para os programas de educação pública e do profissional de saúde. OBJETIVO: Determinar o papel dos pacientes em encontrar suas próprias lesões. MÉTODOS: Foram entrevistados 109 pacientes com diagnóstico anterior de melanoma cutâneo, acompanhados na Unidade de Melanoma da Santa Casa de Misericórdia de São Paulo. Outras variáveis foram anotadas para avaliar suas possíveis influências no resultado da descoberta: sexo, idade, estado civil, escolaridade, antecedente familiar de melanoma, localização da lesão primária e conhecimento sobre câncer da pele. RESULTADOS: Dos 109 pacientes, 59 (54% notaram a própria lesão. Deles, 62% eram mulheres, 51% menores de 60 anos, 90% sem antecedentes familiares de melanoma, 78% negavam conhecimento sobre câncer de pele, 59% eram casados, 52% cursaram apenas a escola primária. Os demais 50 pacientes tiveram sua lesão descoberta em 24% dos casos por profissionais de saúde, 10% pela esposa, 1% pelo marido e 11% por outras pessoas. CONCLUSÃO: 54% dos pacientes notaram sua própria lesão, que em cerca de 25% foi descoberta por leigos. Esses resultados são semelhantes aos da literatura dos países desenvolvidos. A clientela avaliada foi do tipo assistencial, e com esse resultado é possível acreditar que, no Brasil, alguma influência das campanhas públicas de saúde já pode ser notada.BACKGROUND - In Brazil, it is still unknown who first discovers the cases of cutaneous melanoma. The understanding of our “finding patterns” could be used as a basis for public education programs and healthcare professional training. OBJECTIVE - To determine the role of patients in detecting lesions by themselves. METHODS - One hundred and nine patients were interviewed. The patients had a diagnosis of cutaneous melanoma and were regularly seen at the Melanoma

  2. [Cutaneous melanoma - "black death" of modern times? Traces in contemporary literature].

    Science.gov (United States)

    Bahmer, F A; Bahmer, J A

    2013-11-01

    Cutaneous melanoma, sometimes labeled as "black skin cancer", is increasing in frequency and becoming a more common literary motive. In US literature, Sylvia Plath and Charles Bukowski depicted melanoma more than 50 years ago, later Stephen King and Thomas C. Boyle. In German literature, Charlotte Roche shortly mentioned this tumor. Jörg Pönnighaus, both poet and dermatologist, intensively deals in his poems with the effects melanoma has on patients and doctors alike. Melanoma definitely is not the "Black Death" of modern times. However, the perception of this tumor as extremely malignant and as life-threatening makes melanoma a metaphor of the deadly danger of cancer.

  3. Report of a symposium on: diagnosis and treatment of cutaneous head and neck melanoma

    NARCIS (Netherlands)

    Balm, A. J.; Kroon, B. B.; de Boer, J. B.; Israels, S. P.; Jonk, A.; Mooi, W. J.; Neering, H.; Osterlind, A.; Rampen, F. H.; Rankin, E. M.

    1994-01-01

    A series of presentations and discussions was held during a symposium on the diagnosis and treatment of cutaneous head and neck melanoma. The purpose of this meeting was to define certain guidelines on diagnosis and treatment of head and neck melanoma. The results of this symposium are summarized

  4. A multicentre epidemiological study on sunbed use and cutaneous melanoma in Europe

    NARCIS (Netherlands)

    V. Bataille (Veronique); M. Boniol; E.G.E. de Vries (Elisabeth); G. Severi (Gianluca); Y. Brandberg (Yvonne); P. Sasieni (Peter); J. Cuzick (Jack); A.M.M. Eggermont (Alexander); U. Ringborg; A.-R. Grivegnée (André-Robert); J.W.W. Coebergh (Jan Willem); M.C. Chignol (Marie Christine); J.F. Doré; P.J.M. Autier (Philippe)

    2005-01-01

    textabstractA large European case-control study investigated the association between sunbed use and cutaneous melanoma in an adult population aged between 18 and 49 years. Between 1999 and 2001 sun and sunbed exposure was recorded in 597 newly diagnosed melanoma cases and 622 controls in Belgium,

  5. Utility of chest X-ray and abdominal ultrasound for stage III cutaneous malignant melanoma

    DEFF Research Database (Denmark)

    Breitenbauch, M. T. W.; Holm, J.; Rødgaard, J. C.

    2015-01-01

    Background: Current Danish Melanoma Guidelines suggest that stage III cutaneous malignant melanoma receive chest X-ray and abdominal ultrasound to exclude lung and liver metastases. The aim of this study was to examine the sensitivity, specificity, and negative predictive value of chest X-ray and...

  6. Primary tumor sites in relation to ultraviolet radiation exposure and skin visibility correlate with survival in cutaneous melanoma.

    Science.gov (United States)

    Gordon, Daniela; Hansson, Johan; Eloranta, Sandra; Gordon, Max; Gillgren, Peter; Smedby, Karin E

    2017-10-01

    The prognostic value of detailed anatomic site and ultraviolet radiation (UVR) exposure patterns has not been fully determined in cutaneous melanoma. Thus, we reviewed medical records for detailed site in a population-based retrospective Swedish patient cohort diagnosed with primary invasive melanoma 1976-2003 (n = 5,973). We followed the patients from date of diagnosis until death, emigration or December 31 st 2013, and evaluated melanoma-specific survival by subsite in a multivariable regression model adjusting for established prognostic factors. We found that melanoma on chronic UVR exposure sites (face, dorsum of hands; adjusted HR 0.6; CI 0.4-0.7) and moderately intermittent UVR sites (lateral arms, lower legs, dorsum of feet; HR 0.7; CI 0.6-0.8) were associated with a favorable prognosis compared with highly intermittent sites (chest, back, neck, shoulders and thighs). Further, melanoma on poorly visible skin sites upon self-examination (scalp, retroauricular area, back, posterior upper arms and thighs, buttocks, pubic area; HR 1.3; CI 1.1-1.5) had a worse prognosis than those on easily visible sites (face, chest, abdomen, anterior upper arms and thighs, lower arms and legs, dorsum of hands and feet, palms). In conclusion, highly intermittent UVR exposure sites and poor skin visibility presumably correlate with reduced melanoma survival, independent of established tumor characteristics. A limitation of the study was the lack of information on actual individual UVR exposure. © 2017 UICC.

  7. Risco crescente de melanoma de pele no Brasil Increasing risk of cutaneous melanoma in Brazil

    Directory of Open Access Journals (Sweden)

    Guinar Azevedo e Silva Mendonça

    1992-08-01

    Full Text Available A ocorrência de melonoma maligno de pele no Brasil é analisada a partir dos dados de mortalidade disponíveis no Ministério da Saúde e dos dados de incidência dos seis Registros de Câncer de Base Populacional, localizados em seis capitais brasileiras. Os coeficientes de incidência nessas capitais situam-se em padrões intermediários se comparadas às cifras mundiais. Para o Município de Porto Alegre, uma das capitais estudas, que apresentou os maiores coeficientes de incidência, é feita comparação entre os dados relativos ao período 1979-1982 e 1987, constatando-se que houve aumento relativo de 38% entre homens e de 11% entre mulheres. Concluiu-se pela necessidade de se conduzir estudos no Brasil entre comunidades de indivíduos de pele clara, os quais apresentam risco potencializado para o desenvolvimento de melanoma, para que sejam definidas medidas específicas e eficazes de controle.The occurrence of cutaneous malignant melanoma in Brazil is analysed on the basis of available mortality data from the National Ministery of Health and from the incidence data of six Population-based Cancer Registries (Recife, Fortaleza, S.Paulo, Porto Alegre, Goiânia e Belém. The incidence in these State capitals has an intermediate pattern if compared to the world pictures. For Porto Alegre, the capital that had the highest rates, a comparison between the periods 1979-1982 and 1987 showed a proportional increases of 38% among males and 11% among females. The conclusion is reached that it is necessary to undertake studies in Brazil among fairskinned people from particular communities which may show a potentialized risk for the development of cutaneous melanoma in order to be able to define what kind of specific control actions should be developed.

  8. Prognostic Value of Melanoma Inhibitory Activity Protein in Localized Cutaneous Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Angela Sandru

    2014-01-01

    Full Text Available Background. Cutaneous malignant melanoma (CMM is a heterogeneous disease, acknowledged for its lack of predictability regarding clinical evolution. In order to appreciate a patient’s individual prognosis, an attempt is made to find new tumor markers that parallel the disease progression. Objective. To identify if melanoma inhibitory activity (MIA protein could represent a tool for selecting high risk early stages melanoma patients. Method. Between 2008 and 2013, 155 patients with CMM were treated in our clinic. 84 of them were classified into stages I and II, according to TNM 2009. MIA serum concentration was measured in all patients and 50 healthy donors. A cut-off value of 9.4 ng/ml was established using the ROC curve. Results. All patients were followed up by periodic investigations every 6 months. We have noticed that 66% of patients with MIA serum values at diagnosis greater than 9.4 ng/mL have relapsed, while only 5% of patients with MIA serum concentration below the estimated threshold, recurred during the follow-up period (P=0.000. The death risk was 12 times higher in pathological MIA group of patients (P=0.0001. Conclusions. Our data suggest that MIA is an independent prognostic factor for patients with localized CMM.

  9. Prognostic value of melanoma inhibitory activity protein in localized cutaneous malignant melanoma.

    Science.gov (United States)

    Sandru, Angela; Panaitescu, Eugenia; Voinea, Silviu; Bolovan, Madalina; Stanciu, Adina; Cinca, Sabin; Blidaru, Alexandru

    2014-01-01

    Background. Cutaneous malignant melanoma (CMM) is a heterogeneous disease, acknowledged for its lack of predictability regarding clinical evolution. In order to appreciate a patient's individual prognosis, an attempt is made to find new tumor markers that parallel the disease progression. Objective. To identify if melanoma inhibitory activity (MIA) protein could represent a tool for selecting high risk early stages melanoma patients. Method. Between 2008 and 2013, 155 patients with CMM were treated in our clinic. 84 of them were classified into stages I and II, according to TNM 2009. MIA serum concentration was measured in all patients and 50 healthy donors. A cut-off value of 9.4 ng/ml was established using the ROC curve. Results. All patients were followed up by periodic investigations every 6 months. We have noticed that 66% of patients with MIA serum values at diagnosis greater than 9.4 ng/mL have relapsed, while only 5% of patients with MIA serum concentration below the estimated threshold, recurred during the follow-up period (P = 0.000). The death risk was 12 times higher in pathological MIA group of patients (P = 0.0001). Conclusions. Our data suggest that MIA is an independent prognostic factor for patients with localized CMM.

  10. Burden of Melanoma

    NARCIS (Netherlands)

    C. Holterhues (Cynthia)

    2011-01-01

    markdownabstract__Abstract__ Melanoma is a type of skin cancer that arises from melanocytes. More than 95% of all melanomas occur in the skin, but rarely in the pigmented cells of the eye, meninges or mucosa. This thesis will only regard the invasive cutaneous malignant melanomas.

  11. Patients highly value routine follow-up of skin cancer and cutaneous melanoma

    DEFF Research Database (Denmark)

    Themstrup, Lotte; Jemec, Gregor E; Lock-Andersen, Jørgen

    2013-01-01

    : This study included an open sample of patients attending routine follow-up at the outpatient Departments of Plastic Surgery and Dermatology, Roskilde Hospital. A total of 218 follow-up patients diagnosed with cutaneous malignant melanoma (MM), non-melanoma skin cancer (NMSC) or actinic keratosis (AK......INTRODUCTION: Skin cancer follow-up is a substantial burden to outpatient clinics. Few studies have investigated patients' views on skin cancer follow-up and cutaneous melanoma. The objective was to investigate patients' perceived benefits and the impact of follow-up. MATERIAL AND METHODS...

  12. Awareness and early detection of cutaneous melanoma: an analysis of factors related to delay in treatment.

    Science.gov (United States)

    Blum, A; Brand, C U; Ellwanger, U; Schlagenhauff, B; Stroebel, W; Rassner, G; Garbe, C

    1999-11-01

    Factors associated with the detection of cutaneous melanomas and reasons for delay in diagnosis were investigated in 429 patients with histologically proven melanoma operated on between January 1993 and June 1996. Patients were interviewed using a standardized questionnaire. In 25% of patients, treatment was delayed for more than 1 year from the time they first noticed a suspicious pigmented lesion. Melanoma was detected by the patients themselves in 67% of women and 45% of men. The three predominant clinical symptoms of melanoma were change in colour (darker), increase in size and increase in elevation of a pigmented lesion. The role of sun exposure and of naevi as risk factors for melanoma, as well as the potential benefit of early treatment, were known by 87%, 66% and 82% of the patients, respectively. However, melanoma awareness had no impact on the time period between first observation of skin changes and treatment. Among the factors associated with delay in melanoma diagnosis, an initial incorrect diagnosis as a benign lesion by the physician first visited (in 18% of all cases) had the highest significance. Patients detecting their lesions themselves were treated significantly later than patients in whom others had remarked on changes in a naevus. Furthermore, melanomas of the head and neck were treated later than melanomas at other body sites. Further efforts to educate both the public and the medical profession are essential to ensure earlier treatment for cutaneous melanomas.

  13. Germline RAD51B truncating mutation in a family with cutaneous melanoma

    DEFF Research Database (Denmark)

    Wadt, Karin A W; Aoude, Lauren G; Golmard, Lisa

    2015-01-01

    Known melanoma predisposition genes only account for around 40% of high-density melanoma families. Other rare mutations are likely to play a role in melanoma predisposition. RAD51B plays an important role in DNA repair through homologous recombination, and inactivation of RAD51B has been implicated...... in tumorigenesis. Thus RAD51B is a good candidate melanoma susceptibility gene, and previously, a germline splicing mutation in RAD51B has been identified in a family with early-onset breast cancer. In order to find genetic variants associated with melanoma predisposition, whole-exome sequencing was carried out...... on blood samples from a three-case cutaneous melanoma family. We identified a novel germline RAD51B nonsense mutation, and we demonstrate reduced expression of RAD51B in melanoma cells indicating inactivation of RAD51B. This is only the second report of a germline truncating RAD51B mutation. While...

  14. Tumor necrosis is associated with increased alphavbeta3 integrin expression and poor prognosis in nodular cutaneous melanomas

    International Nuclear Information System (INIS)

    Bachmann, Ingeborg M; Ladstein, Rita G; Straume, Oddbjørn; Naumov, George N; Akslen, Lars A

    2008-01-01

    Tumor necrosis and apoptotic activity are considered important in cancer progression, but these features have not been much studied in melanomas. Our hypothesis was that rapid growth in cutaneous melanomas of the vertical growth phase might lead to tissue hypoxia, alterations in apoptotic activity and tumor necrosis. We proposed that these tumor characteristics might be associated with changes in expression of cell adhesion proteins leading to increased invasive capacity and reduced patient survival. A well characterized series of nodular melanoma (originally 202 cases) and other benign and malignant melanocytic tumors (109 cases) were examined for the presence of necrosis, apoptotic activity (TUNEL assay), immunohistochemical expression of hypoxia markers (HIF-1 α, CAIX, TNF-α, Apaf-1) and cell adhesion proteins (α v β 3 integrin, CD44/HCAM and osteopontin). We hypothesized that tumor hypoxia and necrosis might be associated with increased invasiveness in melanoma through alterations of tumor cell adhesion proteins. Necrosis was present in 29% of nodular melanomas and was associated with increased tumor thickness, tumor ulceration, vascular invasion, higher tumor proliferation and apoptotic index, increased expression of α v β 3 integrin and poor patient outcome by multivariate analysis. Tumor cell apoptosis did also correlate with reduced patient survival. Expression of TNF-α and Apaf-1 was significantly associated with tumor thickness, and osteopontin expression correlated with increased tumor cell proliferation (Ki-67). Tumor necrosis and apoptotic activity are important features of melanoma progression and prognosis, at least partly through alterations in cell adhesion molecules such as increased α v β 3 integrin expression, revealing potentially important targets for new therapeutic approaches to be further explored

  15. Similar anatomical distributions of childhood naevi and cutaneous melanoma in young adults residing in northern and southern Sweden.

    Science.gov (United States)

    Karlsson, Maria A; Rodvall, Ylva; Wahlgren, Carl-Fredrik; Wiklund, Kerstin; Lindelöf, Bernt

    2015-09-01

    Common melanocytic naevi are considered early biomarkers associated with risk of cutaneous malignant melanoma. We sought to investigate if residing at different latitudes in Sweden influences the population's anatomical distribution of naevi in children and melanoma in adults. The nationwide Swedish Cancer Registry 1990-2012 gave cumulative number of invasive melanomas per body site, stratified by sex and age in northern (62-69 °N) (n=2823) and southern (55-58 °N) Sweden (n=24,115). A population-based cross-sectional study conducted in 2002 provided the allocation of naevi among 7-year-olds in northern (5695 naevi in 679 children) and southern Sweden (8392 naevi in 681 children). In 2012, northern Sweden had a two-fold lower melanoma incidence: 19.8/100.000 age-standardised population compared with 41.0/100.000 in the south. Similarly, a lower mean naevi density in children was demonstrated: 7.3 (standard deviation (SD) 5.4) in boys and 7.0 (4.7) in girls in the north versus 13.3 (8.4) in boys and 11.9 (8.5) in girls in the south. Across latitudes of residing, gender profiles and proportional body-site distributions of melanoma and naevi, respectively, were largely homogenous, but in southern Sweden slightly higher on the trunk; a body site associated with intermittent sun exposure. Childhood naevi distributions matched with melanomas in young and middle-aged adults. This large population-based study demonstrated that latitude of residing similarly affects the number and anatomical distribution of naevi in children and melanoma in adults. It supports a role of childhood naevi as predictors of overall and subsite risk of melanoma among young adults. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Opportunistic screening strategy for cutaneous melanoma does not change the incidence of nodular and thick lesions nor reduce mortality: a population-based descriptive study in the European region with the highest incidence.

    Science.gov (United States)

    Bordoni, Andrea; Leoni-Parvex, Sandra; Peverelli, Simona; Mazzola, Paola; Mazzucchelli, Luca; Spitale, Alessandra

    2013-10-01

    The aim of the present population-based descriptive study was to evaluate the incidence and mortality trends for melanoma to gain insights on the effectiveness of opportunistic secondary prevention strategies. Data on all invasive cutaneous melanoma cases occurring between 1996 and 2011 were retrieved from the Ticino Cancer Registry, southern Switzerland. The European age-standardized incidence rates were computed by the period of diagnosis, Breslow thickness and histological types. Trends in incidence and mortality rates were measured as the annual per cent change (APC). A total of 1230 patients had a diagnosis of invasive cutaneous melanoma. Cases were categorized as follows: superficial spreading melanoma (55.7%), nodular melanoma (10.0%), lentigo maligna melanoma (5.5%), melanoma not otherwise specified (25.2%) and other types (3.6%). The incidence rate of invasive melanoma rose from 17.4 per 100,000 inhabitants in 1996-2003 to 20.6 in 2004-2011, with an overall APC of +2.1% [95% confidence interval (CI): -0.8%, +5.1%]. An increase in incidence was observed for superficial spreading melanoma (APC = +2.9%; 95% CI: -1.1%, +7.0%) and thin melanomas (i.e. ≤ 1.00 mm) (APC = +3.4%; 95% CI: +0.2%, +6.7%), whereas we detected a descriptive growing incidence of thick melanomas (APC = +2.1%; 95% CI: -1.4%, +5.8%). Mortality trend analysis revealed constant rates throughout the study period (APC = -1.0%; 95% CI: -5.5%, +3.7%). This population-based study confirms that in a country with the highest incidence of cutaneous melanomas, that is, Switzerland, the opportunistic screening strategy does not change the incidence of thick melanomas nor the overall mortality. This study suggests there is still a need for public health efforts in primary and secondary prevention.

  17. RSK1 activation promotes invasion in nodular melanoma.

    Science.gov (United States)

    Salhi, Amel; Farhadian, Joshua A; Giles, Keith M; Vega-Saenz de Miera, Eleazar; Silva, Ines P; Bourque, Caitlin; Yeh, Karen; Chhangawala, Sagar; Wang, Jinhua; Ye, Fei; Zhang, David Y; Hernando-Monge, Eva; Houvras, Yariv; Osman, Iman

    2015-03-01

    The two major melanoma histologic subtypes, superficial spreading and nodular melanomas, differ in their speed of dermal invasion but converge biologically once they invade and metastasize. Herein, we tested the hypothesis that distinct molecular alterations arising in primary melanoma cells might persist as these tumors progress to invasion and metastasis. Ribosomal protein S6 kinase, 90 kDa, polypeptide 1 (RSK1; official name RPS6KA1) was significantly hyperactivated in human melanoma lines and metastatic tissues derived from nodular compared with superficial spreading melanoma. RSK1 was constitutively phosphorylated at Ser-380 in nodular but not superficial spreading melanoma and did not directly correlate with BRAF or MEK activation. Nodular melanoma cells were more sensitive to RSK1 inhibition using siRNA and the pharmacological inhibitor BI-D1870 compared with superficial spreading cells. Gene expression microarray analyses revealed that RSK1 orchestrated a program of gene expression that promoted cell motility and invasion. Differential overexpression of the prometastatic matrix metalloproteinase 8 and tissue inhibitor of metalloproteinases 1 in metastatic nodular compared with metastatic superficial spreading melanoma was observed. Finally, using an in vivo zebrafish model, constitutive RSK1 activation increased melanoma invasion. Together, these data reveal a novel role for activated RSK1 in the progression of nodular melanoma and suggest that melanoma originating from different histologic subtypes may be biologically distinct and that these differences are maintained as the tumors invade and metastasize. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  18. Associations of non-melanoma skin cancer and melanoma, extra-cutaneous cancers and smoking in adults: a US population-based study.

    Science.gov (United States)

    Silverberg, J I; Ratner, D

    2015-07-01

    Non-melanoma skin cancer (NMSC) and melanoma are common malignancies in the US and may be associated with other types of cancer. We sought to determine whether NMSC and melanoma are associated with extra-cutaneous cancers and identify modifiable risk factors for such an association. We analysed data from 447,801 adult participants in the 1997-2011 National Health Interview Surveys. Survey logistic regression models were constructed that accounted for the complex sample weights. History of NMSC, melanoma and 27 primary extra-cutaneous cancers was assessed. NMSC was associated with increased odds of one (multinomial survey logistic regression, unadjusted odds ratio [95% CI]: 2.43 [2.20-2.68]) or multiple (2.94 [2.21-3.92]) extra-cutaneous malignancies. Melanoma was also associated with increased odds of one (3.25 [2.70-3.90]) or multiple (6.11 [4.34-8.61]) extra-cutaneous malignancies. Extra-cutaneous cancers were more common in younger patients (ages 18-39 and 40-49 years) and Caucasians with NMSC or melanoma (P melanoma had even higher odds of extra-cutaneous malignancy at ages 18-39 and 40-49 years compared to smokers without NMSC or melanoma (P melanoma, prostate, soft tissue, throat/pharynx, thyroid and uterus. Melanoma was associated with malignancies of the bladder, breast, colon, kidney, lung, pancreas, prostate, soft tissue, throat/pharynx, thyroid and uterus. The prevalence of extra-cutaneous cancers increased between 1997 and 2011 in all subjects (4.51% and 5.73%, P melanoma. Patients with history of NMSC and melanoma have increased odds of developing extra-cutaneous cancers, especially those with younger age and smoking history. © 2014 European Academy of Dermatology and Venereology.

  19. The incidence of cutaneous melanoma on Crete, Greece.

    Science.gov (United States)

    Lasithiotakis, Konstantinos; Krüger-Krasagakis, Sabine; Manousaki, Aglaia; Ioannidou, Despina; Panagiotides, Ioannis; Tosca, Androniki

    2006-04-01

    For Greece, no data regarding the incidence of cutaneous melanoma (CM) have been reported. In this report, we present epidemiologic data for CM on Crete, an island in southern Greece, during the years 1999-2002. We attempt a comparison with corresponding data reported for the Italian population. One hundred and two CM patients of Cretan origin with primary CM first diagnosed between the years 1999-2002 were interviewed and underwent complete skin examination by the same two experienced dermatologists. Crude and/or age-standardized incidence rates were calculated for Crete as a whole, as well as for each one of the four prefectures of the island. The age-standardized incidence rate according to the Greek population was 4.6 per 100,000 person-years for men and 4.7 per 100,000 person-years for women. The crude incidence rates did not differ significantly between the four prefectures. Significant differences between Cretan and Italian CM patients were found in terms of gender, age at diagnosis, anatomic site and histogenetic type of CM, hair color, skin reaction to sun exposure, history of sunburn before the age of 15 years, presence of solar lentigines, and total common nevus count. The incidence of CM on Crete is higher than that estimated for the whole of Greece and comparable with the incidence reported for other southern European countries.

  20. Critical role of glioma-associated oncogene homolog 1 in maintaining invasive and mesenchymal-like properties of melanoma cells.

    Science.gov (United States)

    Gunarta, I Ketut; Li, Rong; Nakazato, Ryota; Suzuki, Ryusuke; Boldbaatar, Jambaldorj; Suzuki, Takeshi; Yoshioka, Katsuji

    2017-08-01

    Cutaneous melanoma is the most aggressive form of skin cancer. This aggressiveness appears to be due to the cancer cells' ability to reversibly switch between phenotypes with non-invasive and invasive potential, and microphthalmia-associated transcription factor (MITF) is known to play a central role in this process. The transcription factor glioma-associated oncogene homolog 1 (GLI1) is a component of the canonical and noncanonical sonic hedgehog pathways. Although GLI1 has been suggested to be involved in melanoma progression, its precise role and the mechanism underlying invasion remain unclear. Here we investigated whether and how GLI1 is involved in the invasive ability of melanoma cells. Gli1 knockdown (KD) melanoma cell lines, established by using Gli1-targeting lentiviral short hairpin RNA, exhibited a markedly reduced invasion ability, but their MITF expression and activity were the same as controls. Gli1 KD melanoma cells also led to less lung metastasis in mice compared with control melanoma cells. Furthermore, the Gli1 KD melanoma cells underwent a mesenchymal-to-epithelial-like transition, accompanied by downregulation of the epithelial-to-mesenchymal transition (EMT)-inducing transcription factors (EMT-TF) Snail1, Zeb1 and Twist1, but not Snail2 or Zeb2. Collectively, these results indicate that GLI1 is important for maintaining the invasive and mesenchymal-like properties of melanoma cells independent of MITF, most likely by modulating a subset of EMT-TF. Our findings provide new insight into how heterogeneity and plasticity are achieved and regulated in melanoma. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  1. Cathepsin L increases invasion and migration of B16 melanoma

    Directory of Open Access Journals (Sweden)

    Cox James L

    2007-05-01

    Full Text Available Abstract Background Most cancers express elevated protease levels which contribute to certain aspects of tumor behavior such as growth, metastatic spread, and angiogenesis. Elevation of the cathepsins of the cysteine protease family correlates with increased invasion of tumor cells. Cysteine proteases such as cathepsins B, H and L type participate in tumor cell invasion as extracellular proteases, yet are enzymes whose exact roles in metastasis are still being elucidated. Methods We have examined the role of cathepsin L in highly metastatic B16F10 murine melanoma cells through genetic antisense constructs of cathepsin L. The effects of cathepsin L antisense were examined for melanoma cell proliferation, invasion, migration and adhesion. Results Antisense expression of cathepsin L, while decreasing enzyme activity in cell lysates, did not influence cell proliferation. Cathepsin L contributed to melanoma cell invasion and also augmented melanoma cell migration. Further, we demonstrated the adhesion of cathepsin L down-regulated clones was unaltered to fibronectin, laminin, and collagen. Finally, the inhibition of melanoma cell migration via down-regulation of cathepsin L appears to be independent of cystatin C expression. Conclusion This study shows that cathepsin L facilitates high metastatic B16 melanoma cell invasion and migration. The mechanism of migration inhibition by decreased cathepsin L is independent of cystatin C levels. Since metastasis depends upon both the invasiveness and migration of tumor cells, cathepsin L may be a therapeutic target of strong clinical interest.

  2. Correlations between cutaneous malignant melanoma and other cancers: An ecological study in forty European countries

    Directory of Open Access Journals (Sweden)

    Pablo Fernandez-Crehuet Serrano

    2016-01-01

    Full Text Available Background: The presence of noncutaneous neoplasms does not seem to increase the risk of cutaneous malignant melanoma; however, it seems to be associated with the development of other hematological, brain, breast, uterine, and prostatic neoplasms. An ecological transversal study was conducted to study the geographic association between cutaneous malignant melanoma and 24 localizations of cancer in forty European countries. Methods: Cancer incidence rates were extracted from GLOBOCAN database of the International Agency for Research on Cancer. We analyzed the age-adjusted and gender-stratified incidence rates for different localizations of cancer in forty European countries and calculated their correlation using Pearson′s correlation test. Results: In males, significant correlations were found between cutaneous malignant melanoma with testicular cancer (r = 0.83 [95% confidence interval (CI: 0.68-0.89], myeloma (r = 0.68 [95% CI: 0.46-0.81], prostatic carcinoma (r = 0.66 [95% CI: 0.43-0.80], and non-Hodgkin lymphoma (NHL (r = 0.63 [95% CI: 0.39-0.78]. In females, significant correlations were found between cutaneous malignant melanoma with breast cancer (r = 0.80 [95% CI: 0.64-0.88], colorectal cancer (r = 0.72 [95% CI: 0.52-0.83], and NHL (r = 0.71 [95% CI: 0.50-0.83]. Conclusions: These correlations call to conduct new studies about the epidemiology of cancer in general and cutaneous malignant melanoma risk factors in particular.

  3. Study of the histopathological types of cutaneous melanoma in Palmas-TO from 2001 to 2011.

    Science.gov (United States)

    Costa, Nilo Fernandes da; Fernandes, Nurimar Conceição; Borges, Myrlena Regina Machado Mescouto

    2015-01-01

    Cutaneous melanoma (CM) is considered serious for causing frequent metastasis, presenting high mortality, resistance to available therapies and incidences in laboring activity. To study the histopathological types of cutaneous melanoma in Palmas-TO from 2001 to 2011, according to risk factors, location of lesions, Clark levels and Breslow thickness. A descriptive, retrospective and quantitative research in reports of the Serviços de Anatomia Patológica in Palmas (SAPP) and Registro de Câncer de Base Populacional de Palmas (RCBPP). The years of highest incidences were: 2004 (8 cases/17.8%), 2008 and 2011 (7 cases each/15.6%) and 2010 (6 cases/13.3%). Among the 45 cases studied, there were predominance in patients between 41 and 60 years old, women, caucasians, farmers, located in trunk, in situ type, superficial extensive and metastatic cutaneous, Clark levels I (20%) and IV (17.7%), Breslow thickness ≤1 mm (35.5%) and 2.01 to 4 mm (24.4%). The most common histopathological types were: cutaneous melanoma in situ, superficial extensive and metastatic, followed by nodular cutaneous melanoma, and finally, by other forms. In this study, Clark levels and Breslow thickness pointed to greater importance of thin melanomas and sun exposure without appropriate protection in farmers.

  4. Nestin expression is associated with aggressive cutaneous melanoma of the nodular type.

    Science.gov (United States)

    Ladstein, Rita G; Bachmann, Ingeborg M; Straume, Oddbjørn; Akslen, Lars A

    2014-03-01

    The intermediate filament nestin, a neural stem-cell marker, is reported to be expressed more strongly in melanomas compared with benign melanocytic lesions, and increasingly expressed in advanced melanoma stages. However, the prognostic impact of nestin on melanoma has not been well elucidated. The aim of the present study was to evaluate the prognostic influence of nestin expression in cutaneous melanoma in comparison with standard clinico-pathologic variables. In a large series of nodular cutaneous melanoma (n=348), nestin expression was assessed by immunohistochemistry using tissue microarray (TMA) sections. For comparison, nestin staining in corresponding metastases as well as in superficial spreading melanomas and benign nevi was also examined. Nestin was expressed to varying degrees in a majority of nodular melanomas (92%), and was significantly associated with increased tumor thickness, high mitotic count, and the presence of ulceration and tumor necrosis. Also, expression was stronger in the nodular type than in superficial spreading melanomas and benign nevi, but without significant difference when compared with matched metastases from the former. Importantly, strong expression of nestin was significantly associated with reduced survival in multivariate analysis. In conclusion, increased nestin expression was associated with aggressive melanoma features, with independent prognostic impact on multivariate survival analysis when compared with clinico-pathologic factors.

  5. Linear Malignant Melanoma In Situ: Reports and Review of Cutaneous Malignancies Presenting as Linear Skin Cancer.

    Science.gov (United States)

    Cohen, Philip R

    2017-09-18

    Melanomas usually present as oval lesions in which the borders may be irregular. Other morphological features of melanoma include clinical asymmetry, variable color, diameter greater than 6 mm and evolving lesions. Two males whose melanoma in situ presented as linear skin lesions are described and cutaneous malignancies that may appear linear in morphology are summarized in this report. A medical literature search engine, PubMed, was used to search the following terms: cancer, cutaneous, in situ, linear, malignant, malignant melanoma, melanoma in situ, neoplasm, and skin. The 25 papers that were generated by the search and their references, were reviewed; 10 papers were selected for inclusion. The cancer of the skin typically presents as round lesions. However, basal cell carcinoma and squamous cell carcinoma may arise from primary skin conditions or benign skin neoplasms such as linear epidermal nevus and linear porokeratosis. In addition, linear tumors such as basal cell carcinoma can occur. The development of linear cutaneous neoplasms may occur secondary to skin tension line or embryonal growth patterns (as reflected by the lines of Langer and lines of Blaschko) or exogenous factors such as prior radiation therapy. Cutaneous neoplasms and specifically melanoma in situ can be added to the list of linear skin lesions.

  6. Preliminary experiences of intralesional immunotherapy in cutaneous metastatic melanoma.

    Science.gov (United States)

    Ridolfi, Laura; Ridolfi, Ruggero

    2002-01-01

    Antigen presenting cells are inactive within tumor tissue because of local immunosuppression. Tumor infiltrating lymphocyte signal activation transducing mechanisms are also seriously impaired. Administration of granulocyte macrophage-colony stimulating factor may lead to antigen-presenting cell recovery and interleukin-2 may restore local tumor infiltrating lymphocyte activation. Moreover, interleukin-2 increases the systemic lymphocyte population, an event which seems to correlate with a better prognosis. The present phase I-II study was carried out to examine whether intralesional injection of granulocyte macrophage-colony stimulating factor followed by subcutaneous interleukin-2 would induce a clinical response in advanced, pretreated and elderly melanoma patients. Fourteen patients over 60 years of age received intralesional granulocyte macrophage-colony stimulating factor (150 micrograms per lesion on day 1), generally divided between the two largest cutaneous lesions, followed by perilesional subcutaneous interleukin-2 (3.000.000/IU) for 5 days (3 to 7) every 3 weeks. All patients received 6 courses of treatment unless progression occurred. Clinical evaluation of the treated cutaneous lesions was assessed at the baseline and before every cycle. Distant lesions were checked every two cycles. Four clinical responses (2 partial responses and 2 minimal responses) (28.5%), which also involved lesions that had not been directly treated, and seven cases of stable disease were observed. The response duration for partial response and minimal response was 9, 4, 4 and 2.5+ months, respectively. Stable disease (50%) recorded in the 7 patients was short term, 3-6 months. Three patients rapidly progressed after 2, 2, and 1 therapy cycles, respectively. The patient who reached the best partial response had a fairly high absolute lymphocyte count (1600 to 2400/mm3). The second one, who reached a complete remission after subsequent locoregional chemotherapy and hyperthermia

  7. Epidemiología del melanoma cutáneo Epidemiology of cutaneous melanoma

    Directory of Open Access Journals (Sweden)

    R M C Leitner

    2006-06-01

    Full Text Available Durante las últimas décadas hubo un aumento de la incidencia del melanoma cutáneo en la población caucásica del mundo, aunque este tumor puede afectar a cualquier grupo étnico. En la actualidad se considera a la exposición solar intermitente como un factor de riesgo cierto, en el desarrollo del melanoma cutáneo. La incidencia del melanoma cutáneo en Auckland, Nueva Zelanda, es la mayor del mundo. En Europa, la incidencia y la mortalidad fue creciente hasta que en la década de los 80 se estabilizó. En EEUU también se observó una estabilización de la incidencia. Con respecto a la edad, según la bibliografía consultada la incidencia aumenta a partir de los 20 años; en algunos pacientes con más de 200 nevos y sin pautas de protección solar antes de los 5 años de vida. También se observa aumento de la incidencia en los adultos mayores de 60 años de edad. Con respecto al sexo, en los EEUU y la Argentina es más frecuente en los hombres y en Europa en el sexo femenino.During the last decades there was an increase of incidence of cutaneous melanoma in Caucasian population worldwide, but this tumor can affect any ethnic group. Nowadays, the intermittent solar exposition is a well known predisposing factor. The incidence in Auckland, New Zealand, is the highest in the world. In Europe and in the USA, the incidence and mortality rates decreased until the 80's when it stabilized. Regarding the age of appearance, the incidence increases starting at 20 years of age in patients with more than 200 nevi and without history of sun protection in childhood. There was also an increase in the incidence in adults (>60 y-o. The distribution by sex in USA and Argentina is more frequent in males and in Europe in females.

  8. Some interesting prognostic factors related to cutaneous malignant melanoma

    International Nuclear Information System (INIS)

    Joan Figueroa, AlejandroYuri; Diaz Anaya, Amnia; Montero Leon, Jorge Felipe; Jimenez Mendes, Lourdes

    2010-01-01

    INTRODUCTION: The aim of present research was to determine the independent prognostic value and the 3 and 5 years survival of more significant clinicopathological prognostic factors and in each stage, according to pathological staging system of tumor-nodule-metastasis (TNM) in patients with cutaneous malignant melanoma (CMM). METHODS: A longitudinal, descriptive and retrospective study was conducted applying the Cox proportional risk form and the Kaplan-Meier method, aimed to search of different risk variables in patients with CMM. We studied 157 patients with CMM, seen during 8 years (1993 to 2001), diagnosed and treated in National Institute of Oncology and Radiobiology of La Habana. RESULTS: The more powerful prognostic variables related to localized disease (stage I and II) were the Breslow density (P: 0,000), the mitosis rate (P: 0,004), and the Clark level (P: 0,04); among the variables related to the regional disease (stage III) the number of lymphatic ganglia involved was the more weighthy (P:0,000) and the more important in Stage IV was the distant visceral metastasis (P:0,003). Survival was decreasing according to the advance of the pathological stage of disease. CONCLUSIONS: The more involved independent prognostic factors were the Breslow rate, the number of involved regional lymphatic nodules and the distant visceral metastasis, which is endorsed by a world consensus. However, variables as age, sex, lesion site, ulceration, host-tumor inflammatory response, histological subtype, satellitosis and transient metastasis, considered as independent prognostic indicators in big casuistries, had not statistical significance in present paper. (author)

  9. Adjuvant radiotherapy for cutaneous melanoma: Comparing hypofractionation to conventional fractionation

    International Nuclear Information System (INIS)

    Chang, Daniel T.; Amdur, Robert J.; Morris, Christopher G. M.S.; Mendenhall, William M.

    2006-01-01

    Purpose: To examine locoregional control after adjuvant radiotherapy (RT) for cutaneous melanoma and compare outcomes between conventional fractionation and hypofractionation. Methods and Materials: Between January 1980 and June 2004, 56 patients with high-risk disease were treated with adjuvant RT. Indications for RT included: recurrent disease, cervical lymph node involvement, lymph nodes >3 cm, more than three lymph nodes involved, extracapsular extension, gross residual disease, close or positive margins, or satellitosis. Hypofractionation was used in 41 patients (73%) and conventional fractionation was used in 15 patients (27%). Results: The median age was 61 years (21->90). The median follow-up among living patients was 4.4 years (range, 0.6-14.4 years). The primary site was located in the head and neck in 49 patients (87%) and below the clavicles in 7 patients (13%). There were 7 in-field locoregional failures (12%), 3 out-of-field regional failures (5%), and 24 (43%) distant failures. The 5-year in-field locoregional control (ifLRC) and freedom from distant metastases (FFDM) rates were 87% and 43%, respectively. The 5-year cause-specific (CSS) and overall survival (OS) was 57% and 46%, respectively. The only factor associated with ifLRC was satellitosis (p = 0.0002). Nodal involvement was the only factor associated with FFDM (p = 0.0007), CSS (p = 0.0065), and OS (p = 0.016). Two patients (4%) who experienced severe late complications, osteoradionecrosis of the temporal bone and radiation plexopathy, and both received hypofractionation (5%). Conclusions: Although surgery and adjuvant RT provides excellent locoregional control, distant metastases remain the major cause of mortality. Hypofractionation and conventional fractionation are equally efficacious

  10. The Expression Quantitative Trait Loci in Immune Pathways and their Effect on Cutaneous Melanoma Prognosis.

    Science.gov (United States)

    Vogelsang, Matjaz; Martinez, Carlos N; Rendleman, Justin; Bapodra, Anuj; Malecek, Karolina; Romanchuk, Artur; Kazlow, Esther; Shapiro, Richard L; Berman, Russell S; Krogsgaard, Michelle; Osman, Iman; Kirchhoff, Tomas

    2016-07-01

    The identification of personalized germline markers with biologic relevance for the prediction of cutaneous melanoma prognosis is highly demanded but to date, it has been largely unsuccessful. As melanoma progression is controlled by host immunity, here we present a novel approach interrogating immunoregulatory pathways using the genome-wide maps of expression quantitative trait loci (eQTL) to reveal biologically relevant germline variants modulating cutaneous melanoma outcomes. Using whole genome eQTL data from a healthy population, we identified 385 variants significantly impacting the expression of 268 immune-relevant genes. The 40 most significant eQTLs were tested in a prospective cohort of 1,221 patients with cutaneous melanoma for their association with overall (OS) and recurrence-free survival using Cox regression models. We identified highly significant associations with better melanoma OS for rs6673928, impacting IL19 expression (HR, 0.56; 95% CI, 0.41-0.77; P = 0.0002) and rs6695772, controlling the expression of BATF3 (HR, 1.64; 95% CI, 1.19-2.24; P = 0.0019). Both associations map in the previously suspected melanoma prognostic locus at 1q32. Furthermore, we show that their combined effect on melanoma OS is substantially enhanced reaching the level of clinical applicability (HR, 1.92; 95% CI, 1.43-2.60; P = 2.38e-5). Our unique approach of interrogating lymphocyte-specific eQTLs reveals novel and biologically relevant immunomodulatory eQTL predictors of cutaneous melanoma prognosis that are independent of current histopathologic markers. The significantly enhanced combined effect of identified eQTLs suggests the personalized utilization of both SNPs in a clinical setting, strongly indicating the promise of the proposed design for the discovery of prognostic or risk germline markers in other cancers. Clin Cancer Res; 22(13); 3268-80. ©2016 AACR. ©2016 American Association for Cancer Research.

  11. Keratinocytes drive melanoma invasion in a reconstructed skin model.

    NARCIS (Netherlands)

    Kilsdonk, J.W.J. van; Bergers, M.; Kempen, L.C.L.T. van; Schalkwijk, J.; Swart, G.W.

    2010-01-01

    Melanoma progression is a multistep progression from a common melanocytic nevus through the radial growth phase, the invasive vertical growth phase finally leading to metastatic spread into distant organs. Migration and invasion of tumor cells requires secretion of proteases to facilitate remodeling

  12. Interval cancers after skin cancer screening: incidence, tumour characteristics and risk factors for cutaneous melanoma.

    Science.gov (United States)

    Hübner, J; Waldmann, A; Geller, A C; Weinstock, M A; Eisemann, N; Noftz, M; Bertram, S; Nolte, S; Volkmer, B; Greinert, R; Breitbart, E; Katalinic, A

    2017-01-17

    The rate of interval cancers is an established indicator for the performance of a cancer-screening programme. We examined the incidence, tumour characteristics and risk factors of melanoma interval cancers that occurred in participants of the SCREEN project, which was carried out 2003/2004 in Schleswig-Holstein, Germany. Data from 350 306 SCREEN participants, who had been screened negative for melanoma, were linked to data of the state cancer registry. Melanoma interval cancers were defined as melanomas diagnosed within 4-24 months after SCREEN examination. Results were compared with melanomas of the pre-SCREEN era (1999-2002), extracted from the cancer registry. The overall relative incidence of melanoma interval cancers in terms of observed/expected ratio was 0.93 (95% CI: 0.82-1.05; in situ: 1.61 (1.32-1.95), invasive: 0.71 (0.60-0.84)). Compared with melanomas of the pre-SCREEN era, the interval melanomas were thinner and had a slightly greater proportion of lentigo maligna melanomas whereas nodular melanomas were less frequent. The results indicate a moderate performance of the SCREEN intervention with an excess of in situ melanomas. In part, the findings might be due to specifics of the SCREEN project, in particular a short-term follow-up of patients at high risk for melanoma.

  13. Association between dermoscopic and reflectance confocal microscopy features of cutaneous melanoma with BRAF mutational status.

    Science.gov (United States)

    Bombonato, C; Ribero, S; Pozzobon, F C; Puig-Butille, J A; Badenas, C; Carrera, C; Malvehy, J; Moscarella, E; Lallas, A; Piana, S; Puig, S; Argenziano, G; Longo, C

    2017-04-01

    Melanomas harbouring common genetic mutations might share certain morphological features detectable with dermoscopy and reflectance confocal microscopy. BRAF mutational status is crucial for the management of metastatic melanoma. To correlate the dermoscopic characteristics of primary cutaneous melanomas with BRAF mutational status. Furthermore, a subset of tumours has also been analysed for the presence of possible confocal features that might be linked with BRAF status. Retrospectively acquired dermoscopic and confocal images of patients with melanoma in tertiary referral academic centres: Skin Cancer Unit in Reggio Emilia and at the Melanoma Unit in Barcelona. Kruskal-Wallis test, logistic regressions, univariate and multivariate analyses have been performed to find dermoscopic and confocal features significantly correlated with BRAF mutational status. Dermoscopically, the presence of irregular peripheral streaks and ulceration were positive predictors of BRAF-mutated melanomas with a statistically significance value, while dotted vessels were more represented in wild-type melanomas. None of the evaluated reflectance confocal microscopy features were correlated with genetic profiling. Ulceration and irregular peripheral streaks represent dermoscopic feature indicative for BRAF-mutated melanoma, while dotted vessels are suggestive for wild-type melanoma. © 2016 European Academy of Dermatology and Venereology.

  14. Antiestrogen therapy for breast cancer modifies the risk of subsequent cutaneous melanoma.

    Science.gov (United States)

    Huber, Caroline; Bouchardy, Christine; Schaffar, Robin; Neyroud-Caspar, Isabelle; Vlastos, Georges; Le Gal, Frédérique-Anne; Rapiti, Elisabetta; Benhamou, Simone

    2012-01-01

    Increased risk of secondary melanoma after breast cancer has been reported. Several lines of evidence suggest that elevated estrogen levels may be implicated in melanoma etiology. Accordingly, use of antiestrogens should be associated with decreased risk of melanoma. We compared melanoma incidence among a cohort of breast cancer patients with and without antiestrogen therapy, with data from the Geneva Cancer Registry. The cohort consisted of 7,360 women diagnosed with breast cancer between 1980 and 2005. About 54% of these patients received antiestrogens. All women were followed until December 2008. We compared cutaneous melanoma incidence rates among patients with and without antiestrogens with those expected in the general population by age and period standardized incidence ratios (SIR). A total of 34 women developed a melanoma during the follow-up period. Compared with the general population, the risk of melanoma was higher for patients who did not receive antiestrogens (SIR: 1.60, 95% CI: 1.08-2.12, P = 0.02). On the contrary, the risk was close to 1 (SIR: 0.98, 95% CI: 0.40-1.56, P = 0.57) for patients who received antiestrogen therapy. This study suggests that antiestrogen therapy modifies the risk of melanoma after breast cancer. Although our results are in agreement with the hypothesis that estrogens could play a role in melanoma occurrence, they need to be replicated in a larger study with data on potential confounders. . ©2011 AACR

  15. The use of interferon-alpha in the treatment of cutaneous melanoma: a review

    NARCIS (Netherlands)

    Punt, C. J.

    1998-01-01

    During the past few years significant progress has been made in the treatment of cutaneous melanoma. These developments often involve the use of interferon-alpha (IFNalpha). Promising results have been reported in high risk patients using adjuvant treatment with high dose IFNalpha. A confirmatory

  16. Downregulation of miR-125b in metastatic cutaneous malignant melanoma.

    Science.gov (United States)

    Glud, Martin; Rossing, Maria; Hother, Christoffer; Holst, Line; Hastrup, Nina; Nielsen, Finn C; Gniadecki, Robert; Drzewiecki, Krzysztof T

    2010-12-01

    This study aimed to identify microRNA species involved in the earliest metastatic event in cutaneous malignant melanoma (MM). Samples from 28 patients with MM [stage T2 (tumor), M0 (distant metastasis)] were grouped by the presence of micrometastasis in the sentinel lymph nodes (N0/N1). Melanoma cells were harvested from primary, cutaneous MM tumors by laser-capture microdissection, and microRNA expression profiles were obtained by the microarray technique. Results were validated by quantitative reverse transcription PCR. We found that miR-125b was downregulated in the primary cutaneous melanomas that produced early metastases (T2, N1, M0) compared with the sentinel lymph node-negative (T2, N0, M0) melanomas. MiR-125b has earlier been found to be downregulated in other tumor types and in atypic naevi compared with the common acquired naevi. In conclusion, miR-125b may be involved in an early progression of cutaneous MM.

  17. Prognostic importance of the mitotic marker phosphohistone H3 in cutaneous nodular melanoma.

    Science.gov (United States)

    Ladstein, Rita G; Bachmann, Ingeborg M; Straume, Oddbjørn; Akslen, Lars A

    2012-04-01

    Mitotic count is a known prognostic predictor in cutaneous melanoma, and is included in the current American Joint Committee on Cancer tumor-node-metastasis (TNM) staging system. The mitotic marker phosphohistone H3 (PHH3) is considered to facilitate counting of mitosis, and the purpose of this study was to evaluate the prognostic significance and strength of PHH3 in comparison with standard mitotic counting in cutaneous malignant melanoma. A total of 457 consecutive cases of nodular cutaneous melanoma were initially included in this series. The mitotic count was assessed on hematoxylin and eosin sections, and PHH3 was then examined by immunohistochemistry on standard sections of paraffin-embedded tumor tissue. Both the mitotic count and the number of PHH3-stained mitotic figures were recorded in a minimum area of 1 mm(2). Increased mitotic count and PHH3 value were both associated with unfavorable features like tumor thickness and presence of ulceration. Univariate survival analysis showed a highly significant prognostic impact of mitotic count and PHH3, whereas multivariate analysis indicated PHH3 to be a stronger prognostic indicator than mitotic count. Assessment of mitotic activity by PHH3 immunostaining might have important practical advantages, and should be further studied to consider a place in routine examination of all cutaneous melanomas.

  18. A cryptic BAP1 splice mutation in a family with uveal and cutaneous melanoma, and paraganglioma

    DEFF Research Database (Denmark)

    Wadt, K.; Choi, J.; Chung, J.Y.

    2012-01-01

    Inactivating germ line BRCA1-associated protein-1 (BAP1) mutations have recently been reported in families with uveal or cutaneous malignant melanoma (UMM, CMM), mesothelioma, and meningioma. Although apparently predisposing to a wide range of tumors, the exact tumor spectrum associated with germ...

  19. Analysis of trends and seasonal variation in primary cutaneous melanoma: an Irish study.

    LENUS (Irish Health Repository)

    Downes, M R

    2010-11-10

    A seasonal variation in the presentation of cutaneous melanoma has been documented in several studies. We performed a retrospective review of primary cutaneous melanomas (n = 263) from our institution to examine whether the seasonal patterns of presentation noted in the literature would be similar in Ireland, a climate with low ambient sunshine. A summer : winter ratio was determined for age, gender, subtype, location and Breslow thickness. We found an increase in total numbers of melanomas, particularly in men. The summer : winter ratio was 2.39 for all patients (95% CI 1.60-3.57, P < 0.001), with seasonal variations noted for location, thickness and subtype (excluding lentigo). Melanomas presenting over the summer tended towards a greater Breslow thickness than did those presenting in winter. This subclassification of primary cutaneous melanoma with summer : winter ratios based on patient and tumour characteristics gave remarkably similar results to previously published reports, notwithstanding the low levels of annual ambient sunshine in Ireland.

  20. 25-OH Vitamin D and Interleukin-8: Emerging Biomarkers in Cutaneous Melanoma Development and Progression

    Directory of Open Access Journals (Sweden)

    Corina-Daniela Ene

    2015-01-01

    Full Text Available Background. There are several circulatory biomarkers that are involved in forecasting the clinical outcome of cutaneous melanoma. Serum/plasma vitamin D status is one of the markers intensively studied in this type of cutaneous cancer. The combination of validated serum biomarkers (like LDH with new biomarkers such as IL-8, angiogenic factor, and vitamin D is still at the dawn of research. Hence, we are aiming to establish the predictive power of inflammatory biomarkers, such as IL-8, and metabolic ones, such as vitamin D. These candidate biomarkers are intended to aid classical biomarkers, such as LDH, in the prognosis of cutaneous melanoma. Methods. Serum vitamin D and IL-8 were quantified in melanoma patients and in matching healthy controls. Results. Median serum vitamin D concentrations were significantly lower (p=0.003 in melanoma patients as compared to healthy control subjects, while around 65% of the investigated patients have proven a severe circulatory deficiency of this vitamin. IL-8 was found increased (p=0.001 in melanoma patients as compared to controls. Conclusion. Upregulation of proangiogenic factors associated with vitamin D deficiency can prove to be potent future biomarkers candidates, enhancing the predictive power of classical LDH.

  1. Effect of time to sentinel-node biopsy on the prognosis of cutaneous melanoma.

    Science.gov (United States)

    Tejera-Vaquerizo, Antonio; Nagore, Eduardo; Puig, Susana; Robert, Caroline; Saiag, Philippe; Martín-Cuevas, Paula; Gallego, Elena; Herrera-Acosta, Enrique; Aguilera, José; Malvehy, Josep; Carrera, Cristina; Cavalcanti, Andrea; Rull, Ramón; Vilalta-Solsona, Antonio; Lannoy, Emilie; Boutros, Celine; Benannoune, Naima; Tomasic, Gorana; Aegerte, Philippe; Vidal-Sicart, Sergi; Palou, Josep; Alos, L Lúcia; Requena, Celia; Traves, Víctor; Pla, Ángel; Bolumar, Isidro; Soriano, Virtudes; Guillén, Carlos; Herrera-Ceballos, Enrique

    2015-09-01

    In patients with primary cutaneous melanoma, there is generally a delay between excisional biopsy of the primary tumour and sentinel-node biopsy. The objective of this study is to analyse the prognostic implications of this delay. This was an observational, retrospective, cohort study in four tertiary referral hospitals. A total of 1963 patients were included. The factor of interest was the interval between the date of the excisional biopsy of the primary melanoma and the date of the sentinel-node biopsy (delay time) in the prognosis. The primary outcome was melanoma-specific survival and disease-free survival. A delay time of 40 days or less (hazard ratio (HR), 1.7; confidence interval (CI), 1.2-2.5) increased Breslow thickness (Breslow ⩾ 2 mm, HR, > 3.7; CI, 1.4-10.7), ulceration (HR, 1.6; CI, 1.1-2.3), sentinel-node metastasis (HR, 2.9; CI, 1.9-4.2), and primary melanoma localised in the head or neck were independently associated with worse melanoma-specific survival (all P < 0.03). The stratified analysis showed that the effect of delay time was at the expense of the patients with a negative sentinel-node biopsy and without regression. Early sentinel-node biopsy is associated with worse survival in patients with cutaneous melanoma. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Cutaneous malignant melanoma in situ: A Danish cross-sectional study on patient and tumour characteristics in 144 cases

    Directory of Open Access Journals (Sweden)

    Anders Klit

    2015-12-01

    Conclusion: The anatomical distribution of MIS differed with patient age and tumour subtype. The anatomical distribution was different in comparison to invasive malignant melanomas, and MIS cases were generally older. This suggests a non-linear relation between malignant melanoma in situ and invasive malignant melanoma.

  3. Matrix Metalloproteinase-9 (MMP-9 polymorphisms in patients with cutaneous malignant melanoma

    Directory of Open Access Journals (Sweden)

    Busam Klaus

    2007-03-01

    Full Text Available Abstract Background Cutaneous Malignant Melanoma causes over 75% of skin cancer-related deaths, and it is clear that many factors may contribute to the outcome. Matrix Metalloproteinases (MMPs play an important role in the degradation and remodeling of the extracellular matrix and basement membrane that, in turn, modulate cell division, migration and angiogenesis. Some polymorphisms are known to influence gene expression, protein activity, stability, and interactions, and they were shown to be associated with certain tumor phenotypes and cancer risk. Methods We tested seven polymorphisms within the MMP-9 gene in 1002 patients with melanoma in order to evaluate germline genetic variants and their association with progression and known risk factors of melanoma. The polymorphisms were selected based on previously published reports and their known or potential functional relevance using in-silico methods. Germline DNA was then genotyped using pyrosequencing, melting temperature profiles, heteroduplex analysis, and fragment size analysis. Results We found that reference alleles were present in higher frequency in patients who tend to sunburn, have family history of melanoma, higher melanoma stage, intransit metastasis and desmoplastic melanomas among others. However, after adjustment for age, sex, phenotypic index, moles, and freckles only Q279R, P574R and R668Q had significant associations with intransit metastasis, propensity to tan/sunburn and primary melanoma site. Conclusion This study does not provide strong evidence for further investigation into the role of the MMP-9 SNPs in melanoma progression.

  4. Prognostic impact of autophagy biomarkers for cutaneous melanoma.

    Directory of Open Access Journals (Sweden)

    Diana Yao Li Tang

    2016-11-01

    Full Text Available Prognosis and survival for malignant melanoma is highly dependent on early diagnosis and treatment. While the American Joint Committee on Cancer (AJCC criteria provides a means of staging melanomas and guiding treatment approaches, it is unable to identify the risk of disease progression of early stage tumours or provide reliable stratification for novel adjuvant therapies. The demand for credible prognostic/companion biomarkers able to identify high risk melanoma subgroups as well as guide more effective personalised/precision based therapy is therefore of paramount importance. Autophagy, the principle lysosomal-mediated process for the degradation/recycling of cellular debris, is a hot topic in cancer medicine and observations of its deregulation in melanoma have brought its potential as a prognostic biomarker to the forefront of current research. Key regulatory proteins, including Atg8/microtubule-associated light chain 3 (LC3 and BECN1 (Beclin 1 have been proposed as potential prognostic biomarkers. However, given the dynamic nature of autophagy, their expression in vitro does not translate to their use as a prognostic biomarker for melanoma in vivo. We have recently identified the expression levels of Sequestosome1/SQSTM1 (p62 and activating molecule in Beclin 1 regulated autophagy protein 1 (AMBRA1 as novel independent prognostic biomarkers for early stage melanomas. While increasing followed by subsequent decreasing levels of p62 expression reflects the paradoxical role of autophagy in melanoma, expression levels additionally define a novel prognostic biomarker for AJCC stage II tumours. Conversely, loss of AMBRA1 in the epidermis overlying primary melanomas defines a novel prognostic biomarker for AJCC stage I tumours. Collectively, the definition of AMBRA1 and p62 as prognostic biomarkers for early stage melanomas provides novel and accurate means through which to identify tumours at risk of disease progression, facilitating earlier

  5. Melanoma cutâneo: estudo prospectivo de 65 casos Cutaneous melanoma: prospective study of 65 cases

    Directory of Open Access Journals (Sweden)

    Nurimar C. Fernandes

    2005-02-01

    Full Text Available FUNDAMENTOS: A incidência e a mortalidade por melanoma cutâneo vêm aumentando em todo o mundo. Os registros brasileiros de bases populacionais não refletem precisamente a real dimensão do problema. OBJETIVOS: Estudo prospectivo de 65 casos de melanoma cutâneo observados no Hospital Universitário Clementino Fraga Filho no período de 1993 a 2003. MÉTODOS: Foram analisadas as variáveis idade, sexo, cor, localização, tipos clínico-histológicos e estadiamento. RESULTADOS: 64,7% na faixa etária de 40 a 69 anos, distribuição etária homogênea entre o sexo masculino (49,2% e o sexo feminino (50,8%, predominância de brancos (83%, localização no tronco (35,3%, tipo clínico-histológico expansivo superficial (63%/30,7% e relação de significância entre tipo acral localizado no pé em não brancos. Segundo o American Joint Committee on Cancer, em 2002, 22 casos (33,8% no estádio IA, 14 (21,5% melanomas in situ e um caso indeterminado. CONCLUSÕES: O melanoma cutâneo primário na amostra estudada mostrou padrões semelhantes aos classicamente reconhecidos e maior freqüência do estádio IA e melanoma in situ.BACKGROUND: Incidence and mortality of cutaneous melanoma are increasing all over the world. The data base for the Brazilian population is still inadequate. OBJECTIVES: Prospective study of 65 cases seen at University Hospital Clementino Fraga Filho, from 1993 to 2003. METHODS: Patient's age, sex, ethnic group, anatomic site, clinical histological presentation and staging were analyzed. RESULTS: The case distribution was 64.7% aged 40 to 69 years, males (49.2% and females (50.8%, majority white (83.1%, most lesions in the trunk (35.3%, more frequently of the clinical histological superficial spreading type (63%/30.7% and significant relationship between foot acral type in non-whites. According to American Joint Committee on Cancer 2002 system, 22 cases (33.8% in stage IA, 14 (21.5% melanomas in situ, and one indeterminate case

  6. Clinicopathological features and pituitary homeobox 1 gene expression in the progression and prognosis of cutaneous malignant melanoma

    Directory of Open Access Journals (Sweden)

    Figen Barut

    2016-10-01

    Full Text Available The evidence that PITX1 (pituitary homeobox 1 is a significant tumor suppressor in human cancer remains largely circumstantial, but it clearly warrants further study as little is known about the tumor-inhibitory roles of PITX1 in cutaneous malignant melanoma. The aims of this study were to investigate PITX1 gene expression in patients with cutaneous malignant melanoma and to evaluate its potential relevance to clinicopathological characteristics and tumor cell proliferation. Clinicopathological findings of patients with cutaneous malignant melanoma were analyzed retrospectively. PITX1 and Ki-67 expression were detected by immunohistochemistry in malignant melanoma and healthy tissue samples from each patient. Labeling indices were calculated based on PITX1 gene and Ki-67 expression. The correlation between PITX1and Ki-67 expressions was analyzed in cutaneous malignant melanoma cases. The relationship between PITX1 expression intensity and clinicopathological characteristics was also analyzed. PITX1 expression was observed in all (100% normal healthy skin tissue samples. In addition, PITX1 expression was found in 56 (80% and was absent in 14 (20% of the 70 cutaneous malignant melanoma cases. Ki-67 positive expression was only detected in the 14 (20% PITX1-negative cases. PITX1-positive tumor cells were observed on the surface, but Ki-67 positive tumor cells were observed in deeper zones of the tumor nests. PITX1 expression was downregulated in human cutaneous malignant melanoma lesions compared with healthy skin tissue, but Ki-67 expression was upregulated in concordance with the progression of cutaneous malignant melanoma. PITX1 expression may be involved in tumor progression and is a potential tumor suppressor gene and prognostic marker for cutaneous malignant melanoma.

  7. Surgery and radiotherapy in the treatment of cutaneous melanoma

    DEFF Research Database (Denmark)

    Testori, A; Rutkowski, P; Marsden, J

    2009-01-01

    on individual circumstances. Radiotherapy is indicated as a treatment option in select patients with lentigo maligna melanoma and as an adjuvant in select patients with regional metastatic disease. Radiotherapy is also indicated for palliation, especially in bone and brain metastases....

  8. [Regression in primary cutaneous melanoma is not predictive for sentinel lymph node micrometastasis].

    Science.gov (United States)

    Alquier-Bouffard, A; Franck, F; Joubert-Zakeyh, J; Barthélémy, I; Mansard, S; Ughetto, S; Aublet-Cuvelier, B; Déchelotte, P-J; Mondié, J-M; Souteyrand, P; D'incan, M

    2007-01-01

    The predictive value of regression in melanoma is debated. A retrospective single-centre study to evaluate the correlation between regression in primary skin tumor and the presence of micrometastases in sentinel lymph nodes. Histological signs of regression in 84 melanomas (>1 mm) with corresponding sentinel lymph nodes were studied by two independent pathologists. Regression was seen in 40 skin melanoma tumors while micrometastasis was seen in 24. Of the tumors with micrometastasis, only 10 were regressive (RR: 0.47, p=0.49). Breslow value>2 mm and male sex were predictive for node micrometastasis (RR: 4.6, p=0.03 and RR: 7.6, p=0.006, respectively). On multivariate analysis, these two factors were independent. These data suggest that regression in primary cutaneous melanoma is not predictive for lymph node metastasis.

  9. Ciliary body melanoma with optic nerve invasion.

    Science.gov (United States)

    al-Haddab, S; Hidayat, A; Tabbara, K F

    1990-01-01

    A case of melanoma of the ciliary body is presented. Initially the patient was diagnosed and treated for uveitis, but following CT scanning and ultrasound a tumour was detected and the eye enucleated. Histopathologically it was found that the tumour had invaded the optic nerve head, apparently via Cloquet's canal. Images PMID:2310725

  10. Inflammatory Cytokine Pattern Is Sex-Dependent in Mouse Cutaneous Melanoma Experimental Model

    Directory of Open Access Journals (Sweden)

    Mihaela Surcel

    2017-01-01

    Full Text Available We present the evaluation of inflammatory cytokines in mouse cutaneous melanoma experimental model, as markers of disease evolution. Moreover, to test our experimental model, we have used low doses of dacarbazine (DTIC. C57 BL/6J mouse of both sexes were subjected to experimental cutaneous melanoma and treated with low doses of DTIC. Clinical parameters and serum cytokines were followed during tumor evolution and during DTIC therapy. Cytokine/chemokine pattern was assessed using xMAP technology and the following molecules were quantified: interleukins (IL-1-beta, IL-6, IL-10, IL-12 (p70, interferon (IFN-gamma, granulocyte macrophage colony-stimulating factor (GM-CSF, tumor necrosis factor (TNF-alpha, macrophage inflammatory protein (MIP-1alpha, monocyte chemoattractant protein (MCP-1, and keratinocyte-derived chemokine (KC. Significant differences were found between normal females and males mice, female mice having a statistically higher serum concentration of IL-1-beta compared to male mice, while males have a significantly higher concentration of MIP-1-alpha. During melanoma evolution in the female group, IL-1-beta, MIP-1-alpha, and KC circulatory levels were found 10-fold increased, while other cytokines doubled their values. In the male mice group, only circulatory KC increased 4 times, while IL-1-beta and TNF-alpha doubled their circulatory values. Various serum cytokines correlated with the disease evolution in cutaneous melanoma mouse model.

  11. Cutaneous melanoma frequencies and seasonal trend in 20 years of observation of a population characterised by excessive sun exposure

    Directory of Open Access Journals (Sweden)

    Bonin Serena

    2015-12-01

    Full Text Available Background. Cutaneous melanoma is an aggressive form of skin cancer. It has become an increasingly common neoplasm in the most developed countries, especially among individuals of European origin.

  12. Evaluation of primary cutaneous malignant melanoma according to Breslow and Clarke pathological indices

    Directory of Open Access Journals (Sweden)

    Z. Safaii Naraghi

    2006-07-01

    Full Text Available Background: Malignant melanoma is one of the fatal cutaneous neoplasms which are curable by early diagnosis. This neoplasm is diagnosed by the biopsy of the suspected lesion. It is essential to classify the tumor based on its histology, thickness, phase of growth, level of invasion, mitotic rate, presence of regression, inflammatory infiltration and ulceration. These descriptions yield some knowledge about the progression of disease and suggest an estimate of the status of the screening system for early diagnosis. Methods: This is a cross-sectional retrospective descriptive study. Pathological slides with diagnosis of malignant melanoma from 1377 to 1379 that present in the pathology department were assessed according to mentioned pathological indices and the 10-year survival calculated in this regard. Results: We assessed 47 cases with mean age of 57.38 (SD=5.85 and the gender distribution was 51.1% male and 42.2% female. More than 42% of cases were in Clarke level I, 2.1% Clarke level II, 6.4% Clarke level III, 40.4% Clarke level IV and 8.5% Clarke level V. Fifty three percent of patients were breslow thickness equal to or less than 0.75 millimeter(mm , 8.5% between 0.76 to 1.69 mm , 27.7% between 1.7 to 3.6 mm and 10.6% greater than 3.61 mm. Mean breslow thickness show no significant difference between males and females but there is a significant relation between thickness and age of the patients. Mean 10-year survivals of patients were 75% and were greater in females than males. We found a linear relation between patient age and breslow thickness that is calculated by the following equation: Log Breslow thickness (mm = - 0.625 + 0.016×age (year Conclusion: Complete recording of clinical and pathological data of patients with malignant melanoma make a proper stream to reach a surveillance system.

  13. Telomere length and the risk of cutaneous melanoma and non-melanoma skin cancer: a review of the literature and meta-analysis.

    Science.gov (United States)

    Caini, Saverio; Raimondi, Sara; Johansson, Harriet; De Giorgi, Vincenzo; Zanna, Ines; Palli, Domenico; Gandini, Sara

    2015-12-01

    There is much evidence supporting the role of telomeres in cancer pathogenesis, however the studies that investigated the association between telomere length and skin cancer risk provided inconsistent results. To help clarify this issue, we performed a systematic review and meta-analysis of published papers on the association between peripheral leukocytes telomere length (PLTL) and the risk of cutaneous melanoma and non-melanoma skin cancer (NMSC). We calculated summary relative risks (SRR) and 95% confidence intervals (95% CI) using random effect models with maximum likelihood estimates, and explored causes of between-studies heterogeneity of risk estimates. We included 1629 cutaneous melanoma and 1439 NMSC from eight independent studies published until March 2015. The SRR of cutaneous melanoma for those in the lowest (vs. highest) category of PLTL distribution was 0.25 (95% CI 0.09-0.67). The results were less clear for NMSC, with two studies reporting no association and one study showing an increase in risk for those in the lowest (vs. highest) category of PLTL distribution. For both cutaneous melanoma and NMSC, the between-studies heterogeneity was large, mainly due to inclusion of hospital-based case-control studies. Our meta-analysis shows evidence of an association between short PLTL and reduced risk for cutaneous melanoma. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Association of vascular endothelial growth factor expression with patohistological parameters of cutaneous melanoma.

    Science.gov (United States)

    Gacević, Milomir; Jović, Milena; Zolotarevski, Lidija; Stanojević, Ivan; Novaković, Marijan; Miller, Karolina; Šuljagić, Vesna; Mijušković, Željko; Vojvodić, Danilo

    2016-05-01

    Melanoma is the most aggresive malignant tumor of the skin. Contradictory data was published on vascular endothelial growth factor (VGEF) in tumor samples and its role in skin melanoma progression and prognosis. The aim of this study was to investigate the significance of VEGF expression as a prognostic parameter in melanoma. The experimental group included 81 patients with primary skin melanomas treated from 2009 to 2013 at the Military Medical Academy, Belgrade. The control group included 20 patients with dysplastic and 20 with benign naevi. Stratification was done according to gender, age, clinical and patological stage, localization, histologic type, Clark's, Breslow, mitotic count, regression and ulceration, tumor infiltrating lymphocytes and metastatic spread.Immunohistochemical staining was performed on skin biopsies using DAKO anti-VEGF antibodies (Ab), LSAB+HRP, DAB and microvawe antigen (Ag) retrieval in DAKO pH 9.0 solution. For statistical data analysis was done with ANOVA, Bonferroni, Mann Whitney and Wilcox on test. The mean intensity of VEGF staining was statistically significantly higher in melanomas than in benign or dysplastic naevi. Furthermore, the highest recorded values were in Ia and IV clinical stages. The majority of melanomas with high intensity of VEGF staining were in pT1a pathological stage. Melanomas with the highest mitotic count (> 6) had a significantly higher intensity of VEGF staining than those with < 2 mitoses. The higest intensity of staining was in melanomas without significant lymphocytic infiltrate and the lowest was in those with brisk lymphocytic infiltrate, thus a statistical difference was siginifant. The mean intensity of VEGF staining was highest in melanomas with lymphovascular invasion. There was no statistically significant difference between VEGF and any other parameter. VEGF in primary skin melanomas plays an important role in tumor progression and is linked to the absence if tumor infiltrating lymphocytes and the

  15. Cutaneous melanoma attributable to solar radiation in Cali, Colombia.

    Science.gov (United States)

    de Vries, Esther; Amador, Julio R; Rincon, Carlos Javier; Uribe, Claudia; Parkin, Donald Maxwell

    2017-05-01

    Estimating the population attributable fraction (PAF) of melanomas due to sun exposure is challenging as there are no unexposed population nor reliable exposure data. In high incidence countries, a historic cohort of the South Thames cancer registry was used as a minimally exposed population using the formula PAF = (observed incidence-incidence in minimally exposure)/observed incidence. In this study, we apply this method, constructing a minimally exposed cohort for Colombia and also using the historical South Thames data, using melanoma incidence data from the population-based cancer registry of Cali, Colombia for the period 1967-2012. The historic cohort incidence rates were very similar to those of Thames, but cohort effects were smaller for women and nonexistent for men. Age-specific incidence rates of these minimally exposed cohorts were applied to recent population numbers. For females, PAFs were 19% using the historic Thames cohort and 25% using the historic Cali cohort, corresponding numbers for males were 62% (vs. Thames) and 0% (vs. Cali). Taking into account the incidence rates of acral melanomas, which are not sun related, the PAF increased in women to 26% (vs. Thames) and 34% (vs. Cali) and for men 77% (vs. Thames). This exercise shows the modest contribution of exposure to ultraviolet radiation in the burden of melanoma in low-incidence countries, as well as the importance to take into consideration the acral lentiginous melanomas. © 2017 UICC.

  16. MMP19 is upregulated during melanoma progression and increases invasion of melanoma cells

    Czech Academy of Sciences Publication Activity Database

    Muller, M.; Beck, Inken; Gadesmann, J.; Karschuk, N.; Paschen, A.; Proksch, E.; Djonov, V.; Reiss, K.; Sedláček, Radislav

    2010-01-01

    Roč. 23, č. 4 (2010), s. 511-521 ISSN 0893-3952 Institutional research plan: CEZ:AV0Z50520514 Keywords : melanoma * invasion * matrix metalloproteinase Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.176, year: 2010

  17. An incidental finding of a nodal recurrence of cutaneous malignant melanoma after a 45-year disease-free period.

    Science.gov (United States)

    Goodenough, Jenny; Cozon, Caroline Louise; Liew, Se Hwang

    2014-06-03

    We report the case of an 84-year-old woman who had a nodal recurrence of melanoma 45 years after the primary diagnosis of an extremity cutaneous melanoma. It is believed to be the longest disease-free latency period reported between primary melanoma diagnosis and recurrence to date. Late recurrences of melanoma are rare and recurrence after four decades extremely rare. This article suggests melanoma is a disease with a potentially lifelong risk of recurrence and thus clinicians and patients must be vigilant and aware of this risk, particularly if late recurrences are to be recognised early and management optimised. 2014 BMJ Publishing Group Ltd.

  18. Locally advanced colon cancer with cutaneous invasion: case report.

    Science.gov (United States)

    Tenreiro, Nádia; Ferreira, Cátia; Silva, Silvia; Marques, Rita; Ribeiro, Artur; Sousa, Paulo Jorge; Luís, Fernando Próspero

    2017-03-01

    Locally advanced colon cancer with direct abdominal wall and skin invasion is an extremely rare finding with most data being derived from case reports, historical autopsy-based or single-center retrospective studies. We present a unique case of a colon cancer with direct cutaneous invasion and colocutaneous fistulization. Eighty-six year old Caucasian female with multiple comorbidities, referred to Surgical Consultation due to ulcerated skin lesion in the abdomen. She had a long-standing large umbilical hernia but with no previous episodes of incarceration or occlusive symptoms. She denied any digestive or constitutional symptoms. Physical examination showed a large non-reducible umbilical hernia, with an associated painless firm mass within the hernia sac and cutaneous ulcerated growth. Colonoscopy revealed transverse colon cancer (endoscopic biopsy of the tumor and skin punch biopsy confirmed adenocarcinoma of the colon). Computed tomography showed a tumoral mass within the umbilical hernia, with cutaneous infiltration and enlarged regional lymph nodes. Rapid local progression led to colocutaneous fistula with total fecal diversion. We performed an extended right hemicolectomy with en bloc excision of the hernia sac and infiltrating cutaneous mass. In the current era of widespread use of screening colonoscopies, initial diagnosis of locally advanced colon cancer is decreasing. However, this unique case presented an opportunity to recall the advantages of multivisceral resections.

  19. The association between MC1R genotype and BRAF mutation status in cutaneous melanoma: findings from an Australian population.

    Science.gov (United States)

    Hacker, Elke; Hayward, Nicholas K; Dumenil, Troy; James, Michael R; Whiteman, David C

    2010-01-01

    There is increasing epidemiological and molecular evidence that cutaneous melanomas arise through multiple causal pathways. The purpose of this study was to explore the relationship between germline and somatic mutations in a population-based series of melanoma patients to reshape and refine the divergent pathway model for melanoma. Melanomas collected from 123 Australian patients were analyzed for melanocortin-1 receptor (MC1R) variants and mutations in the BRAF and NRAS genes. Detailed phenotypic and sun exposure data were systematically collected from all patients. We found that BRAF-mutant melanomas were significantly more likely from younger patients and those with high nevus counts, and were more likely in melanomas with adjacent neval remnants. Conversely, BRAF-mutant melanomas were significantly less likely in people with high levels of lifetime sun exposure. We observed no association between germline MC1R status and somatic BRAF mutations in melanomas from this population. BRAF-mutant melanomas have different origins from other cutaneous melanomas. These data support the divergent pathways hypothesis for melanoma, which may require a reappraisal of targeted cancer prevention activities.

  20. Multiple pigmentation gene polymorphisms account for a substantial proportion of risk of cutaneous malignant melanoma

    OpenAIRE

    Duffy, David L.; Zhao, Z. Z.; Sturm, Richard A.; Hayward, Nicholas K.; Martin, Nicholas G.; Montgomery, Grant W.

    2009-01-01

    We have previously described the role of red hair (Melanocortin 1 Receptor, MC1R) and blue eye (Oculocutaneous Albinism Type 2, OCA2) gene polymorphisms in modulating risk of cutaneous malignant melanoma (CMM) in a highly sun-exposed population of European descent. A number of recent studies, including genome-wide association studies (GWAS), have identified numerous polymorphisms controlling human hair, eye and skin colour. In this paper, we test a selected set of polymorphisms in pigmentatio...

  1. Multicenter case-control study of risk factors for cutaneous melanoma in Valencia, Spain.

    Science.gov (United States)

    Ballester, I; Oliver, V; Bañuls, J; Moragón, M; Valcuende, F; Botella-Estrada, R; Nagore, E

    2012-11-01

    It is important to identify subgroups within the general population that have an elevated risk of developing cutaneous melanoma because preventive and early-detection measures are useful in this setting. The findings of most studies that have evaluated risk factors for cutaneous melanoma are of limited application in Spain because the populations studied have different pigmentary traits and are subject to different environmental factors. To identify the phenotypic characteristics and amount of exposure to sunlight that constitute risk factors for cutaneous melanoma in the population of the Autonomous Community of Valencia, Spain. We performed a multicenter observational case-control study. In total, the study included 242 patients with melanoma undergoing treatment in 5 hospitals and 173 controls enrolled from among the companions of the patients between January 2007 and June 2008. The information was collected by means of a standardized, validated questionnaire. The odds ratio (OR) was calculated for each variable and adjusted using a multiple logistic regression model. The risk factors found to be statistically significant were skin phototypes I and II, blond or red hair, light eye color, abundant melanocytic nevi, and a personal history of actinic keratosis or nonmelanoma skin cancer. After the multivariate analysis, only blond or red hair (OR=1.9), multiple melanocytic nevi (OR=3.1), skin phototypes i and ii (OR=2.1), and a personal history of actinic keratosis (OR=3.5) or nonmelanoma skin cancer (OR=8.1) maintained significance in the model as independent predictive variables for melanoma. Our study supports the importance of certain factors that indicate genetic predisposition (hair color and skin phototype) and environmental factors associated with exposure to sunlight. Patients with multiple acquired melanocytic nevi and patients with markers of chronic skin sun damage (actinic keratosis and nonmelanoma cancer) presented a significant increase in risk

  2. Anti-SEMA4D Monoclonal Antibody VX15/2503 With Nivolumab or Ipilimumab in Treating Patients With Stage III or IV Melanoma

    Science.gov (United States)

    2018-02-01

    Metastatic Melanoma; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7

  3. [Latest approaches in the surgical treatment of cutaneous malignant melanoma].

    Science.gov (United States)

    Sandru, A; Bordea, C I; Voinea, S C; Gherghe, M; Albert, P; Condrea, I; Blidaru, A

    2011-01-01

    Malignant melanoma is a disease with an unpredictable evolution. Detected in stage I and II has a great chance to cure, if it is correctly treated: excisional biopsy with safety margins in accordance with tumor thickness. Lymphoscintigraphy with sentinel node identification and biopsy became compulsory for staging malignant melanoma, the role of complete lymphadenectomy would be established by publishing the MSLTII data. The sentinel node is analysed using more and more sophisticated techniques (RT-PCR) in order to detect isolated tumoral cells, although their clinical significance is not known yet. Metastases occurrence is a dramatic phenomenon because chemotherapy, radiotherapy or biologic therapy have insignificant results. The only therapeutic modality which may increase survival in this situation is surgery for some carefully selected patients.

  4. Telomerase reverse transcriptase promoter mutations in primary cutaneous melanoma.

    Science.gov (United States)

    Heidenreich, Barbara; Nagore, Eduardo; Rachakonda, P Sivaramakrishna; Garcia-Casado, Zaida; Requena, Celia; Traves, Victor; Becker, Jürgen; Soufir, Nadem; Hemminki, Kari; Kumar, Rajiv

    2014-02-26

    We previously reported a disease segregating causal germline mutation in a melanoma family and recurrent somatic mutations in metastasized tumours from unrelated patients in the core promoter region of the telomerase reverse transcriptase (TERT) gene. Here we show that the TERT promoter mutations, besides causing an increased gene expression, associate with increased patient age, increased Breslow thickness and tumour ulceration in 287 primary melanomas. The mutations are more frequent at both intermittently and chronically sun-exposed sites than non-exposed sites and tend to co-occur with BRAF and CDKN2A alterations. The association with parameters generally connected with poor outcome, coupled with high recurrence and mechanistic relevance, raises the possibility of the eventual use of TERT promoter mutations in the disease management.

  5. Inverse association between dietary vitamin D and risk of cutaneous melanoma in a northern Italy population

    Science.gov (United States)

    Vinceti, Marco; Malagoli, Carlotta; Fiorentini, Chiara; Longo, Caterina; Crespi, Catherine M.; Albertini, Giuseppe; Ricci, Cinzia; Lanzoni, Anna; Reggiani, Maurizio; Virgili, Annarosa; Osti, Federica; Lombardi, Mara; Santini, Marcello; Fanti, Pier Alessandro; Dika, Emi; Sieri, Sabina; Krogh, Vittorio; Seidenari, Stefania; Pellacani, Giovanni

    2010-01-01

    The possibility of an inverse association between vitamin D and risk of cancer and, in particular, of cutaneous malignant melanoma has been suggested, but results of epidemiologic studies are still conflicting. We examined the relation between dietary vitamin D intake and melanoma risk through a population-based case-control study (380 cases, 719 controls) in a northern region of Italy, a country with average vitamin D intake lower than in northern Europe or the US. We assessed average daily intake of vitamin D from foodstuffs using the European Prospective Investigation into Cancer and Nutrition (EPIC) semiquantitative food frequency questionnaire. In this population, levels of vitamin D intake were considerably lower than those observed in recent US studies. We found an inverse relation between dietary vitamin D and melanoma risk in the sample as a whole, in both crude and adjusted analyses. In sex and age-specific analyses, this association appeared to be stronger among males and among older subjects. These findings suggest that, at the relatively low levels of intake observed in this sample, an inverse relation between dietary vitamin D and risk of cutaneous malignant melanoma may exist. PMID:21541899

  6. Accuracy of Diagnostic Biopsy for Cutaneous Melanoma: Implications for Surgical Oncologists

    Directory of Open Access Journals (Sweden)

    Tina J. Hieken

    2013-01-01

    Full Text Available Background and Objectives. While excisional biopsy is recommended to diagnose cutaneous melanoma, various biopsy techniques are used in practice. We undertook this study to identify how frequently final tumor stage and treatment recommendations changed from diagnostic biopsy to final histopathology after wide local excision (WLE. Methods. We compared the histopathology of the dermatopathologist-reviewed diagnostic biopsy and final WLE in 332 cutaneous melanoma patients. Results. Tumor sites were extremity (51%, trunk (33%, and head/neck (16%. Initial biopsy types were excisional (56%, punch (21%, shave (18%, and incisional (5%. Most diagnostic biopsies were margin positive regardless of technique, and 36% of patients had residual melanoma on WLE. T-stage changed in 8% of patients, of whom 59% were diagnosed by punch biopsy, 15% by incisional biopsy, 15% by shave biopsy, and 11% by excisional biopsy (P<0.0001. Treatment recommendations changed in 6%: 2% after excisional biopsy, 5% after shave biopsy, 18% after punch biopsy, and 18% after incisional biopsy (P<0.0001. Conclusions. Although most biopsy margins were positive, T-stage and treatment changed for only a minority of melanoma patients. Our data provide valuable information to inform patient discussion regarding the likelihood of a change in prognosis and the need for secondary procedures after WLE. These data support the superiority of dermatopathologist-reviewed excisional biopsy when feasible.

  7. [Computed tomography evaluation of metastasis of cutaneous melanoma].

    Science.gov (United States)

    Potente, G; Cantisani, C; Cantisani, V; Bottoni, U; Calvieri, S; Andreoli, G M; Arduini, F; Guerrisi, R

    2001-04-01

    To assess the value of Computed Tomography (CT) in the diagnosis and in morphologic characterization of metastatic melanoma. The data of total body CT of 124 consecutive patients with melanoma having a Breslow index 1 mm or a positive sentinel lymph node have been retrospectively reviewed. The CT scan showed loco-regional and/or distant metastases in 36 patients (39%). Ten of these (28%) had metastases only to lymph nodes, whereas 26 patients (72%) had multiple metastases. Nodal, pulmonary, brain, subcutaneous, hepatic, adrenal, bone, gastrointestinal, breast and abdominal wall metastases were detected in 80.6%, 47.2%, 25%, 25%, 16.7%, 13.9%, 11.1%, 5.6%, 5.6% and 2.8% of the patients respectively. All the patients with metastases also had a positive sentinel lymph nodes and/or symptoms of metastatic disease. CT fails to reveal any characteristic feature of metastatic melanoma, but it is of value in the diagnosis of loco-regional and distant metastases in III stage disease.

  8. Cutaneous side-effects during therapy of melanoma by vemurafenib

    Directory of Open Access Journals (Sweden)

    Anna Ankudowicz

    2015-06-01

    Full Text Available Introduction. Vemurafenib is a selective inhibitor of serine-threonine kinase BRAF used in the treatment of advanced melanoma with BRAF mutation. Effectiveness of this drug was confirmed in a large clinical trial, which led to the increase of its usage. During treatment with vemurafenib, particular attention should be paid to the numerous side effects, including those concerning the skin. Vemurafenib is highly toxic to the skin. Skin lesions occurring during the treatment of melanoma with this medicament can be divided into: early (observed 3 to 6 weeks after beginning treatment, late (observed 6 weeks after beginning treatment and hypersensitivity reactions to vemurafenib. Objective. Presentation of vemurafenib toxic effects on the skin and side effects that can be caused by this drug. Case report. We present a 58-year-old woman with metastatic melanoma who was treated with vemurafenib. During the course of therapy, numerous adverse reactions, including inflammatory tumors, emergence of a number of melanocytic naevi, skin horns, alopecia, hyperkeratosis of the palms and soles, and palmar erythrodysesthesia were observed. She was treated with anti-inflammatory drugs, an antibiotic, circulation-improving preparations and local moisturizing and keratolytic treatment. The patient remains under the care of oncologists and dermatologists. Conclusions. The new generation anti-cancer drugs bring hope for a cure or prolongation of life, but can also significantly reduce the quality of life by inducing both general and local adverse side effects. Oncological patients should also be taken care of by dermatologists.

  9. Ki-67 expression is superior to mitotic count and novel proliferation markers PHH3, MCM4 and mitosin as a prognostic factor in thick cutaneous melanoma

    International Nuclear Information System (INIS)

    Ladstein, Rita G; Bachmann, Ingeborg M; Straume, Oddbjørn; Akslen, Lars A

    2010-01-01

    Tumor cell proliferation is a predictor of survival in cutaneous melanoma. The aim of the present study was to evaluate the prognostic impact of mitotic count, Ki-67 expression and novel proliferation markers phosphohistone H3 (PHH3), minichromosome maintenance protein 4 (MCM4) and mitosin, and to compare the results with histopathological variables. 202 consecutive cases of nodular cutaneous melanoma were initially included. Mitotic count (mitosis per mm 2 ) was assessed on H&E sections, and Ki-67 expression was estimated by immunohistochemistry on standard sections. PHH3, MCM4 and mitosin were examined by staining of tissue microarrays (TMA) sections. Increased mitotic count and elevated Ki-67 expression were strongly associated with increased tumor thickness, presence of ulceration and tumor necrosis. Furthermore, high mitotic count and elevated Ki-67 expression were also associated with Clark's level of invasion and presence of vascular invasion. High expression of PHH3 and MCM4 was correlated with high mitotic count, elevated Ki-67 expression and tumor ulceration, and increased PHH3 frequencies were associated with tumor thickness and presence of tumor necrosis. Univariate analyses showed a worse outcome in cases with elevated Ki-67 expression and high mitotic count, whereas PHH3, MCM4 and mitosin were not significant. Tumor cell proliferation by Ki-67 had significant prognostic impact by multivariate analysis. Ki-67 was a stronger and more robust prognostic indicator than mitotic count in this series of nodular melanoma. PHH3, MCM4 and mitosin did not predict patient survival

  10. Investigation of the relationship between dermoscopic features and histopathological prognostic indicators in patients with cutaneous melanoma

    Directory of Open Access Journals (Sweden)

    Özlem Özbağçıvan

    2015-09-01

    Full Text Available Background and Design: Dermoscopy has an important role in the diagnosis of melanoma nowadays. Dermoscopic findings of melanoma had been associated with Breslow thickness and invasion status in previous studies but the relationship between dermatoscopic findings and other histopathological prognostic indicators has not been investigated until today. In this study, our aim is to investigate the relationship between dermatoscopic findings and histopathologic prognostic indicators such as Breslow thickness, invasion status, mitotic rate, lymphovascular invasion (LVI, ulceration and regression in patients who had been diagnosed with melanoma due to their clinical, dermatoscopic and histopatological findings. Materials and Methods: Dermoscopic and histopathological findings of 47 cases of melanoma who applied to our clinic between the years 2000 and 2014 were evaluated. The relationship between the dermoscopic findings which had been reported to be observed in melanomas in previous research and the histopathologic prognostic indicators such as Breslow thickness, invasion status, mitotic rate, lymphovascular invasion, ulceration and regression were investigated. Results: Irregular dots/globules, atypical pigment network, multifocal hypopigmentation, radial streaks and moth-eaten borders have been associated with good prognostic indicators whereas comedo like openings, regular blotch, exophytic papillary structures, dotted, glomerular, lineer irregular vessels, pink/red and blue/gray colors were associated with poor prognostic indicators. Additionally some dermatoscopic findings which are more observed in benign lesions such as multiple milia-like cysts, comedo like openings, moth-eaten borders, regular blotch, exophytic papillary structures and finger print areas have been observed in melanomas in our study. Conclusion: Many dermoscopic findings have demonstrated statistically significant association with the histopathological prognostic indicators

  11. Ethnicity and Cutaneous Melanoma in the City of Sao Paulo, Brazil: A Case-Control Study

    Science.gov (United States)

    Luiz, Olinda C.; Gianini, Reinaldo José; Gonçalves, Fernanda T.; Francisco, Guilherme; Festa-Neto, Cyro; Sanches, José Antonio; Gattas, Gilka J. F.; Chammas, Roger; Eluf-Neto, José

    2012-01-01

    Background Over the last century the incidence of cutaneous melanoma has increased worldwide, a trend that has also been observed in Brazil. The identified risk factors for melanoma include the pattern of sun exposure, family history, and certain phenotypic features. In addition, the incidence of melanoma might be influenced by ethnicity. Like many countries, Brazil has high immigration rates and consequently a heterogenous population. However, Brazil is unique among such countries in that the ethnic heterogeneity of its population is primarily attributable to admixture. This study aimed to evaluate the contribution of European ethnicity to the risk of cutaneous melanoma in Brazil. Methodology/Principal Findings We carried out a hospital-based case-control study in the metropolitan area of Sao Paulo, Brazil. We evaluated 424 hospitalized patients (202 melanoma patients and 222 control patients) regarding phenotypic features, sun exposure, and number of grandparents born in Europe. Through multivariate logistic regression analysis, we found the following variables to be independently associated with melanoma: grandparents born in Europe—Spain (OR = 3.01, 95% CI: 1.03–8.77), Italy (OR = 3.47, 95% CI: 1.41–8.57), a Germanic/Slavic country (OR = 3.06, 95% CI: 1.05–8.93), or ≥2 European countries (OR = 2.82, 95% CI: 1.06–7.47); eye color—light brown (OR = 1.99, 95% CI: 1.14–3.84) and green/blue (OR = 4.62; 95% CI 2.22–9.58); pigmented lesion removal (OR = 3.78; 95% CI: 2.21–6.49); no lifetime sunscreen use (OR = 3.08; 95% CI: 1.03–9.22); and lifetime severe sunburn (OR = 1.81; 95% CI: 1.03–3.19). Conclusions Our results indicate that European ancestry is a risk factor for cutaneous melanoma. Such risk appears to be related not only to skin type, eye color, and tanning capacity but also to others specific characteristics of European populations introduced in the New World by European immigrants. PMID:22558444

  12. BH3-only protein Bim predicts advanced stage of cutaneous melanoma.

    Science.gov (United States)

    Gambichler, T; Rooms, I; Scholl, L; Stockfleth, E; Stücker, M; Sand, M

    2016-11-01

    Bim having strong pro-apoptotic effects belongs to the BH3-only proteins of the Bcl-2 protein family and contributes to survival pathways in cancer cells. We aimed to investigate Bim protein expression in cutaneous melanoma (CM). Bim protein expression was assessed by immunohistochemistry in primary and metastatic melanomas and correlated with clinical and histopathological features. The Bim immunoreactivity score of the primary melanomas investigated (4.6 ± 1.5) was significantly (P Bim expression was significantly associated with primary nodular melanoma type (P = 0.005). Moreover, Bim expression was significantly inversely correlated with tumour thickness (r = -0.36; P = 0.0035), advanced stage of disease (stage III and IV; r = -0.60; P Bim expression (P = 0.0010, odds ratio: 0.22, 95% CI: 0.10-0.56) on multivariate analysis; however, Bim was not shown to be an independent predictor for disease relapse (P = 0.40) and disease-related death (P = 0.77). Our data demonstrate that Bim protein expression is significantly inversely correlated with melanoma features that are associated with worse prognosis. We have shown that Bim protein expression in CM is an independent predictor for advanced disease confirming that this pro-apoptotic BH3-only protein might be a potent biomarker and promising therapeutic target. © 2016 European Academy of Dermatology and Venereology.

  13. Epidemiological trends and clinicopathological features of cutaneous melanoma in sporadic and xeroderma pigmentosum Tunisian patients.

    Science.gov (United States)

    Naouali, Chokri; Jones, Meriem; Nabouli, Imen; Jerbi, Manel; Tounsi, Haifa; Ben Rekaya, Mariem; Ben Ahmed, Melika; Bouhaouala, Balkiss; Messaoud, Olfa; Khaled, Aida; Zghal, Mohamed; Abdelhak, Sonia; Boubaker, Samir; Yacoub-Youssef, Houda

    2017-01-01

    Epidemiological features and trends of cutaneous melanoma (CM) in North-African populations remain unclear. Those populations are of particular interest as they belong to a mosaic of various other origins (sub-Saharan, European Ancestry, and North-African Berbers). The aim of this study is to draw epidemiological profile and clinicopathological features of CM in the Tunisian population. Incidence analyses were based on data from regional cancer registries. Clinical data were collected from dermatological departments and xeroderma pigmentosum (XP) referral centers and provided CM clinicopathological characteristics and progression. Statistical analyses were achieved using R packages and SPSS 20.0. The incidence of CM in Tunisia is relatively low (0.5-0.7 per 100,000 inhabitants per year). Gender differences were observed regarding anatomical distribution (P = 0.004). Acral lentiginous melanoma (ALM) was the most frequent histological subtype (32.3%); however, nodular melanoma (NM) was the most aggressive and responsible for 54.8% of deaths. CM in XP patients develops at a median age that is 42 years earlier than sporadic cases, with preferential localization on the head and neck (P melanoma features in Tunisia are closer to those of non-Caucasians, even though gender differences that are similar to those observed in Caucasians were uncovered. This study also emphasizes the aggressiveness of NM and its effect on melanoma patient deaths. Xeroderma pigmentosum stands as the major predisposing host factor. © 2016 The International Society of Dermatology.

  14. Coffee Drinking and Cutaneous Melanoma Risk in the NIH-AARP Diet and Health Study

    Science.gov (United States)

    Freedman, Neal D.; Graubard, Barry I.; Hollenbeck, Albert R.; Shebl, Fatma M.; Mayne, Susan T.; Sinha, Rashmi

    2015-01-01

    Background: Cutaneous melanoma is the fifth most common cancer in the United States. Modifiable risk factors, with the exception of exposure to ultraviolet radiation (UVR), are poorly understood. Coffee contains numerous bioactive compounds and may be associated inversely with melanoma. However, previous epidemiological evidence is limited. Methods: Coffee intake was assessed at baseline with a food frequency questionnaire in the National Institutes of Health–AARP prospective cohort study. Among 447 357 non-Hispanic whites who were cancer-free at baseline, 2904 incident cases of malignant melanoma were identified during 4 329 044 person-years of follow-up, with a median of 10.5 years of follow-up. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for coffee intake and subsequent melanoma risk with non–coffee drinkers as the reference group. Statistical tests were two-sided, and P values less than .05 were interpreted as statistically significant. Results: The highest category of coffee intake was inversely associated with malignant melanoma (≥4 cups/day: HR = 0.80, 95% CI = 0.68 to 0.93, P trend = .01). This association was statistically significant for caffeinated (≥4 cups/day: HR = 0.75, 95% CI = 0.64 to 0.89, P trend = .01) but not for decaffeinated coffee (P trend = .55). Conclusions: Higher coffee intake was associated with a modest decrease in risk of melanoma in this large US cohort study. Additional investigations of coffee intake and its constituents, particularly caffeine, with melanoma are warranted. PMID:25604135

  15. Correlation of cell cycle regulatory proteins (p53 and p16ink4a and bcl-2 oncoprotein with mitotic index and thickness of primary cutaneous malignant melanoma

    Directory of Open Access Journals (Sweden)

    Miloš Kostov

    2010-11-01

    Full Text Available The purpose of the study was to determine the frequency of expression p53 and p16INK4a proteins and bcl2- oncoprotein in malignant skin melanoma and to determine their correlation with the proliferative index and tumor thickness. The study involved 53 patients: 27 (51% male and 26 (49% female. Mitotic index showed a correlation with p53 protein expression, a negative correlation with p16INK4a protein expression. Statistically significant correlations were determined between the Breslow tumor thickness, Clark invasion level and p53 protein expression, as well as Breslow tumor thickness and bcl-2 oncoprotein expression (p<0.05, whereas there was no correlation between the p16INK4a protein expression and melanoma thicknes and Clark invasion level. Overexpression p53 protein and bcl-2 oncoprotein, with the loss p16INK4a protein of expression in the nodular melanoma, confirms a frequent loss of function of these tumor suppressor gene and oncogene, and indicates a vertical tumor growth phase. The loss of tumor suppression function the p53 protein and bcl-2 oncoprotein overexpression in cutaneous melanoma correlates with larger tumor thickness, whereas the overexpression of mutated p53 protein and loss p16INK4a protein of expression indicate a higher proliferative tumour potential. Therefore, these evaluated proteins may be the aggressive biological tumour activity markers.

  16. A precocidade diagnóstica do melanoma cutâneo: uma observação no sul do Brasil Early diagnosis of cutaneous melanoma: an observation in southern Brazil

    Directory of Open Access Journals (Sweden)

    Raquel Bonfá

    2011-04-01

    , growth phase, Clark level, mitotic index, peritumoral and intratumoral lymphocytic inflammatory infiltrate, angiolymphatic invasion, ulceration, regression, type of regression, microscopic satellitosis, and surgical margins. RESULTS: 328 cases, 57% female and 43% male, were analyzed. Mean age was 55.6 years. For women, the most common tumor location was in inferior(29.26% and superior limbs(23.94%, while for men melanoma was mainly found in the back(35%, followed by anterior chest/abdomen(14.29% (p<0.05. Prevalence of histologic subtypes was the following: superficial spreading melanoma(62.8%, lentigo maligna(14.9%, nodular(14.6%, acral(7.3%, and desmoplastic(0.3% types. Regarding Breslow, 26.2% were in situ, 36.9% had <1 mm, and only 15.9% were ? 4mm in depth. CONCLUSION: the distribution of histopathologic subtypes, as well as Breslow thickness, was in accordance with previous studies in outpatient populations. The profile of cases of cutaneous melanoma diagnosed in a tertiary hospital seems to be experiencing some changes over the last two decades, with a current trend for earlier diagnosis.

  17. Majority of the most-cited articles on cutaneous malignant melanoma are published in non-dermatology/melanoma specialized journals.

    Science.gov (United States)

    Tas, Faruk

    2016-01-01

    The most-cited articles. (MCAs) are likely those that impressed other researchers and had profound influence on clinical practice or future developments in the related scientific field. This study was conducted to explore a bibliometric approach to assess in where the cutaneous malignant melanoma. (CMM) related MCAs have been published. We identified journals for publications with the word "melanoma" in the title by using the ISI Web of Knowledge Database between 2000 and 2010. The term MCAs arbitrarily defined as equal or more than 100 citations. A total of 425 MCAs were published in 93 journals, led by the Cancer Research. (n = 58) and Journal of Clinical Oncology. (n = 53). Journal categories with the MCAs were the Oncology with 232 articles, followed by the Medicine with 138. articles. The median number of citations was 147. The total numbers of citations were most prominent for the journal Nature and the New England Journal of Medicine. (NEJM) (median 385 and 354, respectively). Total number of citations was the highest for the Science.categorized journals. (median 211). Articles categorized as Dermatology and Melanoma was the least (median 132.5). The median number of citations per year was 14.91. The most valuable cited articles of per year were also published in the journal Nature. (median 59.67) and the NEJM. (median 48.67). The number of citation was the highest for the Science-categorized journals. (median 25.92). Majority of the MCAs on CMM were published in non-dermatology/melanoma specialized journals.

  18. Association of vascular endothelial growth factor expression with patohistological parameters of cutaneous melanoma

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    Gačević Milomir

    2016-01-01

    Full Text Available Background/Aim. Melanoma is the most aggresive malignant tumor of the skin. Contradictory data was published on vascular endothelial growth factor (VGEF in tumor samples and its role in skin melanoma progression and prognosis. The aim of this study was to investigate the significance of VEGF expression as a prognostic parameter in melanoma. Methods. The experimental group included 81 patients with primary skin melanomas treated from 2009 to 2013 at the Military Medical Academy, Belgrade. The control group included 20 patients with dysplastic and 20 with benign naevi. Stratification was done according to gender, age, clinical and patological stage, localization, histologic type, Clark’s, Breslow, mitotic count, regression and ulceration, tumor infiltrating lymphocytes and metastatic spread. Immunohistochemical staining was performed on skin biopsies using DAKO anti-VEGF antibodies (Ab, LSABTM +HRP, Dand microvawe antigen (Ag retrieval in DAKO pH 9.0 solution. For statistical data analysis was done with ANOVA, Bonferroni, Mann Whitney and Wilcoxon test. Results. The mean intensity of VEGF staining was statistically significantly higher in melanomas than in benign or dysplastic naevi. Furthermore, the highest recorded values were in Ia and IV clinical stages. The majority of melanomas with high intensity of VEGF staining were in pT1a pathological stage. Melanomas with the highest mitotic count (> 6 had a significantly higher intensity of VEGF staining than those with < 2 mitoses. The higest intensity of staining was in melanomas without significant lymphocytic infiltrate and the lowest was in those with brisk lymphocytic infiltrate, thus a statistical difference was siginifant. The mean intensity of VEGF staining was highest in melanomas with lymphovascular invasion. There was no statistically significant difference between VEGF and any other parameter. Conclusion. VEGF in primary skin melanomas plays an important role in tumor progression and is

  19. Patients highly value routine follow-up of skin cancer and cutaneous melanoma.

    Science.gov (United States)

    Themstrup, Lotte; Jemec, Gregor E; Lock-Andersen, Jørgen

    2013-10-01

    Skin cancer follow-up is a substantial burden to outpatient clinics. Few studies have investigated patients' views on skin cancer follow-up and cutaneous melanoma. The objective was to investigate patients' perceived benefits and the impact of follow-up. This study included an open sample of patients attending routine follow-up at the outpatient Departments of Plastic Surgery and Dermatology, Roskilde Hospital. A total of 218 follow-up patients diagnosed with cutaneous malignant melanoma (MM), non-melanoma skin cancer (NMSC) or actinic keratosis (AK) completed a structured interview. A total of 97% patients found follow-up useful. Continuity and consistency were important. One third of patients felt some degree of pre follow-up anxiety. The number of anxious MM patients was significantly greater than that of NMSC patients. No significant difference was found between the number of anxious MM and AK patients. Female gender, cohabitation and age younger than 50 years were associated with increased levels of anxiety. No relation was found between the number of anxious patients or the level of anxiety and the duration of the follow-up period. The majority of patients who attended found that the follow-up had been useful. Certain demographic characteristics were associated with higher levels of anxiety and may be addressed by supportive efforts targeting these groups.

  20. Dermatologia comparativa: dermatoscopia em melanoma cutâneo Comparative dermatology: dermatoscopy of cutaneous melanoma

    Directory of Open Access Journals (Sweden)

    Otávio Sérgio Lopes

    2008-10-01

    Full Text Available Os autores apresentam imagens de dermatoscopia em uma fruta (manga-rosa, contaminada pela antracnose, mostrando sua semelhança com o melanoma extensivo superficial.The authors present images from a dermatoscopy performed in a fruit (mango that was contaminated by anthracnosis, showing its similarity to superficial spreading melanona.

  1. An attempt at a molecular prediction of metastasis in patients with primary cutaneous melanoma.

    Science.gov (United States)

    Gschaider, Melanie; Neumann, Friederike; Peters, Bettina; Lenz, Florian; Cibena, Michael; Goiser, Malgorzata; Wolf, Ingrid; Wenzel, Jörg; Mauch, Cornelia; Schreiner, Wolfgang; Wagner, Stephan N

    2012-01-01

    Current prognostic clinical and morphological parameters are insufficient to accurately predict metastasis in individual melanoma patients. Several studies have described gene expression signatures to predict survival or metastasis of primary melanoma patients, however the reproducibility among these studies is disappointingly low. We followed extended REMARK/Gould Rothberg criteria to identify gene sets predictive for metastasis in patients with primary cutaneous melanoma. For class comparison, gene expression data from 116 patients with clinical stage I/II (no metastasis) and 72 with III/IV primary melanoma (with metastasis) at time of first diagnosis were used. Significance analysis of microarrays identified the top 50 differentially expressed genes. In an independent data set from a second cohort of 28 primary melanoma patients, these genes were analyzed by multivariate Cox regression analysis and leave-one-out cross validation for association with development of metastatic disease. In a multivariate Cox regression analysis, expression of the genes Ena/vasodilator-stimulated phosphoprotein-like (EVL) and CD24 antigen gave the best predictive value (p = 0.001; p = 0.017, respectively). A multivariate Cox proportional hazards model revealed these genes as a potential independent predictor, which may possibly add (both p = 0.01) to the predictive value of the most important morphological indicator, Breslow depth. Combination of molecular with morphological information may potentially enable an improved prediction of metastasis in primary melanoma patients. A strength of the gene expression set is the small number of genes, which should allow easy reevaluation in independent data sets and adequately designed clinical trials.

  2. An attempt at a molecular prediction of metastasis in patients with primary cutaneous melanoma.

    Directory of Open Access Journals (Sweden)

    Melanie Gschaider

    Full Text Available BACKGROUND: Current prognostic clinical and morphological parameters are insufficient to accurately predict metastasis in individual melanoma patients. Several studies have described gene expression signatures to predict survival or metastasis of primary melanoma patients, however the reproducibility among these studies is disappointingly low. METHODOLOGY/PRINCIPAL FINDINGS: We followed extended REMARK/Gould Rothberg criteria to identify gene sets predictive for metastasis in patients with primary cutaneous melanoma. For class comparison, gene expression data from 116 patients with clinical stage I/II (no metastasis and 72 with III/IV primary melanoma (with metastasis at time of first diagnosis were used. Significance analysis of microarrays identified the top 50 differentially expressed genes. In an independent data set from a second cohort of 28 primary melanoma patients, these genes were analyzed by multivariate Cox regression analysis and leave-one-out cross validation for association with development of metastatic disease. In a multivariate Cox regression analysis, expression of the genes Ena/vasodilator-stimulated phosphoprotein-like (EVL and CD24 antigen gave the best predictive value (p = 0.001; p = 0.017, respectively. A multivariate Cox proportional hazards model revealed these genes as a potential independent predictor, which may possibly add (both p = 0.01 to the predictive value of the most important morphological indicator, Breslow depth. CONCLUSION/SIGNIFICANCE: Combination of molecular with morphological information may potentially enable an improved prediction of metastasis in primary melanoma patients. A strength of the gene expression set is the small number of genes, which should allow easy reevaluation in independent data sets and adequately designed clinical trials.

  3. Biomarkers of carcinogenesis and tumour growth in patients with cutaneous melanoma and obstructive sleep apnoea.

    Science.gov (United States)

    Santamaria-Martos, Fernando; Benítez, Ivan; Girón, Cristina; Barbé, Ferran; Martínez-García, Miguel-Angel; Hernández, Luis; Montserrat, Josep M; Nagore, Eduardo; Martorell, Antonio; Campos-Rodriguez, Francisco; Corral, Jaime; Cabriada, Valentin; Abad, Jorge; Mediano, Olga; Troncoso, Maria F; Cano-Pumarega, Irene; Fortuna Gutierrez, Ana Maria; Diaz-Cambriles, Trinidad; Somoza-Gonzalez, Maria; Almendros, Isaac; Farre, Ramon; Gozal, David; Sánchez-de-la-Torre, Manuel

    2018-03-01

    The goal of this study was to assess the relationship between the severity of obstructive sleep apnoea (OSA) and the levels of carcinogenesis- and tumour growth-related biomarkers in patients with cutaneous melanoma.This multicentre observational study included patients who were newly diagnosed with melanoma. The patients were classified as non-OSA (apnoea-hypopnoea index (AHI) 0-5 events·h -1 ), mild OSA (AHI 5-15 events·h -1 ) and moderate-severe OSA (AHI >15 events·h -1 ). ELISAs were performed to analyse the serum levels of hypoxia- and tumour adhesion-related biomarkers (vascular endothelial growth factor (VEGF), interleukin (IL)-8, intracellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM)-1) and markers of tumour aggressiveness (S100 calcium-binding protein B (S100B) and melanoma inhibitory activity (MIA)). A logistic model adjusted for age, sex and body mass index was fitted to each biomarker, and the AHI served as the dependent variable.360 patients were included (52.2% male, median (interquartile range) age 55.5 (43.8-68.0) years and AHI 8.55 (2.8-19.5) events·h -1 ). The levels of VEGF, IL-8, ICAM-1, S100B and MIA were not related to the severity of OSA. The levels of VCAM-1 were higher in patients with OSA than those without OSA (mild OSA: odds ratio (OR) 2.07, p=0.021; moderate-severe OSA: OR 2.35, p=0.013).In patients with cutaneous melanoma, OSA was associated with elevated circulating levels of VCAM-1 that could indicate the contribution of OSA in tumorigenesis via integrin-based adhesion. Copyright ©ERS 2018.

  4. DNA level, tumor thickness, and stereological estimates of nuclear volume in stage I cutaneous malignant melanomas. A comparative study with analysis of prognostic impact

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Kristensen, I B; Grymer, F

    1991-01-01

    The mutual relation and prognostic value of three quantitative variables were investigated in a retrospective series of 56 stage I cutaneous malignant melanomas. Unbiased stereological estimates of nuclear volume, nuclear nu v were obtained along with measurements of melanoma thickness. The DNA......, nuclear nu v was the only independent, prognostically significant variable. Physical, three-dimensional nuclear volume is not solely a reflection of nuclear DNA content, and may represent a valuable, quantitative prognostic indicator in cutaneous malignant melanomas....

  5. Melanoma

    Science.gov (United States)

    ... Lentigo maligna melanoma; Melanoma in situ; Superficial spreading melanoma; Nodular melanoma; Acral lentiginous melanoma ... and brown. It is most common in Caucasians. Nodular melanoma usually starts as a raised area that is ...

  6. Dermoscopy of difficult-to-diagnose Melanomas

    Directory of Open Access Journals (Sweden)

    Papageorgiou Chrysoula

    2016-09-01

    Full Text Available Dermoscopy is a non-invasive procedure that allows the evaluation of cutaneous lesions, and is considered to be a useful tool that improves the diagnostic accuracy of melanoma. Many dermoscopic criteria of melanoma have been established and several algorithms have been created for melanoma detection. However, the recognition of some melanomas remains challenging. Melanomas on specific body sites, melanomas in patients with multiple atypical moles, and nodular melanomas represent the most difficult-to-recognize melanoma subtypes, since they typically lack the “classic” melanoma-specific criteria. This paper provides an update on dermoscopy of difficult-to-diagnose melanomas by summarizing the newest data. Lastly, we highlight the importance of digital dermoscopy in the follow-up of melanocytic lesions for the detection of incipient melanomas while maintaining a low excision rate.

  7. The features of leptin and its receptor expression in metastatic cutaneous melanoma

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    A. A. Lushnikova

    2015-01-01

    Full Text Available Leptin is a multifunctional hormone with the activity of cytokines, which regulates critical signaling pathways that can induce cell proliferation, invasion, angiogenesis and tumor growth. Leptin plays an important role in the regulation of metabolism, energy exchange, functions of the neuro-endocrine system, including the pituitary, hypothalamus, adrenals, and immune system functions. Recently, some evidences have been appeared concerning the role of leptin in induction of chronic inflammatory processes, autoimmune pathologies, type 2 diabetes and cancer. An elevated blood level of the hormone is considered as a risk factor for different neoplasm developmentObjective. Analysis of the hormone leptin (Lep, the long and short isoforms of its receptor (LepR1 and LepR2 expression in blood, tumor cells and normal skin fibroblasts in the patients with metastatic cutaneous melanoma (CM with various clinico-pathological characteristics for prognostic assessment.Materials and methods. 15 patients with metastatic CM (10 women and 5 men, aged 22 to 67 years with body mass from normal to obese have been studied. The expression of Lep / LepR in the patient and donor blood sera, tumor and normal skin fibroblasts were determined using enzyme-linked immunosorbent assay (ELISA and RT PCR using total RNAs isolated from pairs of tumor samples and normal tissue.Results. Average level of leptin in the blood of CM patients and in tumor cells exceeds the normal one. Concentration of lepin in female CM patients was higher than in male patients. The expression level of Lep and LepR1 genes (but not LepR2 in tumor cells was relatively higher than in normal skin fibroblasts of these patients, and above the level of GAPDH gene expression. In the female patients with overweight (body mass index = 25,00–29,99 kg/m2 there was a trend to higher concentrations of leptin in the blood in comparison of the patients with normal body mass and leptin level in the sera of male CM

  8. High CCL27 immunoreactivity in 'supratumoral' epidermis correlates with better prognosis in patients with cutaneous malignant melanoma.

    Science.gov (United States)

    Martinez-Rodriguez, Miguel; Thompson, Alec K; Monteagudo, Carlos

    2017-01-01

    It has been proposed that the expression of chemokines and chemokine receptors by melanoma cells may have a role in tumour immune escape. Chemokine CCL27 is reported to be expressed specifically on the epidermal keratinocytes. The implication of CCL27 in cutaneous melanomas is currently unresolved. It has been suggested that CCL27 expression in melanomas can induce antitumoral immunity, and that CCL27 may suppress tumour growth probably due to the local lymphocyte recruitment. We studied CCL27 chemokine expression in three different concentric epidermal areas covering the primary cutaneous melanoma in patients with a long clinical follow-up. Our study included 91 cases of primary melanomas of the skin diagnosed during the 10-year period 1992-2002, and a minimum clinical follow-up of 10 years. We evaluated three different concentric and easily reproducible areas in the epidermis: the area covering melanoma (which we called 'supratumoral'), the area adjacent to the tumour ('peritumoral') and the most peripheral epidermal area ('peripheral'). Only CCL27 expression in supratumoral epidermis correlated with clinical outcome. Our study showed that a higher immunostaining of CCL27 in supratumoral epidermis is associated with longer progression-free interval and melanoma-specific survival. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  9. Epitheliotropic cutaneous T-cell lymphoma associated with melanoma in a dog: case report

    Directory of Open Access Journals (Sweden)

    M.I.P. Palumbo

    2015-06-01

    Full Text Available Several types of tumors affect dogs' skin. Simultaneously occurring neoplasms with different histological patterns might be rarely present in the same animal. This paper describes the occurrence of epitheliotropic cutaneous T-cell lymphoma and melanoma in a dog. The animal had nodular lesions in the abdominal region and serpiginous plaques on the dorsal region of the trunk. Cytology evidenced malignant fusiform cells from the abdominal lesions as well as few round cells from the dorsal. The histopathological examination of the abdominal lesions showed dermis with polygonal to spindle-shaped neoplastic cells. The lesion of the dorsal region evidenced neoplastic round cells with generally distinct cell borders and a moderate amount of eosinophilic cytoplasm. Abdominal lesions were positive for Melan A. Dorsal and forelimb lesions were positive for CD3. This study reports the occurrence of epitheliotropic cutaneous T-cell lymphoma and malignant melanoma in a crossbred Boxer dog and discusses the importance of performing immunohistochemical profile to confirm the phenotype of the tumor.

  10. Comparing disciplines: outcomes of non melanoma cutaneous malignant lesions in oral and maxillofacial surgery and dermatology.

    Science.gov (United States)

    Thavarajah, M; Szamocki, S; Komath, D; Cascarini, L; Heliotis, M

    2015-01-01

    300 cases of non-melanoma cutaneous lesion procedures carried out by the Oral and Maxillofacial Surgery and Dermatology departments in a North West London hospital over a 6 month period between September 2011 and February 2012 were included in a retrospective case control study. The results from each speciality were compared. The mean age of the OMFS group was 75.8 years compared to 69.9 years in the dermatology group. There was no statistically significant difference in gender between the 2 groups. The OMFS group treated a higher proportion of atypical (17%) and malignant (64.9%) cases compared to the dermatology group (11.3% and 50.5% respectively). This could also account for the fact that the OMFS group carried out a higher number of full excisions compared to dermatology. Both groups had a similar number of false positives (a benign lesion initially diagnosed as malignant) and a similar proportion of false negatives (a malignant lesion initially diagnosed as benign). Overall, the results show that both specialities had similar outcomes when managing non-melanoma cutaneous lesions. Both groups adhere to the guidelines set out by the British Association of Dermatologists and the National Institute of Clinical Excellence when managing such lesions. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  11. Geographic region: Does it matter in cutaneous melanoma of the head and neck?

    Science.gov (United States)

    Kılıç, Suat; Unsal, Aykut A; Chung, Sei Y; Samarrai, Ruwaa; Kılıç, Sarah S; Baredes, Soly; Eloy, Jean Anderson

    2017-12-01

    The head and neck are two of the most common locations for cutaneous melanoma. We present the first population-based analysis of geographic differences in anatomic subsite, clinicopathologic and demographical traits, histopathologic subtype, treatment modality, and disease-specific survival (DSS) of cutaneous head and neck melanoma (CHNM). Retrospective database analysis. The Surveillance, Epidemiology, and End Results database was queried for cases of CHNM reported between 2000 and 2013. Patients were grouped into East, Midwest, South, and West regions of the United States. Overall incidence, demographic traits, primary tumor site, clinicopathologic traits, histopathologic subtype, treatment modality, and DSS were compared among regions. There were 49,365 patients with CHNM identified. The West (4.60) and the South (4.42) had significantly higher incidence (per 100,000) than the East (3.84) and Midwest (3.65) (P regions (P region may play a significant role in CHNM. Incidence is higher in the South and the West. Incidence, histologic subtype, treatment modality, and DSS vary among regions. DSS is lower in the South than the West, even after accounting for other major prognostic factors. 4. Laryngoscope, 127:2763-2769, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  12. Ultraviolet exposure of melanoma cells induces fibroblast activation protein-α in fibroblasts: Implications for melanoma invasion.

    Science.gov (United States)

    Wäster, Petra; Rosdahl, Inger; Gilmore, Brendan F; Seifert, Oliver

    2011-07-01

    Fibroblast activation protein-α (FAP-α) promotes tumor growth and cell invasiveness through extracellular matrix degradation. How ultraviolet radiation (UVR), the major risk factor for malignant melanoma, influences the expression of FAP-α is unknown. We examined the effect of UVR on FAP-α expression in melanocytes, keratinocytes and fibroblasts from the skin and in melanoma cells. UVR induces upregulation of FAP-α in fibroblasts, melanocytes and primary melanoma cells (PM) whereas keratinocytes and metastatic melanoma cells remained FAP-α negative. UVA and UVB stimulated FAP-α-driven migration and invasion in fibroblasts, melanocytes and PM. In co-culture systems UVR of melanocytes, PM and cells from regional metastases upregulated FAP-α in fibroblasts but only supernatants from non-irradiated PM were able to induce FAP-α in fibroblasts. Further, UV-radiated melanocytes and PM significantly increased FAP-α expression in fibroblasts through secretory crosstalk via Wnt5a, PDGF-BB and TGF-β1. Moreover, UV radiated melanocytes and PM increased collagen I invasion and migration of fibroblasts. The FAP-α/DPPIV inhibitor Gly-ProP(OPh)2 significantly decreased this response implicating FAP-α/DPPIV as an important protein complex in cell migration and invasion. These experiments suggest a functional association between UVR and FAP-α expression in fibroblasts, melanocytes and melanoma cells implicating that UVR of malignant melanoma converts fibroblasts into FAP-α expressing and ECM degrading fibroblasts thus facilitating invasion and migration. The secretory crosstalk between melanoma and tumor surrounding fibroblasts is mediated via PDGF-BB, TGF-β1 and Wnt5a and these factors should be evaluated as targets to reduce FAP-α activity and prevent early melanoma dissemination.

  13. Impact of gender and primary tumor location on outcome of patients with cutaneous melanoma.

    Science.gov (United States)

    Voinea, S; Blidaru, A; Panaitescu, E; Sandru, A

    2016-01-01

    Background. The survival of patients with cutaneous malignant melanoma (MM) depends on multiple factors whose role is continuously updated, as the molecular mechanisms underlying the disease progression are understood. This study intended to assess whether the patient's gender and tumor location affect the disease outcome. Methods. Between 2008 and 2012, 155 patients with cutaneous MM underwent various types of surgeries in our clinic. Patients were staged according to the 2009 TNM classification. There were 90 women and 65 men. Primary tumors were located as it follows head and neck region - 4.5%, limbs - 50.7% and trunk - 44.8%. The disease free and overall survival rates (DFS, OS) were estimated by using the Kaplan-Meier method. Results. Metastases developed in 52.3% of the males and 31.1% of the females (p=0.008). In univariate analysis, distant metastasis risk was significantly higher in men (p = 0.0472 for stage II patients and p = 0.0288 for stage III). In multivariate analysis, male gender almost doubled the risk of relapse (p = 0.044) and death (p = 0.022). Consequently, DFS and OS were significantly higher among females. Primary tumor location seemed to influence the melanoma spreading ability. Half of the trunk MM developed metastases while only a third of limbs MM did. The association between MM location and the recurrence risk was not random (p = 0.033). Conclusions. The patient gender represents an independent prognostic factor for both relapse and death. Although trunk MM had a significantly higher risk of metastasis than limbs MM, the location per se was not an independent prognostic factor for survival (p = 0.078). Abbreviations: MM = malignant melanoma, DFS = disease free survival, OS = overall survival, p = p value, AJCC = American Joint Commission on Cancer, CI = confidence interval.

  14. Predictors of sentinel lymph node status in cutaneous melanoma: a classification and regression tree analysis.

    Science.gov (United States)

    Tejera-Vaquerizo, A; Martín-Cuevas, P; Gallego, E; Herrera-Acosta, E; Traves, V; Herrera-Ceballos, E; Nagore, E

    2015-04-01

    The main aim of this study was to identify predictors of sentinel lymph node (SN) metastasis in cutaneous melanoma. This was a retrospective cohort study of 818 patients in 2 tertiary-level hospitals. The primary outcome variable was SN involvement. Independent predictors were identified using multiple logistic regression and a classification and regression tree (CART) analysis. Ulceration, tumor thickness, and a high mitotic rate (≥6 mitoses/mm(2)) were independently associated with SN metastasis in the multiple regression analysis. The most important predictor in the CART analysis was Breslow thickness. Absence of an inflammatory infiltrate, patient age, and tumor location were predictive of SN metastasis in patients with tumors thicker than 2mm. In the case of thinner melanomas, the predictors were mitotic rate (>6 mitoses/mm(2)), presence of ulceration, and tumor thickness. Patient age, mitotic rate, and tumor thickness and location were predictive of survival. A high mitotic rate predicts a higher risk of SN involvement and worse survival. CART analysis improves the prediction of regional metastasis, resulting in better clinical management of melanoma patients. It may also help select suitable candidates for inclusion in clinical trials. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

  15. Sex differences in the association of cutaneous melanoma incidence rates and geographic ultraviolet light exposure.

    Science.gov (United States)

    Liu-Smith, Feng; Farhat, Ahmed Majid; Arce, Anthony; Ziogas, Argyrios; Taylor, Thomas; Wang, Zi; Yourk, Vandy; Liu, Jing; Wu, Jun; McEligot, Archana J; Anton-Culver, Hoda; Meyskens, Frank L

    2017-03-01

    Cutaneous melanoma (CM) incidence rates continue to increase, and the reasons are unknown. Previously, we reported a unique age-specific sex difference in melanoma that suggested additional causes other than solar ultraviolet (UV) radiation. This study attempted to understand whether and how UV radiation differentially impacts the CM incidence in men and women. CM data and daily UV index (UVI) from 31 cancer registries were collected for association analysis. A second dataset from 42 US states was used for validation. There was no association between log-transformed female CM rates and levels of UVI, but there was a significant association between male rates and UVI and a significant association between overall rates and UVI. The 5-year age-specific rate-UVI association levels (represented by Pearson's coefficient ρ) increased with age in men, but age-specific ρ levels remained low and unchanged in women. The significant rate-UVI association in men and nonassociation in women was validated in a population of white residents of the United States. Confounders, including temperature and latitude, are difficult to separate from UVI. Ambient UVI appears to be associated with melanoma incidence in males but not in females. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  16. Immune Parameters in The Prognosis and Therapy Monitoring of Cutaneous Melanoma Patients: Experience, Role, and Limitations

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    Monica Neagu

    2013-01-01

    Full Text Available Cutaneous melanoma is an immune-dependent aggressive tumour. Up to our knowledge, there are no reports regarding immune parameters monitoring in longitudinal followup of melanoma patients. We report a followup for 36 months of the immune parameters of patients diagnosed in stages I–IV. The circulatory immune parameters comprised presurgery and postsurgery immune circulating peripheral cells and circulating intercommunicating cytokines. Based on our analysis, the prototype of the intratumor inflammatory infiltrate in a melanoma with good prognosis is composed of numerous T cells CD3+, few or even absent B cells CD20+, few or absent plasma cells CD138+, and present Langerhans cells CD1a+ or langerin+. Regarding circulatory immune cells, a marker that correlates with stage is CD4+/CD8+ ratio, and its decrease clearly indicates a worse prognosis of the disease. Moreover, even in advanced stages, patients that have an increased overall survival rate prove the increase of this ratio. The decrease in the circulating B lymphocytes with stage is balanced by an increase in circulating NK cells, a phenomenon observed in stage III. Out of all the tested cytokines in the followup, IL-6 level correlated with the patient’s survival, while in our study, IL-8, IL-10, and IL-12 did not correlate statistically in a significant way with overall survival, or relapse-free survival.

  17. 2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: a randomised, multicentre trial

    DEFF Research Database (Denmark)

    Gillgren, Peter; Drzewiecki, Krzysztof T; Niin, Marianne

    2011-01-01

    Optimum surgical resection margins for patients with clinical stage IIA-C cutaneous melanoma thicker than 2 mm are controversial. The aim of the study was to test whether survival was different for a wide local excision margin of 2 cm compared with a 4-cm excision margin....

  18. [Experience in the treatment of cutaneous in-transit melanoma metastases and satellitosis with intralesional interleukin-2].

    Science.gov (United States)

    Dehesa, L A; Vilar-Alejo, J; Valerón-Almazán, P; Carretero, G

    2009-09-01

    Although metastatic melanoma has a poor prognosis, cutaneous metastases represent a special case given their ready accessibility, making it possible for dermatologists to apply local treatment. We report our experience with intralesional treatment with interleukin (IL) 2 in 7 patients with cutaneous metastases from malignant melanoma. A total of 244 lesions in 7 patients with satellitosis and/or cutaneous metastases from malignant melanoma were treated with intralesional IL-2 twice a week. The maximum dose in each patient ranged from 3 to 18 million units per session, according to the number and size of lesions. Complete or partial remission was achieved in almost all lesions (95.9 % and 3.7 %, respectively).Only 1 lesion (0.4 %) -the largest and located subcutaneously- did not respond to intralesional treatment and required alcoholization and subsequent surgical removal to achieve cure. All partial responses occurred in subcutaneous lesions larger than 2 cm. Treatment was well tolerated with only a few mild side effects (grade 1-2). IL-2 may be an effective and well-tolerated treatment option in patients with satellitosis and cutaneous metastases from melanoma. Lesions smaller than 2 cm and located in the epidermis or superficial dermis respond better than those larger than 2 cm or located in the subcutaneous cellular tissue. More studies are necessary to establish appropriate doses and regimens.

  19. The occurrence of non-melanoma malignant skin lesions and non-cutaneous squamous-cell carcinoma among metastatic melanoma patients: an observational cohort study in Denmark.

    Science.gov (United States)

    Li, Haojie; Pedersen, Lars; Nørgaard, Mette; Ulrichsen, Sinna P; Thygesen, Sandra K; Nelson, Jeanenne J

    2016-05-03

    Inhibitors of mutant BRAF are emerging as standard of care in patients with metastatic melanoma who carry relevant oncogenic mutations. However, BRAF inhibitors are found to induce cutaneous squamous cell carcinoma (cuSCC). Population-based background rates of cuSCC and non-cutaneous squamous cell carcinoma (non-cuSCC) in the metastatic melanoma population may contextualize safety signals from randomized clinical trials or the clinics. However, these background rates are lacking. We conducted a historical cohort study to evaluate the background rates of new-onset non-melanoma skin lesions and non-cuSCC among 2,814 metastatic malignant melanoma patients diagnosed in 1997-2010, identified through the Danish Cancer Registry and the National Pathology Registry. Patients were excluded if they had a history of cancer before the metastatic melanoma diagnosis, other than skin cancers. We determined the incidence of non-melanoma malignant skin lesions and non-cuSCC that occurred post metastatic melanoma diagnosis, censoring patients at death, emigration, or December 31, 2011 (end of study period), whichever came first. The median age at metastatic melanoma diagnosis was 64 years. Over 40% of patients died within one year of metastatic diagnosis and ~70% died within 5 years. The percentages of patients with prior history or prevalent disease at metastatic melanoma diagnosis included: 8.6% with cuSCC or basal cell carcinoma (BCC), 3.9% with actinic keratosis (AK), and 0.7% with Bowen's disease. No patients had past or current non-cuSCC per study exclusion criterion. The incidence of non-melanoma skin lesions during the 6 months post-metastatic melanoma diagnosis was as follows: BCC, 1.8% (42.5 per 1000 person-years [PY]); AK, 0.8% (18.6 per 1000 PY); cuSCC, 0.1% (1.7 per 1000 PY); Bowen's disease, 0.04% (0.8 per 1000 PY); and keratoacanthoma (KA), 0%. Non-cuSCC was observed in 3 patients (0.1%; 2.5 per 1000 PY) at 3 sites: bronchi, heart and lung. CuSCC and non-cuSCC were

  20. Desmoplastic melanoma may mimic a cutaneous peripheral nerve sheath tumor: Report of 3 challenging cases.

    Science.gov (United States)

    Machado, Isidro; Llombart, Beatriz; Cruz, Julia; Traves, Víctor; Requena, Celia; Nagore, Eduardo; Parafioriti, Antonina; Monteagudo, Carlos; Llombart-Bosch, Antonio

    2017-04-12

    Desmoplastic melanoma (DM) and cutaneous malignant peripheral nerve sheath tumors (MPNST) reveal histological and immunohistochemical similarities, including S100 positivity and negative staining for conventional melanocytic markers. We present 3 cases of cutaneous S100-positive spindle cell tumors in elderly patients, in which first findings led to initial misdiagnoses as cutaneous MPNST and benign peripheral sheath nerve tumor (neurofibroma). The identification of adjacent atypical melanocytic hyperplasia in the overlying skin along with tumor cell proliferation, also in the superficial dermis, the neurotropic component and the absence of any relationship between the tumor and a major nerve, pre-existing neural benign tumor or the existence of stigmata suggestive of neurofibromatosis raised consideration of a DM. Careful attention should be paid to the presence of a firm dermal nodule and atypical scar lesions especially in sun-exposed areas (mainly head and neck region) in elderly patients associated with S100-positive spindle cell proliferation, solar elastosis and adjacent atypical melanocytic proliferation. In such cases, the possibility of a DM should be excluded with caution, especially if the tumor reveals a paucicellular morphology resembling various non-melanocytic neoplasms including malignant or benign peripheral sheath nerve tumors. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Melanoma-expressed CD70 is involved in invasion and metastasis.

    Science.gov (United States)

    Pich, Christine; Sarrabayrouse, Guillaume; Teiti, Iotefa; Mariamé, Bernard; Rochaix, Philippe; Lamant, Laurence; Favre, Gilles; Maisongrosse, Véronique; Tilkin-Mariamé, Anne-Françoise

    2016-01-12

    CD70 is a costimulatory molecule of the tumour necrosis factor family expressed in activated immune cells and some solid tumours. In lymphocytes CD70 triggers T cell-mediated cytotoxicity and mitogen-activated protein kinase phosphorylation. We evaluated the expression of CD70 in biopsies and melanoma cell lines. Using melanoma cell lines positive or not for CD70, we analysed CD70 function on melanoma progression. We report CD70 expression in human melanoma cell lines and tumour cells from melanoma biopsies. This expression was observed in 95% of primary melanomas but only 37% of metastases. Both monomeric and trimeric forms of CD70 were detected in tumour cell membrane fractions, whereas cytoplasmic fractions contained almost exclusively monomeric CD70. In vitro and in vivo experiments demonstrated that CD70 expression inhibited melanoma cell migration, invasion and pulmonary metastasis implantation independently of the tumour immune microenvironment. Increasing the levels of the trimeric form of CD70 through monoclonal antibody binding led to an increase in CD70+ melanoma cell invasiveness through MAPK pathway activation, RhoE overexpression, ROCK1 and MYPT1 phosphorylation decrease, and stress fibres and focal adhesions disappearance. Our results describe a new non-immunological function of melanoma-expressed CD70, which involves melanoma invasiveness through MAPK pathway, RhoE and cytoskeletal modulation.

  2. Ki-67 expression is superior to mitotic count and novel proliferation markers PHH3, MCM4 and mitosin as a prognostic factor in thick cutaneous melanoma

    Directory of Open Access Journals (Sweden)

    Bachmann Ingeborg M

    2010-04-01

    Full Text Available Abstract Background Tumor cell proliferation is a predictor of survival in cutaneous melanoma. The aim of the present study was to evaluate the prognostic impact of mitotic count, Ki-67 expression and novel proliferation markers phosphohistone H3 (PHH3, minichromosome maintenance protein 4 (MCM4 and mitosin, and to compare the results with histopathological variables. Methods 202 consecutive cases of nodular cutaneous melanoma were initially included. Mitotic count (mitosis per mm2 was assessed on H&E sections, and Ki-67 expression was estimated by immunohistochemistry on standard sections. PHH3, MCM4 and mitosin were examined by staining of tissue microarrays (TMA sections. Results Increased mitotic count and elevated Ki-67 expression were strongly associated with increased tumor thickness, presence of ulceration and tumor necrosis. Furthermore, high mitotic count and elevated Ki-67 expression were also associated with Clark's level of invasion and presence of vascular invasion. High expression of PHH3 and MCM4 was correlated with high mitotic count, elevated Ki-67 expression and tumor ulceration, and increased PHH3 frequencies were associated with tumor thickness and presence of tumor necrosis. Univariate analyses showed a worse outcome in cases with elevated Ki-67 expression and high mitotic count, whereas PHH3, MCM4 and mitosin were not significant. Tumor cell proliferation by Ki-67 had significant prognostic impact by multivariate analysis. Conclusions Ki-67 was a stronger and more robust prognostic indicator than mitotic count in this series of nodular melanoma. PHH3, MCM4 and mitosin did not predict patient survival.

  3. Embryonic chicken transplantation is a promising model for studying the invasive behaviour of melanoma cells.

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    Aparna eJayachandran

    2015-02-01

    Full Text Available Epithelial-to-mesenchymal transition is a hallmark event in the metastatic cascade conferring invasive ability to tumor cells. There are ongoing efforts to replicate the physiological events occurring during mobilization of tumor cells in model systems. However, few systems are able to capture these complex in vivo events. The embryonic chicken transplantation model has emerged as a useful system to assess melanoma cells including functions that are relevant to the metastatic process, namely invasion and plasticity. The chicken embryo represents an accessible and economical 3-dimensional in vivo model for investigating melanoma cell invasion as it exploits the ancestral relationship between melanoma and its precursor neural crest cells. We describe a methodology which enables the interrogation of melanoma cell motility within the developing avian embryo. This model involves the injection of melanoma cells into the neural tube of chicken embryos. Melanoma cells are labelled using fluorescent tracker dye, Vybrant DiO, then cultured as hanging drops for 24 hours to aggregate the cells. Groups of approximately 700 cells are placed into the neural tube of chicken embryos prior to the onset of neural crest migration at the hindbrain level (embryonic day 1.5 or trunk level (embryonic day 2.5. Chick embryos are reincubated and analysed after 48 hours for the location of melanoma cells using fluorescent microscopy on whole mounts and cross-sections of the embryos. Using this system, we compared the in vivo invasive behavior of epithelial-like and mesenchymal-like melanoma cells. We report that the developing embryonic microenvironment confers motile abilities to both types of melanoma cells. Hence the embryonic chicken transplantation model has potential to become a valuable tool for in vivo melanoma invasion studies. Importantly, it may provide novel insights into and reveal previously unknown mediators of the metastatic steps of invasion and

  4. Title: hypofractionated postoperative irradiation for cutaneous melanoma of the head and neck

    International Nuclear Information System (INIS)

    Omizo, Russ T.; Marquez, Carol M.; Vetto, John T.

    1996-01-01

    Purpose/Objective: To evaluate the efficacy and tolerance of hypofractionated postoperative irradiation in patients with head and neck cutaneous melanoma at high risk for local-regional recurrence. Methods and Materials: Between May 1990 to February 1995, 26 patients with cutaneous melanoma of the head and neck were evaluated in the Department of Radiation Oncology at the Oregon Health Sciences University for elective postoperative hypofractionated irradiation. Twelve patients were excluded from analysis because of simultaneous distant metastatic disease. The remaining 14 patients were at high risk for local-regional recurrence because of either nodal disease, T3 or greater disease, recurrent disease following previous treatment or a combination of the above. TNM stage distribution for patients treated at initial presentation was: T4aN1-2, T4aN0-3, T3bN0-1, T3aN0-1, T2N1-1 and TxN1-1. The initial TNM stage for patients presenting with recurrent disease was: T4aN2-a, T4aN1-1, T1N0-1, T2N0-1 and TxN1-1. All patients received adjuvant irradiation to at least 2 echelons of draining lymph nodes +/- the primary site. The median elapsed time between surgery and irradiation was 4 weeks. Hypofractionated irradiation consisted of 600 cGy fractions given twice weekly for 5 fractions. Twelve patients were treated with electrons of appropriate energy, 1 with photons and 1 with photons and electrons. Median duration of treatment was 15 days. Results: With a median follow-up of 41 months, 2 patients have failed local-regionally and at distant sites and one patient has failed with distant disease only. The actuarial 5 year local-regional control rate is 86% with a standard error of 9%. The actuarial 5 year survival is 60% with a standard error of 16%. Acute side effects were self limiting and were most commonly erythema and mucositis. Chronic side effects were mild and included fibrosis, telangiectasias and xerostomia. Conclusions: Adjuvant hypofractionated irradiation provides

  5. Sentinel lymph node biopsy in cutaneous melanoma Biópsia do linfonodo sentinela no melanoma cutâneo

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    Andrea Fernandes de Oliveira

    2007-10-01

    Full Text Available PURPOSE: To assess the importance of sentinel lymph node biopsy in patients with cutaneous melanoma. METHODS: Ninety consecutive non-randomized patients with stages I and II melanoma who underwent sentinel lymph node biopsy were followed up prospectively for six years. RESULTS: Patients were followed up for a mean period of 30 months. Their mean age was 53.3 years, ranging from 12 to 83 years. Thirty patients were male (37.5% and 50, female (62.5%. Sentinel lymph node was positive in 32.5% and negative in 67.5%. It was found that the thicker the tumor, the greater the incidence of positive sentinel lymph nodes. In the group of patients with positive sentinel lymph nodes, recurrence occurred in 43.5%, but in those with negative sentinel lymph nodes, in only 7%, what points out to the association of tumor recurrence and positive sentinel lymph nodes. There were no major postoperative complications. CONCLUSION: Sentinel lymph node biopsy was demonstrated to be a safe method for selecting patients who need therapeutic lymphadenectomy.OBJETIVO: Avaliar a importância da biópsia do linfonodo sentinela em pacientes com melanoma cutâneo MÉTODOS: Noventa pacientes com estadiamento I e II foram acompanhados prospectivamente no período de seis anos, de forma consecutiva e não randomizada e submetidos a biópsia do linfonodo sentinela. RESULTADOS: Os pacientes foram acompanhados durante tempo médio de 30 meses. A média de idade dos pacientes foi de 53,3 anos, variando de 12 a 83. Quanto ao sexo, foram avaliados 30 pacientes do sexo masculino (37,5% e 50 do sexo feminino (62,5%.32,5% dos pacientes apresentaram linfonodo sentinela positivo e 67,5% linfonodo sentinela negativos. Comparando-se a espessura tumoral com a positividade do LS, verificou-se que quanto maior a espessura, maior a incidência de positividade do linfonodo sentinela. No grupo de pacientes com LS positivo a recorrência surgiu em 43,5% dos casos, mostrando a relação entre a recorr

  6. Analysis of the Clinical and Histopathological Patterns of 100 Consecutive Cases of Primary Cutaneous Melanoma and Correlation with Staging

    Directory of Open Access Journals (Sweden)

    Kyung Wook Nam

    2015-11-01

    Full Text Available BackgroundThis study analyzed 100 consecutive patients with primary cutaneous melanoma over the course of 13 years to determine whether epidemiological differences correspond to different stages of the disease. We also investigated whether epidemiological characteristics affected the survival rate. Our results were compared with those of selected descriptive studies of melanoma in other East Asian populations, in order to determine whether cutaneous melanoma patterns are similar in East Asian populations.MethodsThe patients' medical records were reviewed retrospectively, and we analyzed the relationship of epidemiological characteristics to staging and survival rate. Additionally, papers from Hong Kong and Japan describing these phenomena in East Asian populations were subjected to a statistical comparison.ResultsThe ratio of males to females was 1:1.8, and the foot was the most frequent tumor site (49%. Acral lentiginous melanoma occurred most frequently (55%. Nodular melanoma was associated with a higher stage. Stage III-IV tumors with Clark levels of IV-V were significantly associated with a low survival rate. A statistical analysis of comparable papers reported in Hong Kong and Japan showed similar results with regard to age, tumor location, and histopathological subtypes.ConclusionsThis study provides the first full epidemiological description of 100 consecutive cases of primary cutaneous melanoma in Korea, with results similar to those observed in other East Asian populations. Corresponding to previous findings, nodular melanoma tended to occur at a higher stage than other types, and tumors with high Clark levels and high stages showed a lower survival rate.

  7. Association between autoimmune disease and cutaneous melanoma with regard to melanoma prognosis.

    Science.gov (United States)

    Bottoni, U; Paolino, G; Ambrifi, M; Didona, D; Albanesi, M; Clerico, R; Lido, P; Brachini, A; Corsetti, P; Richetta, A G; Cantisani, C; Calvieri, S

    2015-04-01

    An association between autoimmune disease and malignant melanoma (MM) has often been reported in the literature as a positive prognostic factor for MM. Consequently, we evaluated the influence of different autoimmune diseases on the prognosis of MM. To evaluate the prognosis of patients with MM who also had an autoimmune disorder, whether tumour-associated, paraneoplastic or drug-induced. Autoimmune diseases were classified and analysed as tumour-associated, paraneoplastic or drug-induced. Patients were enrolled according to their clinicopathological features and matched with control groups. Kaplan-Meier analysis was used to estimate disease-free survival (DFS) and overall survival (OS), and log-rank test was used to evaluate differences between the survival curves. In total, 49 patients with MM and tumour-associated autoimmune disease were included in our analysis. No case of paraneoplastic autoimmune disease was detected. The survival analyses showed a range of results, from a worsening of DFS and OS to a lack of any difference. In a second analysis, we separately analysed patients who developed autoimmune disorders after starting adjuvant therapy with interferon-α; we did not find significant differences between these patients and the untreated patients. Autoimmune disease, whether tumour-associated or drug-induced, was not associated with better prognosis in patients with MM. The results suggest that the reported relationship between autoimmunity and MM may be a result of individual variation in sensitivity to the autoimmune disease, the tumour or the treatments. © 2014 British Association of Dermatologists.

  8. The burden of occupationally-related cutaneous malignant melanoma in Britain due to solar radiation.

    Science.gov (United States)

    Rushton, Lesley; J Hutchings, Sally

    2017-02-14

    Increasing evidence highlights the association of occupational exposure and cutaneous malignant melanoma (CMM). We estimated the burden of CMM and total skin cancer burden in Britain due to occupational solar radiation exposure. Attributable fractions (AF) and numbers were estimated for CMM mortality and incidence using risk estimates from the published literature and national data sources for proportions exposed. We extended existing methods to account for the exposed population age structure. The estimated total AF for CMM is 2.0% (95% CI: 1.4-2.7%), giving 48 (95% CI: 33-64) deaths in (2012) and 241 (95% CI: 168-325) registrations (in 2011) attributable to occupational exposure to solar radiation. Higher exposure and larger numbers exposed led to much higher numbers for men than women. Industries of concern are construction, agriculture, public administration and defence, and land transport. These results emphasise the urgent need to develop appropriate strategies to reduce this burden.

  9. Bilateral Multifocal Central Serous-Like Chorioretinopathy due to MEK Inhibition for Metastatic Cutaneous Melanoma

    Directory of Open Access Journals (Sweden)

    Scott D. Schoenberger

    2013-01-01

    Full Text Available Newer chemotherapeutic agents target extracellular signaling, including the mitogen-activated protein kinase kinase (MEK pathway. We present a case of a 54-year-old female who developed bilateral multifocal central serous-like chorioretinopathy shortly after starting MEK inhibition for metastatic cutaneous melanoma. There was a complete resolution of findings after drug stoppage. After resuming a lower dose of the MEK inhibitor, the findings recurred again but resolved after drug stoppage. Other etiologies were unlikely given the clinical course. The presumed mechanism involves toxicity to the retinal pigment epithelium, with breakdown of the blood-retinal barrier. Recognition of this side effect is important with this new class of chemotherapy.

  10. A 3-Year Follow-up of Sun Behavior in Patients With Cutaneous Malignant Melanoma

    DEFF Research Database (Denmark)

    Idorn, Luise Winkel; Datta, Pameli; Heydenreich, Jakob

    2014-01-01

    IMPORTANCE UV radiation (UVR) exposure is the primary environmental risk factor for developing cutaneous malignant melanoma (CMM). OBJECTIVE To measure changes in sun behavior from the first until the third summer after the diagnosis of CMM using matched controls as a reference. DESIGN, SETTING...... that measured time-related UVR in standard erythema dose (SED) and corresponding sun diaries (mean, 74 days per participant each participation year). RESULTS Patients' daily UVR dose and UVR dose in connection with various behaviors increased during follow-up (quantified as an increase in daily UVR dose each...... suggest that patients with CMM do not maintain a cautious sun behavior in connection with an increase in UVR exposure, especially on days with body exposure, when abroad, and on holidays....

  11. Long Noncoding RNA HOTAIR Is Associated with Motility, Invasion, and Metastatic Potential of Metastatic Melanoma

    Directory of Open Access Journals (Sweden)

    Lihua Tang

    2013-01-01

    Full Text Available Metastatic melanoma, the primary cause of skin cancer-related death, warrants new therapeutic approaches that target the regulatory machinery at molecular level. While long noncoding RNAs (lncRNAs are dysregulated in a number of cancer types, limited data are available on the expression and function of lncRNAs in melanoma metastasis. The primary objective of this study was to investigate the role of 6 metastasis-related lncRNAs in pairs of primary melanoma and matched lymph node metastatic tissues. Among the tested lncRNAs, HOTAIR was the most highly expressed in lymph node metastasis. The role of HOTAIR in melanoma cell motility and invasion was further evaluated by knocking down HOTAIR with siRNAs. Knockdown of HOTAIR resulted in the reduction of motility and invasion of human melanoma cell line A375, as assessed by wound healing assay and Matrigel-based invasion assay. siHOTAIR also suppressed the degradation of gelatin matrix, suggesting that HOTAIR promotes gelatinase activity. Together, our study shows that HOTAIR is overexpressed in metastatic tissue, which is associated with the ability of HOTAIR to promote melanoma cell motility and invasion. These data indicate that lncRNAs may be involved in the metastasis of melanoma and provide support for further evaluation of lncRNAs in melanoma.

  12. Risk factors for the development of locoregional cutaneous metastases as the sole form of recurrence in patients with melanoma.

    Science.gov (United States)

    Messeguer, F; Agustí-Mejías, A; Traves, V; Alegre, V; Oliver, V; Nagore, E

    2013-01-01

    While locoregional cutaneous metastases (in transit and satellite) in melanoma have received little attention from researchers to date, they have pathogenic and prognostic features that distinguish them from other forms of locoregional recurrence. Identifying predictors of these metastases would be of great value for their prevention, early diagnosis, and treatment. The aim of this study was to identify the risk factors associated with locoregional cutaneous metastases as the first form of recurrence in the metastatic progression of melanoma. Between 2000 and 2010, we prospectively collected the data of 1327 patients diagnosed with stage I and II melanoma. During follow up, 112 patients (8.4%) developed metastases. Of these, 36 had exclusively locoregional cutaneous metastases. The clinical and histological characteristics of this subgroup were evaluated. In the univariate analysis, significant predictors were patient age, primary tumor thickness, site, ulceration, mitotic index, and histological type. After multivariate analysis, the independent risk factors were tumor thickness (risk ratio [RR] 5.6; 95% CI: 2.7-11.5) and the location of the primary tumor on the lower limbs (RR 3.4; 95% CI: 1.0-11.5), on the head or neck (RR 4.8; 95% IC: 1.7-13.5), or in acral sites (RR 6.7; 95% IC: 2.2-20.8). Patients who have melanomas with a Breslow thickness of more than 2mm located on the lower limbs, head, neck, or acral sites have a higher risk of developing locoregional cutaneous metastases. These findings could be useful in the design of future guidelines for the monitoring and management of melanoma. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

  13. Treatment of regional cutaneous nodular metastases from melanoma using high-dose rate mould brachytherapy.

    Science.gov (United States)

    Chaudhuri, Anupam; De-Groot, Charles; Seel, Matthew; Jolly, Mike; Cameron, Tina

    2011-04-01

    The involvement of a wide body surface area by regional cutaneous nodular metastases (RCNM) from melanoma poses a significant therapeutic challenge. We report our experience from Waikato Hospital, Hamilton, New Zealand in successfully treating this condition with high-dose rate (HDR) surface mould brachytherapy (BT). We analysed six patients who had surgery and then developed RCNM, which was treated in our department by HDR mould BT using Iridium 192. Five out of six patients were treated with a dose of 30 Gy in five fractions to wide field with a further 6 Gy boost to tumour nodules. Our first patient received a higher dose of 36 Gy in six fractions followed by 6 Gy boost to tumour nodules. All patients experienced a complete response (CR). Median follow up was 23 months and side effects were minimal, only Radiation Therapy Oncology Group (RTOG) grade I/II early and late toxicity. To date, no in-field recurrence has been observed. Two patients died from metastatic disease at 33 and 34 months of follow up. There was a CR in all cases without in-field recurrence. To our knowledge, this is the first reported experience in treating skin melanoma with a BT surface mould. We recommend that BT surface mould should be considered when treating patients with RCNM. © 2011 The Authors. Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists.

  14. Real-world use, safety, and survival of ipilimumab in metastatic cutaneous melanoma in The Netherlands.

    Science.gov (United States)

    Jochems, Anouk; Leeneman, Brenda; Franken, Margreet G; Schouwenburg, Maartje G; Aarts, Maureen J B; van Akkooi, Alexander C J; van den Berkmortel, Franchette W P J; van den Eertwegh, Alfonsus J M; Groenewegen, Gerard; de Groot, Jan Willem B; Haanen, John B A G; Hospers, Geke A P; Kapiteijn, Ellen; Koornstra, Rutger H; Kruit, Wim H J; Louwman, Marieke W J; Piersma, Djura; van Rijn, Rozemarijn S; Ten Tije, Albert J; Vreugdenhil, Gerard; Wouters, Michel W J M; Uyl-de Groot, Carin A; van der Hoeven, Koos J M

    2018-04-13

    Phase III trials with ipilimumab showed an improved survival in patients with metastatic melanoma. We evaluated the use and safety of ipilimumab, and the survival of all patients with metastatic cutaneous melanoma (N=807) receiving ipilimumab in real-world clinical practice in The Netherlands using data from the Dutch Melanoma Treatment Registry. Patients who were registered between July 2012 and July 2015 were included and analyzed according to their treatment status: treatment-naive (N=344) versus previously-treated (N=463). Overall, 70% of treatment-naive patients and 62% of previously-treated patients received all four planned doses of ipilimumab. Grade 3 and 4 immune-related adverse events occurred in 29% of treatment-naive patients and 21% of previously-treated patients. No treatment-related deaths occurred. Median time to first event was 5.4 months [95% confidence interval (CI): 4.7-6.5 months] in treatment-naive patients and 4.4 months (95% CI: 4.0-4.7 months) in previously-treated patients. Median overall survival was 14.3 months (95% CI: 11.6-16.7 months) in treatment-naive patients and 8.7 months (95% CI: 7.6-9.6 months) in previously-treated patients. In both patient groups, an elevated lactate dehydrogenase level (hazard ratio: 2.25 and 1.70 in treatment-naive and previously-treated patients, respectively) and American Joint Committee on Cancer M1c-stage disease (hazard ratio: 1.81 and 1.83, respectively) were negatively associated with overall survival. These real-world outcomes of ipilimumab slightly differed from outcomes in phase III trials. Although phase III trials are crucial for establishing efficacy, real-world data are of great added value enhancing the generalizability of outcomes of ipilimumab in clinical practice.

  15. Optic nerve invasion of uveal melanoma: clinical characteristics and metastatic pattern

    DEFF Research Database (Denmark)

    Lindegaard, Jacob; Isager, Peter; Prause, Jan Ulrik

    2006-01-01

    PURPOSE: To determine the frequency of optic nerve invasion in uveal melanoma, to identify clinical factors associated with optic nerve invasion, and to analyze the metastatic pattern and the association with survival. METHODS: All iris, ciliary body, and choroidal melanomas (N = 2758) examined...... between 1942 and 2001 at the Eye Pathology Institute, University of Copenhagen, Denmark, and the Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark, were reviewed. Cases with optic nerve invasion were identified and subdivided into prelaminar or laminar invasion and postlaminar invasion....... Clinical characteristics were compared with those from 85 cases randomly drawn from all ciliary body and choroidal melanomas without optic nerve invasion from the same period. Survival data were obtained by the Kaplan-Meier method, and the Mantel-Cox log-rank test was used to test differences in survival...

  16. Patterns of recurrence after sentinel lymph node biopsy for cutaneous melanoma.

    Science.gov (United States)

    Fincher, Timothy R; McCarty, Todd M; Fisher, Tammy L; Preskitt, John T; Lieberman, Zelig H; Stephens, Jeffrey F; O'Brien, John C; Kuhn, Joseph A

    2003-12-01

    Previous sentinel lymph node (SLN) studies for cutaneous melanoma have shown that the SLN accurately reflects the nodal status of the corresponding nodal basin. However, there are few long-term studies that describe recurrence site patterns, predictors for recurrence, and overall survival and disease-free survival after SLN biopsy. A retrospective review of patients over a 6-year period was performed to determine patient outcomes and the patterns of recurrence. In all cases, Tc-99 sulfur colloid along with isosulfan blue dye was injected at the primary melanoma site. After resection, the SLN was serially sectioned and evaluated by hematoxylin and eosin staining and immunohistochemistry. One hundred ninety-eight patients were identified who underwent SLN biopsy for cutaneous melanoma including T1 (n = 21), T2 (n = 88), T3 (n = 75), and T4 (n = 14) primary tumors. Of these patients, 38 had a positive SLN. Of the 38 patients with a positive SLN (mean follow-up 38 months), recurrent disease was identified in 10 (26.3%) at a mean interval of 14.2 months. The site of first recurrence was distant (n = 4) and local (n = 6). Regional lymphatic basin recurrence was not identified. Of the 160 patients with a negative SLN (mean follow-up 50 months), recurrent disease was identified in 16 (10.0%) at a mean interval of 31.3 months. The site of first recurrence was systemic (n = 11), local (n = 4), and nodal (n = 1). Overall survival and disease-free survival for patients with a positive SLN at 55 months was 53.3% and 47.7% respectively, while overall survival and disease-free survival for patients with a negative SLN at 53 months was 92.2% and 87.7% respectively (P analysis of the entire cohort (n = 198) identified primary tumor depth and positive SLN status as significant predictors of recurrence. The incidence of nodal basin recurrence after SLN biopsy was found to be 0.6%. Primary tumor depth and pathological status of the SLN are significant predictors of local and systemic

  17. Melanoma

    Science.gov (United States)

    Melanoma is the most serious type of skin cancer. Often the first sign of melanoma is a change in the size, shape, color, or feel of a mole. Most melanomas have a black or black-blue area. Melanoma ...

  18. Association between risk factors and detection of cutaneous melanoma in the setting of a population-based skin cancer screening.

    Science.gov (United States)

    Hübner, Joachim; Waldmann, Annika; Eisemann, Nora; Noftz, Maria; Geller, Alan C; Weinstock, Martin A; Volkmer, Beate; Greinert, Rüdiger; Breitbart, Eckhard W; Katalinic, Alexander

    2017-07-07

    Early detection is considered to improve the prognosis of cutaneous melanoma. The value of population-based screening for melanoma, however, is still controversial. The aim of this study was to evaluate the predictive power of established risk factors in the setting of a population-based screening and to provide empirical evidence for potential risk stratifications. We reanalyzed data (including age, sex, risk factors, and screening results) of 354 635 participants in the Skin Cancer Research to provide Evidence for Effectiveness of Screening in Northern Germany project conducted in the German state of Schleswig-Holstein (2003-2004). In multivariable analysis, atypical nevi [odds ratio (OR): 17.4; 95% confidence interval (CI): 14.4-20.1], personal history of melanoma (OR: 5.3; 95% CI: 3.6-7.6), and multiple (≥40) common nevi (OR: 1.3; 95% CI: 1.1-1.6) were associated with an increased risk of melanoma detection. Family history and congenital nevi were not significantly associated with melanoma detection in the Skin Cancer Research to provide Evidence for Effectiveness of Screening in Northern Germany population. The effects of several risk-adapted screening strategies were evaluated. Hypothesizing a screening of individuals aged more than or equal to 35 years, irrespective of risk factors (age approach), the number needed to screen is 559 (95% CI: 514-612), whereas a screening of adults (aged ≥20) with at least one risk factor (risk approach) leads to an number needed to screen of 178 (95% CI: 163-196). Converted into one screen-detected melanoma, the number of missed melanomas is 0.15 (95% CI: 0.12-0.18) with the age approach and 0.22 (95% CI: 0.19-0.26) with the risk approach. The results indicate that focusing on individuals at high risk for melanoma may improve the cost-effectiveness and the benefit-to-harm balance of melanoma screening programs.

  19. MHC Class I Chain-Related Gene A Diversity in Patients with Cutaneous Malignant Melanoma from Southeastern Spain

    Science.gov (United States)

    Campillo, José Antonio; López-Hernández, Ruth; Martínez-Banaclocha, Helios; Bolarín, José Miguel; Gimeno, Lourdes; Mrowiec, Anna; López, Manuela; Heras, Beatriz Las; Minguela, Alfredo; Moya-Quiles, Maria Rosa; Legáz, Isabel; Frías-Iniesta, José Francisco; García-Alonso, Ana María; Álvarez-López, María Rocío; Martínez-Escribano, Jorge Antonio; Muro, Manuel

    2015-01-01

    A limited number of studies have been performed so far on the polymorphism in the transmembrane region (exon 5) of the major histocompatibility complex class I chain-related gene A (MICA) in patients with melanoma. However, the influence of MICA polymorphism in extracellular domains (exons 2, 3, and 4) has not been investigated on melanoma disease. This study aims to characterize the influence of extracellular MICA polymorphism, and its previously described linkage disequilibrium with HLA-B locus, on patients with cutaneous melanoma from southeastern Spain. For this purpose, MICA and HLA-B genotyping was performed in 233 patients and 200 ethnically matched controls by luminex technology. Patients were classified according to the presence of methionine or valine at codon 129 of MICA gene. We found a high frequency of MICA*009 in melanoma patients compared with controls (P = 0.002, Pc = 0.03). Our results also showed an association between MICA*009 and HLA-B*51 alleles in both patients and controls. This association was stronger in patients than controls (P = 0.015). However, a multivariate logistic regression model showed that neither MICA*009 nor the combination MICA*009/HLA-B*51 was associated with melanoma susceptibility. No relationship was observed between MICA-129 dimorphism and melanoma nor when MICA polymorphism was evaluated according to clinical findings at diagnosis. PMID:25838620

  20. Total skin self-examination at home for people treated for cutaneous melanoma: development and pilot of a digital intervention

    Science.gov (United States)

    Murchie, Peter; Allan, Julia L; Brant, William; Dennis, Matthew; Hall, Susan; Masthoff, Judith; Walter, Fiona M; Johnston, Marie

    2015-01-01

    Objectives To develop a digital intervention to prompt, support, and respond to the outcomes of total skin self-examinations (TSSEs) at home by people treated for cutaneous melanoma. Design A complex intervention development study. Setting Northeast Scotland. Participants Semistructured scoping interviews; people previously treated for cutaneous melanoma (n=21). Pilot testing: people treated for melanoma stages 0–2C (n=20); general practitioners (n=6); and a nurse specialist in dermatology (n=1). Intervention A tablet-based digital intervention designed to prompt and support TSSEs comprising instructional videos and electronic reporting (including photographs) to a clinical nurse specialist in dermatology, with subsequent clinical triage. Primary and secondary outcome measures Qualitative assessment of intervention feasibility and acceptability, and quantitative assessment of intentions and confidence to perform TSSEs in pilot participants. Results The majority of pilot participants were strongly positive and adhered well to the intervention (n=15), with 7 of these reporting symptoms of concern at some point during the 6-month pilot. 4 patients complied intermittently, 3 reporting skin problems at least once during the pilot, and 1 withdrew. 2 patients underwent skin surgery as a result of participating in the pilot, with 1 diagnosed as having a recurrent melanoma and the other, a benign lesion. A number of practical issues to improve the usability of the intervention were identified. The proportion of participants reporting intention to check their skin at least monthly increased during the intervention as did confidence to conduct a skin check. Conclusions People previously treated for cutaneous melanoma are prepared to use digital technology to support them in conducting TSSE. An intervention has been developed which is practical, effective and safe, and after addressing minor practical issues, could now be evaluated for clinical outcomes in a randomised

  1. Risk of invasive melanoma in patients with rheumatoid arthritis treated with biologics: results from a collaborative project of 11 European biologic registers.

    Science.gov (United States)

    Mercer, Louise K; Askling, Johan; Raaschou, Pauline; Dixon, William G; Dreyer, Lene; Hetland, Merete Lund; Strangfeld, Anja; Zink, Angela; Mariette, Xavier; Finckh, Axel; Canhao, Helena; Iannone, Florenzo; Zavada, Jakub; Morel, Jacques; Gottenberg, Jacques-Eric; Hyrich, Kimme L; Listing, Joachim

    2017-02-01

    Some studies have reported a possible association between exposure to tumour necrosis factor (TNF) inhibitors and an increased risk of melanoma. The aim of this study was to investigate the incidence of invasive cutaneous melanomas in patients with rheumatoid arthritis (RA) treated with TNF inhibitors (TNFi), other biologic disease modifying drugs and non-biologic therapy. Eleven biologic registers from nine European countries participated in this collaborative project. According to predefined exposure definitions, cohorts of patients with RA were selected. Using the country-specific general population of each register as reference, age, sex and calendar year standardised incidence ratios (SIRs) of invasive histology-confirmed cutaneous melanoma were calculated within each register. Pooled SIR and incidence rate ratios (IRRs) comparing biologic cohorts to biologic-naïve were calculated across countries by taking the size of the register into account. Overall 130 315 RA patients with a mean age of 58 years contributing 579 983 person-years were available for the analysis and 287 developed a first melanoma. Pooled SIRs for biologic-naïve, TNFi and rituximab-exposed patients were 1.1 (95% CI 0.9 to 1.4), 1.2 (0.99 to 1.6) and 1.3 (0.6 to 2.6), respectively. Incidence rates in tocilizumab and abatacept-exposed patients were also not significantly increased. IRR versus biologic-naïve patients were: TNFi 1.1 (95% CI 0.8 to 1.6); rituximab 1.2 (0.5 to 2.9). This large European collaborative project did not confirm an overall increased risk of melanoma following exposure to TNFi. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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

    Science.gov (United States)

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

    2017-09-01

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

  3. Multiple primary cutaneous melanomas in patients with FAMMM syndrome and sporadic atypical mole syndrome (AMS): what's worse?

    Science.gov (United States)

    Tchernev, Georgi; Ananiev, Julian; Cardoso, José-Carlos; Chokoeva, Anastasiya Atanasova; Philipov, Stanislav; Penev, Plamen Kolev; Lotti, Torello; Wollina, Uwe

    2014-08-01

    Atypical Mole Syndrome is the most important phenotypic risk factor for cutaneous melanoma, a malignancy that accounts for about 80% of deaths from skin cancer. Since early diagnosis of melanoma is of great prognostic relevance, the identification of Atypical Mole Syndrome carriers (sporadic and familial) is essential, as well as the recommendation of preventative measures that must be undertaken by these patients.We report two rare cases concerning patients with multiple primary skin melanomas in the setting of a familial and a sporadic syndrome of dysplastic nevi: the first patient is a 67-year-old patient with a history of multiple superficial spreading melanomas localized on his back. The second patient presented with multiple primary melanomas in advanced stage in the context of the so-called sporadic form of the syndrome of dysplastic nevi-AMS (atypical mole syndrome). In the first case, excision of the melanomas was carried out with an uneventful post-operative period. In the second case, disseminated metastases were detected, involving the right fibula, the abdominal cavity as well as multiple lesions in the brain. The patient declined BRAF mutation tests as well as chemotherapy or targeted therapies, and suffered a rapid deterioration in his general condition leading to death. We classified the second case as a sporadic form of the atypical mole syndrome, associated with one nodular and two superficial spreading melanomas.There are no data in the literature to allow us to understand if, in patients with multiple primary melanomas, there is any difference in terms of prognosis between those with and without a family history of a similar phenotype. To answer this and other questions related to these rare cases, further studies with a significant number of patients should be carried out.

  4. Eye and hair colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma. A Danish case-control study

    DEFF Research Database (Denmark)

    Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

    1999-01-01

    carcinoma and 174 matched controls, and 168 cases with cutaneous malignant melanoma and 176 matched controls. Controls were matched on age, gender and place of residence. Subjects indicated their hair colour before 7 years of age, and at 25 years of age and their skin phototype. Interviewers assessed...... colour and skin type were found to be independent risk factors for cutaneous malignant melanoma; red hair vs. black/brown: OR >9.7, blond hair vs. brown/black: OR = 2.4, and skin type 11 vs. type IV: OR=2.0. There were no gender-related differences in risk factors for basal cell carcinoma and cutaneous......To assess the importance of hair and eye colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma in fair-skinned Caucasians, we conducted two identical case-control studies in Denmark. We studied 145 cases with basal cell...

  5. Cutaneous melanoma: hints from occupational risks by anatomic site in Swedish men

    Science.gov (United States)

    Perez-Gomez, B; Pollan, M; Gustavsson, P; Plato, N; Aragones, N; Lopez-Abente, G

    2004-01-01

    Aims: To improve knowledge of the epidemiology of melanoma by comparing occupational risks of cutaneous melanoma (CM) by anatomic site in Swedish workers. Methods: Male workers employed in 1970 and living in the country in 1960 were followed up from 1971 to 1989 using the Swedish Registers of Death and Cancer. A more specifically exposed subcohort included men reporting the same occupation in 1960 and 1970. For each location, occupational risk ratios (RRs) were extracted from Poisson regression models adjusted by age, period, town size, and geographical area. To diminish the influence of socioeconomic factors, intrasector analyses, comparing only jobs belonging to the same occupational sector, were performed. Risk patterns for different locations were compared. Results: High RRs for different sites were found among workers exposed to UV sources (dentists, physiotherapists, and lithographers), and sun exposed workers (harbour masters, and lighthouse/related work). Risk excesses were seen in fur tailors, tanners/fur dressers, patternmakers/cutters, electrical fitters/wiremen, telephone/telegraph installers/repairmen, and some glass/pottery/tile workers. Results for lower and upper limbs were significantly correlated but somewhat independent of those found in thorax, the most frequent location. Correlation between head/neck and thorax was moderate. Specific risk excesses were found for rolling mill workers in head/neck, for chimney sweeps in upper limbs, and for aircraft pilots/navigators/flight engineers in lower limbs. Conclusions: High RRs in the trunk among occupations with UV exposure from artificial sources suggest an effect not restricted to exposed sites. An unusual distribution of cases and RRs in chimney sweeps, rolling-mill, or glass/pottery/tile workers suggests local effects of exposures. The not previously reported risk excess in this job and in fur related processes, and the RR in electrical fitters and telephone/telegraph installers deserve further

  6. Non-invasive spectroscopic techniques in the diagnosis of non-melanoma skin cancer

    Science.gov (United States)

    Drakaki, E.; Sianoudis, IA; Zois, EN; Makropoulou, M.; Serafetinides, AA; Dessinioti, C.; Stefanaki, E.; Stratigos, AJ; Antoniou, C.; Katsambas, A.; Christofidou, E.

    2017-11-01

    The number of non-melanoma skin cancers is increasing worldwide and has become an important health and economic issue. Early detection and treatment of skin cancer can significantly improve patient outcome. Therefore there is an increase in the demand for proper management and effective non-invasive diagnostic modalities in order to avoid relapses or unnecessary treatments. Although the gold standard of diagnosis for non-melanoma skin cancers is biopsy followed by histopathology evaluation, optical non-invasive diagnostic tools have obtained increased attention. Emerging non-invasive or minimal invasive techniques with possible application in the diagnosis of non-melanoma skin cancers include high-definition optical coherence tomography, fluorescence spectroscopy, oblique incidence diffuse reflectance spectrometry among others spectroscopic techniques. Our findings establish how those spectrometric techniques can be used to more rapidly and easily diagnose skin cancer in an accurate and automated manner in the clinic.

  7. Cystatin E/M suppresses legumain activity and invasion of human melanoma

    Directory of Open Access Journals (Sweden)

    Fodstad Øystein

    2010-01-01

    Full Text Available Abstract Background High activity of cysteine proteases such as legumain and the cathepsins have been shown to facilitate growth and invasion of a variety of tumor types. In breast cancer, several recent studies have indicated that loss of the cysteine protease inhibitor cystatin E/M leads to increased growth and metastasis. Although cystatin E/M is normally expressed in the skin, its role in cysteine protease regulation and progression of malignant melanoma has not been studied. Methods A panel of various non-melanoma and melanoma cell lines was used. Cystatin E/M and C were analyzed in cell media by immunoblotting and ELISA. Legumain, cathepsin B and L were analyzed in cell lysates by immunoblotting and their enzymatic activities were analyzed by peptide substrates. Two melanoma cell lines lacking detectable secretion of cystatin E/M were transfected with a cystatin E/M expression plasmid (pCST6, and migration and invasiveness were studied by a Matrigel invasion assay. Results Cystatin E/M was undetectable in media from all established melanoma cell lines examined, whereas strong immunobands were detected in two of five primary melanoma lines and in two of six lines derived from patients with metastatic disease. Among the four melanoma lines secreting cystatin E/M, the glycosylated form (17 kD was predominant compared to the non-glycosylated form (14 kD. Legumain, cathepsin B and L were expressed and active in most of the cell lines, although at low levels in the melanomas expressing cystatin E/M. In the melanoma lines where cystatin E/M was secreted, cystatin C was generally absent or expressed at a very low level. When melanoma cells lacking secretion of cystatin E/M were transfected with pCST6, their intracellular legumain activity was significantly inhibited. In contrast, cathepsin B activity was not affected. Furthermore, invasion was suppressed in cystatin E/M over-expressing melanoma cell lines as measured by the transwell Matrigel

  8. Telomere length and the risk of cutaneous malignant melanoma in melanoma-prone families with and without CDKN2A mutations.

    Directory of Open Access Journals (Sweden)

    Laura S Burke

    Full Text Available INTRODUCTION: Recent evidence suggests a link between constitutional telomere length (TL and cancer risk. Previous studies have suggested that longer telomeres were associated with an increased risk of melanoma and larger size and number of nevi. The goal of this study was to examine whether TL modified the risk of melanoma in melanoma-prone families with and without CDKN2A germline mutations. MATERIALS AND METHODS: We measured TL in blood DNA in 119 cutaneous malignant melanoma (CMM cases and 208 unaffected individuals. We also genotyped 13 tagging SNPs in TERT. RESULTS: We found that longer telomeres were associated with an increased risk of CMM (adjusted OR = 2.81, 95% CI = 1.02-7.72, P = 0.04. The association of longer TL with CMM risk was seen in CDKN2A- cases but not in CDKN2A+ cases. Among CMM cases, the presence of solar injury was associated with shorter telomeres (P = 0.002. One SNP in TERT, rs2735940, was significantly associated with TL (P = 0.002 after Bonferroni correction. DISCUSSION: Our findings suggest that TL regulation could be variable by CDKN2A mutation status, sun exposure, and pigmentation phenotype. Therefore, TL measurement alone may not be a good marker for predicting CMM risk.

  9. Clinicopathological features and clinical outcomes associated with TP53 and BRAFNon-V600mutations in cutaneous melanoma patients.

    Science.gov (United States)

    Kim, Dae Won; Haydu, Lauren E; Joon, Aron Y; Bassett, Roland L; Siroy, Alan E; Tetzlaff, Michael T; Routbort, Mark J; Amaria, Rodabe N; Wargo, Jennifer A; McQuade, Jennifer L; Kemnade, Jan; Hwu, Patrick; Woodman, Scott E; Roszik, Jason; Kim, Kevin B; Gershenwald, Jeffrey E; Lazar, Alexander J; Davies, Michael A

    2017-04-15

    BRAF V600 , NRAS, TP53, and BRAF Non-V600 are among the most common mutations detected in non-acral cutaneous melanoma patients. Although several studies have identified clinical and pathological features associated with BRAF V600 and NRAS mutations, limited data are available regarding the correlates and significance of TP53 and BRAF Non-V600 mutations. This study analyzed the patient demographics, primary tumor features, and clinical outcomes of a large cohort of non-acral cutaneous melanoma patients who had undergone clinically indicated molecular testing (n = 926). The prevalence of BRAF V600 , NRAS, TP53, and BRAF Non-V600 mutations was 43%, 21%, 19%, and 7%, respectively. The presence of a TP53 mutation was associated with older age (P = .019), a head and neck primary tumor site (P = .0001), and longer overall survival (OS) from the diagnosis of stage IV disease in univariate (P = .039) and multivariate analyses (P = .015). BRAF Non-V600 mutations were associated with older age (P = .005) but not with primary tumor features or OS from stage IV. Neither TP53 nor BRAF Non-V600 mutations correlated significantly with OS with frontline ipilimumab treatment, and the TP53 status was not significantly associated with outcomes with frontline BRAF inhibitor therapy. Eleven patients with BRAF Non-V600 mutations were treated with a BRAF inhibitor. Three patients were not evaluable for a response because of treatment cessation for toxicities; the remaining patients had disease progression as the best response to therapy. These results add to the understanding of the clinical features associated with TP53 and BRAF Non-V600 mutations in advanced cutaneous melanoma patients, and they support the rationale for evaluating the prognostic significance of TP53 in other cohorts of melanoma patients. Cancer 2017;123:1372-1381. © 2016 American Cancer Society. © 2016 American Cancer Society.

  10. Peculiarities of lymphatic drainage in cutaneous malignant melanoma: clinical experience in 75 cases.

    Science.gov (United States)

    Voinea, S; Sandru, A; Gherghe, M; Blidaru, A

    2014-01-01

    In the recent years, the identification and biopsy of the sentinel lymph node (SLN) has become standard in the treatment of cutaneous malignant melanoma (CMM). In order to correctly apply the technique and to decrease the risk of false negatives,it is compulsory to track the lymphatic drainage of the primary tumor and to detect all SLN, regardless of their site. At the Bucharest Oncologic Institute, over the last three years, selective lymphadenectomy was performed in 75 patients with CMM, stages I and II (AJCC). In 39 cases, the primary tumor was at the level of the upper and lower limbs and in 36 on the trunk. In all patients, lymphoscintigraphy was performed through intradermal injection of Nanocoll,with dynamic follow up of the radiotracer, with the purpose of finding the possible unusual locations of the SLN. The sentinel lymph nodes were identified in 100%of the cases. In 63 patients (84%), the primary tumor drained in only one lymphatic field and in the other 12 the drainage was towards 2 or more lymphatic basins. The CMM situated on the trunk had a particular behaviour, presenting more often (33%) with multiple nodal basin drainage. CMM of the trunk, mostly those situated close to the midline, but others as well, tend to drain into several lymphatic areas. The existence of interval lymph nodes and atypical lymphatic drainage, in a minor lymphatic basin,must be determined preoperatively in order to allow the biopsy of all SLN and establish the right therapy. Celsius.

  11. Whole Body Microwave Irradiation for Improved Dacarbazine Therapeutical Action in Cutaneous Melanoma Mouse Model

    Directory of Open Access Journals (Sweden)

    Monica Neagu

    2013-01-01

    Full Text Available A cutaneous melanoma mouse model was used to test the efficacy of a new therapeutical approach that uses low doses of cytostatics in conjunction with mild whole body microwave exposure of 2.45 GHz in order to enhance cytostatics antitumoral effect. Materials and Methods. A microwave exposure system for C57BL/6 mouse whole body microwave irradiation was designed; groups of 40 mice (males and females bearing experimental tumours were subjected to a combined therapy comprising low doses of dacarbazine in combination with mild whole body irradiation. Clinical parameters and serum cytokine testing using xMAP technology were performed. Results. The group that was subjected to combined therapy, microwave and cytostatic, had the best clinical evolution in terms of overall survival, tumour volume, and metastatic potential. At day 14 the untreated group had 100% mortality, while in the combined therapy group 40% of mice were surviving. Quantifying serum IL-1β, IL-6, IL-10, IL-12 (p70, IFN-γ, GM-CSF, TNF-α, MIP-1α, MCP-1, and KC during tumorigenesis and therapy found that the combined experimental therapy decreases all the inflammatory cytokines, except chemokine MCP-1 that was found increased, suggesting an increase of the anti-tumoral immune response triggered by the combined therapy. The overall metastatic process is decreased in the combined therapy group.

  12. Thymosin beta-10 expression in melanoma cell lines and melanocytic lesions: a new progression marker for human cutaneous melanoma

    NARCIS (Netherlands)

    Weterman, M. A.; van Muijen, G. N.; Ruiter, D. J.; Bloemers, H. P.

    1993-01-01

    When screening a subtraction library for sequences that were specifically expressed in highly metastatic human melanoma cell lines, a cDNA clone was isolated encoding thymosin beta-10. We found that expression of thymosin beta-10 mRNA was associated with metastatic behavior of various human melanoma

  13. Analysis of the B-RAFV600E mutation in cutaneous melanoma patients with occupational sun exposure

    Science.gov (United States)

    CANDIDO, SAVERIO; RAPISARDA, VENERANDO; MARCONI, ANDREA; MALAPONTE, GRAZIA; BEVELACQUA, VALENTINA; GANGEMI, PIETRO; SCALISI, AURORA; McCUBREY, JAMES A.; MAESTRO, ROBERTA; SPANDIDOS, DEMETRIOS A.; FENGA, CONCETTINA; LIBRA, MASSIMO

    2014-01-01

    Sun-exposure is one of the risk factors associated with the development of a cutaneous neoplasm. In melanoma, the Ras-Raf-MEK-ERK (MAPK) signaling pathway is constitutively activated through multiple mechanisms, including B-RAF mutation. It has been hypothesized that B-RAF mutations in melanocytic lesions arise from DNA damage induced by ultraviolet (UV) radiation. However, it is still discussed if B-RAF mutations are associated with melanoma patients exposed to the sun. Therefore, in the present study, the known B-RAFV600E mutation was analysed in melanoma samples from 30 indoor and 38 outdoor workers. B-RAFV600E mutation was detected in 52 and 73% of outdoor workers and indoor workers, respectively. Of note, this mutation was identified in 12 of 14 (85%) melanoma of the trunk diagnosed in indoor workers and in 9 of 19 (47%) samples from outdoor workers (p=0.03). By analyzing melanomas of other body sites, no statistical difference in the frequency of B-RAFV600E mutation was identified between the groups of workers. It appears that the mutation detected among indoor workers may be associated with a recreational or intermittent exposure to the sun, as usually the trunk is a sun-protected body site. Overall, these data indicate that the B-RAFV600E mutation detected in melanoma is not associated with a chronic exposure to the sun. Mutations detected in other genes may also contribute to melanoma development in the subset of patients exposed to UV radiation. PMID:24424406

  14. Antitumor effects of the investigational selective MEK inhibitor TAK733 against cutaneous and uveal melanoma cell lines

    Directory of Open Access Journals (Sweden)

    von Euw Erika

    2012-04-01

    Full Text Available Abstract Background TAK733 is a novel allosteric, non-ATP-binding, inhibitor of the BRAF substrates MEK-1/2. Methods The growth inhibitory effects of TAK733 were assessed in a panel of 27 cutaneous and five uveal melanoma cell lines genotyped for driver oncogenic mutations. Flow cytometry, Western blots and metabolic tracer uptake assays were used to characterize the changes induced by exposure to TAK733. Results Fourteen cutaneous melanoma cell lines with different driver mutations were sensitive to the antiproliferative effects of TAK733, with a higher proportion of BRAFV600E mutant cell lines being highly sensitive with IC50s below 1 nM. The five uveal melanoma cell lines had GNAQ or GNA11 mutations and were either moderately or highly sensitive to TAK733. The tested cell lines wild type for NRAS, BRAF, GNAQ and GNA11 driver mutations were moderately to highly resistant to TAK733. TAK733 led to a decrease in pERK and G1 arrest in most of these melanoma cell lines regardless of their origin, driver oncogenic mutations and in vitro sensitivity to TAK733. MEK inhibition resulted in increase in pMEK more prominently in NRASQ61L mutant and GNAQ mutant cell lines than in BRAFV600E mutant cell lines. Uptake of the metabolic tracers FDG and FLT was inhibited by TAK733 in a manner that closely paralleled the in vitro sensitivity assays. Conclusions The MEK inhibitor TAK733 has antitumor properties in melanoma cell lines with different oncogenic mutations and these effects could be detectable by differential metabolic tracer uptake.

  15. Lymphatic Invasion Revealed by Multispectral Imaging is Common in Primary Melanomas and Associates with Prognosis

    OpenAIRE

    Xu, Xiaowei; Gimotty, Phyllis A; Guerry, DuPont; Karakousis, Giorgos; VanBelle, Patricia; Liang, Haohai; Montone, Katharine; Pasha, Terry; Ming, Michael E; Acs, Geza; Feldman, Michael; Barth, Stephen; Hammond, Rachel; Elenitsas, Rosalie; Zhang, Paul J

    2008-01-01

    Lymphatic invasion by tumor cells has been noted infrequently in primary melanomas. Our primary hypotheses were that using immunohistochemical markers of lymphatic vessels and of tumor cells would improve detection of lymphatic invasion and that lymphatic invasion would correlate with regional nodal metastatic disease. This study included 106 patients who were diagnosed between 1972 and 1991 and who had ≥ 10 years of follow up. We performed dual immunohistochemical stains for podoplanin (for ...

  16. Comparing Melanoma Invasiveness in Dermatologist- versus Patient-Detected Lesions: A Retrospective Chart Review.

    Science.gov (United States)

    Lamerson, Cindy L; Eaton, Kristina; Sax, Joel L; Kashani-Sabet, Mohammed

    2012-01-01

    This study examined whether patient-identified melanomas were more advanced than dermatologist-identified tumors at routine clinic visits, and whether a personal or family history of skin cancer was associated with patterns of detection. A retrospective chart review was performed on melanoma patients (N = 201) in a private dermatology clinic. Variables included age, gender, pattern of detection (i.e., patient or a board certified dermatologist), personal or family history of skin cancer, skin type, and previous sun exposure, as well as tumor location and severity. Dermatologist-diagnosed melanomas were less invasive (P < 0.0005), and more likely present on the chest, back, and legs (P < 0.01). Conversely, patient-identified lesions were more likely to occur on the face, neck and scalp, be associated with younger patients, and a family history of melanoma, but not other types of skin cancer (P < 0.01). In a post-hoc analysis examining these factors as predictors of tumor invasiveness, only diagnostic source was significant. Specifically, dermatologist-identified tumors were significantly less invasive than patient-identified tumors. Although age, family history, and tumor location played roles in the early detection of melanomas, the most important factor was diagnostic source. Thus, board-certified dermatologists play a key role in the early detection of malignant melanoma.

  17. Comparing Melanoma Invasiveness in Dermatologist- versus Patient-Detected Lesions: A Retrospective Chart Review

    Directory of Open Access Journals (Sweden)

    Cindy L. Lamerson

    2012-01-01

    Full Text Available This study examined whether patient-identified melanomas were more advanced than dermatologist-identified tumors at routine clinic visits, and whether a personal or family history of skin cancer was associated with patterns of detection. A retrospective chart review was performed on melanoma patients (N=201 in a private dermatology clinic. Variables included age, gender, pattern of detection (i.e., patient or a board certified dermatologist, personal or family history of skin cancer, skin type, and previous sun exposure, as well as tumor location and severity. Dermatologist-diagnosed melanomas were less invasive (P<0.0005, and more likely present on the chest, back, and legs (P<0.01. Conversely, patient-identified lesions were more likely to occur on the face, neck and scalp, be associated with younger patients, and a family history of melanoma, but not other types of skin cancer (P<0.01. In a post-hoc analysis examining these factors as predictors of tumor invasiveness, only diagnostic source was significant. Specifically, dermatologist-identified tumors were significantly less invasive than patient-identified tumors. Although age, family history, and tumor location played roles in the early detection of melanomas, the most important factor was diagnostic source. Thus, board-certified dermatologists play a key role in the early detection of malignant melanoma.

  18. Total-body cutaneous examination, total-body photography, and dermoscopy in the care of a patient with xeroderma pigmentosum and multiple melanomas.

    Science.gov (United States)

    Green, W Harris; Wang, Steven Q; Cognetta, Armand B

    2009-08-01

    Xeroderma pigmentosum (XP) is an autosomal recessive disorder characterized by a defect in DNA repair and subsequent increased frequency of cutaneous malignant neoplasms, including melanoma. In patients with XP, patient and family education and aggressive UV radiation protection are the primary means of skin cancer prevention. An important secondary measure in decreasing morbidity and mortality in these patients involves early detection of skin cancers, particularly melanomas. We describe a 39-year-old woman with XP who developed 38 primary melanomas along with 6 squamous cell carcinomas and 70 basal cell carcinomas over a 23-year period. During this time, a 3-fold management approach of total-body cutaneous examination, total-body photography, and dermoscopy was used in the care of the patient. The thickest melanoma had a Breslow thickness of 1.07 mm, and the mean Breslow thickness of her detected melanomas was 0.18 mm. The ratio of benign to malignant biopsied suspicious melanocytic lesions during 23 years of follow-up was 0.9:1. All melanomas were treated using wide local excision, and she had no evidence of local or in-transit metastases of any of her malignant neoplasms at the most recent follow-up examination. Conclusion Monthly follow-up using total-body cutaneous examinations, total-body photography, and dermoscopy is an important 3-fold secondary management technique for this unique patient, allowing early detection of her melanomas.

  19. The regulation of miRNA-211 expression and its role in melanoma cell invasiveness.

    Directory of Open Access Journals (Sweden)

    Joseph Mazar

    2010-11-01

    Full Text Available The immediate molecular mechanisms behind invasive melanoma are poorly understood. Recent studies implicate microRNAs (miRNAs as important agents in melanoma and other cancers. To investigate the role of miRNAs in melanoma, we subjected human melanoma cell lines to miRNA expression profiling, and report a range of variations in several miRNAs. Specifically, compared with expression levels in melanocytes, levels of miR-211 were consistently reduced in all eight non-pigmented melanoma cell lines we examined; they were also reduced in 21 out of 30 distinct melanoma samples from patients, classified as primary in situ, regional metastatic, distant metastatic, and nodal metastatic. The levels of several predicted target mRNAs of miR-211 were reduced in melanoma cell lines that ectopically expressed miR-211. In vivo target cleavage assays confirmed one such target mRNA encoded by KCNMA1. Mutating the miR-211 binding site seed sequences at the KCNMA1 3'-UTR abolished target cleavage. KCNMA1 mRNA and protein expression levels varied inversely with miR-211 levels. Two different melanoma cell lines ectopically expressing miR-211 exhibited significant growth inhibition and reduced invasiveness compared with the respective parental melanoma cell lines. An shRNA against KCNMA1 mRNA also demonstrated similar effects on melanoma cells. miR-211 is encoded within the sixth intron of TRPM1, a candidate suppressor of melanoma metastasis. The transcription factor MITF, important for melanocyte development and function, is needed for high TRPM1 expression. MITF is also needed for miR-211 expression, suggesting that the tumor-suppressor activities of MITF and/or TRPM1 may at least partially be due to miR-211's negative post transcriptional effects on the KCNMA1 transcript. Given previous reports of high KCNMA1 levels in metastasizing melanoma, prostate cancer and glioma, our findings that miR-211 is a direct posttranscriptional regulator of KCNMA1 expression as well

  20. Dynamic infrared imaging of cutaneous melanoma and normal skin in patients treated with BNCT

    Energy Technology Data Exchange (ETDEWEB)

    Santa Cruz, G.A. [Dpto. de Instrumentacion y Control, Comision Nacional de Energia Atomica, Av. del Libertador 8250 (1429), Buenos Aires (Argentina)], E-mail: santacr@cnea.gov.ar; Bertotti, J.; Marin, J. [Universidad Favaloro, Solis 453 (1078), Buenos Aires (Argentina); Gonzalez, S.J. [Dpto. de Instrumentacion y Control, Comision Nacional de Energia Atomica, Av. del Libertador 8250 (1429), Buenos Aires (Argentina); CONICET, Avda. Rivadavia 1917 (1033), Buenos Aires (Argentina); Gossio, S. [FCEyN, Pabellon II, Ciudad Universitaria (1428), Buenos Aires (Argentina); Alvarez, D. [Fundacion Favaloro, Av. Belgrano 1746 (1093), Buenos Aires (Argentina); Roth, B.M.C.; Menendez, P. [Instituto de Oncologia Angel H. Roffo, Av. San Martin 5481 (1417), Buenos Aires (Argentina); Pereira, M.D. [Agencia Nacional de Promocion Cientifica y Tecnologica, PAV 22393 (Argentina); Albero, M.; Cubau, L.; Orellano, P. [INVAP S.E., F.P. Moreno 1089 (R8400AMU), S.C. de Bariloche, Rio Negro (Argentina); Liberman, S.J. [Dpto. de Instrumentacion y Control, Comision Nacional de Energia Atomica, Av. del Libertador 8250 (1429), Buenos Aires (Argentina)

    2009-07-15

    We recently initiated a program aimed to investigate the suitability of dynamic infrared imaging for following-up nodular melanoma patients treated with BNCT. The reason that makes infrared imaging attractive is the fact that it constitutes a functional and non-invasive imaging method, providing information on the normal and abnormal physiologic response of the nervous and vascular systems, as well as the local metabolic rate and inflammatory processes that ultimately appear as differences in the skin temperature. An infrared camera, with a focal plane array of 320x240 uncooled ferroelectric detectors is employed, which provides a video stream of the infrared emission in the 7-14 {mu}m wavelength band. A double blackbody is used as reference for absolute temperature calibration. After following a protocol for patient preparation and acclimatization, a basal study is performed. Subsequently, the anatomic region of interest is subjected to a provocation test (a cold stimulus), which induces an autonomic vasoconstriction reflex in normal structures, thus enhancing the thermal contrast due to the differences in the vasculature of the different skin regions. Radiation erythema reactions and melanoma nodules possess typically a faster temperature recovery than healthy, non-irradiated skin. However, some other non-pathological structures are also detectable by infrared imaging, (e.g. scars, vessels, arteriovenous anastomoses and injuries), thus requiring a multi-study comparison in order to discriminate the tumor signal. Besides the superficial nodules, which are readily noticeable by infrared imaging, we have detected thermal signals that are coincident with the location of non-palpable nodules, which are observable by CT and ultrasound. Diffuse regions of fast temperature recovery after a cold stimulus were observed between the third and sixth weeks post-BNCT, concurrent with the clinical manifestation of radiation erythema. The location of the erythematous visible and

  1. Dynamic infrared imaging of cutaneous melanoma and normal skin in patients treated with BNCT

    International Nuclear Information System (INIS)

    Santa Cruz, G.A.; Bertotti, J.; Marin, J.; Gonzalez, S.J.; Gossio, S.; Alvarez, D.; Roth, B.M.C.; Menendez, P.; Pereira, M.D.; Albero, M.; Cubau, L.; Orellano, P.; Liberman, S.J.

    2009-01-01

    We recently initiated a program aimed to investigate the suitability of dynamic infrared imaging for following-up nodular melanoma patients treated with BNCT. The reason that makes infrared imaging attractive is the fact that it constitutes a functional and non-invasive imaging method, providing information on the normal and abnormal physiologic response of the nervous and vascular systems, as well as the local metabolic rate and inflammatory processes that ultimately appear as differences in the skin temperature. An infrared camera, with a focal plane array of 320x240 uncooled ferroelectric detectors is employed, which provides a video stream of the infrared emission in the 7-14 μm wavelength band. A double blackbody is used as reference for absolute temperature calibration. After following a protocol for patient preparation and acclimatization, a basal study is performed. Subsequently, the anatomic region of interest is subjected to a provocation test (a cold stimulus), which induces an autonomic vasoconstriction reflex in normal structures, thus enhancing the thermal contrast due to the differences in the vasculature of the different skin regions. Radiation erythema reactions and melanoma nodules possess typically a faster temperature recovery than healthy, non-irradiated skin. However, some other non-pathological structures are also detectable by infrared imaging, (e.g. scars, vessels, arteriovenous anastomoses and injuries), thus requiring a multi-study comparison in order to discriminate the tumor signal. Besides the superficial nodules, which are readily noticeable by infrared imaging, we have detected thermal signals that are coincident with the location of non-palpable nodules, which are observable by CT and ultrasound. Diffuse regions of fast temperature recovery after a cold stimulus were observed between the third and sixth weeks post-BNCT, concurrent with the clinical manifestation of radiation erythema. The location of the erythematous visible and

  2. Multiple pigmentation gene polymorphisms account for a substantial proportion of risk of cutaneous malignant melanoma.

    Science.gov (United States)

    Duffy, David L; Zhao, Zhen Z; Sturm, Richard A; Hayward, Nicholas K; Martin, Nicholas G; Montgomery, Grant W

    2010-02-01

    We have previously described the role of red hair (melanocortin-1 receptor, MC1R) and blue eye (oculocutaneous albinism type II, OCA2) gene polymorphisms in modulating the risk of cutaneous malignant melanoma (CMM) in a highly sun-exposed population of European descent. A number of recent studies, including genome-wide association studies, have identified numerous polymorphisms controlling human hair, eye, and skin color. In this paper, we test a selected set of polymorphisms in pigmentation loci (ASIP (Agouti signalling protein, nonagouti homolog (mouse) gene), TYR (tyrosinase), TYRP1 (tyrosinase-related protein 1), MC1R, OCA2, IRF4 (interferon regulatory factor 4), SLC24A4 (solute carrier family 24, member 4), and SLC45A2 (solute carrier family 45, member 2)) for association with CMM risk in a large Australian population-based case-control study. Variants in IRF4 and SLC24A4, despite being strongly associated with pigmentation in our sample, did not modify CMM risk, but the other six did. Three single nucleotide polymorphisms (rs28777, rs35391, and rs16891982) in the MATP gene (SLC45A2) exhibited the strongest crude association with risk, but this was attenuated to approximately the same effect size as that of a MC1R red hair color allele by controlling for ancestry of cases and controls. We also detected significant epistatic interactions between SLC45A2 and OCA2 alleles, and MC1R and ASIP alleles. Overall, these measured variants account for 12% of the familial risk of CMM in our population.

  3. Role of PET in the initial staging of cutaneous malignant melanoma: systematic review.

    Science.gov (United States)

    Krug, Bruno; Crott, Ralph; Lonneux, Max; Baurain, Jean-François; Pirson, Anne-Sophie; Vander Borght, Thierry

    2008-12-01

    To calculate summary estimates of the diagnostic performance of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomographic (PET) imaging in the initial staging of cutaneous malignant melanoma (CMM), following the new American Joint Committee on Cancer (AJCC) staging classification on per-patient and per-lesion bases. MEDLINE, EMBASE, Web of Science, and Cochrane Database of Systematic Reviews databases, and reference lists of reviews and included papers were searched, without any language restrictions, for relevant articles published before March 2007. Two reviewers independently assessed study eligibility and methodologic quality by using the quality assessment of diagnostic accuracy studies checklist. A pooled random effect was estimated and a fixed coefficient regression model was used to explore the existing heterogeneity. Twenty-eight studies involving 2905 patients met the inclusion criteria. The pooled estimates of FDG PET for the detection of metastasis in the initial staging of CMM were sensitivity, 83% (95% confidence interval [CI]: 81%, 84%); specificity, 85% (95% CI: 83%, 87%); positive likelihood ratio (LR), 4.56 (95% CI: 3.12, 6.64); negative LR, 0.27 (95% CI: 0.18, 0.40); and diagnostic odds ratio, 19.8 (95% CI: 10.8, 36.4). Results from eight studies suggested that FDG PET was associated with 33% disease management changes (range, 15%-64%). There is good preliminary evidence that FDG PET is useful for the initial staging of patients with CMM, especially as adjunctive role in AJCC stages III and IV, to help detect deep soft-tissue, lymph node, and visceral metastases. FDG PET-computed tomographic imaging seemed to be more precise than PET alone, as suggested by four eligible studies. Further evaluation by using a well-designed prospective study, with clinical outcome-focused measures and cost effectiveness analysis, is needed to clarify the appropriate role of FDG PET in CMM staging. http://radiology.rsnajnls.org/cgi/content/full/249/3/836/DC

  4. Local cryosurgery and imiquimod: A successful combination for the treatment of locoregional cutaneous metastasis of melanoma: A case series.

    Science.gov (United States)

    Rivas-Tolosa, Nancy; Ortiz-Brugués, Ariadna; Toledo-Pastrana, Tomás; Baradad, Manel; Traves, Víctor; Soriano, Virtudes; Sanmartín, Verónica; Requena, Celia; Martí, Rosa; Nagore, Eduardo

    2016-05-01

    Locoregional cutaneous metastases of melanoma (LCMM) represent a therapeutic challenge. Many treatment options are available with varying results. The combination of cryotherapy and imiquimod, two treatments with a possible synergistic effect, has not yet been described for treating this disease. In this paper, we aimed to show the response of LCMM to cryotherapy combined with topical imiquimod 5%. A retrospective review of 20 patients diagnosed with LCMM and treated with cryotherapy combined with topical imiquimod 5% between November 2000 and May 2014 at three institutions was performed. The locoregional cutaneous response was evaluated. After a mean of five sessions, 13 patients (65%) responded to treatment, eight (40%) of these completely and five (25%) partially. Systemic disease progressed in 16 (80%) patients. Cryotherapy followed by topical imiquimod 5% is simple to apply, has minimal adverse effects and provides response rates similar to other, more complex treatment options. © 2015 Japanese Dermatological Association.

  5. Cutaneous head and neck melanoma in OPTiM, a randomized phase 3 trial of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor for the treatment of unresected stage IIIB/IIIC/IV melanoma.

    Science.gov (United States)

    Andtbacka, Robert H I; Agarwala, Sanjiv S; Ollila, David W; Hallmeyer, Sigrun; Milhem, Mohammed; Amatruda, Thomas; Nemunaitis, John J; Harrington, Kevin J; Chen, Lisa; Shilkrut, Mark; Ross, Merrick; Kaufman, Howard L

    2016-12-01

    Cutaneous head and neck melanoma has poor outcomes and limited treatment options. In OPTiM, a phase 3 study in patients with unresectable stage IIIB/IIIC/IV melanoma, intralesional administration of the oncolytic virus talimogene laherparepvec improved durable response rate (DRR; continuous response ≥6 months) compared with subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF). Retrospective review of OPTiM identified patients with cutaneous head and neck melanoma given talimogene laherparepvec (n = 61) or GM-CSF (n = 26). Outcomes were compared between talimogene laherparepvec and GM-CSF treated patients with cutaneous head and neck melanoma. DRR was higher for talimogene laherparepvec-treated patients than for GM-CSF treated patients (36.1% vs 3.8%; p = .001). A total of 29.5% of patients had a complete response with talimogene laherparepvec versus 0% with GM-CSF. Among talimogene laherparepvec-treated patients with a response, the probability of still being in response after 12 months was 73%. Median overall survival (OS) was 25.2 months for GM-CSF and had not been reached with talimogene laherparepvec. Treatment with talimogene laherparepvec was associated with improved response and survival compared with GM-CSF in patients with cutaneous head and neck melanoma. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1752-1758, 2016. © 2016 The Authors Head & Neck Published by Wiley Periodicals, Inc.

  6. Cutaneous Ulceration in Dermatomyositis: Association With Anti–Melanoma Differentiation–Associated Gene 5 Antibodies and Interstitial Lung Disease

    Science.gov (United States)

    NARANG, NEERA S.; CASCIOLA-ROSEN, LIVIA; LI, SHUFENG; CHUNG, LORINDA; FIORENTINO, DAVID F.

    2015-01-01

    Objective To identify clinical and serologic correlates of cutaneous ulcers in dermatomyositis (DM). Methods We retrospectively examined a cohort of 152 DM patients. We compared the features of patients with ulcers to those without ulcers using chi-square or Fisher’s exact tests and used univariate and multivariate logistic regression models to assess the association between ulcers and clinical features such as malignancy, interstitial lung disease (ILD), and amyopathic disease. Results Forty-three patients (28%) had cutaneous ulcers. Nearly half the patients had ulcers present in more than 1 location: 24 (56%) had ulcers over the extensor surfaces of joints, 18 (42%) at the digital pulp or periungual areas, and 25 (58%) had ulcers located elsewhere. In univariate analysis ulcers were associated with Asian race, but not with other clinical and demographic features, including malignancy or ILD. In multivariate analysis ulcers were significantly associated with anti–melanoma differentiation gene 5 (anti-MDA5) antibodies (odds ratio 10.14, 95% confidence interval 1.95–52.78, P = 0.0059) and this was greatest for ulcers located at the digital pulp. In patients with cutaneous ulcers, ILD risk was specifically increased only in patients with anti-MDA5+ antibodies. Conclusion We confirmed the strong association between anti-MDA5 antibodies and cutaneous ulcers, with the novel finding that the association of cutaneous ulcers with ILD depends upon the presence of anti-MDA5 antibodies. DM patients who display this cutaneous phenotype should undergo appropriate evaluation for ILD. PMID:25331610

  7. Female Urethral Malignant Melanoma With Vesical Invasion: A Case Report

    Directory of Open Access Journals (Sweden)

    Alpaslan Akbas

    2010-02-01

    Full Text Available We report a 75-year-old female with a primary urethral malignant melanoma. A mass protruding from inside the urethra was detected on physical examination. Abdominopelvic magnetic resonance imaging revealed a mass extending from the urethra with dimensions of 4 × 2 cm, and periurethral heterogenous fatty planes consistent with infiltration. The histopathologic examination was consistent with HMB45(+ malignant melanoma. We performed cystourethrectomy and bilateral inguinal and pelvic lymphadenectomy in one session. The pathology report revealed primary malignant melanoma of the urethra invading the inferior bladder wall. The patient received no adjuvant therapy because of cardiopulmonary morbidities and the presence of multiple pulmonary metastases. The patient eventually died 13 months after surgery.

  8. The role of lysosomal proteolytic enzymes in invasion and dissemination of malignant melanoma

    International Nuclear Information System (INIS)

    Bassalyk, L.S.; Tsanev, P.E.; Parshikova, S.M.; Demidov, L.V.

    1992-01-01

    Preoperative chemo- and radiation therapy was followed by a decrease in lysosomal cathepsins activity in metastatic lymph nodes which, however, did not reach the level established for intact lymph nodes. The pathogenetic role of proteolytic endopeptidases in invasion and sissemination of malignant melanoma is discussed as well as the value of their level measurement for assessing metastatic potential of tumor and prognosis of disease of disease on the basis of tumor site, degree of invasion regional lymph node status

  9. Further development of thermal neutron capture therapy for metastatic and deeply-invasive human malignant melanoma

    International Nuclear Information System (INIS)

    Mishima, Yutaka

    1995-03-01

    This issue is the collection of the papers presented thermal neutron capture therapy for metastatic and deeply-invasive human malignant melanoma. Separate abstracts were prepared for 2 of the papers in this report. The remaining 32 papers were considered outside the subject scope of INIS. (J.P.N.)

  10. Associations of Statins and Diabetes with Diagnosis of Ulcerated Cutaneous Melanoma.

    Science.gov (United States)

    von Schuckmann, Lena A; Smith, David; Hughes, Maria Celia B; Malt, Maryrose; van der Pols, Jolieke C; Khosrotehrani, Kiarash; Smithers, Bernard M; Green, Adele C

    2017-12-01

    Ulcerated primary melanomas are associated with an inflammatory tumor microenvironment. We hypothesized that systemic proinflammatory states and anti-inflammatory medications are also associated with a diagnosis of ulcerated melanoma. In a cross-sectional study of 787 patients with newly diagnosed clinical stage IB or II melanoma, we estimated odds ratios for the association of proinflammatory factors (high body mass index, diabetes, cardiovascular disease, hypertension, and smoking) or the use of anti-inflammatory medications (statins, aspirin, corticosteroids, and nonsteroidal anti-inflammatory drugs), with ulcerated primary melanoma using regression models and subgroup analyses to control for melanoma thickness and mitotic rate. On the basis of information from 194 patients with ulcerated and 593 patients with nonulcerated primary melanomas, regular statin users had lower likelihood of a diagnosis of ulcerated primary melanoma (odds ratio 0.67, 95% confidence interval 0.45-0.99), and this association remained after adjusting for age, sex, thickness, and mitosis. When analysis was limited to melanomas that were ≤2 mm thick and had ≤2 mitoses/mm 2 (40 ulcerated; 289 without ulceration), patients with diabetes had significantly raised odds of diagnosis of ulcerated melanoma (odds ratio 2.90, 95% confidence interval 1.07-7.90), adjusted for age, sex, body mass index, and statin use. These findings support our hypotheses that statin use is inversely associated, and diabetes is positively associated, with ulcerated melanoma. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  11. The Danish Melanoma Database

    DEFF Research Database (Denmark)

    Hölmich, Lisbet Rosenkrantz; Klausen, Siri; Spaun, Eva

    2016-01-01

    AIM OF DATABASE: The aim of the database is to monitor and improve the treatment and survival of melanoma patients. STUDY POPULATION: All Danish patients with cutaneous melanoma and in situ melanomas must be registered in the Danish Melanoma Database (DMD). In 2014, 2,525 patients with invasive......-node-metastasis stage. Information about the date of diagnosis, treatment, type of surgery, including safety margins, results of lymphoscintigraphy in patients for whom this was indicated (tumors > T1a), results of sentinel node biopsy, pathological evaluation hereof, and follow-up information, including recurrence......, nature, and treatment hereof is registered. In case of death, the cause and date are included. Currently, all data are entered manually; however, data catchment from the existing registries is planned to be included shortly. DESCRIPTIVE DATA: The DMD is an old research database, but new as a clinical...

  12. Ultraviolet Radiation-Induced Cytogenetic Damage in White, Hispanic and Black Skin Melanocytes: A Risk for Cutaneous Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Dasgupta, Amrita [Hampton University Skin of Color Research Institute, Hampton, VA 23668 (United States); Katdare, Meena, E-mail: mkatdare@gmail.com [Hampton University Skin of Color Research Institute, Hampton, VA 23668 (United States); Department of Dermatology, Eastern Virginia Medical School, Norfolk, VA 23507 (United States)

    2015-08-14

    Cutaneous Melanoma (CM) is a leading cause of cancer deaths, with reports indicating a rising trend in the incidence rate of melanoma among Hispanics in certain U.S. states. The level of melanin pigmentation in the skin is suggested to render photoprotection from the DNA-damaging effects of Ultraviolet Radiation (UVR). UVR-induced DNA damage leads to cytogenetic defects visualized as the formation of micronuclei, multinuclei and polymorphic nuclei in cells, and a hallmark of cancer risk. The causative relationship between Sun exposure and CM is controversial, especially in Hispanics and needs further evaluation. This study was initiated with melanocytes from White, Hispanic and Black neonatal foreskins which were exposed to UVR to assess their susceptibility to UVR-induced modulation of cellular growth, cytogenetic damage, intracellular and released melanin. Our results show that White and Hispanic skin melanocytes with similar levels of constitutive melanin are susceptible to UVR-induced cytogenetic damage, whereas Black skin melanocytes are not. Our data suggest that the risk of developing UVR-induced CM in a skin type is correlated with the level of cutaneous pigmentation and its ethnic background. This study provides a benchmark for further investigation on the damaging effects of UVR as risk for CM in Hispanics.

  13. The relationship between mitotic rate and depth of invasion in biopsies of malignant melanoma

    Directory of Open Access Journals (Sweden)

    Ghasemi Basir HR

    2018-03-01

    Full Text Available Hamid Reza Ghasemi Basir,1,2 Pedram Alirezaei,2 Sara Ahovan,3 Abbas Moradi3 1Department of Pathology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran; 2Psoriasis Research Center, Hamadan University of Medical Sciences, Hamadan, Iran; 3School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran Background: Malignant melanoma of the skin is a potentially lethal neoplasm that generally originates from atypical melanocytes in the dermal–epidermal junction. When the neoplasm penetrates into the dermis, several variables can affect the extent of its spread, among which depth of invasion has the most important prognostic value. Mitotic rate is another prognostic factor that reflects the biological behavior of the neoplasm.Objective: This study was designed to evaluate the probable relationship between the depth of invasion of malignant melanoma and its mitotic rate.Materials and methods: This study was performed on 50 excisional biopsy specimens that had received the diagnosis of malignant melanoma histopathologically. Tumor characteristics including Breslow thickness, Clark level, T-stage, and tumor mitotic rate were recorded.Results: We observed that at higher Clark levels and higher T-stages, and the mean mitotic rate was significantly increased. Moreover, there was a positive and significant correlation between Breslow thickness and mitotic rate. We demonstrated that one unit increase in mitotic rate was correlated with 0.8 mm increase in Breslow thickness of the tumor.Conclusion: In malignant melanoma, mitotic activity may probably indicate the depth of tumor invasion. Therefore, in incisional biopsies where depth of invasion cannot be accurately determined, the mitotic activity may be used to estimate Breslow thickness, which is necessary for planning surgical management. Keywords: melanoma, mitosis, Breslow, invasion, thickness, proliferation

  14. TRAF6 regulates melanoma invasion and metastasis through ubiquitination of Basigin

    Science.gov (United States)

    Luo, Zhongling; Zhang, Xu; Zeng, Weiqi; Su, Juan; Yang, Keda; Lu, Lixia; Lim, Chuan Bian; Tang, Wen; Wu, Lisha; Zhao, Shuang; Jia, Xuekun; Peng, Cong; Chen, Xiang

    2016-01-01

    TRAF6 plays a crucial role in the regulation of the innate and adaptive immune responses. Although studies have shown that TRAF6 has oncogenic activity, the role of TRAF6 in melanoma is unclear. Here, we report that TRAF6 is overexpressed in primary as well as metastatic melanoma tumors and melanoma cell lines. Knockdown of TRAF6 with shRNA significantly suppressed malignant phenotypes including cell proliferation, anchorage-independent cell growth and metastasis in vitro and in vivo. Notably, we demonstrated that Basigin (BSG)/CD147, a critical molecule for cancer cell invasion and metastasis, is a novel interacting partner of TRAF6. Furthermore, depletion of TRAF6 by shRNA reduced the recruitment of BSG to the plasma membrane and K63-linked ubiquitination, in turn, which impaired BSG-dependent MMP9 induction. Taken together, our findings indicate that TRAF6 is involved in regulating melanoma invasion and metastasis, suggesting that TRAF6 may be a potential target for therapy or chemo-prevention in melanoma. PMID:26769849

  15. Effects of Zeaxanthin on Growth and Invasion of Human Uveal Melanoma in Nude Mouse Model

    Directory of Open Access Journals (Sweden)

    Xiaoliang L. Xu

    2015-01-01

    Full Text Available Uveal melanoma cells were inoculated into the choroid of nude mice and treated with or without intraocular injection of zeaxanthin. After 21 days, mice were sacrificed and the eyes enucleated. Histopathological analysis was performed in hematoxylin and eosin stained frozen sections. Melanoma developed rapidly in the control group (without treatment of zeaxanthin. Tumor-bearing eye mass and tumor mass in the control group were significantly greater than those in zeaxanthin treated group. Melanoma in the controlled eyes occupied a large part of the eye, was epithelioid in morphology, and was with numerous mitotic figures. Scleral perforation and extraocular extension were observed in half of the eyes. Melanomas in zeaxanthin treated eyes were significantly smaller with many necrosis and apoptosis areas and no extraocular extension could be found. Quantitative image analysis revealed that the tumor size was reduced by 56% in eyes treated with low dosages of zeaxanthin and 92% in eyes treatment with high dosages of zeaxanthin, as compared to the controls. This study demonstrated that zeaxanthin significantly inhibits the growth and invasion of human uveal melanoma in nude mice, suggesting that zeaxanthin may be a promising agent to be explored for the prevention and treatment of uveal melanoma.

  16. New target genes of MITF-induced microRNA-211 contribute to melanoma cell invasion.

    Directory of Open Access Journals (Sweden)

    Christiane Margue

    Full Text Available The non-coding microRNAs (miRNA have tissue- and disease-specific expression patterns. They down-regulate target mRNAs, which likely impacts on most fundamental cellular processes. Differential expression patterns of miRNAs are currently being exploited for identification of biomarkers for early disease diagnosis, prediction of progression for melanoma and other cancers and as promising drug targets, since they can easily be inhibited or replaced in a given cellular context. Before successfully manipulating miRNAs in clinical settings, their precise expression levels, endogenous functions and thus their target genes have to be determined. MiR-211, a melanocyte lineage-specific small non-coding miRNA, is located in an intron of TRPM1, a target gene of the microphtalmia-associated transcription factor (MITF. By transcriptionally up-regulating TRPM1, MITF, which is critical for both melanocyte differentiation and survival and for melanoma progression, indirectly drives the expression of miR-211. Expression of this miRNA is often reduced in melanoma samples. Here, we investigated functional roles of miR-211 by identifying and studying new target genes. We show that MITF-correlated miR-211 expression levels are mostly but not always reduced in a panel of 11 melanoma cell lines and in primary and metastatic melanoma compared to normal melanocytes and nevi, respectively. MiR-211 itself only marginally impacted on cell invasion and migration, while perturbation of some new miR-211 target genes, such as AP1S2, SOX11, IGFBP5, and SERINC3 significantly increased invasion. These results and the variable expression levels of miR-211 raise serious doubts on the value of miR-211 as a melanoma tumor-suppressing miRNA and/or as a biomarker for melanoma.

  17. Clinical value of FDG-PET in cutaneous malignant melanoma: First experience in Estonia

    International Nuclear Information System (INIS)

    Nazarenko, S.; Niin, M.; Paats, A.; Tonnov, A.

    2004-01-01

    Full text: In November 2002 first 18F-FDG-PET was performed in Estonia using a mobile truck-mounted scanning technology (Accel, Siemens) provided by the International Healthcare Group (IHG, Amersfoort, Netherlands). The FDG was provided by MAP Medical Technologies, Schering, (Helsinki, Finland). In 2003 this scheme was repeated for further scanning sessions. Evaluation of cutaneous malignant melanoma (CMM) using nuclear technique is of particular interest in Estonia as its incidence is on the rise. F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in CMM has a well-documented high diagnostic accuracy, especially in staging of the disease. The aim of the current study was to assess the impact of 18F-FDG-PET on detailed staging and clinical management in CMM. 30 patients of CMM, 16 males and 14 females, all non-diabetic, in the age range of 26 to 69 years were studied. Of these 30 patients, 12 were of high risk primary CMM, 7 had regional lymph node metastases and 11 had distant metastases. Patients were asked to consume a low-carbohydrate diet 3 days prior to the FDG-PET scan. 194 to 410 MBq (average 335 MBq) 18F-FDG was administered to the patients who were asked to come fasting for a minimum of 6 hours. Whole body scan was performed 40 to 65 minutes after the administration of FDG on the mobile PET. In 13 of the 30 patients (43%) 18F-FDG-PET changed the staging. In remaining 17 patients (57%) 18F-FDG-PET increased confidence level for the chosen treatment. Lymphadenectomy was planned in 2 patients showing lymph node involvement on FDG-PET. In other 2 patients, one with small pulmonary and other with a liver lesions found on PET but negative on radiological examination 'wait-and-watch' strategy was chosen. An unexpected hypermetabolic lesion seen in 1 case turned out to be a benign focus of connective tissue. One patient shown to have multiple distant metastases was started on chemotherapy. Finally in 8 of the 30 (27%) patients an immediate positive

  18. MGMT promoter methylation is associated with temozolomide response and prolonged progression-free survival in disseminated cutaneous melanoma.

    Science.gov (United States)

    Tuominen, Rainer; Jewell, Rosalyn; van den Oord, Joost J; Wolter, Pascal; Stierner, Ulrika; Lindholm, Christer; Hertzman Johansson, Carolina; Lindén, Diana; Johansson, Hemming; Frostvik Stolt, Marianne; Walker, Christy; Snowden, Helen; Newton-Bishop, Julia; Hansson, Johan; Egyházi Brage, Suzanne

    2015-06-15

    To investigate the predictive and prognostic value of O(6) -methylguanine DNA methyltransferase (MGMT) inactivation by analyses of promoter methylation in pretreatment tumor biopsies from patients with cutaneous melanoma treated with dacarbazine (DTIC) or temozolomide (TMZ) were performed. The patient cohorts consisted of Belgian and Swedish disseminated melanoma patients. Patients were subdivided into those receiving single-agent treatment with DTIC/TMZ (cohort S, n = 74) and those treated with combination chemotherapy including DTIC/TMZ (cohort C, n = 79). Median follow-up was 248 and 336 days for cohort S and cohort C, respectively. MGMT promoter methylation was assessed by three methods. The methylation-related transcriptional silencing of MGMT mRNA expression was assessed by real-time RT-PCR. Response to chemotherapy and progression-free survival (PFS) and overall survival were correlated to MGMT promoter methylation status. MGMT promoter methylation was detected in tumor biopsies from 21.5 % of the patients. MGMT mRNA was found to be significantly lower in tumors positive for MGMT promoter methylation compared to tumors without methylation in both treatment cohorts (p MGMT promoter methylation in cohort S (p = 0.0005), but did not reach significance in cohort C (p = 0.16). Significantly longer PFS was observed among patients with MGMT promoter-methylated tumors (p = 0.002). Multivariate Cox regression analysis identified presence of MGMT promoter methylation as an independent variable associated with longer PFS. Together, this implies that MGMT promoter methylation is associated with response to single-agent DTIC/TMZ and longer PFS in disseminated cutaneous melanoma. © 2014 UICC.

  19. Clinicopathological predictors of recurrence in nodular and superficial spreading cutaneous melanoma: a multivariate analysis of 214 cases

    Directory of Open Access Journals (Sweden)

    Maria A. Pizzichetta

    2017-11-01

    Full Text Available Abstract Background Nodular melanoma (NM accounts for most thick melanomas and because of their frequent association with ulceration, fast growth rate and high mitotic rate, contribute substantially to melanoma-related mortality. In a multicentric series of 214 primary melanomas including 96 NM and 118 superficial spreading melanoma (SSM, histopathological features were examined with the aim to identify clinicopathological predictors of recurrence. Methods All consecutive cases of histopathologically diagnosed primary invasive SSM and NM during the period 2005–2010, were retrieved from the 12 participating Italian Melanoma Intergroup (IMI centers. Each center provided clinico-pathological data such as gender, age at diagnosis, anatomical site, histopathological conventional parameters, date of excision and first melanoma recurrence. Results Results showed that NM subtype was significantly associated with Breslow thickness (BT at multivariate analysis: [BT 1.01–2 mm (OR 7.22; 95% CI 2.73–19.05, BT 2.01–4 mm (OR 7.04; 95% CI 2.54–19.56, and BT > 4 mm (OR 51.78; 95% CI 5.65–474.86 (p  5 mitoses/mm2 (OR 4.87; 95% CI 1.77–13.40 (p = 0.002]. The risk of recurrence was not significantly associated with NM histotype while BT [BT 1.01–2.00 mm (HR 1.55; 95% CI 0.51–4.71, BT 2.01–4.00 mm (HR 2.42; 95% CI 0.89–6.54, BT > 4.00 mm. (HR 3.13; 95% CI 0.95–10.28 (p = 0.05], mitotic rate [MR > 2 mitoses/mm2 (HR 2.34; 95% CI, 1.11–4.97 (p = 0.03] and the positivity of lymph node sentinel biopsy (SNLB (HR 2.60; 95% CI 1.19–5.68 (p = 0.007 were significantly associated with an increased risk of recurrence at multivariate analysis. Conclusions We found that NM subtype was significantly associated with higher BT and MR but it was not a prognostic factor since it did not significantly correlate with melanoma recurrence rate. Conversely, increased BT and MR as well as SNLB positivity were significantly associated with a

  20. Clinicopathological predictors of recurrence in nodular and superficial spreading cutaneous melanoma: a multivariate analysis of 214 cases.

    Science.gov (United States)

    Pizzichetta, Maria A; Massi, Daniela; Mandalà, Mario; Queirolo, Paola; Stanganelli, Ignazio; De Giorgi, Vincenzo; Ghigliotti, Giovanni; Cavicchini, Stefano; Quaglino, Pietro; Corradin, Maria T; Rubegni, Pietro; Alaibac, Mauro; Astorino, Stefano; Ayala, Fabrizio; Magi, Serena; Mazzoni, Laura; Manganoni, Maria Ausilia; Talamini, Renato; Serraino, Diego; Palmieri, Giuseppe

    2017-11-07

    Nodular melanoma (NM) accounts for most thick melanomas and because of their frequent association with ulceration, fast growth rate and high mitotic rate, contribute substantially to melanoma-related mortality. In a multicentric series of 214 primary melanomas including 96 NM and 118 superficial spreading melanoma (SSM), histopathological features were examined with the aim to identify clinicopathological predictors of recurrence. All consecutive cases of histopathologically diagnosed primary invasive SSM and NM during the period 2005-2010, were retrieved from the 12 participating Italian Melanoma Intergroup (IMI) centers. Each center provided clinico-pathological data such as gender, age at diagnosis, anatomical site, histopathological conventional parameters, date of excision and first melanoma recurrence. Results showed that NM subtype was significantly associated with Breslow thickness (BT) at multivariate analysis: [BT 1.01-2 mm (OR 7.22; 95% CI 2.73-19.05), BT 2.01-4 mm (OR 7.04; 95% CI 2.54-19.56), and BT > 4 mm (OR 51.78; 95% CI 5.65-474.86) (p  5 mitoses/mm 2 (OR 4.87; 95% CI 1.77-13.40) (p = 0.002)]. The risk of recurrence was not significantly associated with NM histotype while BT [BT 1.01-2.00 mm (HR 1.55; 95% CI 0.51-4.71), BT 2.01-4.00 mm (HR 2.42; 95% CI 0.89-6.54), BT > 4.00 mm. (HR 3.13; 95% CI 0.95-10.28) (p = 0.05)], mitotic rate [MR > 2 mitoses/mm 2 (HR 2.34; 95% CI, 1.11-4.97) (p = 0.03)] and the positivity of lymph node sentinel biopsy (SNLB) (HR 2.60; 95% CI 1.19-5.68) (p = 0.007) were significantly associated with an increased risk of recurrence at multivariate analysis. We found that NM subtype was significantly associated with higher BT and MR but it was not a prognostic factor since it did not significantly correlate with melanoma recurrence rate. Conversely, increased BT and MR as well as SNLB positivity were significantly associated with a higher risk of melanoma recurrence.

  1. The measurement of constitutive and facultative skin pigmentation and estimation of sun exposure in Caucasians with basal cell carcinoma and cutaneous malignant melanoma

    DEFF Research Database (Denmark)

    Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

    1998-01-01

    In two identical and simultaneously performed case-control studies of basal cell carcinoma (BCC) and cutaneous malignant melanoma (CMM) with age-matched, sex-matched and residence-matched controls, skin pigmentation was measured objectively by skin reflectance spectroscopy in 145 BCC patients...

  2. Individual risk of cutaneous melanoma in New Zealand: developing a clinical prediction aid.

    Science.gov (United States)

    Sneyd, Mary Jane; Cameron, Claire; Cox, Brian

    2014-05-22

    New Zealand and Australia have the highest melanoma incidence rates worldwide. In New Zealand, both the incidence and thickness have been increasing. Clinical decisions require accurate risk prediction but a simple list of genetic, phenotypic and behavioural risk factors is inadequate to estimate individual risk as the risk factors for melanoma have complex interactions. In order to offer tailored clinical management strategies, we developed a New Zealand prediction model to estimate individual 5-year absolute risk of melanoma. A population-based case-control study (368 cases and 270 controls) of melanoma risk factors provided estimates of relative risks for fair-skinned New Zealanders aged 20-79 years. Model selection techniques and multivariate logistic regression were used to determine the important predictors. The relative risks for predictors were combined with baseline melanoma incidence rates and non-melanoma mortality rates to calculate individual probabilities of developing melanoma within 5 years. For women, the best model included skin colour, number of moles > =5 mm on the right arm, having a 1st degree relative with large moles, and a personal history of non-melanoma skin cancer (NMSC). The model correctly classified 68% of participants; the C-statistic was 0.74. For men, the best model included age, place of occupation up to age 18 years, number of moles > =5 mm on the right arm, birthplace, and a history of NMSC. The model correctly classified 67% of cases; the C-statistic was 0.71. We have developed the first New Zealand risk prediction model that calculates individual absolute 5-year risk of melanoma. This model will aid physicians to identify individuals at high risk, allowing them to individually target surveillance and other management strategies, and thereby reduce the high melanoma burden in New Zealand.

  3. Expression profiles analysis of long non-coding RNAs identified novel lncRNA biomarkers with predictive value in outcome of cutaneous melanoma.

    Science.gov (United States)

    Ma, Xu; He, Zhijuan; Li, Ling; Yang, Daping; Liu, Guofeng

    2017-09-29

    Recent advancements in cancer biology have identified a large number of lncRNAs that are dysregulated expression in the development and tumorigenesis of cancers, highlighting the importance of lncRNAs as a key player for human cancers. However, the prognostic value of lncRNAs still remains unclear and needs to be further investigated. In the present study, we aim to assess the prognostic value of lncRNAs in cutaneous melanoma by integrated lncRNA expression profiles from TCGA database and matched clinical information from a large cohort of patients with cutaneous melanoma. We finally identified a set of six lncRNAs that are significantly associated with survival of patients with cutaneous melanoma. A linear combination of six lncRNAs ( LINC01260, HCP5, PIGBOS1, RP11-247L20.4, CTA-292E10.6 and CTB-113P19.5 ) was constructed as a six-lncRNA signature which classified patients of training cohort into the high-risk group and low-risk group with significantly different survival time. The prognostic value of the six-lncRNA signature was validated in both the validation cohort and entire TCGA cohort. Moreover, the six-lncRNA signature is independent of known clinic-pathological factors by multivariate Cox regression analysis and demonstrated good performance for predicting three- and five-year overall survival by time-dependent receiver operating characteristic (ROC) analysis. Our study provides novel insights into the molecular heterogeneity of cutaneous melanoma and also shows potentially important implications of lncRNAs for prognosis and therapy for cutaneous melanoma.

  4. Localization of integrin alpha(v)beta3 and vascular endothelial growth factor receptor-2 (KDR/Flk-1) in cutaneous and oral melanomas of dog.

    Science.gov (United States)

    Rawlings, N G; Simko, E; Bebchuk, T; Caldwell, S J; Singh, B

    2003-07-01

    Melanomas are common neoplasms of dogs and arise from pigment-producing cells called melanocytes or melanoblasts. Melanomas of skin are often easily cured by surgical excision, but those of oral mucosa are aggressive, metastasize to the regional lymph nodes and lungs, and respond poorly to conventional therapy. Tumor growth is sustained by proliferation of microvessels via a process called angiogenesis. Integrin alpha(v)beta3 is expressed in proliferating but not in quiescent microvessels suggesting a role in angiogenesis. Vascular endothelial growth factor (VEGF) manifests its mitogenic and angiogenic effects mainly via VEGF receptor-2 (VEGFR-2/Flk-1). We conducted this immunocytochemical study to investigate the expression of integrin alpha(v)beta3 and VEGFR-2 in archival and fresh samples from cases of canine melanomas. Results show that integrin alpha(v)beta3 was expressed in 72% and 88% of cutaneous and oral melanomas, respectively, and the expression was restricted to and immediately around the melanocytes and endothelial cells. VEGFR-2 staining of selected cases of melanoma revealed that its expression overlapped with the alpha(v)beta3 integrin. Dual immuno-gold electron microscopy confirmed co-localization of integrin alpha(v)beta3 and VEGFR-2 in melanocytes and endothelial cells. These data demonstrate expression and co-localization of integrin alpha(v)beta3 and VEGFR-2 in cutaneous and oral melanomas of dogs.

  5. Value of sentinel lymph node biopsy and adjuvant interferon treatment in thick (>4 mm) cutaneous melanoma: an observational study.

    Science.gov (United States)

    Morera-Sendra, Natalia; Tejera-Vaquerizo, Antonio; Traves, Víctor; Requena, Celia; Bolumar, Isidro; Pla, Angel; Vázquez, Carlos; Soriano, Virtudes; Nagore, Eduardo

    2016-01-01

    The role of sentinel lymph node biopsy and the benefit of immunotherapy with interferon in thick (>4 mm) melanomas remain uncertain. Our aim was to assess the value of both sentinel lymph node (SLN) biopsy and immunotherapy in the prognosis of thick melanomas. A retrospective study based on a computerized patient database in which patients have been prospectively collected since 2005 was performed. Age, sex, location, Breslow thickness, tumor ulceration, regression, Clark level, tumor infiltrating lymphocytes, tumor mitotic rate, microscopic satellite and vascular invasion were included in the analysis. Disease-free (DFS), disease-specific (DSS) and overall (OS) survivals were evaluated by the Kaplan-Meier method and Cox regression analysis. A series of 141 patients with melanomas thicker than 4 mm were included. Multivariate regression showed a worse prognosis in SLN-positive patients with respect to SLN biopsy-negative patients (DFS, hazard ratio [HR] 2, p = 0.04; DSS, HR 2.2, p = 0.002; OS, HR 2.4, p = 0.02). The observational group was shown to have a worse prognosis than the SLN-positive group but was very similar to the clinically positive group. Immunotherapy with high-dose interferon showed a protective effect (DFS, HR 0.5, p = 0.02; DSS, HR 0.3, p = 0.001; OS, HR 0.3, p = 0.001). Our data indicate that SLN biopsy and adjuvant interferon should be considered for patients with thick melanomas.

  6. Hypoxia promotes uveal melanoma invasion through enhanced Notch and MAPK activation.

    Directory of Open Access Journals (Sweden)

    Laura Asnaghi

    Full Text Available The transcriptional response promoted by hypoxia-inducible factors has been associated with metastatic spread of uveal melanoma. We found expression of hypoxia-inducible factor 1α (HIF-1α protein in well-vascularized tumor regions as well as in four cell lines grown in normoxia, thus this pathway may be important even in well-oxygenated uveal melanoma cells. HIF-1α protein accumulation in normoxia was inhibited by rapamycin. As expected, hypoxia (1% pO2 further induced HIF-1α protein levels along with its target genes VEGF and LOX. Growth in hypoxia significantly increased cellular invasion of all 5 uveal melanoma lines tested, as did the introduction of an oxygen-insensitive HIF-1α mutant into Mel285 cells with low HIF-1α baseline levels. In contrast, HIF-1α knockdown using shRNA significantly decreased growth in hypoxia, and reduced by more than 50% tumor invasion in four lines with high HIF-1α baseline levels. Pharmacologic blockade of HIF-1α protein expression using digoxin dramatically suppressed cellular invasion both in normoxia and in hypoxia. We found that Notch pathway components, including Jag1-2 ligands, Hes1-Hey1 targets and the intracellular domain of Notch1, were increased in hypoxia, as well as the phosphorylation levels of Erk1-2 and Akt. Pharmacologic and genetic inhibition of Notch largely blocked the hypoxic induction of invasion as did the pharmacologic suppression of Erk1-2 activity. In addition, the increase in Erk1-2 and Akt phosphorylation by hypoxia was partially reduced by inhibiting Notch signaling. Our findings support the functional importance of HIF-1α signaling in promoting the invasive capacity of uveal melanoma cells in both hypoxia and normoxia, and suggest that pharmacologically targeting HIF-1α pathway directly or through blockade of Notch or Erk1-2 pathways can slow tumor spread.

  7. Expression of monoacylglycerol lipase as a marker of tumour invasion and progression in malignant melanoma.

    Science.gov (United States)

    Baba, Yuko; Funakoshi, T; Mori, M; Emoto, K; Masugi, Y; Ekmekcioglu, S; Amagai, M; Tanese, K

    2017-12-01

    Accumulating evidence suggests that the lipid lytic enzyme monoacylglycerol lipase (MAGL) promotes tumour invasion and metastasis through up-regulation of pro-tumorigenic signalling lipids in several tumour cell lines. However, the expression status of MAGL in clinical melanoma tissues and its clinicopathological significance remain unclear. To correlate the tumour expression status of MAGL with the clinicopathological information of patients with malignant melanoma. Polymerase chain reaction (PCR) array screening was performed, and the results were validated using immunocytochemical analysis of tumour and non-tumour melanocytic cell lines. Immunohistochemical staining for MAGL was performed for 74 melanoma samples, including 48 primary and 26 metastatic tumours, in which the expression of MAGL was determined by evaluating the percentage of MAGL-positive tumour cells and the MAGL staining intensity. Finally, we analysed the association of MAGL expression status with tumour progression, tumour thickness and vascular invasion of the primary lesion. Immunocytochemical analysis revealed that MAGL was expressed in all 12 melanoma cell lines, but not in normal human epidermal melanocytes. In the immunohistochemical analysis, positive staining for MAGL was noted in 32 of 48 (64.5%) primary lesions, 14 of 17 (82.4%) lymph node metastatic lesions and 7 of 9 (77.8%) skin metastatic lesions. Metastatic tumours had a significantly higher staining intensity (P = 0.033 for lymph node, P = 0.010 for skin). In the analysis of primary lesions, higher MAGL expression correlated with greater tumour thickness (P = 0.015) and the presence of vascular invasion (P = 0.017). On further evaluation of MAGL-positive primary lesions, staining intensity of MAGL tended to be higher in deeper areas of the tumour mass. The expression of MAGL in tumour cells reflects the aggressiveness of melanoma cells and may serve as a marker of tumour progression. © 2017 European Academy of Dermatology and

  8. Surgical resection margins do not influence health related quality of life or emotional distress in patients with cutaneous melanoma: results of a prospective randomised trial.

    Science.gov (United States)

    Bergenmar, Mia; Månsson-Brahme, Eva; Hansson, Johan; Brandberg, Yvonne

    2010-06-01

    In a prospective randomised Scandinavian trial, patients with localised invasive cutaneous melanoma of the trunk or extremities with tumours more than 2 mm thick were randomly assigned to excision with narrow (2 cm) or wide (4 cm) margins after primary surgery. The aims of the present study were to find out if there were any differences in health-related quality of life (QoL) and emotional distress between patients in the two arms over time. Patients were assessed at four time points: before randomisation, and at 3, 9, and 15 months after inclusion, using the EORTC QLQ-C30, the Hospital Anxiety and Depression Scale and the Impact of Event Scale. A study-specific questionnaire was used to assess patient-reported problems related to the scar. A total of 144 patients were included; 70 randomised to narrow excision and 74 to wide excision margins. The response rate was >85% at all assessment points. No differences between the two arms were found for health-related QoL or emotional distress. Emotional functioning, insomnia, anxiety, intrusion, and avoidance improved over time (p emotional distress were found between the two arms, indicating that resection margins have limited impact on these variables.

  9. A novel non-invasive diagnostic sampling technique for cutaneous leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Yasaman Taslimi

    2017-07-01

    Full Text Available Accurate diagnosis of cutaneous leishmaniasis (CL is important for chemotherapy and epidemiological studies. Common approaches for Leishmania detection involve the invasive collection of specimens for direct identification of amastigotes by microscopy and the culturing of promastigotes from infected tissues. Although these techniques are highly specific, they require highly skilled health workers and have the inherent risks of all invasive procedures, such as pain and risk of bacterial and fungal super-infection. Therefore, it is essential to reduce discomfort, potential infection and scarring caused by invasive diagnostic approaches especially for children. In this report, we present a novel non-invasive method, that is painless, rapid and user-friendly, using sequential tape strips for sampling and isolation of DNA from the surface of active and healed skin lesions of CL patients. A total of 119 patients suspected of suffering from cutaneous leishmaniasis with different clinical manifestations were recruited and samples were collected both from their lesions and from uninfected areas. In addition, 15 fungal-infected lesions and 54 areas of healthy skin were examined. The duration of sampling is short (less than one minute and species identification by PCR is highly specific and sensitive. The sequential tape stripping sampling method is a sensitive, non-invasive and cost-effective alternative to traditional diagnostic assays and it is suitable for field studies as well as for use in health care centers.

  10. Survival after a psychoeducational intervention for patients with cutaneous malignant melanoma: a replication study

    DEFF Research Database (Denmark)

    Boesen, Ellen H; Boesen, Sidsel H; Frederiksen, Kirsten

    2007-01-01

    The results of a randomized, intervention study done in 1993 of psychoeducation for patients with early-stage malignant melanoma showed a beneficial effect on recurrence and survival 6 years after the intervention. In the present study, we replicated the study with 258 Danish patients with malign...... with malignant melanoma. We also compared recurrence and survival among the participants in the randomized study with 137 patients who refused to participate....

  11. Objective histopathologic grading of cutaneous malignant melanomas by stereologic estimation of nuclear volume. Prediction of survival and disease-free period

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt

    1989-01-01

    and two-dimensional morphometric estimates. The averaged Vv was 226 microns3 and 457 microns3 in Stage I and II melanomas, respectively. The Vv was significantly increased in the case of ulceration, nodular melanoma, and Clark's level greater than III. The Vv showed only poor correlation to two......Modern stereologic techniques enable unbiased and shape-independent estimation of the three-dimensional nuclear volume (Vv). This study investigates the prognostic impact of Vv in 47 patients with malignant melanomas (10 years of follow-up) and compares Vv to traditional prognostic parameters...... independent prognostic significance, which may be due to attributes of the small data base. It is concluded that Vv may be a powerful prognostic indicator in cutaneous melanomas, suitable for objective malignancy grading. The clinical and prognostic value of nuclear Vv needs further investigation in a larger...

  12. Ultraviolet-induced formation of micronuclei and sister chromatid exchange in cultured fibroblasts of patients with cutaneous malignant melanoma

    International Nuclear Information System (INIS)

    Roser, M.; Boehm, A.O.; Oldigs, M.; Weichenthal, M.; Reimers, U.; Schmidt-Preuss, U.; Breitbart, E.W.; Ruediger, H.W.

    1989-01-01

    Genetically enhanced sensitivity to ultraviolet (UV) radiation may play an important role in the development of cutaneous malignant melanoma (CMM). This was studied in cultured fibroblasts of 26 CMM patients and controls by micronucleus (MN) test and sister chromatid exchange (SCE) after UV irradiation (375 J/m2). Sister chromatid exchange and MN formation were used as parameters to detect the UV-induced genotoxic damage in the individual cell strains. We found that the UV-induced level of MN was significantly increased in CMM patients (p = 0.0005), being most pronounced in the familial cases (p = 0.0001). Ultraviolet-induced SCE was also elevated in CMM patients (p = 0.001), but there was no difference between familial and nonfamilial cases. The present findings indicate that genetic predisposition contributes to the development of CMM in a subset of CMM patients and may be due to an enhanced susceptibility to UV light

  13. Cystatin E/M suppresses legumain activity and invasion of human melanoma

    OpenAIRE

    Briggs, Jon J; Haugen, Mads H; Johansen, Harald T; Riker, Adam I; Abrahamson, Magnus; Fodstad, ?ystein; M?landsmo, Gunhild M; Solberg, Rigmor

    2010-01-01

    Background High activity of cysteine proteases such as legumain and the cathepsins have been shown to facilitate growth and invasion of a variety of tumor types. In breast cancer, several recent studies have indicated that loss of the cysteine protease inhibitor cystatin E/M leads to increased growth and metastasis. Although cystatin E/M is normally expressed in the skin, its role in cysteine protease regulation and progression of malignant melanoma has not been studied. ...

  14. Eye and hair colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma. A Danish case-control study

    DEFF Research Database (Denmark)

    Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

    1999-01-01

    were of skin type II than skin type IV; skin type 11 was a risk factor for basal cell carcinoma with an odds ratio (OR) of 2.3. For cutaneous malignant melanoma, more cases than controls were red-haired or blond and of skin type II, but there was no difference in constitutive skin pigmentation. Hair...... colour and skin type were found to be independent risk factors for cutaneous malignant melanoma; red hair vs. black/brown: OR >9.7, blond hair vs. brown/black: OR = 2.4, and skin type 11 vs. type IV: OR=2.0. There were no gender-related differences in risk factors for basal cell carcinoma and cutaneous......To assess the importance of hair and eye colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma in fair-skinned Caucasians, we conducted two identical case-control studies in Denmark. We studied 145 cases with basal cell...

  15. Effect of vaccination with N-glycolyl GM3/VSSP vaccine by subcutaneous injection in patients with advanced cutaneous melanoma

    International Nuclear Information System (INIS)

    Osorio, Marta; Gracia, Elias; Reigosa, Edmundo; Hernandez, Julio; Torre, Ana de la; Saurez, Giselle; Perez, Kirenia; Viada, Carmen; Cepeda, Meylán; Carr, Adriana; Ávila, Yisel; Rodríguez, Migdalia; Fernandez, Luis E

    2012-01-01

    NeuGc-containing gangliosides have been described in melanoma cells and are an attractive target for cancer immunotherapy because they are minimally or not expressed in normal human tissues. Melanoma patients treated with a vaccine based on N-glycolyl gangliosides have shown benefit in progression free survival and overall survival. We conducted a multicenter Phase I/II clinical trial in patients with metastatic cutaneous melanoma treated with the N-gycolyl GM3/very-small-size proteoliposomes vaccine by the subcutaneous route. Selecting the optimal biological dose of the vaccine was the principal objective based on immunogenicity, efficacy, and safety results. Six dose levels were studied and the treatment schedule consisted of five doses administered every 2 weeks and then monthly until 15 doses had been given. Dose levels evaluated were 150, 300, 600, 900, 1200, and 1500 μg with five patients included in each dose level except the 900 μg dose (n = 10). Immunogenicity was determined by antibody titers generated in patients after vaccination. Antitumor effect was measured by response criteria of evaluation in solid tumors and safety was evaluated by common toxicity criteria of adverse events. The vaccine was safe and immunogenic at all doses levels. The most frequent adverse events related to vaccination were mild to moderate injection site reactions and flu-like symptoms. Vaccination induced specific anti-NeuGcGM3 immunoglobulin M and immunoglobulin G antibody responses in all patients. Disease control (objective response or stable disease) was obtained in 38.46% of patients. Global median overall survival was 20.20 months. Two patients achieved overall survival duration of about 4 and 5 years, respectively. The 900 μg dose resulted in overall survival duration of 19.40 months and was selected as the biological optimal dose

  16. Tumor Infiltrating Lymphocytes (TILs) May be Only an Independent Predictor of Nodal Involvement but not for Recurrence and Survival in Cutaneous Melanoma Patients.

    Science.gov (United States)

    Tas, Faruk; Erturk, Kayhan

    2017-09-14

    Tumor infiltrating lymphocytes (TILs) invade and disrupt melanoma cells and their clinical roles remain controversial. In this study, we aimed to determine the clinical significance of the TILs status in cutaneous melanoma patients (CMPs). Of 750 CMPs enrolled into this study 486 (64.8%) had lesions with TILs. The patients with TILs more likely had nodular histology, presence of histological regression, and absence of regional lymph node involvement. However, its presence was not associated with outcome. In conclusion, presence of TILs may be only an independent predictor for absence of nodal involvement but it is not associated with recurrence and survival in CMPs.

  17. Risk of developing multiple primary cutaneous melanomas in patients with the classic atypical-mole syndrome: a case-control study.

    Science.gov (United States)

    Marghoob, A A; Slade, J; Kopf, A W; Salopek, T G; Rigel, D S; Bart, R S

    1996-11-01

    The classic atypical-mole syndrome (CAMS) and/or a history of malignant melanoma (MM) increases the risk for multiple melanomas. Case notes of 118 CAMS and 173 control patients, each with a history of MM, were reviewed for the occurrence of second primary MMs. The mean (+/-SD) age at diagnosis of the first MM was 38.8 +/- 12.8 and 48.9 +/- 14.7 years (P table risk of 35.5% and 17.0%, respectively (P Periodic total cutaneous examinations are indicated for life in an attempt to identify new MMs when they are thin.

  18. Simultaneous primary invasive cutaneous aspergillosis in two preterm twins: case report and review of the literature.

    Science.gov (United States)

    Gallais, Floriane; Denis, Julie; Koobar, Olfa; Dillenseger, Laurence; Astruc, Dominique; Herbrecht, Raoul; Candolfi, Ermanno; Letscher-Bru, Valérie; Sabou, Marcela

    2017-08-02

    Primary invasive cutaneous aspergillosis is a rare fungal infection that occurs mostly in immunocompromised patients. Newborns of very low birth weight present a high risk for this type of infection due to an immaturity of the cutaneous barrier and of the immune system. We describe here a case of simultaneous invasive cutaneous aspergillosis in two preterm twins. Two male preterm bichorionic biamniotic twins (A & B) were born at a general hospital by spontaneous normal delivery at 24 weeks and 6 days of gestation. They were transferred to our hospital where they receive surfactant, antibiotics and hydrocortisone. Six days later, twin A showed greenish lesions in the umbilical region. The spectrum of antibiotic therapy was broadened and fluconazole was added. The umbilical catheters of the two twins were removed and replaced by epicutaneo-cava venous catheters and the cultures were positive for Aspergillus fumigatus. Fluconazole was replaced in both twins by liposomal amphotericin B and the incubators were changed. The serum galactomannan was also positive for both twins. At day 10, yellowish lesions appeared in the abdominal region in twin B. He died on day 18 following complications related to his prematurity. Concerning the twin A, serum galactomannan was negative on day 30; liposomal amphotericin B was stopped 1 week later, with a relay by econazole (cream). His condition improved and on day 66 he was transferred for follow-up at the general hospital where he was born. The source of contamination by A. fumigatus was not identified, but other similar cases from the literature include construction work at or near the hospital, oximeter sensors, latex finger stalls, non-sterile gloves, humidifying chambers of incubators, bedding and adhesive tapes. The skin fragility of preterm newborns is an excellent potential entry point for environmental fungal infections. These cases highlight the importance of suspecting primary cutaneous aspergillosis in extremely low

  19. Sinclair swine melanoma

    International Nuclear Information System (INIS)

    Hook, R.R.; Berkelhammer, J.; Hamby, C.V.

    1986-01-01

    Sinclair(S-1) miniature swine spontaneously develop melanomas which have many biologic and histologic features in common with human superficial spreading melanoma. Host control of this neoplasm was indicated by the high incidence of spontaneous regression, a decrease in tumor development with age and a decrease in progressive growth of the tumor as age of tumor development increases. Immunologic mechanisms were implicated in host control by histologic observation of a mononuclear inflammatory infiltration of tumors which lead to depigmentation and fibrosis. In vitro immunologic studies revealed that leukocytes from melanoma swine were sensitized specifically to a tumor associated antigen like substance present in extracts of cutaneous melanomas and cultured swine melanoma cells and that melanoma swine leukocytes were cytotoxic for swine melanoma cells. Furthermore, these studies suggested the existence of a common cross reactive, melanoma associated antigen shared by human and swine melanomas. Antigenic analyses of swine melanomas with mouse monoclonal antibodies developed to a single swine melanoma cell culture and with rabbit antisera developed to pooled extracts of cutaneous melanomas demonstrated the presence of tumor associated antigens in swine melanoma cell culture and cutaneous melanomas. The failure of mouse monoclonal antibodies to detect antigens in cutaneous melanoma extracts and the failure of rabbit antisera to detect antigens in melanoma cell culture extracts suggested a differential in antigen expression between swine melanoma cells grown in vitro and in vivo

  20. New diagnostic techniques in staging in the surgical treatment of cutaneous malignant melanoma

    NARCIS (Netherlands)

    Cobben, DCP; Koopal, S; Tiebosch, ATMG; Jager, PL; Elsinga, PH; Wobbes, T; Hoekstra, HJ

    2002-01-01

    The emphasis of the research on the surgical treatment of melanoma has been on the resection margins, the role of elective lymph node dissection. in high risk patients and the value of adjuvant regional treatment with hyperthermic isolated lymph perfusion with melphalan. Parallel to this research,

  1. Presence of a fluid-conducting meshwork in xenografted cutaneous and primary human uveal melanoma.

    NARCIS (Netherlands)

    Clarijs, Ruud; Otte-Holler, I.; Ruiter, D.J.; Waal, R.M.W. de

    2002-01-01

    PURPOSE: Recently, it was reported that tumor cells themselves generate channels and networks in three-dimensional culture and can be found lining channels (some containing red blood cells [RBCs]) in vivo, and they express endothelial or vascular genes in aggressive uveal melanoma. The implications

  2. Recurrence and survival after neck dissections in cutaneous head and neck melanoma

    DEFF Research Database (Denmark)

    Andersen, Peter Stemann; Chakera, Annette Hougaard; Thamsborg, Andreas Key Milan

    2014-01-01

    INTRODUCTION: An important prognostic factor in head and neck melanoma is the status of the regional lymph nodes since the presence of metastatic disease in the nodes greatly aggravates the prognosis. There is no consensus on the surgical treatment algorithm for this group. Our aim was to study i...

  3. Detailed dosimetry and clinical outcome analysis for the argentine BNCT trials of cutaneous nodular melanomas

    International Nuclear Information System (INIS)

    Gonzalez, S.J.; Santa Cruz, G.A.; Casal, M.R.

    2006-01-01

    Three female patients with biopsy-proven nodular melanoma were treated to six separate sites as part of the Phase I/II BNCT clinical trial conducted at the Comision Nacional de Energia Atomica (CNEA) and the Instituto A. Roffo, Argentina. This work reports on the detailed dosimetry for the clinical trials, and presents a preliminary analysis to investigate the possible influence of tumor size and total equivalent dose on the observed local tumor response. Also, the appropriateness of applying 3.5 tumor-to-blood 10 B concentration ratio for the BPA compound in nodular melanoma cases is discussed. The statistical analysis showed that tumor response depends not only on the dose but also, and highly, on the tumor size. For these three patients, there was no significant difference between minimum and mean equivalent doses as explicative for tumor response. The collection of sixteen experimental-based tumor-to-blood ratios determined by CNEA in nodular melanoma patients derived an average value and standard deviation of 2.5 ± 0.6. This result suggests that a lower ratio could be more suitable for estimating the clinical dosimetry. It is also consistent with the worse tumor control rate in nodular melanomas observed by other researchers. (author)

  4. Eye and hair colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma. A Danish case-control study

    DEFF Research Database (Denmark)

    Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

    1999-01-01

    To assess the importance of hair and eye colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma in fair-skinned Caucasians, we conducted two identical case-control studies in Denmark. We studied 145 cases with basal cell...... the present hair colour and eye colour, and the constitutive skin pigmentation was measured objectively by skin reflectance of UV unexposed buttock skin. There were no differences between basal cell carcinoma cases and controls in hair colour or eye colour or constitutive skin pigmentation, but more cases...... were of skin type II than skin type IV; skin type 11 was a risk factor for basal cell carcinoma with an odds ratio (OR) of 2.3. For cutaneous malignant melanoma, more cases than controls were red-haired or blond and of skin type II, but there was no difference in constitutive skin pigmentation. Hair...

  5. Eye and hair colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma. A Danish case-control study

    DEFF Research Database (Denmark)

    Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

    1999-01-01

    To assess the importance of hair and eye colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma in fair-skinned Caucasians, we conducted two identical case-control studies in Denmark. We studied 145 cases with basal cell...... carcinoma and 174 matched controls, and 168 cases with cutaneous malignant melanoma and 176 matched controls. Controls were matched on age, gender and place of residence. Subjects indicated their hair colour before 7 years of age, and at 25 years of age and their skin phototype. Interviewers assessed...... the present hair colour and eye colour, and the constitutive skin pigmentation was measured objectively by skin reflectance of UV unexposed buttock skin. There were no differences between basal cell carcinoma cases and controls in hair colour or eye colour or constitutive skin pigmentation, but more cases...

  6. Nodular melanoma: a distinct clinical entity and the largest contributor to melanoma deaths in Victoria, Australia.

    Science.gov (United States)

    Mar, Victoria; Roberts, Hugh; Wolfe, Rory; English, Dallas R; Kelly, John W

    2013-04-01

    There is a growing body of evidence that nodular melanoma (NM), because of its association with increased growth rate and thickness at diagnosis, accounts for a substantial proportion of melanoma deaths. We sought to assess the contribution of NM to melanoma deaths in comparison with other tumor subtypes. Four cohorts were established comprising 5775 cases of invasive primary cutaneous melanoma reported to the Victorian Cancer Registry during 1989, 1994, 1999, and 2004. Original pathology reports were reviewed. Age-standardized melanoma incidence rates were compared from 1989 to 2004 with annual percentage change using Poisson regression. The incidence of thick tumors (>4 mm) increased by 3.8% (95% confidence interval 1.4 to 6.2) and 2.5% (95% confidence interval -0.5 to 5.5) per year for male and female patients, respectively. The median thickness of NM at diagnosis was 2.6 mm compared with 0.6 mm for superficial spreading melanoma. A third of patients who died from melanoma during the follow-up period had thick tumors (>4 mm), most of which were nodular subtype (61%). NM accounted for 14% of invasive melanomas, but was responsible for 43% of melanoma deaths in a total of 57,461 person-years of follow-up. By comparison, superficial spreading melanoma contributed 56% of invasive melanoma but only 30% of deaths. Pathology review was limited to reports only. Mortality information relied mostly on death certificate information. The incidence of thick melanomas continues to increase. Nodular melanoma is clinically distinct and the predominant contributor to melanoma-related deaths, representing a public health challenge in reducing skin cancer mortality. Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  7. miR-203 inhibits melanoma invasive and proliferative abilities by targeting the polycomb group gene BMI1

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Xiao [Department of Dermatology and Venereal Disease, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Sun, Yong [Department of Burn and Plastic Surgery, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an 223300 (China); Han, Siqi [Department of Medical Oncology, Jinling Hospital, Nanjing 210002 (China); Zhu, Wei [Department of Dermatology and Venereal Disease, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Zhang, Haiping, E-mail: zhanghaiping_2000@163.com [Department of Dermatology and Venereal Disease, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Lian, Shi, E-mail: lianshi_2020@163.com [Department of Dermatology and Venereal Disease, Capital Medical University, Beijing 100069 (China)

    2015-01-02

    Highlights: • First reported deregulation of miR-203 and up-regulation of BMI1 in metastatic melanoma. • miR-203 decreased BMI1 expression by directly binding to 3′UTR. • Further found miR-203 overexpression suppressed cell invasion and stemness. • Re-expression of BMI1 rescued miR-203-mediated suppression. • miR-203-BMI1 axis may be potential therapeutic targets of melanoma metastasis. - Abstract: Metastasis is the major problem in malignant melanoma, posing a therapeutic challenge to clinicians. The investigation of the underlying mechanism driving this progress remains a large unmet need. In this study, we revealed a miR-203-BMI1 axis that regulated melanoma metastasis. We found significantly deregulation of miR-203 and up-regulation of BMI1 in melanoma, particularly in metastatic melanoma. An inverse correlation between the levels of miR-203 and BMI1 was further observed in melanoma tissues and cell lines. We also identified BMI1 as a downstream target gene of miR-203, which bound to the 3′UTR of BMI1. Overexpression of miR-203 was associated with decreased BMI1 expression and impaired cell invasion and tumor sphere formation activities. Re-expression of BMI1 markedly rescued miR-203-mediated suppression of these events. Taken together, our results demonstrated that miR-203 regulated melanoma invasive and proliferative abilities in part by targeting BMI1, providing new insights into potential mechanisms of melanoma metastasis.

  8. Malignant melanoma

    NARCIS (Netherlands)

    de Braud, Filippo; Khayat, David; Kroon, Bin B. R.; Valdagni, Riccardo; Bruzzi, Paolo; Cascinelli, Natale

    2003-01-01

    In the European Community cutaneous melanoma accounts for 1 and 1.8% of cancers occurring in men and women, respectively. The incidence rate is increasing faster than that of any other tumour. Sun exposure, patient's phenotype, family history, and history of a previous melanoma are the major risk

  9. Nodular malignant melanoma and multiple cutaneous neoplasms under immunosuppression with azathioprine.

    Science.gov (United States)

    Guenova, Emmanuella; Lichte, Verena; Hoetzenecker, Wolfram; Woelbing, Florian; Moehrle, Matthias; Roecken, Martin; Schaller, Martin

    2009-08-01

    Immunosuppressed patients are at increased risk of skin cancer. A 67-year-old renal transplant recipient developed a nodular malignant melanoma after 30 years of immunosuppression with azathioprine and prednisolone. The patient died of metastatic disease 3 months after the diagnosis was made. The function of the renal graft was not affected at all. Renal transplant recipients are at high risk of developing nonmelanocytic skin tumors when on immunosuppressive therapy with cyclosporine A. Less common is the development of skin cancer during immunosuppression with azathioprine. Latest reports show the increased incidence of malignant melanoma in immunosuppressed patients. Our case illustrates the necessity of close dermatological surveillance of allograft recipients, to assure an early recognition of any malignant skin tumor and to reduce the risk of systemic metastatic disease.

  10. Melanoma cutâneo: estudo epidemiológico de 30 anos em cidade do sul do Brasil, de 1980-2009 Cutaneous melanoma: a 30-year-long epidemiological study conducted in a city in southern Brazil, from 1980-2009

    Directory of Open Access Journals (Sweden)

    Nilton Naser

    2011-10-01

    Full Text Available FUNDAMENTOS: A incidência do melanoma e a mortalidade pela doença aumentaram nos últimos 30 anos na população caucasiana. No Brasil, dados em municípios não-capitais são escassos, necessitando de estudos epidemiológicos. OBJETIVOS: Avaliar a incidência e classificar melanomas cutâneos em Blumenau de 1980 a 2009. MÉTODO: Foram coletadas informações de 1.002 exames histopatológicos de indivíduos de Blumenau, considerando sexo, idade, localização primária, tipo histológico, nível de invasão (Clark e espessura tumoral (Breslow. Os coeficientes de incidência anuais brutos e ajustados foram calculados utilizandose o número de melanomas e a população estimada pelo Instituto Brasileiro de Geografia e Estatística entre 1980 e 2009. RESULTADOS: As taxas de incidência do melanoma atingiram 22,4 casos/100.000 habitantes/ano, 31,5 nas mulheres e 30,4 nos homens na taxa ajustada. As taxas de incidência padronizadas por década, faixa etária e sexo atingiram 141 casos em homens e 103 no sexo feminino por 100.000 habitantes/ano entre 65 a 69 anos. O melanoma disseminativo superficial aconteceu em 53% dos casos, seguido do melanoma nodular com 37%, e a principal localização foi no tronco (47%. Os diagnósticos precoces atingiram 62,5% com Breslow BACKGROUND: Melanoma incidence and mortality rates have increased over the past 30 years in the Caucasian population. In Brazil, data on non-capital cities are scarce, making epidemiological stu dies necessary. OBJECTIVES: To evaluate the incidence of and classify cutaneous melanomas in Blumenau from 1980 to 2009. METHOD: Data from 1002 histopathological examinations of individuals from Blumenau were collected, considering sex, age, primary site of involvement, histological type, level of invasion (Clark's level and tumor thickness (Breslow's depth. The gross and adjusted coefficients of annual incidences were calculated based on the number of melanoma cases and the population estimated

  11. Cutaneous phenotype and MC1R variants as modifying factors for the development of melanoma in CDKN2A G101W mutation carriers from 4 countries.

    Science.gov (United States)

    Goldstein, Alisa M; Chaudru, Valerie; Ghiorzo, Paola; Badenas, Celia; Malvehy, Josep; Pastorino, Lorenza; Laud, Karine; Hulley, Benjamin; Avril, Marie-Francoise; Puig-Butille, Joan A; Miniere, Annie; Marti, Rosa; Chompret, Agnes; Cuellar, Francisco; Kolm, Isabel; Mila, Montserrat; Tucker, Margaret A; Demenais, Florence; Bianchi-Scarra, Giovanna; Puig, Susana; de-Paillerets, Brigitte Bressac

    2007-08-15

    The G101W founder mutation is the most common CDKN2A mutation in Italy, Spain, and France. As the background of modifying genes, environmental exposures, and sun behavior vary across countries, studying G101W carriers from distinct countries offers a unique opportunity to evaluate possible modifying factors in melanoma development. We evaluated 76 G101W cases and 59 carrier controls from France, Italy, Spain, and the United States. Hair color and dysplastic nevi distributions differed significantly in cases and controls across the 4 study groups. Cases also varied significantly for eye color, freckling, and nevi. The distribution of MC1R variants in cases differed significantly across study groups because 12% of Italian melanoma patients had > or =2 MC1R variants vs. >50% for the other case groups. Several MC1R covariates showed significant associations with melanoma risk in all groups combined and in the American, French, and Spanish samples; no significant findings were observed in the Italian sample. In multiple-case families, the number and type of MC1R variants varied significantly between multiple-primary-melanoma and single-primary-melanoma patients from the 4 groups; there was also a significant decrease in median age at melanoma diagnosis as the number or type of MC1R variants increased. The variation in the effects of the cutaneous phenotypic and MC1R factors across the study sample suggests that these factors differentially contribute to development of melanoma even on a common genetic background of a germline CDKN2A mutation. Differences in melanoma risk across geographic regions justify the need for individual studies in each country before counseling should be considered.

  12. Melanoma

    Science.gov (United States)

    ... if they're dark skinned, young, and have no family history. Even for them, behaviors like too much sun exposure and not enough skin protection are important risk factors. How Do People Know They Have It? Many melanomas start out as a mole or a bump ...

  13. Genetic susceptibility to cutaneous melanoma in southern Switzerland: role of CDKN2A, MC1R and MITF.

    Science.gov (United States)

    Mangas, C; Potrony, M; Mainetti, C; Bianchi, E; Carrozza Merlani, P; Mancarella Eberhardt, A; Maspoli-Postizzi, E; Marazza, G; Marcollo-Pini, A; Pelloni, F; Sessa, C; Simona, B; Puig-Butillé, J A; Badenas, C; Puig, S

    2016-11-01

    Nearly 10% of all cases of cutaneous melanoma (CM) occur in patients with a personal or family history of the disease. To obtain information about genetic predisposition to CM in Ticino, the southern region of Switzerland, a zone with moderate-to-high CM incidence. We identified germline mutations in highly CM-associated genes (CDKN2A and CDK4) and low/medium-penetrance variants (MC1R and MITF) in patients with multiple primary CMs or individuals with one or more CM and a positive family history for CM or pancreatic cancer among first- or second-degree relatives. Healthy blood donors (n = 146) were included as a control group. From July 2010 to July 2012, 57 patients (41 pedigrees) were included. Twenty-six were melanoma-prone families (with at least two cases) and 15 had multiple CMs. Pancreatic cancer was found in six families. The CDKN2A mutation p.V126D was identified in seven patients (four families) with a founder effect, whereas CDKN2A A148T was detected in seven cases (five families) and seven healthy donors (odds ratio 2·76, 95% confidence interval 0·83-9·20). At least one MC1R melanoma-associated polymorphism was detected in 32 patients (78%) and 97 healthy donors (66%), with more than one polymorphism in 12 patients (29%) and 25 healthy donors (17%). The MITF variant p.E318K was identified in four patients from three additional pedigrees (7%) and one healthy control (0·7%). Inclusion criteria for the Ticino population for genetic assessment should follow the rule of two (two affected individuals in a family or a patient with multiple CMs), as we detected a CDKN2A mutation in almost 10% of our pedigrees (four of 41), MITF p.E318K in 7% (three of 41) and a higher number of MC1R variants than in the control population. © 2016 British Association of Dermatologists.

  14. Up-regulation of hepatoma-derived growth factor facilitates tumor progression in malignant melanoma [corrected].

    Directory of Open Access Journals (Sweden)

    Han-En Tsai

    Full Text Available Cutaneous malignant melanoma is the fastest increasing malignancy in humans. Hepatoma-derived growth factor (HDGF is a novel growth factor identified from human hepatoma cell line. HDGF overexpression is correlated with poor prognosis in various types of cancer including melanoma. However, the underlying mechanism of HDGF overexpression in developing melanoma remains unclear. In this study, human melanoma cell lines (A375, A2058, MEL-RM and MM200 showed higher levels of HDGF gene expression, whereas human epidermal melanocytes (HEMn expressed less. Exogenous application of HDGF stimulated colony formation and invasion of human melanoma cells. Moreover, HDGF overexpression stimulated the degree of invasion and colony formation of B16-F10 melanoma cells whereas HDGF knockdown exerted opposite effects in vitro. To evaluate the effects of HDGF on tumour growth and metastasis in vivo, syngeneic mouse melanoma and metastatic melanoma models were performed by manipulating the gene expression of HDGF in melanoma cells. It was found that mice injected with HDGF-overexpressing melanoma cells had greater tumour growth and higher metastatic capability. In contrast, mice implanted with HDGF-depleted melanoma cells exhibited reduced tumor burden and lung metastasis. Histological analysis of excised tumors revealed higher degree of cell proliferation and neovascularization in HDGF-overexpressing melanoma. The present study provides evidence that HDGF promotes tumor progression of melanoma and targeting HDGF may constitute a novel strategy for the treatment of melanoma.

  15. Up-Regulation of Hepatoma-Derived Growth Factor Facilities Tumor Progression in Malignant Melanoma

    Science.gov (United States)

    Kung, Mei-Lang; Liu, Li-Feng; Kuo, Lai-Hsin; Kuo, Hsiao-Mei; Chen, San-Cher; Chan, Elsa C.; Wu, Chieh-Shan; Tai, Ming-Hong; Liu, Guei-Sheung

    2013-01-01

    Cutaneous malignant melanoma is the fastest increasing malignancy in humans. Hepatoma-derived growth factor (HDGF) is a novel growth factor identified from human hepatoma cell line. HDGF overexpression is correlated with poor prognosis in various types of cancer including melanoma. However, the underlying mechanism of HDGF overexpression in developing melanoma remains unclear. In this study, human melanoma cell lines (A375, A2058, MEL-RM and MM200) showed higher levels of HDGF gene expression, whereas human epidermal melanocytes (HEMn) expressed less. Exogenous application of HDGF stimulated colony formation and invasion of human melanoma cells. Moreover, HDGF overexpression stimulated the degree of invasion and colony formation of B16–F10 melanoma cells whereas HDGF knockdown exerted opposite effects in vitro. To evaluate the effects of HDGF on tumour growth and metastasis in vivo, syngeneic mouse melanoma and metastatic melanoma models were performed by manipulating the gene expression of HDGF in melanoma cells. It was found that mice injected with HDGF-overexpressing melanoma cells had greater tumour growth and higher metastatic capability. In contrast, mice implanted with HDGF-depleted melanoma cells exhibited reduced tumor burden and lung metastasis. Histological analysis of excised tumors revealed higher degree of cell proliferation and neovascularization in HDGF-overexpressing melanoma. The present study provides evidence that HDGF promotes tumor progression of melanoma and targeting HDGF may constitute a novel strategy for the treatment of melanoma. PMID:23536873

  16. Melanoma genetics

    DEFF Research Database (Denmark)

    Read, Jazlyn; Wadt, Karin A W; Hayward, Nicholas K

    2015-01-01

    Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence of herita......Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence...... in a combined total of approximately 50% of familial melanoma cases, the underlying genetic basis is unexplained for the remainder of high-density melanoma families. Aside from the possibility of extremely rare mutations in a few additional high penetrance genes yet to be discovered, this suggests a likely...... polygenic component to susceptibility, and a unique level of personal melanoma risk influenced by multiple low-risk alleles and genetic modifiers. In addition to conferring a risk of cutaneous melanoma, some 'melanoma' predisposition genes have been linked to other cancers, with cancer clustering observed...

  17. FT-Raman spectroscopy for the differentiation between cutaneous melanoma and pigmented nevus Espectroscopia FT-Raman na diferenciação entre melanoma cutâneo e nevo pigmentado

    Directory of Open Access Journals (Sweden)

    Sidney Bandeira Cartaxo

    2010-08-01

    Full Text Available Cutaneous melanoma is the most aggressive type of skin cancer and Ft-Raman spectroscopy has been studied as a potential method that could be a real alternative for early diagnosis of neoplasms. PURPOSE: To qualify the spectral FT-Raman data, in order to differentiate cutaneous melanoma and pigmented nevus. METHODS: For this study, 10 samples of cutaneous melanoma, 9 samples of pigmented nevi, and 10 samples of normal skin were obtained by incisional biopsies performed during plastic surgeries ex vivo, immediately after removing the surgical sample. RESULTS: The FT-Raman spectra of each group presented a high correlation between the elements of the same group, thus favoring the elaboration of spectral averages. When analyzing the spectral standard of each group, the normal skin standard did not show a significant variation between the spectra; the standard of the pigmented nevi group showed significant variation, and the cutaneous melanoma group also showed variation. Through univariate analysis, specific bands were detected for each vibrational mode identified. The discriminatory analysis of the data showed a 75.3% efficiency of the differentiation between the three groups studied. CONCLUSION: The vibrational modes Polysaccharides, Tyrosine and Amide-I differentiated the melanoma from the pigmented nevus.O melanoma cutâneo é o câncer de pele mais agressivo, e a espectroscopia FT-Raman tem sido estudada como um método em potencial que pode ser uma verdadeira alternativa no diagnóstico precoce de neoplasias. OBJETIVO: Qualificar os dados espectrais FT-Raman de modo a diferenciar melanoma cutâneo de nevo pigmentado. MÉTODOS: Foram utilizadas 10 amostras de melanoma cutâneo, obtidas por meio de biopsias incisionais realizadas "ex-vivo"; nove amostras de nevo pigmentado e 10 amostras de pele normal foram coletadas durante cirurgias plásticas. RESULTADOS: Os espectros FT-Raman de cada grupo diagnóstico apresentaram alta correlação entre os

  18. Treatment of regional cutaneous nodular metastases from melanoma using high-dose rate mould brachytherapy

    International Nuclear Information System (INIS)

    Chaudhuri, Anupam; De-Groot, Charles; Seel, Matthew; Jolly, Mike; Cameron Tina

    2011-01-01

    Full text: The involvement of a wide body surface area by regional cuta neous nodular metastases (RCNM) from melanoma poses a significant thera peutic challenge. We report our experience from Waikato Hospital, Hamilton, New Zealand in successfully treating this condition with high-dose rate (HDR) surface mould brachytherapy (BT). Methods: We analysed six patients who had surgery and then developed RCNM, which was treated in our department by HDR mould BT using Iridium 192. Five out of six patients were treated with a dose of 30 Gy in five fractions to wide field with a further 6 Gy boost to tumour nodules. Our first patient received a higher dose of 36 Gy in six fractions followed by 6 Gy boost to tumour nodules. Results: All patients experienced a complete response (CR). Median follow up was 23 months and side effects were minimal, only Radiation Therapy Oncol ogy Group (RTOG) grade I/ll early and late toxicity. To date, no in-field recurrence has been observed. Two patients died from metastatic disease at 33 and 34 months of follow up. Conclusion: There was a CR in all cases without in-field recurrence. To our knowledge, this is the first reported experience in treating skin melanoma with a BT surface mould. We recommend that BT surface mould should be considered when treating patients with RCNM.

  19. Quantifying rates of cell migration and cell proliferation in co-culture barrier assays reveals how skin and melanoma cells interact during melanoma spreading and invasion.

    Science.gov (United States)

    Haridas, Parvathi; Penington, Catherine J; McGovern, Jacqui A; McElwain, D L Sean; Simpson, Matthew J

    2017-06-21

    Malignant spreading involves the migration of cancer cells amongst other native cell types. For example, in vivo melanoma invasion involves individual melanoma cells migrating through native skin, which is composed of several distinct subpopulations of cells. Here, we aim to quantify how interactions between melanoma and fibroblast cells affect the collective spreading of a heterogeneous population of these cells in vitro. We perform a suite of circular barrier assays that includes: (i) monoculture assays with fibroblast cells; (ii) monoculture assays with SK-MEL-28 melanoma cells; and (iii) a series of co-culture assays initiated with three different ratios of SK-MEL-28 melanoma cells and fibroblast cells. Using immunostaining, detailed cell density histograms are constructed to illustrate how the two subpopulations of cells are spatially arranged within the spreading heterogeneous population. Calibrating the solution of a continuum partial differential equation to the experimental results from the monoculture assays allows us to estimate the cell diffusivity and the cell proliferation rate for the melanoma and the fibroblast cells, separately. Using the parameter estimates from the monoculture assays, we then make a prediction of the spatial spreading in the co-culture assays. Results show that the parameter estimates obtained from the monoculture assays lead to a reasonably accurate prediction of the spatial arrangement of the two subpopulations in the co-culture assays. Overall, the spatial pattern of spreading of the melanoma cells and the fibroblast cells is very similar in monoculture and co-culture conditions. Therefore, we find no clear evidence of any interactions other than cell-to-cell contact and crowding effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. NFIB Mediates BRN2 Driven Melanoma Cell Migration and Invasion Through Regulation of EZH2 and MITF

    Directory of Open Access Journals (Sweden)

    Mitchell E. Fane

    2017-02-01

    Full Text Available While invasion and metastasis of tumour cells are the principle factor responsible for cancer related deaths, the mechanisms governing the process remain poorly defined. Moreover, phenotypic divergence of sub-populations of tumour cells is known to underpin alternative behaviors linked to tumour progression such as proliferation, survival and invasion. In the context of melanoma, heterogeneity between two transcription factors, BRN2 and MITF, has been associated with phenotypic switching between predominantly invasive and proliferative behaviors respectively. Epigenetic changes, in response to external cues, have been proposed to underpin this process, however the mechanism by which the phenotypic switch occurs is unclear. Here we report the identification of the NFIB transcription factor as a novel downstream effector of BRN2 function in melanoma cells linked to the migratory and invasive characteristics of these cells. Furthermore, the function of NFIB appears to drive an invasive phenotype through an epigenetic mechanism achieved via the upregulation of the polycomb group protein EZH2. A notable target of NFIB mediated up-regulation of EZH2 is decreased MITF expression, which further promotes a less proliferative, more invasive phenotype. Together our data reveal that NFIB has the ability to promote dynamic changes in the chromatin state of melanoma cells to facilitate migration, invasion and metastasis.

  1. Factores de riesgo para melanoma cutáneo: Estudio de casos y controles en Córdoba, Argentina Risk factors for cutaneous melanoma: case-control study in Cordoba, Argentina

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    Alejandro Ruiz Lascano

    2004-12-01

    Full Text Available En los últimos años se han realizado considerables esfuerzos para identificar factores de riesgo asociados al incremento en la incidencia de melanoma maligno en la población blanca mundial. En Argentina los datos concernientes a factores de riesgo para melanoma maligno son limitados. Realizamos en el Hospital Privado de Córdoba un estudio de casos-controles con el objetivo de determinar factores de riesgo para melanoma maligno. El grupo de estudio fue de 65 pacientes con melanoma maligno y 195 controles pareados por sexo y edad. Los siguientes factores de riesgo fueron significativos en el análisis estadístico univariado: abuelos nacidos en Italia o España y en otros países europeos, color de pelo castaño y claro, color de piel claro, color de ojos marrón y claros, efélides, presencia de nevos melanocíticos, quemaduras solares graves antes de los 18 años de edad, exposición solar tanto laboral como recreativa y antecedente familiar de melanoma maligno, de éstos se mantienen como factores de riesgo independientes en el análisis multivariado abuelos nacidos en países europeos (OR 2.27, IC95% 1.08 a 3.46, piel clara (OR 4.99, IC95% 2.72 a 7.28 quemadura solar grave en más de 3 episodios antes de los 18 años (OR 6.47, IC95% 5.29 a 7.65 y antecedentes familiares de melanoma (OR 1525, IC95% 1467 a 1584. La mayoría de los datos que obtuvimos guardan semejanza con los descriptos en otras poblaciones.Over the past years, considerable effort has been directed toward the identification of risk factors associated with the increasing incidence of cutaneous melanoma in white populations worldwide. Limited data are available from Argentine populations concerning risk factors for malignant melanoma. A case-control study was performed in Cordoba to estimate the risk factors for cutaneous malignant melanoma. The study group comprised 65 patients and 195 controls, matched by age and sex. The following risk factors were significant in the

  2. Invasão do nervo óptico por melanoma peripapilar: relato de caso Optic nerve invasion by juxtapapillary melanoma: case report

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    Eduardo Ferrari Marback

    2003-06-01

    Full Text Available Tumores pigmentados localizados sobre o disco óptico são raros e representam desafio diagnóstico. Paciente masculino, 60 anos, apresenta baixa da acuidade visual no olho esquerdo devido à lesão pigmentada que cobre o disco óptico. Foi indicada a enucleação com recusa pelo paciente. O quadro evoluiu com descolamento de retina. Examinado em outro serviço teve indicação de vitrectomia também recusada. Retorna aos nossos cuidados; feita a enucleação o diagnóstico anatomopatológico revelou melanoma maligno da coróide com invasão pós-laminar do nervo óptico. A importância prognóstica da invasão do nervo óptico por melanoma da coróide ainda não está totalmente esclarecida. Embora raro, tumor pigmentado cobrindo o nervo óptico pode representar melanoma maligno. O diagnóstico diferencial destes casos é geralmente difícil, porém seu reconhecimento à ultra-sonografia ocular é patente e descolamento de retina associado é sinal de atividade tumoral. Os riscos de disseminação da doença exigem atenção na suspeita diagnóstica e conduta precisa.Small-pigmented lesions over the optic disc are very rare and may represent a diagnostic challenge. To report a case of a small malignant choroidal melanoma invading the optic nerve. A 60-year-old male presents with low vision in the left eye due to a small, pigmented lesion over the optic disc. At first the patient refused enucleation. One month later, after further drop in visual acuity, the patient was seen at another service, diagnosed as having a retinal detachment, and pars plana vitrectomy was proposed but also refused by the patient. Returning to our service, the eye was enucleated and a final diagnosis of choroidal melanoma with post-laminar optic nerve invasion was made. Although rare, pigmented lesions over the optic disc may represent a malignant melanoma. The prognostic significance of optic nerve invasion by choroidal melanoma is not clear yet. The differential

  3. Microvessel Density in Patients with Cutaneous Melanoma: An Up-to-Date Systematic Review and Meta-Analysis

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    Konstantinos Perivoliotis

    2017-01-01

    Full Text Available Background. We conducted a meta-analysis, in order to appraise the effect of microvessel density (MVD on the survival of patients with cutaneous melanoma. Methods. This study was conducted according to the PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. A systematic literature search in electronic databases (MEDLINE, Web of Science, and Cochrane Central Register of Controlled Clinical Trials was performed. Fixed Effects or Random Effects model was used, based on the Cochran Q test. Results. In total 9 studies (903 patients were included. Pooled HR for overall survival (OS and disease-free survival (DFS were 2.62 (95% CI: 0.71–9.60, p=0.15 and 2.64 (95% CI: 0.82–8.47, p=0.10, respectively. Odds ratios of overall survival between high and low MVD groups, at 12 (1.45, 95% CI: 0.16–13.24, 36 (2.93, 95% CI: 0.63–13.59, and 60 (4.09, 95% CI: 0.85–19.77 months did not reach statistical significance. Significant superiority of low MVD group, in terms of DFS, at all time intervals (OR: 4.69, p<0.0001; OR: 2.18, p=0.004; OR: 7.46, p=0.01, resp. was documented. Discussion. MVD does not affect the HR of OS and DFS. A strong correlation with DFS rates at 12, 36, and 60 months was recorded.

  4. Up-regulation of Rho-associated kinase 1/2 by glucocorticoids promotes migration, invasion and metastasis of melanoma.

    Science.gov (United States)

    Huang, Gao-Xiang; Wang, Yan; Su, Jie; Zhou, Peng; Li, Bo; Yin, Li-Juan; Lu, Jian

    2017-12-01

    Although glucocorticoids (GCs) regulate proliferation, differentiation and apoptosis of tumor cells, their influence on metastasis of tumor cells is poorly understood. Melanoma is a type of skin cancers with high metastasis. We investigated the effect of GCs on metastasis of melanoma cells and its mechanism. We found that GCs significantly promoted the adhesion, migration, invasion of melanoma cells in vitro and lung metastasis in experimental melanoma metastasis mice. Dexamethasone (Dex), a synthetic GC, did not change the RhoA, RhoB and RhoC signalings, but significantly increased the expression and activity of Rho-associated kinase 1/2 (ROCK1/2). The effect of Dex was to increase ROCK1/2 stability mediated by glucocorticoid receptor. Inhibiting ROCK1/2 activity with Y-27632, a ROCK1/2 inhibitor abrogated the pro-migration and pro-metastasis effects of GCs in vitro and in vivo, indicating that ROCK1/2 mediated the pro-metastasis effects of GCs. Activation of PI3K/AKT also contributed to the pro-migration and pro-invasion effects of Dex partially through up-regulating ROCK1/2 expression. Additionally, Dex also down-regulated the expression of tissue inhibitors of matrix metalloproteinase-2. Taken together, our findings provide new data to understand the possible promoting roles and mechanisms of GCs in melanoma metastasis. Copyright © 2017. Published by Elsevier B.V.

  5. The measurement of constitutive and facultative skin pigmentation and estimation of sun exposure in Caucasians with basal cell carcinoma and cutaneous malignant melanoma

    DEFF Research Database (Denmark)

    Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

    1998-01-01

    In two identical and simultaneously performed case-control studies of basal cell carcinoma (BCC) and cutaneous malignant melanoma (CMM) with age-matched, sex-matched and residence-matched controls, skin pigmentation was measured objectively by skin reflectance spectroscopy in 145 BCC patients...... by all subjects. There were no statistically significant differences in constitutive skin pigmentation at the buttocks between BCC patients and controls (P = 0.96) or between CMM patients and controls (P = 0.13). Facultative skin pigmentation in ultraviolet-exposed sites was not significantly different...

  6. Evaluation of optical coherence tomography as a non-invasive diagnostic tool in cutaneous wound healing.

    Science.gov (United States)

    Kuck, Monika; Strese, Helene; Alawi, Seyed Arash; Meinke, Martina C; Fluhr, Joachim W; Burbach, Guido J; Krah, Martin; Sterry, Wolfram; Lademann, Jürgen

    2014-02-01

    The monitoring of wound-healing processes is indispensable for the therapeutic effectiveness and improved care of chronic wounds. Histological sections provide the best morphological assessment of wound recovery, but cause further tissue destruction and increase the risk of infection. Therefore, it is reasonable to apply a diagnostic tool that allows a non-invasive and reliable observation of morphological changes in wound healing. Optical coherence tomography (OCT) is an imaging technique for in vivo evaluation of skin diseases with a resolution close to histopathology. The aim of this study was to investigate whether OCT is suited to display the phases of wound healing. For this purpose, six patients with chronic wounds were objectively characterized by OCT during a period of 2 weeks. Comparable results between histological findings and OCT were achieved. OCT allowed the detection of partial loss of the epidermis, vasoconstriction, vasodilatation and epithelialization. Consequently, OCT could be a potential non-invasive diagnostic tool for the characterization and monitoring of cutaneous wound-healing processes over time. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Wogonin suppresses melanoma cell B16-F10 invasion and migration by inhibiting Ras-medicated pathways.

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    Kai Zhao

    Full Text Available The patients diagnosed with melanoma have a bad prognosis for early regional invasion and distant metastases. Wogonin (5,7-dihydroxy-8-methoxyflavone is one of the active components of flavonoids that extracts from Scutellariae radix. Several previous studies reported that wogonin possesses antitumor effect against leukemia, gastrointestinal cancer and breast cancer. In this study, we used melanoma cell B16-F10 to further investigate the anti-invasive and anti-migratory activity of wogonin. Our date showed that wogonin caused suppression of cell migration, adhesion, invasion and actin remodeling by inhibiting the expression of matrix metalloproteinase-2 and Rac1 in vitro. Wogonin also reduced the number of the tumor nodules on the whole surface of the lung in vivo. Furthermore, the examination of mechanism revealed that wogonin inhibited Extracellular Regulated protein Kinases and Protein Kinase B pathways, which are both medicated by Ras. Insulin-like growth factor-1-induced or tumor necrosis factor-α-induced invasion was also inhibited by wogonin. Therefore, the inhibitory mechanism of melanoma cell invasion by wogonin might be elucidated.

  8. Histologic and Phenotypic Factors and MC1R Status Associated with BRAF(V600E), BRAF(V600K), and NRAS Mutations in a Community-Based Sample of 414 Cutaneous Melanomas.

    Science.gov (United States)

    Hacker, Elke; Olsen, Catherine M; Kvaskoff, Marina; Pandeya, Nirmala; Yeo, Abrey; Green, Adèle C; Williamson, Richard M; Triscott, Joe; Wood, Dominic; Mortimore, Rohan; Hayward, Nicholas K; Whiteman, David C

    2016-04-01

    Cutaneous melanomas arise through causal pathways involving interplay between exposure to UV radiation and host factors, resulting in characteristic patterns of driver mutations in BRAF, NRAS, and other genes. To gain clearer insights into the factors contributing to somatic mutation genotypes in melanoma, we collected clinical and epidemiologic data, performed skin examinations, and collected saliva and tumor samples from a community-based series of 414 patients aged 18 to 79, newly diagnosed with cutaneous melanoma. We assessed constitutional DNA for nine common polymorphisms in melanocortin-1 receptor gene (MC1R). Tumor DNA was assessed for somatic mutations in 25 different genes. We observed mutually exclusive mutations in BRAF(V600E) (26%), BRAF(V600K) (8%), BRAF(other) (5%), and NRAS (9%). Compared to patients with BRAF wild-type melanomas, those with BRAF(V600E) mutants were significantly younger, had more nevi but fewer actinic keratoses, were more likely to report a family history of melanoma, and had tumors that were more likely to harbor neval remnants. BRAF(V600K) mutations were also associated with high nevus counts. Both BRAF(V600K) and NRAS mutants were associated with older age but not with high sun exposure. We also found no association between MC1R status and any somatic mutations in this community sample of cutaneous melanomas, contrary to earlier reports. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Differentially expressed circRNAs in melanocytes and melanoma cells and their effect on cell proliferation and invasion.

    Science.gov (United States)

    Wang, Qi; Chen, Jia; Wang, Aijun; Sun, Lichun; Qian, Li; Zhou, Xiao; Liu, Yu; Tang, Shijie; Chen, Xiang; Cheng, Yan; Cao, Ke; Zhou, Jianda

    2018-04-01

    Circular RNAs (circRNAs) play critical roles in the occurrence of human diseases, including cancer. However, the detailed functions of circRNAs in melanoma have not been fully elucidated. In the present study, a circRNA microarray was performed to analyze the variability of circRNAs in the low-metastatic melanoma WM35 cell line and in the high-metastatic melanoma WM451 cell line in comparison to control human melanocytes. The results revealed that five circRNAs were upregulated and four circRNAs were downregulated in both the WM35 and WM451 cells. qRT-PCR revealed an upregulated expression of circ0000082 and circ0016418 and a downregulation of circ0023988, circ0008157 and circ0030388 in the cells which was consistent with the results of the microarray assay. Functional tests revealed that knockdown of circ0023988, circ0008157 or circ0030388 significantly promoted the proliferation and invasion of the WM35 cells. Following the silencing of circ0000082 or circ0016418 in WM451 cells, the proliferation and invasion of the WM451 cells were inhibited. Bioinformatic analysis predicted that the circ0000082-, circ0023988- and circ0008157-circRNA-miRNA-mRNA network may participate in the occurrence, development, invasion and metastasis of malignant tumors. The present study revealed several differentially expressed circRNAs, indicating that the newly identified circRNAs may provide new therapeutic targets for melanoma.

  10. Differential diagnosis in primary and metastatic cutaneous melanoma by FT-Raman spectroscopy Diagnóstico diferencial no melanoma primário e metastático por espectroscopia FT-Raman

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    Andrea Fernandes de Oliveira

    2010-10-01

    Full Text Available PURPOSE: To qualify the FT-Raman spectral data of primary and metastatic cutaneous melanoma in order to obtain a differential diagnosis. METHODS: Ten normal human skin samples without any clinical or histopathological alterations, ten cutaneous melanoma fragments, and nine lymph node metastasis samples were used; 105, 140 and 126 spectra were obtained respectively. Each sample was divided into 2 or 3 fragments of approximately 2 mm³ and positioned in the Raman spectrometer sample holder in order to obtain the spectra; a monochrome laser light Nd:YAG at 1064 nm was used to excite the inelastic effect. RESULTS: To differentiate the three histopathological groups according to their characteristics extracted from the spectra, data discriminative analysis was undertaken. Phenylalanine, DNA, and Amide-I spectral variables stood out in the differentiation of the three groups. The percentages of correctly classified groups based on Phenylalanine, DNA, and Amide-I spectral features was 93.1%. CONCLUSION: FT-Raman spectroscopy is capable of differentiating melanoma from its metastasis, as well as from normal skin.OBJETIVO: Qualificar os dados espectrais FT-Raman do melanoma cutâneo primário e metastático e assim realizar o diagnóstico diferencial. MÉTODOS: Foram utilizadas amostras de 10 fragmentos de pele sem alterações clínicas ou histopatológicas, 10 de melanomas cutâneos e 9 de metástases linfonodais; 105, 140 and 126 espectros foram obtidos respectivamente. Cada amostra foi dividida em 2 ou 3 frações de 2 mm³ e posicionada no porta amostras do espectrômetro Raman para obtenção dos espectros, por meio da excitação do espalhamento inelástico pelo laser de Nd:YAG em 1064 nm incididos na amostra. RESULTADOS: Para diferenciar os três grupos formados de acordo com as características fornecidas pelos espectros, realizamos a análise discriminante dos dados. As variáveis espectrais Fenilalanina, DNA e Amida-I se destacaram na

  11. Objective histopathologic grading of cutaneous malignant melanomas by stereologic estimation of nuclear volume. Prediction of survival and disease-free period

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt

    1989-01-01

    Modern stereologic techniques enable unbiased and shape-independent estimation of the three-dimensional nuclear volume (Vv). This study investigates the prognostic impact of Vv in 47 patients with malignant melanomas (10 years of follow-up) and compares Vv to traditional prognostic parameters...... and two-dimensional morphometric estimates. The averaged Vv was 226 microns3 and 457 microns3 in Stage I and II melanomas, respectively. The Vv was significantly increased in the case of ulceration, nodular melanoma, and Clark's level greater than III. The Vv showed only poor correlation to two......-dimensional morphometric estimates. Cox regression analysis indicated Vv to possess excellent prognostic information, only rivaled by tumor ulceration, the latter being a 100% predictor of metastatic spread. Histologic type, Clark's level of invasion, tumor thickness (according to Breslow), and patient sex were without...

  12. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces matrix metalloproteinase (MMP) expression and invasion in A2058 melanoma cells

    International Nuclear Information System (INIS)

    Villano, C.M.; Murphy, K.A.; Akintobi, A.; White, L.A.

    2006-01-01

    There has been a 34% increase in melanoma related mortality in the United States from 1973 to 1992. Although few successful treatments for malignant melanoma exist, it is known that genetic susceptibility and environmental factors contribute to the initiation and progression of melanoma. Excessive UV exposure is considered the main etiological factor in melanoma initiation, however, epidemiological and experimental evidence suggests that exposure to environmental carcinogens contribute to melanoma. We propose that exposure to environmental chemicals that activate the aryl hydrocarbon receptor pathway contribute to melanoma progression, specifically through stimulation of the expression and activity of the matrix metalloproteinases (MMPs). Therefore, we investigated the effect of AhR activation on normal human melanocytes and several melanoma cell lines. The data presented here demonstrate that normal melanocytes and melanoma cells express the AhR and Arnt and are responsive to activation by TCDD. Furthermore, activation of this pathway in transformed melanoma cells (A2058) results in increased expression and activity of MMP-1, MMP-2 and MMP-9, as well as increased invasion using in vitro invasion assays. Furthermore, TCDD-induced expression of the MMP-1 promoter in melanoma cells appears to require different elements than those required in untransformed cells, indicating that this pathway may have multiple mechanisms for activation of MMP expression

  13. Drug effects on melanoma

    NARCIS (Netherlands)

    Koomen, Elsje Rosalie

    2010-01-01

    Cutaneous melanoma is the most aggressive form of skin cancer and its incidence among Caucasian populations has increased whereas mortality rates are stabilizing or decreasing. The total burden of melanoma is expected to be increasing. As effective treatment options for advanced melanoma are

  14. Sporadic naturally occurring melanoma in dogs as a preclinical model for human melanoma.

    Science.gov (United States)

    Simpson, R Mark; Bastian, Boris C; Michael, Helen T; Webster, Joshua D; Prasad, Manju L; Conway, Catherine M; Prieto, Victor M; Gary, Joy M; Goldschmidt, Michael H; Esplin, D Glen; Smedley, Rebecca C; Piris, Adriano; Meuten, Donald J; Kiupel, Matti; Lee, Chyi-Chia R; Ward, Jerrold M; Dwyer, Jennifer E; Davis, Barbara J; Anver, Miriam R; Molinolo, Alfredo A; Hoover, Shelley B; Rodriguez-Canales, Jaime; Hewitt, Stephen M

    2014-01-01

    Melanoma represents a significant malignancy in humans and dogs. Different from genetically engineered models, sporadic canine melanocytic neoplasms share several characteristics with human disease that could make dogs a more relevant preclinical model. Canine melanomas rarely arise in sun-exposed sites. Most occur in the oral cavity, with a subset having intra-epithelial malignant melanocytes mimicking the in situ component of human mucosal melanoma. The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis. Growing evidence of distinct subtypes in humans, differing in somatic and predisposing germ-line genetic alterations, cell of origin, epidemiology, relationship to ultraviolet radiation and progression from benign to malignant tumors, may also exist in dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c-kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation. We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas. This represents opportunity to explore canine oral cavity melanoma as a preclinical model. © 2013 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.

  15. Cutaneous melanoma in Latin America: the need for more data El melanoma cutáneo en América Latina: la necesidad de más datos

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    Rafael A Schmerling

    2011-11-01

    Full Text Available OBJECTIVE: To identify the scientific literature on cutaneous melanoma in Latin America and compile all available epidemiologic data to demonstrate the need for reliable regional and country-specific data on incidence and mortality estimates. METHODS: Literature searches were conducted in PubMed, Embase, LILACS, and Google Scholar databases for epidemiologic studies from 1 January 2000 to 31 October 2010 related to melanoma in Argentina, Brazil, Colombia, Mexico, Puerto Rico, and Venezuela. A final search on melanoma cases was carried out using country-specific population-based cancer registries. No statistical analyses were conducted. RESULTS: For all six countries, most epidemiological research on cutaneous melanoma consists of hospital-based or case-control studies. Very few studies report incidence and mortality rates. Attempts to estimate disease rates have relied on national incidence and mortality data and information extracted from cancer registries. While predominance of European ancestry is a known risk factor for developing melanoma, the association of melanoma and ethnicity is not well-documented in some of the populations reviewed. Latin Americans are frequently exposed to ultraviolet (UV radiation due to the tropical weather, high altitude, and thinning ozone layer in some regions. Tanned skin is viewed as healthy and beautiful. While melanoma public health campaigns have been under way in Latin America for decades, increasing melanoma awareness remains imperative. CONCLUSIONS: There is an urgent need to collect accurate epidemiologic melanoma data in Latin America. Future research in the region should include more comprehensive, countryspecific, population-based studies to allow for comparative evaluation of incidence and mortality ratesOBJETIVO: Identificar la literatura científica sobre el melanoma cutáneo en América Latina y recopilar todos los datos epidemiológicos disponibles, con objeto de demostrar la necesidad de

  16. The role of positron emission tomography with computed tomography in the follow-up of asymptomatic cutaneous malignant melanoma patients with a high risk of disease recurrence.

    Science.gov (United States)

    Abbott, Rachel Angharad; Acland, Katharine M; Harries, Mark; O'Doherty, Michael

    2011-10-01

    The aim of this study was to evaluate the role of [F] fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) as a surveillance tool in asymptomatic patients with primary cutaneous melanoma with the American Joint Committee on Cancer stage 3 disease. Thirty-four patients with primary cutaneous malignant melanoma with American Joint Committee on Cancer stage 3 disease, who underwent at least one annual surveillance PET/CT scan, were retrospectively identified from our PET Centre Database in May 2008 and their characteristics, PET/CT results and disease course were reviewed. In 20 patients with microscopic stage 3 disease at diagnosis, annual surveillance PET/CT detected two of three recurrences and detected one incidental breast carcinoma. In 14 patients with macroscopic stage 3 disease at, or subsequent to, their initial diagnosis, annual PET/CT detected four of four recurrences, detected metastases in one patient who remains asymptomatic and detected one incidental thyroid carcinoma. PET/CT seems to be a useful surveillance tool in patients with macroscopic stage 3 disease, although the numbers in this study are small. However, the role of PET/CT in patients initially presenting with microscopic stage 3 disease requires further confirmation.

  17. Two-year randomized controlled prospective trial converting treatment of stable renal transplant recipients with cutaneous invasive squamous cell carcinomas to sirolimus

    NARCIS (Netherlands)

    Hoogendijk-van den Akker, J.M.; Harden, P.N.; Hoitsma, A.J.; Proby, C.M.; Wolterbeek, R..; Bavinck, J.N.; Fijter, J.W. de

    2013-01-01

    PURPOSE In light of the significant morbidity and mortality of cutaneous invasive squamous cell carcinomas (SCCs) in renal transplant recipients, we investigated whether conversion to sirolimus-based immunosuppression from standard immunosuppression could diminish the recurrence rate of these skin

  18. Melanoma cutâneo: estudo de base populacional em Goiânia, Brasil, de 1988 a 2000 Cutaneous melanoma: population-based study in Goiania, Brazil, from 1988 to 2000

    Directory of Open Access Journals (Sweden)

    Ana Maria Sortino-Rachou

    2006-10-01

    Full Text Available FUNDAMENTOS: O Registro de Câncer de Base Populacional de Goiânia disponibiliza dados de melanoma de uma série temporal de 13 anos, com 96,6% de confirmação histopatológica. OBJETIVO: Comparar incidência, mortalidade e tendências mundiais com os dados do primeiro estudo de base populacional de melanoma cutâneo do Brasil. MÉTODOS: Foram analisados 290 casos novos diagnosticados em residentes do município (incidência e 54 óbitos reportados ao Registro de Câncer de Goiânia (mortalidade, entre 1988 e 2000. Os coeficientes padronizados por idade e sexo foram calculados pela população mundial. Para análise das tendências, um modelo de regressão linear simples foi utilizado. RESULTADOS: Cento e quarenta e quatro casos de melanoma em mulheres e 146 em homens. Os coeficientes padronizados médios de incidência foram crescentes tanto para homens (r²=0,33; p=0,040 como para mulheres (r²=0,41; p=0,019, com tendência crescente nos homens acima de 60 anos e mulheres até 59 anos. Os coeficientes padronizados médios de mortalidade foram crescentes nos homens (r²=0,32; p=0,042 e estáveis nas mulheres, com tendência crescente para homens acima de 60 anos. CONCLUSÃO: Tanto em Goiânia como no mundo, a incidência de melanoma cutâneo é crescente para ambos os sexos. A mortalidade tende à estabilidade nas mulheres e é crescente para homens.BACKGROUND: The Goiania Population-Based Cancer Registry grants access to a 13-year temporal series on melanoma data, with a histopathologic confirmation of 96.6%. OBJECTIVE: To compare the world incidence, mortality and trends with data of the first populationbased study on cutaneous melanoma in Brazil. METHODS: Two hundred and ninety new cases of melanoma diagnosed in city residents (incidence and 54 deaths reported to the Goiania Cancer Registry (mortality were analyzed between 1988 and 2000. The standardized coefficients of age and sex were calculated using the world population. The trends

  19. P-cadherin counteracts myosin II-B function: implications in melanoma progression

    Directory of Open Access Journals (Sweden)

    De Wever Olivier

    2010-09-01

    Full Text Available Abstract Background Malignant transformation of melanocytes is frequently attended by a switch in cadherin expression profile as shown for E- and N-cadherin. For P-cadherin, downregulation in metastasizing melanoma has been demonstrated, and over-expression of P-cadherin in melanoma cell lines has been shown to inhibit invasion. The strong invasive and metastatic nature of cutaneous melanoma implies a deregulated interplay between intercellular adhesion and migration-related molecules Results In this study we performed a microarray analysis to compare the mRNA expression profile of an invasive BLM melanoma cell line (BLM LIE and the non-invasive P-cadherin over-expression variant (BLM P-cad. Results indicate that nonmuscle myosin II-B is downregulated in BLM P-cad. Moreover, myosin II-B plays a major role in melanoma migration and invasiveness by retracting the tail during the migratory cycle, as shown by the localization of myosin II-B stress fibers relative to Golgi and the higher levels of phosphorylated myosin light chain. Analysis of P-cadherin and myosin II-B in nodular melanoma sections and in a panel of melanoma cell lines further confirmed that there is an inverse relationship between both molecules. Conclusions Therefore, we conclude that P-cadherin counteracts the expression and function of myosin II-B, resulting in the suppression of the invasive and migratory behaviour of BLM melanoma cells

  20. The Danish Melanoma Database

    Directory of Open Access Journals (Sweden)

    Hölmich Lr

    2016-10-01

    Full Text Available Lisbet Rosenkrantz Hölmich,1 Siri Klausen,2 Eva Spaun,3 Grethe Schmidt,4 Dorte Gad,5 Inge Marie Svane,6,7 Henrik Schmidt,8 Henrik Frank Lorentzen,9 Else Helene Ibfelt10 1Department of Plastic Surgery, 2Department of Pathology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, 3Institute of Pathology, Aarhus University Hospital, Aarhus, 4Department of Plastic and Reconstructive Surgery, Breast Surgery and Burns, Rigshospitalet – Glostrup, University of Copenhagen, Copenhagen, 5Department of Plastic Surgery, Odense University Hospital, Odense, 6Center for Cancer Immune Therapy, Department of Hematology, 7Department of Oncology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, 8Department of Oncology, 9Department of Dermatology, Aarhus University Hospital, Aarhus, 10Registry Support Centre (East – Epidemiology and Biostatistics, Research Centre for Prevention and Health, Glostrup – Rigshospitalet, University of Copenhagen, Glostrup, Denmark Aim of database: The aim of the database is to monitor and improve the treatment and survival of melanoma patients.Study population: All Danish patients with cutaneous melanoma and in situ melanomas must be registered in the Danish Melanoma Database (DMD. In 2014, 2,525 patients with invasive melanoma and 780 with in situ tumors were registered. The coverage is currently 93% compared with the Danish Pathology Register.Main variables: The main variables include demographic, clinical, and pathological characteristics, including Breslow’s tumor thickness, ± ulceration, mitoses, and tumor–node–metastasis stage. Information about the date of diagnosis, treatment, type of surgery, including safety margins, results of lymphoscintigraphy in patients for whom this was indicated (tumors > T1a, results of sentinel node biopsy, pathological evaluation hereof, and follow-up information, including recurrence, nature, and treatment hereof is registered. In case of death, the cause and date

  1. Abnormal responses to the carcinogen 4-nitroquinoline 1-oxide of cultured fibroblasts from patients with dysplastic nevus syndrome and hereditary cutaneous malignant melanoma

    International Nuclear Information System (INIS)

    Smith, P.J.; Greene, M.H.; Adams, D.; Paterson, M.C.

    1983-01-01

    The dysplastic nevus syndrome (DNS) is a preneoplastic melanocyte abnormality which occurs in families affected by hereditary cutaneous malignant melanoma (HCMM). A putative role of host-environmental interactions in the etiology of hereditary melanoma has been strengthened by the recent finding that fibroblasts derived from HCMM/DNS patients demonstrated enhanced sensitivity to u.v.-irradiation in vitro. An extension of these studies is reported in which we have examined the invitro responses to a model environmental carcinogen, 4-nitroquinoline 1-oxide (4NQO), of six non-tumor skin fibroblast strains from HCMM/DNS patients representing five families. Three of the six HCMM/DNS strains showed enhanced cell killing with sensitivities greater than that of a xeroderma pigmentosum (XP) variant strain but less than those of ataxia telangiectasia and XP Group D cell strains. The inhibition and recovery of de novo DNA synthesis, together with the expression of repair synthesis, following 4NQO exposure appeared to be normal in HCMM/DNS strains, irrespective of their subsequent clonogenic potential. The data point to a metabolic anomaly which may contribute to the carcinogenic risk of the melanoma prone preneoplastic state presented by some DNS patients

  2. Osteopontin promotes the invasive growth of melanoma cells by activating integrin αvβ3 and down-regulating tetraspanin CD9.

    Science.gov (United States)

    Yin, Miao; Soikkeli, Johanna; Jahkola, Tiina; Virolainen, Susanna; Saksela, Olli; Hölttä, Erkki

    2014-03-01

    Overexpression of osteopontin (OPN) is strongly associated with the invasiveness/metastasis of many cancers, including melanomas. However, the molecular mechanisms of OPN in these processes remain poorly understood. We found that forced expression of OPN in early vertical-growth-phase melanoma cells dramatically increased their migration/invasion and growth/survival in a three-dimensional collagen I gel. Neutralizing antibodies to OPN, integrin β1, and integrin αvβ3, but not to CD44, negated the effects of OPN. Conversely, knocking down OPN in metastatic melanoma cells abrogated the invasive growth. OPN overexpression activated and OPN knockdown inactivated αvβ3 and αvβ5 integrins, negligibly affecting their expression. We further found OPN expression to inversely correlate with tetraspanin CD9 expression. Early-stage melanoma cells displayed low OPN and high CD9 expression, and conversely, metastatic cells displayed high OPN and low CD9 expression. Overexpression of OPN in vertical-growth-phase melanoma cells induced down-regulation of CD9, and knockdown of OPN in metastatic melanoma cells up-regulated CD9. Reversion of these CD9 changes abolished the effects of OPN. Furthermore, knockdown of CD9 in early-stage melanoma cells stimulated their invasive capacity in three-dimensional collagen. Similarly, microarray analyses of benign nevi and primary melanomas from different stages revealed an inverse correlation between OPN and CD9. These data suggest that OPN promotes melanoma cell invasion by activating integrin αvβ3 and down-regulating CD9, a putative metastasis suppressor. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. Non-invasive objective devices for monitoring the inflammatory, proliferative and remodelling phases of cutaneous wound healing and skin scarring.

    Science.gov (United States)

    Ud-Din, Sara; Bayat, Ardeshir

    2016-08-01

    Objective evaluation of cutaneous wounds through the use of non-invasive devices is important for diagnosis, monitoring treatment response and can lead to the development of improved theranostic strategies. The need for objective monitoring of wound healing and scar formation is evident as this enables accurate diagnosis, evaluation and prognosis for clinicians and allows for the standardisation and validation of methodology for researchers. Therefore, this review provides an overview of the current application of non-invasive objective technologies for the assessment of wound healing through the different phases of repair. We propose that cutaneous healing parameters can be split into three core domains: anatomical, mechanical and physiological. These categories can be further subdivided with respect to specific phases of healing. There is no single instrument, which can measure all the parameters of healing simultaneously; thus, it is important to choose the correct device for the particular healing characteristics being monitored. However, multiprobe systems, which include a number of devices connected to one main unit, are useful as they enable multiple measurements of different parameters. Many of the devices have not been validated against histological examination. Additionally, some of the instruments have not been evaluated in all wound or scar types and may not be useful throughout all phases of cutaneous wound healing. In conclusion, non-invasive objective devices are useful in the assessment of cutaneous wound healing, as these tools can link the treatment and diagnosis by evaluating response to treatment and thus could aid as a marker for healing and scar maturation. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Patients' Characteristics, Histopathological Findings, and Tumor Stage in Different Types of Malignant Melanoma: A Retrospective Multicenter Study

    Directory of Open Access Journals (Sweden)

    Ali-Mohammad Farahmand

    2017-07-01

    Full Text Available Cutaneous malignant melanoma (CMM is currently the most fatal of skin cancers accounting for 50000 deaths annually. Five distinct melanomas are described histopathologically: superficial spreading, lentigo maligna, nodular, acral lentiginous and mucosal melanoma. The aim of this study was to investigate the characteristics of patients with various types of malignant melanoma and evaluate histopathological findings. In this retrospective study, we obtained our data from the records of 111 patients with melanoma. Biopsied specimens were collected and re-evaluated. Demographic information and histopathological findings were noted. SPSS 16 was used for analyzing data. Chi-square and one-way ANOVA was conducted for comparing categorical and numerical variables respectively. The mean age of patients was 59.33±14.68 years old. Most common melanoma type was acral lentiginous (40.5%, followed by nodular (35.1% and mucosal (10.8%. The highest tumor thickness was viewed in nodular melanoma followed by mucosal melanoma. The highest rate of metastasis, microsatellitosis, perineural invasion and Clark level of the invasion were reported in nodular and acral lentiginous respectively. The most frequent rate of ulceration and vascular invasion was reported in mucosal melanoma. Distribution of melanoma types varies largely in different regions. Lack of classic presentations in some types necessitate specific public education about warning signs. Histopathological and pathological characteristics in melanoma can aid in better staging and management of the tumor.

  5. Patients' Characteristics, Histopathological Findings, and Tumor Stage in Different Types of Malignant Melanoma: A Retrospective Multicenter Study.

    Science.gov (United States)

    Farahmand, Ali-Mohammad; Ehsani, Amir-Hoshang; Mirzaei, Mojtaba; Mohsenian, Maryam; Ghanadan, Alireza

    2017-05-01

    Cutaneous malignant melanoma (CMM) is currently the most fatal of skin cancers accounting for 50000 deaths annually. Five distinct melanomas are described histopathologically: superficial spreading, lentigo maligna, nodular, acral lentiginous and mucosal melanoma. The aim of this study was to investigate the characteristics of patients with various types of malignant melanoma and evaluate histopathological findings. In this retrospective study, we obtained our data from the records of 111 patients with melanoma. Biopsied specimens were collected and re-evaluated. Demographic information and histopathological findings were noted. SPSS 16 was used for analyzing data. Chi-square and one-way ANOVA was conducted for comparing categorical and numerical variables respectively. The mean age of patients was 59.33±14.68 years old. Most common melanoma type was acral lentiginous (40.5%), followed by nodular (35.1%) and mucosal (10.8%). The highest tumor thickness was viewed in nodular melanoma followed by mucosal melanoma. The highest rate of metastasis, microsatellitosis, perineural invasion and Clark level of the invasion were reported in nodular and acral lentiginous respectively. The most frequent rate of ulceration and vascular invasion was reported in mucosal melanoma. Distribution of melanoma types varies largely in different regions. Lack of classic presentations in some types necessitate specific public education about warning signs. Histopathological and pathological characteristics in melanoma can aid in better staging and management of the tumor.

  6. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, simvastatin, lovastatin and mevastatin inhibit proliferation and invasion of melanoma cells

    International Nuclear Information System (INIS)

    Glynn, Sharon A; O'Sullivan, Dermot; Eustace, Alex J; Clynes, Martin; O'Donovan, Norma

    2008-01-01

    A number of recent studies have suggested that cancer incidence rates may be lower in patients receiving statin treatment for hypercholesterolemia. We examined the effects of statin drugs on in vitro proliferation, migration and invasion of melanoma cells. The ability of lovastatin, mevastatin and simvastatin to inhibit the melanoma cell proliferation was examined using cytotoxicity and apoptosis assays. Effects on cell migration and invasion were assessed using transwell invasion and migration chambers. Hypothesis testing was performed using 1-way ANOVA, and Student's t-test. Lovastatin, mevastatin and simvastatin inhibited the growth, cell migration and invasion of HT144, M14 and SK-MEL-28 melanoma cells. The concentrations required to inhibit proliferation of melanoma cells (0.8–2.1 μM) have previously been achieved in a phase I clinical trial of lovastatin in patients with solid tumours, (45 mg/kg/day resulted in peak plasma concentrations of approximately 3.9 μM). Our results suggest that statin treatment is unlikely to prevent melanoma development at standard doses. However, higher doses of statins may have a role to play in adjuvant therapy by inhibiting growth and invasion of melanoma cells

  7. Upregulation of annexin A1 expression by butyrate in human melanoma cells induces invasion by inhibiting E-cadherin expression.

    Science.gov (United States)

    Shin, Jimin; Song, In-Sung; Pak, Jhang Ho; Jang, Sung-Wuk

    2016-11-01

    Epithelial to mesenchymal transition (EMT) is a critical step in the metastasis of epithelial cancer cells. Butyrate, which is produced from dietary fiber by colonic bacterial fermentation, has been reported to influence EMT. However, some studies have reported that butyrate promotes EMT, while others have reported an inhibitory effect. To clarify these controversial results, it is necessary to elucidate the mechanism by which butyrate can influence EMT. In this study, we examined the potential role of annexin A1 (ANXA1), which was previously reported to promote EMT in breast cancer cells, as a mediator of EMT regulation by butyrate. We found that ANXA1 mRNA and protein were expressed in highly invasive melanoma cell lines (A2058 and A375), but not in SK-MEL-5 cells, which are less invasive. We also showed that butyrate induced ANXA1 mRNA and protein expression and promoted EMT-related cell invasion in SK-MEL-5 cells. Downregulation of ANXA1 expression using specific small interfering RNAs in butyrate-treated SK-MEL-5 cells resulted in increased expression of the epithelial marker E-cadherin and decreased cell invasion. Moreover, overexpressing ANXA1 decreased the expression of the E-cadherin. Collectively, these results indicate that butyrate induces the expression of ANXA1 in human melanoma cells, which then promotes invasion through activating the EMT signaling pathway.

  8. Skin cancer and melanoma

    International Nuclear Information System (INIS)

    Moylan, D.J.

    1991-01-01

    In this chapter, the author discusses various types of non-melanoma malignant skin cancer, as well as malignant melanoma. Non-melanoma skin cancer, such as basal cell and squamous cell carcinomas, occasionally metastasize, but only late in the course of the disease. On the other hand, even relatively small primary melanomas tend to disseminate to regional lymph nodes and to distant sites. The author presents various treatment plans, including radiation therapy. Cutaneous melanomas have been considered relatively radioresistant. This is the rationale for the use of large fraction radiation therapy in the treatment of melanomas with the fraction sizes varying from 4--8 Gy

  9. Primary Anorectal Melanoma: An Update

    Directory of Open Access Journals (Sweden)

    P Carcoforo, M.T Raiji, G.M Palini, M Pedriali, U Maestroni, G Soliani, A Detroia, M.V Zanzi, A.L Manna, J.G Crompton, R.C Langan, A Stojadinovic, I Avital

    2012-01-01

    Full Text Available The anorectum is a rare anatomic location for primary melanoma. Mucosal melanoma is a distinct biological and clinical entity from the more common cutaneous melanoma. It portrays worse prognosis than cutaneous melanoma, with distant metastases being the overwhelming cause of morbidity and mortality. Surgery is the treatment of choice, but significant controversy exists over the extent of surgical resection. We present an update on the state of the art of anorectal mucosal melanoma. To illustrate the multimodality approach to anorectal melanoma, we present a typical patient.

  10. In Vivo Targeting of Cutaneous Melanoma Using an Melanoma Stimulating Hormone-Engineered Human Protein Cage with Fluorophore and Magnetic Resonance Imaging Tracers

    Czech Academy of Sciences Publication Activity Database

    Vannucci, Luca; Falvo, E.; Failla, C. M.; Carbo, M.; Fornara, M.; Canese, R.; Cecchetti, S.; Rajsiglová, Lenka; Stakheev, Dmitry; Křižan, Jiří; Boffi, A.; Carpinelli, G.; Morea, V.; Ceci, P.

    2015-01-01

    Roč. 11, č. 1 (2015), s. 81-92 ISSN 1550-7033 Institutional support: RVO:61388971 Keywords : Protein-Based Nanoparticles * Ferritin * In Vivo Melanoma-Targeting Subject RIV: EC - Immunology Impact factor: 3.929, year: 2015

  11. Regulator of G protein signaling 4 inhibits human melanoma cells proliferation and invasion through the PI3K/AKT signaling pathway.

    Science.gov (United States)

    Xue, Xiaotong; Wang, Lihua; Meng, Xianguang; Jiao, Jing; Dang, Ningning

    2017-10-03

    Melanoma is a tumor produced by skin melanocytes, which has a high metastatic rate and poor prognosis. So far, plenty of work has been done on melanoma, but mechanisms underlying melanoma development have not been fully elucidated. Here we identified regulator of G protein signaling 4(RGS4) as novel therapeutic target for malignant melanoma and its regulating effect on melanoma. We found that endogenous RGS4 expression was much lower in melanoma tissues and cells. In A375 cell line with low endogenous RGS4 expression, the function of RGS4 was detected by up-regulation its expression with pcDNA3.1-RGS4 and knockdown its expression with siRNA. Our results showed that RGS4 could significantly reduce the proliferation, migration and invasion of melanoma cells. RGS4 is an important regulator for the apoptosis of melanocyte, and the apoptosis rate is significantly decreased in low RGS4 enviroment. RGS4 induced non-activation of PI3K/AKT pathway, resulting in decreased expression of E2F1 and Cyclin D1, thus constraining cell proliferation and invasion. These results were further confirmed in M14 cell lines. Collectively, our findings show that RGS4 plays an important role in multiple cellular functions of melanoma development and is valuable to be a therapeutic target.

  12. Inhibition of cell proliferation, migration and invasion of B16-F10 melanoma cells by α-mangostin

    Energy Technology Data Exchange (ETDEWEB)

    Beninati, Simone, E-mail: beninati@bio.uniroma2.it [Department of Biology, University “Tor Vergata”, Rome (Italy); Oliverio, Serafina [Department of Biology, University “Tor Vergata”, Rome (Italy); Cordella, Martina [Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome (Italy); Rossi, Stefania; Senatore, Cinzia [Regina Elena National Cancer Institute, Rome (Italy); Liguori, Immacolata; Lentini, Alessandro; Piredda, Lucia [Department of Biology, University “Tor Vergata”, Rome (Italy); Tabolacci, Claudio [Department of Biology, University “Tor Vergata”, Rome (Italy); Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome (Italy)

    2014-08-08

    Highlights: • We studied the anticancer potential of a new emerging molecule, α-mangostin (α-M). • We provide first evidences on the effects of α-M on transglutaminase activity. • We deeply examined the antimetastatic effects of α-M through many in vitro assays. • Proteomic analysis revealed that α-M promotes a reorganization at cellular level. - Abstract: In this study, we have evaluated the potential antineoplastic effects of α-mangostin (α-M), the most representative xanthone in Garcinia mangostana pericarp, on melanoma cell lines. This xanthone markedly inhibits the proliferation of high-metastatic B16-F10 melanoma cells. Furthermore, by deeply analyzing which steps in the metastatic process are influenced by xanthone it was observed that α-M strongly interferes with homotypic aggregation, adhesion, plasticity and invasion ability of B16-F10 cells, probably by the observed reduction of metalloproteinase-9 activity. The antiproliferative and antimetastatic properties of α-M have been established in human SK-MEL-28 and A375 melanoma cells. In order to identify pathways potentially involved in the antineoplastic properties of α-M, a comparative mass spectrometry proteomic approach was employed. These findings may improve our understanding of the molecular mechanisms underlying the anti-cancer effects of α-M on melanoma.

  13. Contemporary Management of Early-Stage Melanoma: A Systematic Review.

    Science.gov (United States)

    Rosko, Andrew J; Vankoevering, Kyle K; McLean, Scott A; Johnson, Timothy M; Moyer, Jeffrey S

    2017-05-01

    The incidence of melanoma is increasing, with 76 380 new cases of invasive melanoma and 68 480 new cases of melanoma in situ expected in 2016. To review the contemporary management of early-stage melanoma. We searched PubMed, MEDLINE, and the Cochrane Database of Systematic Reviews databases from January 1, 2011, to May 1, 2016, yielding 966 articles. We focused our search on early-stage (melanoma in situ, stage I, and stage II) cutaneous melanoma. After excluding articles, 41 articles were manually reviewed. A review of the bibliographies of selected articles generated additional references. While the majority of recent advances have been in the treatment of advanced melanoma, surgical excision with margins based on the presence and depth of invasion continues to be the cornerstone of management. Sentinel lymph node biopsy plays a central role in the staging and treatment of melanoma. Accurate diagnosis and adequate surgical excision are critical in reducing local recurrences and improving outcomes. Sentinel lymph node biopsy is useful in staging the regional nodal basin and guiding treatment in appropriately selected patients.

  14. Membrane-type-3 matrix metalloproteinase (MT3-MMP functions as a matrix composition-dependent effector of melanoma cell invasion.

    Directory of Open Access Journals (Sweden)

    Olga Tatti

    Full Text Available In primary human melanoma, the membrane-type matrix metalloproteinase, MT3-MMP, is overexpressed in the most aggressive nodular-type tumors. Unlike MT1-MMP and MT2-MMP, which promote cell invasion through basement membranes and collagen type I-rich tissues, the function of MT3-MMP in tumor progression remains unclear. Here, we demonstrate that MT3-MMP inhibits MT1-MMP-driven melanoma cell invasion in three-dimensional collagen, while yielding an altered, yet MT1-MMP-dependent, form of expansive growth behavior that phenocopies the formation of nodular cell colonies. In melanoma cell lines originating from advanced primary or metastatic lesions, endogenous MT3-MMP expression was associated with limited collagen-invasive potential. In the cell lines with highest MT3-MMP expression relative to MT1-MMP, collagen-invasive activity was increased following stable MT3-MMP gene silencing. Consistently, MT3-MMP overexpression in cells derived from less advanced superficially spreading melanoma lesions, or in the MT3-MMP knockdown cells, reduced MT1-MMP-dependent collagen invasion. Rather than altering MT1-MMP transcription, MT3-MMP interacted with MT1-MMP in membrane complexes and reduced its cell surface expression. By contrast, as a potent fibrinolytic enzyme, MT3-MMP induced efficient invasion of the cells in fibrin, a provisional matrix component frequently found at tumor-host tissue interfaces and perivascular spaces of melanoma. Since MT3-MMP was significantly upregulated in biopsies of human melanoma metastases, these results identify MT3-MMP as a matrix-dependent modifier of the invasive tumor cell functions during melanoma progression.

  15. CASE REPORT: NODULAR MELANOMA

    Directory of Open Access Journals (Sweden)

    Tina Zupančič

    2015-05-01

    Full Text Available Nodular melanoma is a rare type of cutaneous melanoma with an increased risk of death. It often mimics benign cutaneous tumors and inflammatory lesions. It has pronounced vertical growth phase and greater thickness at the time of diagnosis which caries ominous prognostic value. Nodular melanoma quickly develops metastases which are often present before the disease is clinically recognised. Here, we report a case of nodular melanoma clinically mimicking seborrheic keratosis. Therapy and 36 months follow-up after primal excision are also presented.

  16. Black light visualized solar lentigines on the shoulders and upper back are associated with objectively measured UVR exposure and cutaneous malignant melanoma

    DEFF Research Database (Denmark)

    Idorn, Luise Winkel; Datta, Pameli; Heydenreich, Jakob

    2015-01-01

    , and to investigate the association between solar lentigines and cutaneous malignant melanoma (CMM). Forty-eight patients with CMM and 48 controls that matched the patients individually by age, sex, constitutive skin type and occupation participated. Solar lentigines on the shoulders and upper back were counted....... Among controls, the number of solar lentigines was positively associated with daily hours spent outdoors between noon and 3 pm on holidays (P = 0.027), days at the beach (P = 0.048) and reported number of life sunburns (P ... lentigines (P = 0.044). There was a positive association between CMM and higher solar lentigines grade; Category III versus Category I (P = 0.002) and Category II versus Category I (P = 0.014). Our findings indicate that solar lentigines in healthy individuals are associated with number of life sunburns...

  17. Cost-effectiveness of preoperative SPECT/CT combined with lymphoscintigraphy vs. lymphoscintigraphy for sentinel lymph node excision in patients with cutaneous malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Stoffels, Ingo; Leyh, Julia; Schadendorf, Dirk; Klode, Joachim [University of Duisburg-Essen, Department of Dermatology, Venerology and Allergology, University-Hospital Essen, Essen (Germany); Mueller, Markus [University of Duisburg-Essen, Department of Medical controlling, University-Hospital Essen, Essen (Germany); Geisel, Marie Henrike [University of Duisburg-Essen, Institute for Medical Informatics, Biometry and Epidemiology, University-Hospital Essen, Essen (Germany); Poeppel, Thorsten [University of Duisburg-Essen, Department of Nuclear Medicine, University-Hospital Essen, Essen (Germany)

    2014-09-15

    Malignant melanoma has become a major growing interdisciplinary problem in public health worldwide. Sentinel lymph node excision (SLNE) in conjunction with preoperative SPECT/CT is considered the most sensitive and specific staging test for the detection of micrometastatic melanoma in regional lymph nodes. Among patients with clinically lymph node-negative melanoma, the use of SPECT/CT-aided SLNE compared with SLNE alone has been found to be associated with a higher frequency of metastatic involvement and a higher rate of disease-free survival. The aim of this study was to analyse the cost-effectiveness of SLNE with preoperative SPECT/CT for detecting sentinel lymph nodes versus that of standard SLNE with preoperative lymphoscintigraphy from a single-institution database. Cost-effectiveness analysis of two surgical approaches for SLNE for malignant melanoma at the University Hospital Essen, Skin Cancer Center in Essen, Germany. Between March 2003 and April 2011 464 patients eligible for SLNE were identified. Of these patients, 403 with clinically negative lymph nodes who underwent SLNE with or without preoperative SPECT/CT qualified for subsequent analysis. Between March 2003 and October 2008, 254 patients were operated upon with the standard technique. From November 2008, 149 patients underwent the SPECT/CT technique. Cost analysis showed a mean cost saving of EUR 710.50 when SPECT/CT was added to preoperative imaging. This was achieved by a reduction in operative time (median, Q1;Q3, 40 min, 40;50 min, vs. 45 min, 35;60 min; p = 0.002), hospital stay duration (5 days, 3;8 days, vs. 8 days, 4.5;14.5 days; p < 0.001) and more frequent use of local anaesthesia (90.6 % vs. 70.5 %; p < 0.001). The median cost of SLNE using SPECT/CT was EUR 1,619.7 (Q1;Q3 EUR 1,317.0;2,603.4) and of SLNE without SPECT/CT was EUR 2,330.2 (EUR 1,468.3;4,058.1; p < 0.001), a cost saving of 30.5 %. In patients with cutaneous melanoma, the use of preoperative SPECT/CT-aided SLNE compared

  18. Primary orbital melanoma in association with cellular blue nevus.

    Science.gov (United States)

    El-Sawy, Tarek; Bakhoum, Mathieu F; Tetzlaff, Michael; Nasser, Qasiem J; Prieto, Victor G; Ivan, Doina; Sniegowski, Matthew C; Yin, Vivian T; Pan, Caroline; Durairaj, Vikram; Esmaeli, Bita

    2014-01-01

    To describe 3 cases of primary orbital melanoma associated with either known or subsequently discovered cellular blue nevus. The clinical records and surgical specimens of 3 patients who underwent orbital exenteration for primary orbital melanoma and who had a cellular blue nevus diagnosed before or after detection of the melanoma were retrospectively reviewed. All 3 patients presented with signs and symptoms of an orbital mass. Subsequent biopsy revealed invasive melanoma. One patient had a known history of congenital cellular blue nevus of the eyelid from which the orbital melanoma originated. The other 2 patients had no known history of cutaneous pigmentation or blue nevus. In these 2 patients, the cellular blue nevus was detected on pathologic review of the orbital exenteration specimen (1 patient) or surgical biopsy specimen (1 patient). All 3 patients underwent total body positron emission tomography/computed tomography, and in all 3 results were negative for other sites of disease involvement. In the 2 patients without a previously known nevus a total body skin check was negative for other primary melanoma lesions. All 3 patients underwent orbital exenteration followed by postoperative radiation therapy. Thorough evaluation of biopsy specimens of "primary" orbital melanoma is warranted to ensure identification of any associated blue nevus because blue nevi are precursor lesions for orbital melanoma, and the presence of a blue nevus would support a primary orbital melanoma rather than a metastatic lesion. Patients with a known blue nevus of the periocular skin and ocular adnexa should be monitored closely for signs of malignant transformation.

  19. Thin melanoma.

    Science.gov (United States)

    Elder, David E

    2011-03-01

    The incidence of malignant melanoma is increasing and a preponderance of the melanomas diagnosed today are "thin in terms of Breslow criteria. Although thin melanomas, as a group, are associated with a very good prognosis, a subset of these tumors may metastasize and cause death. These cases can be identified by using prognostic models, including the "standard" American Joint Committee on Cancer criteria, and other attributes identified in follow-up studies. To review the history of concepts of prognostic modeling in melanoma, focusing on thin melanomas. Selected literature. About 40 years ago, it was realized that malignant melanoma, once almost uniformly fatal, could be divided into categories with better or worse prognosis through the use of prognostic models. The first simple models, Clark levels of invasion and Breslow thickness, are still in use. Thickness remains the single most useful variable. Breslow recognized that melanomas less than 0.76 mm in thickness were associated with a very good prognosis, with no metastases in his limited initial study. The American Joint Committee on Cancer selected a cutoff of 1.0 mm, which achieves a similar result, with stage modifiers, although some metastases and deaths do occur with stage I lesions. Clark demonstrated an almost equally good prognosis for his level II invasive melanomas and recognized that most of these lesions, although invasive, lacked the ability to form tumors or to undergo mitosis in the dermis and were therefore "nontumorigenic" and "nonmitogenic" and lacked competence for metastasis. Studies of these low-risk melanomas have led to the development of criteria for earlier diagnosis and a steady, but still inadequate, improvement in prognosis for melanoma overall. Multivariable models currently can identify groups of patients within the "thin melanoma" category whose prognosis varies, from a disease-free survival of close to 100% to about 70%. Prognosis declines more or less linearly with increasing

  20. Melanoma cutâneo: características clínicas, epidemiológicas e histopatológicas no Hospital Universitário de Brasília entre janeiro de 1994 e abril de 1999 Cutaneous Melanoma: clinical, epidemiological and histopathological characteristics at the University Hospital of Brasília between January 1994 and April 1999

    Directory of Open Access Journals (Sweden)

    Ana Maria Costa Pinheiro

    2003-04-01

    characteristics of primary cutaneous melanoma, at the University Hospital of Brasília, during a period of five years. MATERIAL AND METHODS: A review was conducted of the data registry concerning primary cutaneous melanoma cases, in the University Hospital of Brasília, diagnosed and treated between January 1994 and April 1999, with a total of 32 cases. The patients were analyzed, characterizing the tumor distribution according to gender, age, skin color, topography, symptomatology, histopathological type, Clark level, Breslow index and presence of metastasis. Data was analyzed by simple statistics and by Chi-square (chi2. RESULTS: A predominance was observed of lesions in the limbs, corresponding to sixteen patients (50.0%. There was the primary nodular form in nine (45% patients, and seventeen (58.6% patients did not have any complaint. According to the presence or absence of metastasis and Clark level, it was found that the patients with a level of invasion up to the subcutaneous layer (Clark V presented a relative risk of 2.94 (1.24cutaneous melanoma at the University Hospital of Brasília, between January 1994 and April 1999, comprised of elderly females (from 61 to 80 years old, Caucasians, whose tumor was located predominantly in the limbs, the nodular type was the most frequent, and the patients did not present symptoms at the time of diagnosis.

  1. Nonlethal Levels of Zeaxanthin Inhibit Cell Migration, Invasion, and Secretion of MMP-2 via NF-κB Pathway in Cultured Human Uveal Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Ming-Chao Bi

    2016-01-01

    Full Text Available Zeaxanthin at nonlethal dosages (3–10 μM significantly inhibited the cell migration of cultured uveal melanoma cells (C918 cell line as determined by wound healing assay and Boyden chamber assay. Matrigel invasion assay showed that cell invasion of uveal melanoma cells could be significantly inhibited by zeaxanthin. Secretion of MMP-2 by melanoma cells was significantly inhibited by zeaxanthin in a dose-dependent manner as measured by ELISA kit. Zeaxanthin also significantly inhibited the NF-κB levels in nuclear extracts of the UM cells, which is the upstream of the MMP-2 secretion. These results suggest that zeaxanthin might be a potentially therapeutic approach in the prevention of metastasis in uveal melanoma.

  2. Factors related to the presentation of thin and thick nodular melanoma from a population-based cancer registry in Queensland Australia.

    Science.gov (United States)

    Geller, Alan C; Elwood, Mark; Swetter, Susan M; Brooks, Daniel R; Aitken, Joanne; Youl, Philippa H; Demierre, Marie-France; Baade, Peter D

    2009-03-15

    Worldwide, the incidence of thick melanoma has not declined, and the nodular melanoma (NM) subtype accounts for nearly 40% of newly diagnosed thick melanoma. To assess differences between patients with thin (or=2.01 mm) nodular melanoma, the authors evaluated factors such as demographics, melanoma detection patterns, tumor visibility, and physician screening for NM alone and compared clinical presentation and anatomic location of NM with superficial spreading melanoma (SSM). The authors used data from a large population-based study of Queensland (Australia) residents diagnosed with melanoma. Queensland residents aged 20 to 75 years with histologically confirmed first primary invasive cutaneous melanoma were eligible for the study, and all questionnaires were conducted by telephone (response rate, 77.9%). During this 4-year period, 369 patients with nodular melanoma were interviewed, of whom 56.7% were diagnosed with tumors nodular tumors of greater thickness. Thickest nodular melanoma (4 mm+) was also most common in persons who had not been screened by a physician within the past 3 years (odds ratio, 3.75; 95% confidence interval, 1.47-9.59). Forty-six percent of patients with thin nodular melanoma (nodular melanoma (>2.00 mm). Awareness of factors related to earlier detection of potentially fatal nodular melanomas, including the benefits of a physician examination, should be useful in enhancing public and professional education strategies. Particular awareness of clinical warning signs associated with thin nodular melanoma should allow for more prompt diagnosis and treatment of this subtype. Copyright (c) 2009 American Cancer Society.

  3. A prospective multicenter cohort study of cutaneous melanoma: clinical staging and potential associations with HIF-1α and VEGF expressions.

    Science.gov (United States)

    Martínez-García, Miguel Ángel; Riveiro-Falkenbach, Erica; Rodríguez-Peralto, José L; Nagore, Eduardo; Martorell-Calatayud, Antonio; Campos-Rodríguez, Francisco; Farré, Ramón; Hernández Blasco, Luis; Bañuls Roca, Jose; Chiner Vives, Eusebi; Sánchez-de-la-Torre, Alicia; Abad Capa, Jorge; Montserrat, Josep Maria; Almendros, Isaac; Pérez-Gil, Amalia; Cabriada Nuño, Valentin; Cano-Pumarega, Irene; Corral Peñafiel, Jaime; Diaz Cambriles, Trinidad; Mediano, Olga; Dalmau Arias, Joan; Gozal, David

    2017-12-01

    Melanoma is a highly prevalent cancer that is associated with substantial mortality. Although clinical staging procedures can serve as relatively robust prognostic indicators, we aimed to determine whether assessments of the abundance of hypoxia inducible factor-1α (HIF-1α) or vascular endothelial growth factor (VEGF) in postexcisional melanoma tumor tissues may enable more accurate determination of tumor aggressiveness. We carried out a multicenter prospective study, in which we systematically evaluated 376 consecutive patients diagnosed with melanoma, and performed histochemical assessments for both HIF-1α and VEGF immunoreactivity in the tumor biopsies. Multivariate analyses showed that higher HIF-1α expression, but not high VEGF, were associated significantly and independently with increased tumor aggressiveness as derived from several well-established aggressiveness criteria. A limitation of this study was that this was a descriptive prospective study lacking a post-hoc verification arm. Thus, the presence of increased numbers of positively labeled HIF-1α cells in melanoma tumors may potentially serve as an indicator of tumor phenotype and prognosis, and accordingly guide therapy.

  4. Clinical Relevance of Detection of Lymphovascular Invasion in Primary Melanoma Using Endothelial Markers D2-40 and CD34

    Science.gov (United States)

    Rose, Amy E.; Christos, Paul J.; Lackaye, Dan; Shapiro, Richard L.; Berman, Russell; Mazumdar, Madhu; Kamino, Hideko; Osman, Iman; Darvishian, Farbod

    2013-01-01

    Immunohistochemistry (IHC) using endothelial markers may facilitate the detection of lymphovascular invasion (LVI) in primary melanoma; however, the clinical implications of enhanced detection are unknown. We evaluated whether the use of lymphatic endothelial marker D2-40 and panvascular marker CD34 increases LVI positivity relative to routine histology alone and then evaluated the prognostic relevance of LVI detected using these markers in terms of disease-free (DFS) and overall survival (OS). A total of 246 primary melanomas were assessed for LVI using D2-40, CD34, and routine histology. Associations between LVI positivity and clinicopathologic variables, DFS, and OS were compared using univariate and multivariate analyses. The use of endothelial markers increased the rate of LVI positivity (18% using D2-40 and/or CD34 vs. 3% by routine histology, P nodular subtype) compared with LVI detected by routine histology (thickness and ulceration only). In a multivariate model controlling for stage, LVI detected using IHC markers remained a significant marker of both reduced DFS [hazard ratio (HR), 2.01; 95% confidence interval (CI): 1.27–3.18; P = 0.003] and OS (HR, 2.08; 95% CI: 1.25–3.46; P = 0.005). Results show that D2-40 and CD34 increase the detection of LVI in primary melanoma and that cases missed by routine histology have prognostic relevance. PMID:21881483

  5. Comparing Melanoma Invasiveness in Dermatologist- versus Patient-Detected Lesions: A Retrospective Chart Review

    OpenAIRE

    Cindy L. Lamerson; Kristina Eaton; Joel L. Sax; Mohammed Kashani-Sabet

    2012-01-01

    This study examined whether patient-identified melanomas were more advanced than dermatologist-identified tumors at routine clinic visits, and whether a personal or family history of skin cancer was associated with patterns of detection. A retrospective chart review was performed on melanoma patients (N = 201) in a private dermatology clinic. Variables included age, gender, pattern of detection (i.e., patient or a board certified dermatologist), personal or family history of skin cancer, skin...

  6. Incidence of In Situ and Invasive Melanoma in Denmark From 1985 Through 2012

    DEFF Research Database (Denmark)

    Helvind, Neel Maria; Hölmich, Lisbet Rosenkrantz; Smith, Sigrun

    2015-01-01

    in melanoma incidence. Results may indicate the importance of secondary melanoma prevention in Denmark. Future efforts could intensify primary prevention aimed at young adults, adolescents, and children and maintain and target secondary prevention at the population older than 60 years........0% to -2.6%] in men and -3.4% [-4.0% to -2.8%] in women). More proximal tumor location occurred over time (P defined by codes...

  7. Epigenetic regulation of microRNA genes and the role of miR-34b in cell invasion and motility in human melanoma.

    Directory of Open Access Journals (Sweden)

    Joseph Mazar

    Full Text Available Invasive melanoma is the most lethal form of skin cancer. The treatment of melanoma-derived cell lines with 5-aza-2'-deoxycytidine (5-Aza-dC markedly increases the expression of several miRNAs, suggesting that the miRNA-encoding genes might be epigenetically regulated, either directly or indirectly, by DNA methylation. We have identified a group of epigenetically regulated miRNA genes in melanoma cells, and have confirmed that the upstream CpG island sequences of several such miRNA genes are hypermethylated in cell lines derived from different stages of melanoma, but not in melanocytes and keratinocytes. We used direct DNA bisulfite and immunoprecipitated DNA (Methyl-DIP to identify changes in CpG island methylation in distinct melanoma patient samples classified as primary in situ, regional metastatic, and distant metastatic. Two melanoma cell lines (WM1552C and A375 derived from stage 3 and stage 4 human melanoma, respectively were engineered to ectopically express one of the epigenetically modified miRNA: miR-34b. Expression of miR-34b reduced cell invasion and motility rates of both WM1552C and A375, suggesting that the enhanced cell invasiveness and motility observed in metastatic melanoma cells may be related to their reduced expression of miR-34b. Total RNA isolated from control or miR-34b-expressing WM1552C cells was subjected to deep sequencing to identify gene networks around miR-34b. We identified network modules that are potentially regulated by miR-34b, and which suggest a mechanism for the role of miR-34b in regulating normal cell motility and cytokinesis.

  8. [Ocular melanomas : An update].

    Science.gov (United States)

    Kalirai, H; Müller, P L; Jaehne, D; Coupland, S E

    2017-11-01

    Melanoma is the most common type of primary cancer to affect the adult eye. Approximately 95% of ocular melanomas are intraocular and arise from the uvea (i. e. iris, ciliary body, and choroid), while the remaining 5% are located in the conjunctiva. Although both uveal and conjunctival melanomas are thought to derive from malignantly transformed melanocytes, uveal melanoma is clinically and biologically distinct from conjunctival melanoma, and indeed from its more common cutaneous counterpart. Intense efforts have been recently made to understand the molecular biology involved in the development of ocular melanomas, and in their progression. Molecular advances, particularly for uveal melanoma, have enhanced prognostication and the identification of rational therapeutic targets for disseminated disease. In this review, recent advances in the molecular characterisation of both uveal and conjunctival melanomas are discussed, and how these may be used to develop personalised therapeutic strategies.

  9. Minimally invasive liver resection to obtain tumor-infiltrating lymphocytes for adoptive cell therapy in patients with metastatic melanoma

    Directory of Open Access Journals (Sweden)

    Alvarez-Downing Melissa M

    2012-06-01

    Full Text Available Abstract Background Adoptive cell therapy (ACT with tumor-infiltrating lymphocytes (TIL in patients with metastatic melanoma has been reported to have a 56% overall response rate with 20% complete responders. To increase the availability of this promising therapy in patients with advanced melanoma, a minimally invasive approach to procure tumor for TIL generation is warranted. Methods A feasibility study was performed to determine the safety and efficacy of laparoscopic liver resection to generate TIL for ACT. Retrospective review of a prospectively maintained database identified 22 patients with advanced melanoma and visceral metastasis (AJCC Stage M1c who underwent laparoscopic liver resection between 1 October 2005 and 31 July 2011. The indication for resection in all patients was to receive postoperative ACT with TIL. Results Twenty patients (91% underwent resection utilizing a closed laparoscopic technique, one required hand-assistance and another required conversion to open resection. Median intraoperative blood loss was 100 mL with most cases performed without a Pringle maneuver. Median hospital stay was 3 days. Three (14% patients experienced a complication from resection with no mortality. TIL were generated from 18 of 22 (82% patients. Twelve of 15 (80% TIL tested were found to have in vitro tumor reactivity. Eleven patients (50% received the intended ACT. Two patients were rendered no evidence of disease after surgical resection, with one undergoing delayed ACT with generated TIL after relapse. Objective tumor response was seen in 5 of 11 patients (45% who received TIL, with one patient experiencing an ongoing complete response (32+ months. Conclusions Laparoscopic liver resection can be performed with minimal morbidity and serve as an effective means to procure tumor to generate therapeutic TIL for ACT to patients with metastatic melanoma.

  10. Clinical characteristics and management of melanoma families

    NARCIS (Netherlands)

    Rhee, Jasper Immanuel van der

    2013-01-01

    Being a member of a melanoma family is a major risk factor for cutaneous malignant melanoma. In this thesis clinical characteristics and management of melanoma families are discussed. In the first part of the thesis clinical and histological characteristics of melanoma (patients) from families with

  11. MALDI MSI of MeLiM melanoma: Searching for differences in protein profiles.

    Directory of Open Access Journals (Sweden)

    Roman Guran

    Full Text Available Treatment of advanced cutaneous melanoma remains challenging, and new data on melanoma biology are required. The most widely accepted criteria for the prognostic evaluation of melanoma are histopathological and clinical parameters, and the identification of additional tumor markers is thus of paramount importance. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI, an important tool in cancer research, is useful for unraveling the molecular profile of melanoma.In this report, we used the melanoma-bearing Libechov minipig (MeLiM, a unique animal model that allows observation of the complete spontaneous regression of invasive cutaneous melanoma, to investigate i the differences between melanoma and healthy skin protein profiles and ii the proteins potentially involved in spontaneous regression. The MeLiM tissues were cryosected, histologically characterized, analyzed by MALDI MSI, and immunohistologically stained. Multivariate statistical analyses of the MALDI MSI data revealed ten relevant m/z ions, of which the expression levels varied significantly among the studied MeLiM tissues. These ion peaks were used to create mass ion images/maps and visualize the differences between tumor and healthy skin specimens, as well as among histologically characterized tissue regions.Protein profiles comprising ten statistically significant mass ion peaks useful for differentiating cutaneous melanoma and healthy skin tissues were determined. Peaks at m/z 3044, 6011, 6140 and 10180 were overexpressed in melanoma compared with healthy skin tissue. More specifically, m/z 6140 was expressed at significantly (p < 0.05 higher levels in normally growing melanoma regions than in regions with early and late spontaneous regression. This study demonstrates the clinical utility of MALDI MSI for the analysis of tissue cryosections at a molecular level.

  12. Melanoma: Genetic Abnormalities, Tumor Progression, Clonal Evolution and Tumor Initiating Cells

    Science.gov (United States)

    Castelli, Germana; Pelosi, Elvira

    2017-01-01

    Melanoma is an aggressive neoplasia issued from the malignant transformation of melanocytes, the pigment-generating cells of the skin. It is responsible for about 75% of deaths due to skin cancers. Melanoma is a phenotypically and molecularly heterogeneous disease: cutaneous, uveal, acral, and mucosal melanomas have different clinical courses, are associated with different mutational profiles, and possess distinct risk factors. The discovery of the molecular abnormalities underlying melanomas has led to the promising improvement of therapy, and further progress is expected in the near future. The study of melanoma precursor lesions has led to the suggestion that the pathway of tumor evolution implies the progression from benign naevi, to dysplastic naevi, to melanoma in situ and then to invasive and metastatic melanoma. The gene alterations characterizing melanomas tend to accumulate in these precursor lesions in a sequential order. Studies carried out in recent years have, in part, elucidated the great tumorigenic potential of melanoma tumor cells. These findings have led to speculation that the cancer stem cell model cannot be applied to melanoma because, in this malignancy, tumor cells possess an intrinsic plasticity, conferring the capacity to initiate and maintain the neoplastic process to phenotypically different tumor cells. PMID:29156643

  13. Melanoma: Genetic Abnormalities, Tumor Progression, Clonal Evolution and Tumor Initiating Cells

    Directory of Open Access Journals (Sweden)

    Ugo Testa

    2017-11-01

    Full Text Available Melanoma is an aggressive neoplasia issued from the malignant transformation of melanocytes, the pigment-generating cells of the skin. It is responsible for about 75% of deaths due to skin cancers. Melanoma is a phenotypically and molecularly heterogeneous disease: cutaneous, uveal, acral, and mucosal melanomas have different clinical courses, are associated with different mutational profiles, and possess distinct risk factors. The discovery of the molecular abnormalities underlying melanomas has led to the promising improvement of therapy, and further progress is expected in the near future. The study of melanoma precursor lesions has led to the suggestion that the pathway of tumor evolution implies the progression from benign naevi, to dysplastic naevi, to melanoma in situ and then to invasive and metastatic melanoma. The gene alterations characterizing melanomas tend to accumulate in these precursor lesions in a sequential order. Studies carried out in recent years have, in part, elucidated the great tumorigenic potential of melanoma tumor cells. These findings have led to speculation that the cancer stem cell model cannot be applied to melanoma because, in this malignancy, tumor cells possess an intrinsic plasticity, conferring the capacity to initiate and maintain the neoplastic process to phenotypically different tumor cells.

  14. Non-malignant migration of B16 mouse melanoma cells in the neural crest and invasive growth in the eye cup of the chick embryo.

    Science.gov (United States)

    Oppitz, Matthias; Busch, Christian; Schriek, Gernot; Metzger, Marco; Just, Lothar; Drews, Ulrich

    2007-02-01

    Melanocytes originate from the neural crest. In a previous study, we observed that human SK-Mel 28 human melanoma cells resumed neural crest cell migration after transplantation into the chick embryo neural tube. Here, we used transgenic mouse B16-F1 melanoma cells transfected with green fluorescent protein-vasodilator-stimulated phosphoprotein construct to extend these observations. After the injection of a cell suspension into the trunk neural tube of E2 chick embryos, the migration of melanoma cells was followed by live fluorescence microscopy. Within 12 h, the melanoma cells formed clusters in the neural tube at the levels of the intersegmental clefts between somites. After 24 h, a segmental pattern of emigration was visible. Emigrated melanoma cells were identified in serial paraffin sections by immunohistochemistry with ab732 as a marker for melanoma cells and by in-situ hybridization of mouse-specific repetitive genomic sequence mL1. After 24 h, melanoma cells were found along the medial neural crest pathway and in the sympathetic trunk ganglia and, after 48 h, also in the lateral melanocytic pathway. During migration along the neural crest pathways, mouse melanoma cells underwent apoptosis, which was assessed by anti-caspase 3 and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling staining. To prove the ablation of malignant behavior after back-transplantation into the original embryonic neural crest environment, we injected the same cell suspension into the eye cup of the E3 embryo. In this location, invasive melanomas formed.

  15. [Clinical and histopathological characteristics of malignant melanoma cases seen at "Dr. Manuel Gea González" General Hospital].

    Science.gov (United States)

    Káram-Orantes, Marcia; Toussaint-Caire, Sonia; Domínguez-Cherit, Judith; Veja-Memije, Elisa

    2008-01-01

    Melanoma is a type of tumor that arises from melanocytes generally located in the dermoepidermal junction. Although melanoma is found in less than 10% of cases, mortality is high representing 75% of deaths attributed to cutaneous cancer. There are four major subtypes: Superficial spreading melanoma, lentigo malignant melanoma, acral lentiginous melanoma and nodular melanoma. Superficial spreading melanoma is the most common type among Caucasians. In a Mexican case series, the nodular type is the most common type reported. The aim of this study was to determine the most common type seen at our medical facility. We analyzed patient's medical records from March 1981 to December 2006. Demographic data included sex, age, place of residence, occupation, tumor progression, location and clinical description. Histologically we evaluated tumor thickness using the Breslow scale; invasion was measured using the Clark scale. This is a descriptive, cross-sectional and retrospective study. 165 patients were studied, 112 were females and 53 males. The most common location was the lower limb. Acral lentiginous melanoma was the most common subtype. Our findings differ from the other series where they report nodular and superficial spreading melanoma as the most common types. The most common subtypes in our study were acral lentiginous melanoma and lentigo malignant melanoma among females, with a ratio of female-male of 2.1:1.

  16. Risk of invasive melanoma in patients with rheumatoid arthritis treated with biologics

    DEFF Research Database (Denmark)

    Mercer, Louise K; Askling, Johan; Raaschou, Pauline

    2017-01-01

    with TNF inhibitors (TNFi), other biologic disease modifying drugs and non-biologic therapy. METHODS: Eleven biologic registers from nine European countries participated in this collaborative project. According to predefined exposure definitions, cohorts of patients with RA were selected. Using the country......: This large European collaborative project did not confirm an overall increased risk of melanoma following exposure to TNFi....

  17. Population exposure to ultraviolet radiation in Finland 1920-1995: Exposure trends and a time-series analysis of exposure and cutaneous melanoma incidence

    International Nuclear Information System (INIS)

    Kojo, Katja; Jansen, Christer T.; Nybom, Pia; Huurto, Laura; Laihia, Jarmo; Ilus, Taina; Auvinen, Anssi

    2006-01-01

    Ultraviolet radiation (UVR) is the principal cause of cutaneous malignant melanoma (CMM). However, the relation between CMM and UVR exposure is not clear. We present the trends of population exposure to UVR and conduct a time-series analysis of the relation between UVR exposure and incidence of CMM. Data on CMM incidence were obtained from the Finnish Cancer Registry. Clothing coverage of the body was scored from archival photographs and the proportion of uncovered skin was used as a measure of solar exposure. Information on the number of sunny resort holidays, duration of annual holidays, and sunscreen sales were obtained from various sources. Exposed skin area doubled from 1920 to 1985. The average duration of annual holidays increased 30-fold. The number of sunny resort holidays and the sales of sunscreens increased rapidly from 1980. CMM was most strongly associated with solar exposure of 5-19 years earlier. There is a considerable decrease in clothing coverage during the 20th century. UVR exposure preceding CMM occurrence 4 years or less does not appear relevant, whereas the period 5-19 years prior to CMM occurrence might be the most relevant period. However, findings of ecological studies may not be applicable at the individual level

  18. In vivo overexpression of tumstatin domains by tumor cells inhibits their invasive properties in a mouse melanoma model

    International Nuclear Information System (INIS)

    Pasco, Sylvie; Ramont, Laurent; Venteo, Lydie; Pluot, Michel; Maquart, Francois-Xavier; Monboisse, Jean-Claude

    2004-01-01

    Our previous studies demonstrated that a synthetic peptide encompassing residues 185-203 of the noncollagenous (NC1) domain of the α3 chain of type IV collagen, named tumstatin, inhibits in vitro melanoma cell proliferation and migration. In the present study, B16F1 melanoma cells were stably transfected to overexpress the complete tumstatin domain (Tum 1-232) or its C-terminal part, encompassing residues 185-203 (Tum 183-232). Tumstatin domain overexpression inhibited B16F1 in vitro cell proliferation, anchorage-independent growth, and invasive properties. For studying the in vivo effect of overexpression, representative clones were subcutaneously injected into the left side of C57BL6 mice. In vivo tumor growth was decreased by -60% and -56%, respectively, with B16F1 cells overexpressing Tum 1-232 or Tum 183-232 compared to control cells. This inhibitory effect was associated with a decrease of in vivo cyclin D1 expression. We also demonstrated that the overexpression of Tum 1-232 or Tum 183-232 induced an in vivo down-regulation of proteolytic cascades involving matrix metalloproteinases (MMPs), especially the production or activation of MMP-2, MMP-9, MMP-13, as well as MMP-14. The plasminogen activation system was also altered in tumors with a decrease of urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA) and a strong increase of plasminogen activator inhibitor-1 (PAI-1). Collectively, our results demonstrate that tumstatin or its C-terminal antitumor fragment, Tum 183-232, inhibits in vivo melanoma progression by triggering an intracellular transduction pathway, which involves a cyclic AMP (cAMP)-dependent mechanism

  19. Multiple Cutaneous (pre)-Malignancies

    NARCIS (Netherlands)

    R.J.T. van der Leest (Robert)

    2015-01-01

    markdownabstract__Abstract__ The three most common cutaneous malignancies are derived from melanocytes and keratinocytes (ordered in decreasing aggressiveness): melanoma, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). This thesis focuses only on these three types of cancer and

  20. NM23 deficiency promotes metastasis in a UV radiation-induced mouse model of human melanoma.

    Science.gov (United States)

    Jarrett, Stuart G; Novak, Marian; Harris, Nathan; Merlino, Glenn; Slominski, Andrezj; Kaetzel, David M

    2013-01-01

    Cutaneous malignant melanoma is the most lethal form of skin cancer, with 5-year survival rates of melanoma are not well understood, in part due to a paucity of animal models that accurately recapitulate the disease in its advanced forms. We have employed a transgenic mouse strain harboring a tandem deletion of the nm23-m1 and nm23-m2 genes to assess the combined contribution of these genes to suppression of melanoma metastasis. Crossing of the nm23-h1/nm23-h2 knockout in hemizygous-null form ([m1m2](+/-)) to a transgenic mouse strain (hepatocyte growth factor/scatter factor-overexpressing, or HGF(+) strain) vulnerable to poorly-metastatic, UVR-induced melanomas resulted in UVR-induced melanomas with high metastatic potential. Metastasis to draining lymph nodes was seen in almost all cases of back skin melanomas, while aggressive metastasis to lung, thoracic cavity, liver and bone also occurred. Interestingly, no differences were observed in the invasive characteristics of primary melanomas of HGF(+) and HGF(+) × [m1m2](+/-) strains, with both exhibiting invasion into the dermis and subcutis, indicating factors other than simple invasive activity were responsible for metastasis of HGF(+) × [m1m2](+/-) melanomas. Stable cell lines were established from the primary and metastatic melanoma lesions from these mice, with HGF(+) × [m1m2](+/-) lines exhibiting increased single cell migration and genomic instability. These studies demonstrate for the first time in vivo a potent metastasis suppressor activity of NM23 in UVR-induced melanoma, and have provided new tools for identifying molecular mechanisms that underlie melanoma metastasis.

  1. The initiator methionine tRNA drives cell migration and invasion leading to increased metastatic potential in melanoma

    Directory of Open Access Journals (Sweden)

    Joanna Birch

    2016-10-01

    Full Text Available The cell's repertoire of transfer RNAs (tRNAs has been linked to cancer. Recently, the level of the initiator methionine tRNA (tRNAiMet in stromal fibroblasts has been shown to influence extracellular matrix (ECM secretion to drive tumour growth and angiogenesis. Here we show that increased tRNAiMet within cancer cells does not influence tumour growth, but drives cell migration and invasion via a mechanism that is independent from ECM synthesis and dependent on α5β1 integrin and levels of the translation initiation ternary complex. In vivo and ex vivo migration (but not proliferation of melanoblasts is significantly enhanced in transgenic mice which express additional copies of the tRNAiMet gene. We show that increased tRNAiMet in melanoma drives migratory, invasive behaviour and metastatic potential without affecting cell proliferation and primary tumour growth, and that expression of RNA polymerase III-associated genes (which drive tRNA expression are elevated in metastases by comparison with primary tumours. Thus, specific alterations to the cancer cell tRNA repertoire drive a migration/invasion programme that may lead to metastasis.

  2. T-Cadherin Expression in Melanoma Cells Stimulates Stromal Cell Recruitment and Invasion by Regulating the Expression of Chemokines, Integrins and Adhesion Molecules

    Energy Technology Data Exchange (ETDEWEB)

    Rubina, Kseniya A., E-mail: rkseniya@mail.ru; Surkova, Ekaterina I.; Semina, Ekaterina V.; Sysoeva, Veronika Y.; Kalinina, Natalia I. [Department of Biochemistry and Molecular Medicine, Faculty of Medicine, M.V. Lomonosov Moscow State University, Lomonosovsky av., 31/5, Moscow 119192 (Russian Federation); Poliakov, Alexei A. [Division of Developmental Neurobiology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA (United Kingdom); Treshalina, Helena M. [Federal State Budgetary Scietific Institution «N.N. Blokhin Russian Cancer Research Center» (FSBSI “N.N.Blokhin RCRC”), Kashirskoe Shosse 24, Moscow 115478 (Russian Federation); Tkachuk, Vsevolod A. [Department of Biochemistry and Molecular Medicine, Faculty of Medicine, M.V. Lomonosov Moscow State University, Lomonosovsky av., 31/5, Moscow 119192 (Russian Federation)

    2015-07-21

    T-cadherin is a glycosyl-phosphatidylinositol (GPI) anchored member of the cadherin superfamily involved in the guidance of migrating cells. We have previously shown that in vivo T-cadherin overexpression leads to increased melanoma primary tumor growth due to the recruitment of mesenchymal stromal cells as well as the enhanced metastasis. Since tumor progression is highly dependent upon cell migration and invasion, the aim of the present study was to elucidate the mechanisms of T-cadherin participation in these processes. Herein we show that T-cadherin expression results in the increased invasive potential due to the upregulated expression of pro-oncogenic integrins, chemokines, adhesion molecules and extracellular matrix components. The detected increase in chemokine expression could be responsible for the stromal cell recruitment. At the same time our previous data demonstrated that T-cadherin expression inhibited neoangiogenesis in the primary tumors. We demonstrate that T-cadherin overexpression leads to the increase in the expression of anti-angiogenic molecules and reduction in pro-angiogenic factors. Thus, T-cadherin plays a dual role in melanoma growth and progression: T-cadherin expression results in anti-angiogenic effects in melanoma, however, this also stimulates transcription of genes responsible for migration and invasion of melanoma cells.

  3. Molecular Prognostic Markers in Uveal Melanoma: Expression Profiling and Genomic Studies

    NARCIS (Netherlands)

    W. Gils (Walter)

    2008-01-01

    textabstractUveal Melanomas (UMs) arise from melanocytes. This cell type originates from neural crest cells and thereby uveal melanomas share their origin with pheochromocytomas, neuroblastomas, paragangliomas and cutaneous melanomas, other tumors that develop from neural crest originating cells.

  4. Non-genetic risk factors for cutaneous melanoma and keratinocyte skin cancers: An umbrella review of meta-analyses.

    Science.gov (United States)

    Belbasis, Lazaros; Stefanaki, Irene; Stratigos, Alexander J; Evangelou, Evangelos

    2016-12-01

    Skin cancers have a complex disease mechanism, involving both genetic and non-genetic risk factors. Numerous meta-analyses have been published claiming statistically significant associations between non-genetic risk factors and skin cancers without applying a thorough methodological assessment. The present study maps the literature on the non-genetic risk factors of skin cancers, assesses the presence of statistical biases and identifies the associations with robust evidence. We searched PubMed up to January 20, 2016 to identify systematic reviews and meta-analyses of observational studies that examined associations between non-genetic factors and skin cancers. For each meta-analysis, we estimated the summary effect size by random-effects and fixed-effects models, the 95% confidence interval and the 95% prediction interval. We also assessed the between-study heterogeneity (I 2 metric), evidence for small-study effects and excess significance bias. Forty-four eligible papers were identified and included a total of 85 associations. Twenty-one associations were significant at Pmelanoma, skin type, sunburns, premalignant skin lesions, common and atypical nevi for melanoma) presented high level of credibility. The majority of meta-analyses on non-genetic risk factors for skin cancers suffered from large between-study heterogeneity and small-study effects or excess significance bias. The associations with convincing and highly suggestive evidence were mainly focused on skin photosensitivity and phenotypic characteristics. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  5. An Australian cohort of 210 patients with multiple invasive squamous cell carcinomas: risk factors and associated increased risk of melanoma and internal malignancies.

    Science.gov (United States)

    Banan, Parastoo; Marvi, Salman K; McMeniman, Erin; De'Ambrosis, Brian

    2016-02-01

    Patients with a history of non-melanoma skin cancer (NMSC) have a 50% risk of developing subsequent NMSC.(13) Currently there are limited data on the association between multiple squamous cell carcinomas (SCC) and the risk of other cancers, including melanomas. To assess the risk factors in a cohort of 210 Australians with a history of multiple invasive SCC, focusing on the association between multiple SCC and other cancers. Data were collected from patients of a private practice in south-east Queensland. A fair complexion and childhood sun exposure were found to be common in this cohort. Approximately half the patients who had their first SCC at or before the age of 30 years subsequently developed a melanoma. There was also an increased risk of internal cancer, prostate cancer being the commonest, followed by bowel and breast cancer. Patients with a history of multiple invasive SCC should be aware of their increased risk of future NMSC and of melanomas. The results of thisstudy suggest such patients and their care providers should also consider an appropriate screening for internal malignancies. © 2015 The Australasian College of Dermatologists.

  6. Sun exposure and skin cancer, and the puzzle of cutaneous melanoma: A perspective on Fears et al. Mathematical models of age and ultraviolet effects on the incidence of skin cancer among whites in the United States. American Journal of Epidemiology 1977; 105: 420-427.

    Science.gov (United States)

    Armstrong, Bruce K; Cust, Anne E

    2017-06-01

    Sunlight has been known as an important cause of skin cancer since around the turn of the 20th Century. A 1977 landmark paper of US scientists Fears, Scotto, and Schneiderman advanced a novel hypothesis whereby cutaneous melanoma was primarily caused by intermittent sun exposure (i.e. periodic, brief episodes of exposure to high-intensity ultraviolet radiation) while the keratinocyte cancers, squamous cell carcinoma and basal cell carcinoma, were primarily caused by progressive accumulation of sun exposure. With respect to cutaneous melanoma, this became known as the intermittent exposure hypothesis. The hypothesis stemmed from analysis of measured ambient ultraviolet radiation and age-specific incidence rates of melanoma and keratinocyte cancers collected as an extension to the US Third National Cancer Survey in several US States. In this perspective paper, we put this novel hypothesis into the context of knowledge at the time, and describe subsequent epidemiological and molecular research into melanoma that elaborated the intermittent exposure hypothesis and ultimately replaced it with a dual pathway hypothesis. Our present understanding is of two distinct biological pathways by which cutaneous melanoma might develop; a nevus prone pathway initiated by early sun exposure and promoted by intermittent sun exposure or possibly host factors; and a chronic sun exposure pathway in sun sensitive people who progressively accumulate sun exposure to the sites of future melanomas. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Pregnancy and early-stage melanoma

    NARCIS (Netherlands)

    Daryanani, D; Plukker, JT; De Hullu, JA; Kuiper, H; Nap, RE; Hoekstra, HJ

    2003-01-01

    BACKGROUND. Cutaneous melanomas are aggressive tumors with an unpredictable biologic behavior. It has been suggested that women who present with melanoma during pregnancy have a worse prognosis due to more aggressive behavior of the melanoma. The objective of the current study was to evaluate the

  8. Genetic prognostic factors in uveal melanoma

    NARCIS (Netherlands)

    Maat, Willem

    2012-01-01

    Uveal melanoma (UM) is the most common malignancy of the eye in adults and it is the second most common form of melanoma after cutaneous melanoma (CM). The identification of patients who have a high risk of developing metastases would allow the possibility of providing adjuvant therapies to prevent

  9. Voriconazole Exposure and Risk of Cutaneous Squamous Cell Carcinoma, Aspergillus Colonization, Invasive Aspergillosis and Death in Lung Transplant Recipients.

    Science.gov (United States)

    Mansh, M; Binstock, M; Williams, K; Hafeez, F; Kim, J; Glidden, D; Boettger, R; Hays, S; Kukreja, J; Golden, J; Asgari, M M; Chin-Hong, P; Singer, J P; Arron, S T

    2016-01-01

    Voriconazole is a triazole antifungal used to prevent and treat invasive fungal infections after lung transplantation, but it has been associated with an increased risk of developing cutaneous squamous cell carcinoma (SCC). Despite widespread use, there are no clear guidelines for optimal prophylactic regimens that balance the competing risks and benefits. We conducted a retrospective cohort study of all lung transplant recipients at the University of California, San Francisco, who were transplanted between October 1991 and December 2012 (n = 455) to investigate whether voriconazole exposure affected development of SCC, Aspergillus colonization, invasive aspergillosis and all-cause mortality. Voriconazole exposure was associated with a 73% increased risk of developing SCC (hazard ratio [HR] 1.73; 95% confidence interval [CI]: 1.04-2.88; p = 0.03), with each additional 30-day exposure at the standard dose increasing the risk by 3.0% (HR 1.03; 95% CI: 1.02-1.04; p Voriconazole exposure reduced risk of Aspergillus colonization by 50% (HR 0.50; 95% CI: 0.34-0.72; p Voriconazole exposure significantly reduced all-cause mortality among subjects who developed Aspergillus colonization (HR 0.34; 95% CI: 0.13-0.91; p = 0.03) but had no significant impact on those without colonization. Physicians should consider patient-specific factors that modify the potential risks and benefits of voriconazole for the care of lung transplant recipients. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  10. Characteristics, treatment, and survival of invasive malignant melanoma (MM) in giant pigmented nevi (GPN) in adults: 976 cases from the National Cancer Data Base (NCDB).

    Science.gov (United States)

    Turkeltaub, Ashley E; Pezzi, Todd A; Pezzi, Christopher M; Dao, Harry

    2016-06-01

    Malignant melanoma (MM) arising in a giant pigmented nevus (GPN) is a rare disease in adults with no large series published to our knowledge. We sought to describe the characteristics, treatment, and survival of MM in GPN for adults. Adults with invasive MM in GPN (n = 976) reported to the National Cancer Data Base from 1998 to 2012 were evaluated for patient and tumor characteristics, treatment, and survival. For comparison, data from adults with invasive superficial spreading melanoma (SSM) (n = 111,870) and nodular melanoma (n = 35,962) were used. Compared with patients with SSM, patients with MM in GPN had a thicker Breslow depth, more positive lymph nodes, and distant metastasis more frequently. Multivariate analysis identified age older than 65 years, Breslow thickness greater than 2 mm, presence of ulceration, presence of distant metastasis, and positive margins as independent predictors of survival in patients with MM in GPN. At all stages, having MM in GPN has similar overall survival compared with SSM. The study is retrospective and registry-based. Invasive MM in GPN occurs in adults, with overall survival similar to SSM. Clinicians should be aware of the continued risk of MM in adults with GPN with low threshold for biopsy. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  11. A clinicopathological study of malignant melanoma with special reference to atypical presentation

    Directory of Open Access Journals (Sweden)

    Mukhopadhyay Subhalakshmi

    2008-10-01

    Full Text Available Malignant melanoma is a tumor of melanocytic origin. Lymphatic and hematogenous metastases are common in this condition. Retrospective analysis was performed in 16 consecutive cases diagnosed histopathologically as malignant melanoma at the pathology department of a medial college in eastern India. 75% of the patients were male; majority of them was in their sixth decade. All (100% the lesions were pigmented. The primary site was known in all cases, except two (12.5%. Out of the 14 cases with known primary site 11 (78.57% were cutaneous melanomas, including one arising in labia minora, two (14.29% were ocular and one (7.14% was vaginal in origin. Among cutaneous melanomas, superficial spreading type was the commonest variety and mixed population of epithelioid and spindle cell was the commonest histopathological pattern. The commonest grade of invasion was grade III (Clark′s. The clinical presentation of the case of vaginal melanoma and the two cases of secondary melanomas, including the one with obscure primary tumor, were bewildering and hence are discussed separately.

  12. Identification of an Immunogenic Subset of Metastatic Uveal Melanoma.

    Science.gov (United States)

    Rothermel, Luke D; Sabesan, Arvind C; Stephens, Daniel J; Chandran, Smita S; Paria, Biman C; Srivastava, Abhishek K; Somerville, Robert; Wunderlich, John R; Lee, Chyi-Chia R; Xi, Liqiang; Pham, Trinh H; Raffeld, Mark; Jailwala, Parthav; Kasoji, Manjula; Kammula, Udai S

    2016-05-01

    Uveal melanoma is a rare melanoma variant with no effective therapies once metastases develop. Although durable cancer regression can be achieved in metastatic cutaneous melanoma with immunotherapies that augment naturally existing antitumor T-cell responses, the role of these treatments for metastatic uveal melanoma remains unclear. We sought to define the relative immunogenicity of these two melanoma variants and determine whether endogenous antitumor immune responses exist against uveal melanoma. We surgically procured liver metastases from uveal melanoma (n = 16) and cutaneous melanoma (n = 35) patients and compared the attributes of their respective tumor cell populations and their infiltrating T cells (TIL) using clinical radiology, histopathology, immune assays, and whole-exomic sequencing. Despite having common melanocytic lineage, uveal melanoma and cutaneous melanoma metastases differed in their melanin content, tumor differentiation antigen expression, and somatic mutational profile. Immunologic analysis of TIL cultures expanded from these divergent forms of melanoma revealed cutaneous melanoma TIL were predominantly composed of CD8(+) T cells, whereas uveal melanoma TIL were CD4(+) dominant. Reactivity against autologous tumor was significantly greater in cutaneous melanoma TIL compared with uveal melanoma TIL. However, we identified TIL from a subset of uveal melanoma patients which had robust antitumor reactivity comparable in magnitude with cutaneous melanoma TIL. Interestingly, the absence of melanin pigmentation in the parental tumor strongly correlated with the generation of highly reactive uveal melanoma TIL. The discovery of this immunogenic group of uveal melanoma metastases should prompt clinical efforts to determine whether patients who harbor these unique tumors can benefit from immunotherapies that exploit endogenous antitumor T-cell populations. Clin Cancer Res; 22(9); 2237-49. ©2015 AACR. ©2015 American Association for Cancer Research.

  13. Clinical characteristics, management and survival in young adults diagnosed with malignant melanoma: A population-based cohort study.

    Science.gov (United States)

    Plym, Anna; Ullenhag, Gustav J; Breivald, Mats; Lambe, Mats; Berglund, Anders

    2014-05-01

    Few studies to date have described the clinical features of malignant melanoma in young adulthood. Also, little is known about patterns of care in young patients. We examined and compared clinical characteristics, management and survival between young adult (15-39 years) and older adult melanoma patients in Central Sweden. Patients diagnosed with invasive malignant melanoma between 1997 and 2011 were identified in the Regional Quality Register of Cutaneous Malignant Melanoma in Central Sweden, a population-based register covering a source population of about two million. Data on clinical characteristics, management and survival were retrieved and compared according to age at diagnosis. Of 5915 patients included in the study, 584 (9.9%) were between 15 and 39 years of age at diagnosis. Compared with older patients, young adult patients were more likely to be female, with higher proportions of thin, non-ulcerated melanomas, superficial spreading melanoma and melanomas located on the lower extremity. Young adults had shorter waiting times for surgical procedures and a higher proportion received surgical treatment according to guidelines. Overall, young patients had better relative survival than older patients. Age-related survival differences varied by stage of disease at diagnosis, and were most prominent in stage II disease. The observed differences in clinical characteristics, management and survival between young adult and older melanoma patients call for an improved understanding of not only disease etiology but also factors driving management decisions. A better understanding of these differences may help improve care and prognosis for melanoma patients of all ages.

  14. Cutaneous invasive micropapillary carcinoma of probable apocrine sweat gland origin in a cat.

    Science.gov (United States)

    Machida, Yukino; Yoshimura, Hisashi; Nakahira, Rei; Michishita, Masaki; Ohkusu-Tsukada, Kozo; Takahashi, Kimimasa

    2011-07-01

    An invasive micropapillary carcinoma (IMC) occurred in the buccal skin of an 18-year-old female cat. Histologically, the tumor had a honeycomb pattern characterized by clusters of neoplastic epithelial cells that were surrounded by empty clear spaces and lined with fibrocollagenous stroma. On immunohistochemistry, the neoplastic cells were positive for cytokeratin (clone CAM5.2; pancytokeratin, clone AE1/AE3) and carcinoembryonic antigen (CEA) but negative for cytokeratin 14, vimentin, S100, smooth muscle actin, and p63. The CEA-positive staining reaction was present along the outermost rim of the neoplastic cell clusters consistent with an "inside-out" immunoreactivity pattern. Examination of the tumor cells by electron microscopy revealed microvilli on the outermost rim of neoplastic cells that were directed toward the surrounding vacant space. Based on histomorphological characteristics, the neoplasm was defined as an IMC of "pure-type." The location site and immunohistochemical features suggest the tumor was most likely derived from the apocrine sweat glands in the buccal skin.

  15. Incidence and survival in patients with cutaneous melanoma by morphology, anatomical site and TNM stage: a Danish Population-based Register Study 1989-2011.

    Science.gov (United States)

    Bay, Christiane; Kejs, Anne Mette Tranberg; Storm, Hans H; Engholm, Gerda

    2015-02-01

    The incidence of melanoma of the skin has risen in Denmark in recent decades, the increase being steeper from 2004. It is unclear whether this represents a true rise in incidence or whether it is caused by an increased awareness of the condition. To assess whether the increase was characterised by early-stage melanomas and a higher proportion of melanomas with superficial spreading morphology, we studied all skin melanoma patients registered in the Danish Cancer Register 1989-2011 (n=27,010) and followed up for death through 2013. Trends in age-standardised incidence by sex, subsite and morphology, relative survival, TNM stage distribution and stage-specific relative survival from 2004 were analysed. The incidence of melanoma more than doubled over 23 years. A steeper increase from 2004 was driven mainly by superficial spreading tumours, but the proportion of nodular melanomas in patients 50 years of age and over also increased significantly. The largest increase occurred for stage I tumours and for tumours on the trunk. From 1989-1993 to 2009-2011 the 5-year relative survival increased at 12% and 6% points for male and female patients, respectively. Greater awareness, and thus lower stage at diagnosis (mediated by a large skin cancer prevention campaign from 2007), might explain part of the increase, but the increase in nodular melanoma also points to a genuine increase in the risk of melanoma. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Unusual presentations of melanoma: melanoma of unknown primary site, melanoma arising in childhood, and melanoma arising in the eye and on mucosal surfaces.

    Science.gov (United States)

    Sondak, Vernon K; Messina, Jane L

    2014-10-01

    Most melanomas present as primary tumors on the skin surface in adults; however, melanomas also arise in the eye and on the mucosal surfaces or present as apparently metastatic disease without any known history of a cutaneous primary. Melanoma is also being diagnosed during childhood more frequently than ever. Surgeons need to be aware of and understand these unusual presentations of melanoma to optimally manage their patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Quantifying melanin distribution using pump-probe microscopy and a 2D morphological autocorrelation transformation for melanoma diagnosis

    Science.gov (United States)

    Robles, Francisco E.; Wilson, Jesse W.; Warren, Warren S.

    2014-03-01

    Pump-probe microscopy is a quantitative molecular imaging technique that yields diagnostically relevant information from endogenous pigments, like melanin, by probing their ultrafast photodynamic properties. Previously, the method was applied to image thin, pigmented, cutaneous samples at different stages of melanoma, and results have shown a correlation between melanin photodynamic behavior and malignancy. Here, we add to the diagnostic power of the method by applying principles of mathematical morphology to parameterize melanins' image structure. Along with bulk melanin chemical information, results show that this method can differentiate invasive melanomas from non-invasive and benign lesions with high sensitivity and specificity (92.3% and 97.5%, respectively, with N = 53). The mathematical method and the statistical analysis are described in detail and results from cutaneous and ocular conjuctival melanocytic lesions are presented.

  18. ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

    International Nuclear Information System (INIS)

    Ungerer, Christopher; Doberstein, Kai; Buerger, Claudia; Hardt, Katja; Boehncke, Wolf-Henning; Boehm, Beate; Pfeilschifter, Josef; Dummer, Reinhard; Mihic-Probst, Daniela; Gutwein, Paul

    2010-01-01

    Research highlights: → Strong ADAM15 expression is found in normal melanocytes. → ADAM15 expression is significantly downregulated in patients with melanoma metastasis. → TGF-β can downregulate ADAM15 expression in melanoma cells. → Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. → Conclusion: ADAM15 represents an tumor suppressor protein in melanoma. -- Abstract: In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-γ and TGF-β downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.

  19. ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Ungerer, Christopher; Doberstein, Kai [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany); Buerger, Claudia; Hardt, Katja; Boehncke, Wolf-Henning [Department of Dermatology, Clinic of the Goethe-University, Theodor-Stern-Kai, Frankfurt (Germany); Boehm, Beate [Division of Rheumatology, Goethe University, Frankfurt am Main (Germany); Pfeilschifter, Josef [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany); Dummer, Reinhard [Department of Pathology, Institute of Surgical Pathology, University Hospital, Zurich (Switzerland); Mihic-Probst, Daniela [Department of Dermatology, University Hospital Zurich (Switzerland); Gutwein, Paul, E-mail: p.gutwein@med.uni-frankfurt.de [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany)

    2010-10-22

    Research highlights: {yields} Strong ADAM15 expression is found in normal melanocytes. {yields} ADAM15 expression is significantly downregulated in patients with melanoma metastasis. {yields} TGF-{beta} can downregulate ADAM15 expression in melanoma cells. {yields} Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. {yields} Conclusion: ADAM15 represents an tumor suppressor protein in melanoma. -- Abstract: In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-{gamma} and TGF-{beta} downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.

  20. Casticin impairs cell migration and invasion of mouse melanoma B16F10 cells via PI3K/AKT and NF-κB signaling pathways.

    Science.gov (United States)

    Shih, Yung-Luen; Chou, Hsiao-Min; Chou, Hsiu-Chen; Lu, Hsu-Feng; Chu, Yung-Lin; Shang, Hung-Sheng; Chung, Jing-Gung

    2017-09-01

    Casticin, a polymethoxyflavone, is one of the major active components obtained from Fructus viticis, which have been shown to have anticancer activities including induce cell apoptosis in human cancer cells. The aim of this study was to investigate the molecular mechanisms by which casticin inhibits cell migration and invasion of mouse melanoma B16F10 cells. Cell viability was examined by MTT assay and the results indicated that casticin decreased the total percentages of viable cells in dose-dependent manners. Casticin affected cell migration and invasion in B16F10 cells were examined by wound healing mobility assay and Boyden chamber migration and invasion assay and results indicated that casticin inhibited cell migration and invasion in dose-dependent manners. Western blotting was used to examine the protein expression of B16F10 cells after exposed to casticin and the results showed that casticin decreased the expressions of MMP-9, MMP-2, MMP-1, FAK, 14-3-3, GRB2, Akt, NF-κB p65, SOS-1, p-EGFR, p-JNK 1/2, uPA, and Rho A in B16F10 cells. Furthermore, cDNA microarray assay was used to show that casticin affected associated gene expression of cell migration and invasion and the results indicated that casticin affected some of the gene expression such as increased SCN1B (cell adhesion molecule 1) and TIMP2 (TIMP metallopeptidase inhibitor 2) and decreased NDUFS4 (NADH dehydrogenase (ubiquinone) Fe-S protein4), VEGFA (vascular endothelial growth factor A), and DDIT3 (DNA-damage-inducible transcript 3) which associated cell migration and invasion in B16F10 cells. Based on those observations, we suggest that casticin could be used as a novel anticancer metastasis of melanoma cancer in the future. © 2017 Wiley Periodicals, Inc.

  1. Is initial excision of cutaneous melanoma by General Practitioners (GPs) dangerous? Comparing patient outcomes following excision of melanoma by GPs or in hospital using national datasets and meta-analysis.

    Science.gov (United States)

    Murchie, Peter; Amalraj Raja, Edwin; Brewster, David H; Iversen, Lisa; Lee, Amanda J

    2017-11-01

    Melanomas are initially excised in primary care, and rates vary internationally. Until now, there has been no strong evidence one way or the other that excising melanomas in primary care is safe or unsafe. European guidelines make no recommendations, and the United Kingdom (UK) melanoma guidelines require all suspicious skin lesions to be initially treated in secondary care based on an expert consensus, which lacks supporting evidence, that primary care excision represents substandard care. Despite this, studies have found that up to 20% of melanomas in the UK are excised by general practitioners (GPs). Patients receiving primary care melanoma excision may fear that their care is substandard and their long-term survival threatened, neither of which may be justified. Scottish cancer registry data from 9367 people diagnosed with melanoma in Scotland between 2005 and 2013 were linked to pathology records, hospital data and death records. A Cox proportional hazards regression analysis, adjusting for key confounders, explored the association between morbidity and mortality and setting of primary melanoma excision (primary versus secondary care). A pooled estimate of the relative hazard of death of having a melanoma excised in primary versus secondary care including 7116 patients from a similar Irish study was also performed. The adjusted hazard ratio (95% CI) of death from melanoma for those having primary care excision was 0.82 (0.61-1.10). Those receiving primary care excision had a median (IQR) of 8 (3-14) out-patient attendances compared to 10 (4-17) for the secondary care group with an adjusted relative risk (RR) (95% CI) of 0.98 (0.96-1.01). Both groups had a median of 1 (0-2) hospital admissions with an adjusted rate ratio of 1.05 (0.98-1.13). In the meta-analysis, with primary care as the reference, the pooled adjusted hazard ratio (HR, 95% CI) was 1.26 (1.07-1.50) indicating a significantly higher all-cause mortality among those with excision in secondary care

  2. Transformation of a Silent Adrencorticotrophic Pituitary Tumor Into Central Nervous System Melanoma

    Directory of Open Access Journals (Sweden)

    Brandon A. Miller MD, PhD

    2013-06-01

    Full Text Available Silent adrenocorticotrophic pituitary adenomas are nonfunctioning pituitary adenomas that express adrenocorticotrophic hormone (ACTH but do not cause the clinical or laboratory features of hypercortisolemia. Primary central nervous system (CNS melanoma is well documented, but rarely originates in the sellar region or pituitary gland. Here we report transformation of an aggressive silent adrenocorticotrophic pituitary adenoma that transformed into CNS melanoma and review other presentations of pituitary melanoma. A 37-year-old woman initially presented with apoplexy and an invasive nonfunctioning pituitary macroadenoma for which she underwent transphenoidal surgery. The patient underwent 3 subsequent surgeries as the tumor continued to progress. Pathology from the first 3 operations showed pituitary adenoma or carcinoma. Pathology from the final surgery showed melanoma and the magnetic resonance imaging characteristics of the tumor had changed to become consistent with CNS melanoma. Dermatologic and ophthalmologic examinations did not identify cutaneous or ocular melanoma. The patient’s disease progressed despite aggressive surgical, medical and radiologic treatment. To our knowledge, this is the first report demonstrating transformation of a primary pituitary tumor into melanoma. The mechanism of tumor transformation is unclear, but it is possible that a mutation in the original ACTH-producing tumor lead to increased cleavage of pro-opiomelanocortin or ACTH into α-melanocyte-stimulating hormone, which in turn stimulated the expression of microopthalmia transcription factor, leading to melanocytic phenotype transformation.

  3. Recommendations for Solid Organ Transplantation for Transplant Candidates With a Pretransplant Diagnosis of Cutaneous Squamous Cell Carcinoma, Merkel Cell Carcinoma and Melanoma: A Consensus Opinion From the International Transplant Skin Cancer Collaborative (ITSCC).

    Science.gov (United States)

    Zwald, F; Leitenberger, J; Zeitouni, N; Soon, S; Brewer, J; Arron, S; Bordeaux, J; Chung, C; Abdelmalek, M; Billingsley, E; Vidimos, A; Stasko, T

    2016-02-01

    Advancements in solid organ transplantation successfully extend the lives of thousands of patients annually. The tenet of organ stewardship aims to prevent the futile expenditure of scarce donor organs in patient populations with high mortality risk, to the detriment of potential recipients with greater predicted life expectancy. The development of skin cancer posttransplantation portends tremendous morbidity, adversely affecting quality of life for many transplant recipients. This special article, provided by of members of the International Transplant Skin Cancer Collaborative (ITSCC), will provide the transplant professional with a consensus opinion and recommendations as to an appropriate wait period pretransplantation for transplant candidates with a history of either cutaneous squamous cell carcinoma, malignant melanoma, or Merkel cell carcinoma. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  4. Primary malignant melanoma

    Directory of Open Access Journals (Sweden)

    A. Ferhat Mısır

    2016-04-01

    Full Text Available Malignant melanomas (MM of the oral cavity are extremely rare, accounting for 0.2% to 8.0% of all malignant melanomas. Malignant melanomas is more frequently seen at the level of the hard palate and gingiva. Early diagnosis and treatment are important for reducing morbidity. Malignant melanoma cells stain positively with antibodies to human melanoma black 45, S-100 protein, and vimentin; therefore, immunohistochemistry can play an important role in evaluating the depth of invasion and the location of metastases. A 76-year-old man developed an oral malignant melanoma, which was originally diagnosed as a bluish reactive denture hyperplasia caused by an ill-fitting lower denture. The tumor was removed surgically, and histopathological examination revealed a nodular-type MM. There was no evidence of recurrence over a 4-year follow-up period.

  5. Targeting antisense mitochondrial ncRNAs inhibits murine melanoma tumor growth and metastasis through reduction in survival and invasion factors.

    Science.gov (United States)

    Lobos-González, Lorena; Silva, Verónica; Araya, Mariela; Restovic, Franko; Echenique, Javiera; Oliveira-Cruz, Luciana; Fitzpatrick, Christopher; Briones, Macarena; Villegas, Jaime; Villota, Claudio; Vidaurre, Soledad; Borgna, Vincenzo; Socias, Miguel; Valenzuela, Sebastián; Lopez, Constanza; Socias, Teresa; Varas, Manuel; Díaz, Jorge; Burzio, Luis O; Burzio, Verónica A

    2016-09-06

    We reported that knockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptotic death of several human tumor cell lines, but not normal cells, suggesting this approach for selective therapy against different types of cancer. In order to translate these results to a preclinical scenario, we characterized the murine noncoding mitochondrial RNAs (ncmtRNAs) and performed in vivo knockdown in syngeneic murine melanoma models. Mouse ncmtRNAs display structures similar to the human counterparts, including long double-stranded regions arising from the presence of inverted repeats. Knockdown of ASncmtRNAs with specific antisense oligonucleotides (ASO) reduces murine melanoma B16F10 cell proliferation and induces apoptosis in vitro through downregulation of pro-survival and metastasis markers, particularly survivin. For in vivo studies, subcutaneous B16F10 melanoma tumors in C57BL/6 mice were treated systemically with specific and control antisense oligonucleotides (ASO). For metastasis studies, tumors were resected, followed by systemic administration of ASOs and the presence of metastatic nodules in lungs and liver was assessed. Treatment with specific ASO inhibited tumor growth and metastasis after primary tumor resection. In a metastasis-only assay, mice inoculated intravenously with cells and treated with the same ASO displayed reduced number and size of melanoma nodules in the lungs, compared to controls. Our results suggest that ASncmtRNAs could be potent targets for melanoma therapy. To our knowledge, the ASncmtRNAs are the first potential non-nuclear targets for melanoma therapy.

  6. Differing Efficacies of Lead Group A Streptococcal Vaccine Candidates and Full-Length M Protein in Cutaneous and Invasive Disease Models

    Directory of Open Access Journals (Sweden)

    Tania Rivera-Hernandez

    2016-06-01

    Full Text Available Group A Streptococcus (GAS is an important human pathogen responsible for both superficial infections and invasive diseases. Autoimmune sequelae may occur upon repeated infection. For this reason, development of a vaccine against GAS represents a major challenge, since certain GAS components may trigger autoimmunity. We formulated three combination vaccines containing the following: (i streptolysin O (SLO, interleukin 8 (IL-8 protease (Streptococcus pyogenes cell envelope proteinase [SpyCEP], group A streptococcal C5a peptidase (SCPA, arginine deiminase (ADI, and trigger factor (TF; (ii the conserved M-protein-derived J8 peptide conjugated to ADI; and (iii group A carbohydrate lacking the N-acetylglucosamine side chain conjugated to ADI. We compared these combination vaccines to a “gold standard” for immunogenicity, full-length M1 protein. Vaccines were adjuvanted with alum, and mice were immunized on days 0, 21, and 28. On day 42, mice were challenged via cutaneous or subcutaneous routes. High-titer antigen-specific antibody responses with bactericidal activity were detected in mouse serum samples for all vaccine candidates. In comparison with sham-immunized mice, all vaccines afforded protection against cutaneous challenge. However, only full-length M1 protein provided protection in the subcutaneous invasive disease model.

  7. TCGA study of genetic drivers of melanoma

    Science.gov (United States)

    A comprehensive analysis of the genome of cutaneous melanoma has provided new insights into the roles of frequently mutated cancer genes and other genomic alterations that drive the development of this disease.

  8. Do polychlorinated biphenyls cause cancer? A systematic review and meta-analysis of epidemiological studies on risk of cutaneous melanoma and non-Hodgkin lymphoma.

    Science.gov (United States)

    Zani, Claudia; Ceretti, Elisabetta; Covolo, Loredana; Donato, Francesco

    2017-09-01

    In 2015 a IARC Working Group upgraded the classification of PCBs to Group 1 "Carcinogenic to humans", also on the basis of evidence from epidemiological studies showing an excess risk for melanoma. Increased risks for non-Hodgkin lymphoma (NHL) and breast cancer were also reported though the evidence was limited. However, some recent reviews of studies on PCB exposure and risk of cancer provided discrepant findings. Therefore, we re-evaluated the association between exposure to PCBs and risk of melanoma and NHL by a systematic review and meta-analysis. We retrieved 11 independent cohort studies on occupationally exposed workers. About half of them showed increased standardized mortality or incidence ratios (SMRs or SIRs) for melanoma and none for NHL. The pooled SMRs were 1.32 (95% CI: 1.05-1.64) for melanoma and 0.94 (0.73-1.23) for NHL. Among population-based cohort and case-control studies with individual measures of PCB exposure, one only study was carried out on PCB exposure and melanoma, showing an odds ratio (OR) of 6.0 (2.0-18.2) for the highest compared to lowest quartile of PCB distribution. 13 cohort and case-control studies evaluated the association between NHL and PCB concentration in blood or subcutaneous fat, with summary OR = 1.5 (1.1-1.7) for the highest vs lowest quantile of PCB distribution. However, two cohort studies on people intoxicated by rice oil containing PCBs found no excess of deaths for skin cancer and inconsistent results for NHL. In conclusion, these findings do not provide a strong evidence that PCB exposure can increase the risk of melanoma and NHL in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Sentinel lymph node biopsy has no benefit for patients with primary cutaneous melanoma metastatic to a lymph node: an assertion based on comprehensive, critical analysis: part I.

    Science.gov (United States)

    Medalie, N S; Ackerman, A Bernard

    2003-10-01

    The thesis is set forth in this treatise that there is no place in the routine practice of medicine for the procedure for melanoma known conventionally and universally as sentinel node biopsy. Our assertion is based on assessment of the extensive body of literature devoted to the subject of treatment of melanoma before any metastasis has manifested itself clinically and of that dedicated to therapy for overt metastatic melanoma by a variety of modalities, chief among those addressed here being elective lymph node dissection and sentinel lymph node biopsy. In this era of sentinel lymph node biopsy, elective lymph node dissection has been modified to include only patients with metastasis of melanoma to lymph nodes, a procedure now termed "selective complete lymph node dissection." Among adjuvant medical therapies, the most popular today is interferon alpha-2B. Critical, incisive scrutiny of the literature leads to the conclusion, incontrovertibly, that elective lymph node dissection has no benefit for a patient and that all modifications of it also are devoid of value. The reason, logically, for the lack of utility of elective lymph node dissection becomes apparent by virtue of the route taken by cells of melanoma as they metastasize; those cells proceed in the same fashion as does lymph, bacteria, foreign material (including vital dyes and radioactive tracers), and other kinds of cells, to wit, by passing rapidly through nodes, including the sentinel one, and even bypassing entirely the nodes. In reality, cells of metastatic melanoma are not held up in nodes for any significant period of time, contrary to what is asserted repeatedly, but without any basis in fact, by many students of the subject. Moreover, not a single adjuvant medical therapy available currently is effective against metastatic melanoma and, therefore, none of them should be invoked to justify performance of sentinel node biopsy. Even if the sentinel node is found to house cells of melanoma, which

  10. Inhibition of proliferation and invasion in 2D and 3D models by 2-methoxyestradiol in human melanoma cells.

    Science.gov (United States)

    Massaro, R R; Faião-Flores, F; Rebecca, V W; Sandri, S; Alves-Fernandes, D K; Pennacchi, P C; Smalley, K S M; Maria-Engler, S S

    2017-05-01

    Despite the recent advances in the clinical management of melanoma, there remains a need for new pharmacological approaches to treat this cancer. 2-methoxyestradiol (2ME) is a metabolite of estrogen that has shown anti-tumor effects in many cancer types. In this study we show that 2ME treatment leads to growth inhibition in melanoma cells, an effect associated with entry into senescence, decreased pRb and Cyclin B1 expression, increased p21/Cip1 expression and G2/M cell cycle arrest. 2ME treatment also inhibits melanoma cell growth in colony formation assay, including cell lines with acquired resistance to BRAF and BRAF+MEK inhibitors. We further show that 2ME is effective against melanoma with different BRAF and NRAS mutational status. Moreover, 2ME induced the retraction of cytoplasmic projections in a 3D spheroid model and significantly decreased cell proliferation in a 3D skin reconstruct model. Together our studies bring new insights into the mechanism of action of 2ME allowing melanoma targeted therapy to be further refined. Continued progress in this area is expected to lead to improved anti-cancer treatments and the development of new and more effective clinical analogues. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Topical treatment of melanoma skin metastases with Imiquimod: a review

    OpenAIRE

    Sisti, Andrea; Sisti, Giovanni; Oranges, Carlo Maria

    2015-01-01

    Background: At present, case studies are the only source of results on imiquimod (IMQ) as monotherapy in cutaneous metastases from melanoma. We analyzed these studies in the literature with the aim to review the efficacy of IMQ as topical treatment for melanoma skin metastases. Objective: The aim of our review was to critically assess the studies evaluating the monotherapy with IMQ cream in the treatment of cutaneous metastases from melanoma.  Methods: A PubMed search was conducted using the ...

  12. Detection of novel quantitative trait loci for cutaneous melanoma by genome-wide scan in the MeLiM swine model

    Czech Academy of Sciences Publication Activity Database

    Du, Z. Q.; Vincent-Naulleau, S.; Gilbert, H.; Vignoles, F.; Créchet, F.; Shimogiri, T.; Yasue, H.; Leplat, J. J.; Bouet, S.; Gruand, J.; Horák, Vratislav; Milan, D.; Le Roy, P.; Geffrotin, C.

    2006-01-01

    Roč. 120, - (2006), s. 303-320 ISSN 0020-7136 Institutional research plan: CEZ:AV0Z50450515 Keywords : swine melanoma * quantitative trait loci * MC1R Subject RIV: FD - Oncology ; Hematology Impact factor: 4.693, year: 2006

  13. Up-to-date survival estimates and historical trends of cutaneous malignant melanoma in the south-east of The Netherlands

    NARCIS (Netherlands)

    E. de Vries (Esther); S. Houterman (Saskia); M.L.G. Janssen-Heijnen (Maryska); T.E.C. Nijsten (Tamar); S.A.M. van de Schans (Saskia); A.M.M. Eggermont (Alexander); J.W.W. Coebergh (Jan Willem)

    2007-01-01

    textabstractBackground: We present survival outcomes of patients registered in the Dutch population-based Eindhoven Cancer Registry (ECR). Patients and methods: Data on patients diagnosed with a melanoma between 1980 and 2002 were obtained from the ECR. Data on vital status up to 1 January 2005 were

  14. Immunotherapy of metastatic melanoma by reversal of immune suppression

    Energy Technology Data Exchange (ETDEWEB)

    Biggs, M.W.; Eiselein, J.E.

    1997-01-01

    Beginning with the observation that the human enteorvirus, Poliovirus Sabin 1, will lyse human melanoma cells in culture, clinical trials involving two patients with advance melanoma were performed. Parenteral injection of the viable Poliovirus into cutaneous melanoma metastases followed in 24 hours by oral administration of cyclophosphamide. The results of these two trials are described.

  15. MicroRNA Expression Profile in Conjunctival Melanoma

    DEFF Research Database (Denmark)

    Larsen, Ann-Cathrine; Mikkelsen, Lauge H.; Borup, Rehannah

    2016-01-01

    Purpose: Conjunctival melanoma (CM) is a rare disease associated with considerable mortality. As opposed to cutaneous melanoma, the epigenetic mechanisms involved in the development of CM and other mucosal melanomas (MMs) are unclear. The purpose of this study was to identify tumor-specific and p...

  16. Epidermotropic metastatic melanoma with perilesional depigmentation in an Indian male

    Directory of Open Access Journals (Sweden)

    Bhavana Doshi

    2013-01-01

    Full Text Available Melanoma is a rare form of cutaneous malignancy encountered in the dark skin population. Epidermotropic metastatic melanoma is a rare form of cutaneous metastatic melanoma which can mimic primary melanoma on histopathology. Hence its differentiation is of immense prognostic importance. The occurrence of rim of depigmentation around the primary cutaneous melanoma has previously been reported to portend a bad prognosis. The occurrence of vitiligo like lesions in patients with metastatic melanoma in comparison has a better prognosis. However the occurrence of depigmentation around the secondaries is rare and its importance is not well known. Hence we wish to report a case of epidermotropic metastatic melanoma with perilesional depigmentation in a 78 year old Indian male.

  17. Novel biomarkers and therapeutic targets for optimizing the therapeutic management of melanomas.

    Science.gov (United States)

    Mimeault, Murielle; Batra, Surinder K

    2012-03-10

    Cutaneous malignant melanoma is the most aggressive form of skin cancer with an extremely poor survival rate for the patients diagnosed with locally invasive and metastatic disease states. Intensive research has led in last few years to an improvement of the early detection and curative treatment of primary cutaneous melanomas that are confined to the skin by tumor surgical resection. However, locally advanced and disseminated melanomas are generally resistant to conventional treatments, including ionizing radiation, systemic chemotherapy, immunotherapy and/or adjuvant stem cell-based therapies, and result in the death of patients. The rapid progression of primary melanomas to locally invasive and/or metastatic disease states remains a major obstacle for an early effective diagnosis and a curative therapeutic intervention for melanoma patients. Importantly, recent advances in the melanoma research have led to the identification of different gene products that are often implicated in the malignant transformation of melanocytic cells into melanoma cells, including melanoma stem/progenitor cells, during melanoma initiation and progression to locally advanced and metastatic disease states. The frequent deregulated genes products encompass the oncogenic B-RafV600E and N-RasQ61R mutants, different receptor tyrosine kinases and developmental pathways such as epidermal growth factor receptor (EGFR), stem cell-like factor (SCF) receptor KIT, hedgehog, Wnt/β-catenin, Notch, stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4) and vascular endothelial growth factor (VEGF)/VEGFR receptor. These growth factors can cooperate to activate distinct tumorigenic downstream signaling elements and epithelial-mesenchymal transition (EMT)-associated molecules, including phosphatidylinositol 3'-kinase (PI3K)/Akt/ molecular target of rapamycin (mTOR), nuclear factor-kappaB (NF-κB), macrophage inhibitory cytokine-1 (MIC-1), vimentin, snail and twist. Of therapeutic

  18. Umbilicus reconstruction after melanoma excision

    Directory of Open Access Journals (Sweden)

    Miguel Costa-Silva

    2017-01-01

    Full Text Available An 81-year-old woman was admitted with a nodular cutaneous melanoma of the abdominal wall involving the umbilicus. After performing wide excision with 2 cm margin of the melanoma, umbilical reconstruction and defect closure were planned. After careful consideration, we decided to use an island pedicle flap which allowed closure of the defect and reconstruction of the umbilicus.

  19. FHOD1 formin is upregulated in melanomas and modifies proliferation and tumor growth

    Energy Technology Data Exchange (ETDEWEB)

    Peippo, Minna, E-mail: minna.peippo@utu.fi [Department of Pathology and Forensic Medicine, University of Turku and Turku University Hospital, Turku (Finland); MediCity Research Laboratory, University of Turku (Finland); Gardberg, Maria, E-mail: maria.gardberg@utu.fi [Department of Pathology and Forensic Medicine, University of Turku and Turku University Hospital, Turku (Finland); Lamminen, Tarja, E-mail: tarja.lamminen@utu.fi [Department of Pathology and Forensic Medicine, University of Turku and Turku University Hospital, Turku (Finland); MediCity Research Laboratory, University of Turku (Finland); Kaipio, Katja, E-mail: katja.kaipio@utu.fi [Department of Pathology and Forensic Medicine, University of Turku and Turku University Hospital, Turku (Finland); MediCity Research Laboratory, University of Turku (Finland); Carpén, Olli, E-mail: olli.carpen@utu.fi [Department of Pathology and Forensic Medicine, University of Turku and Turku University Hospital, Turku (Finland); Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki (Finland); Heuser, Vanina D., E-mail: vanina.heuser@utu.fi [Department of Pathology and Forensic Medicine, University of Turku and Turku University Hospital, Turku (Finland); MediCity Research Laboratory, University of Turku (Finland)

    2017-01-01

    The functional properties of actin-regulating formin proteins are diverse and in many cases cell-type specific. FHOD1, a formin expressed predominantly in cells of mesenchymal lineage, bundles actin filaments and participates in maintenance of cell shape, migration and cellular protrusions. FHOD1 participates in cancer-associated epithelial to mesenchymal transition (EMT) in oral squamous cell carcinoma and breast cancer. The role of FHOD1 in melanomas has not been characterized. Here, we show that FHOD1 expression is typically strong in cutaneous melanomas and cultured melanoma cells while the expression is low or absent in benign nevi. By using shRNA to knockdown FHOD1 in melanoma cells, we discovered that FHOD1 depleted cells are larger, rounder and have smaller focal adhesions and inferior migratory capacity as compared to control cells. Importantly, we found FHOD1 depleted cells to have reduced colony-forming capacity and attenuated tumor growth in vivo, a finding best explained by the reduced proliferation rate caused by cell cycle arrest. Unexpectedly, FHOD1 depletion did not prevent invasive growth at the tumor margins. These results suggest that FHOD1 participates in key cellular processes that are dysregulated in malignancy, but may not be essential for melanoma cell invasion.

  20. RARE METASTASES OF MALIGNANT MELANOMA

    Directory of Open Access Journals (Sweden)

    Marija Trenkić-Božinović

    2014-09-01

    Full Text Available Melanomas are malignant neoplasms that originate from melanocytes. The most common are on the skin and mucous membranes. Choroidal melanomas are quite different from cutaneous melanomas with regard to presentation, metastases, and treatment. We report two cases of metastatic gastric malignant melanoma of the eye and skin, with reference to the literature. The first patient was a woman aged 23 years, who underwent gastrectomy 22 months after enucleation of the eye due to malignant choroid melanoma. The second patient was a man, 72 years old, who underwent surgery 28 months before because of malignant melanoma of the skin of the forehead. Paraffin sections, 4 μm thick were stained using a classic method, as well as immunohistochemical DAKO APAAP method, using a specific S - 100 antibody and Melan A antibodies. The stomach is considered a rare place for the development of metastases. Metastases in the stomach are often limited to the submucosal as well as the serousmuscular layer, as noted in one of our patients. Metastatic melanoma of the gastrointestinal tract should be suspected in any patient with a history of malignant melanoma and new gastrointestinal symptoms. Because of the similarity between certain common histopathological types of malignant melanoma, primarily achromatic, and types of primary cancers of the stomach, the following immunohistochemical studies are needed: Melan A and S - 100 protein ( markers of malignant melanoma , as well as mucins: MUC5AC, MUC2 and CDX2 ( markers of different types of primary gastric carcinoma.

  1. Prospective study of melanoma in the Paris Region in 2004

    Energy Technology Data Exchange (ETDEWEB)

    Souques, M.; Baccard, M.; Barrazza, V.; Havard, S.; Verrier, A.; Wechsler, J. [Prevention et Epidemiologie des Tumeurs en Region Ile de France (PETRI), Domus Medica, 75 - Paris (France)

    2006-07-01

    Introduction: Melanoma remains an important public health problem because of its increasing incidence and its responsibility for the deaths of young individuals. A first study was carried out by the P.E.T.R.I. association in 1994 to estimate the incidence of melanoma in the Paris region. A second one was carried out in 2004, with the same methodology, to estimate the increase of melanoma incidence in the Paris region and the main clinical and histological characteristics of these cancers, comparing to 1994 data. Methodology: Every pathologist of the region has been contacted to fill a questionnaire for each primary cutaneous melanoma excised between January 1. and December 31. 2004, from patients living in the Paris region (departments 75, 77, 91, 92, 93, 94, 95). The information requested included melanoma characteristics (localisation, type, Breslow thickness, Clark level, regression signs, pre existence of a nevus) and demographic data (age, sex, zip code of residence). Results: 98 % of pathologists in the region agree to participate in the study. They send 1453 questionnaires, among them 160 were excluded (double, non cutaneous melanoma, secondary lesion, non resident in the region, diagnoses out of the inclusion dates, biopsy followed by exeresis). The analyse included 1293 lesions in 1269 patients. More than 2/3 of diagnoses were confirmed by 2 laboratories and 10 laboratories (on 98) reported 86 % of the diagnoses. Incidence:The crude incidence of melanoma in the Paris region during 2004 was 11.4 cases per 100 000 inhabitants, by sex:11.1 per 100 000 males and 12.4 cases per 100 000 females. The sex ratio men/women was 0.82. The crude incidence of invasive melanoma (Clark 2 to 5) was 8,9 cases per 100 000 inhabitants, 9,2 per 100 000 women and 8,6 per 100 000 men, with a sex ratio men/women of 0,93. Demographic characteristics: Melanoma diagnosis was more often in women (54.9 %) than in men (45.1 %). The patients mean age was 59.3 years (S.D.: 17.3). The

  2. Prospective study of melanoma in the Paris Region in 2004

    International Nuclear Information System (INIS)

    Souques, M.; Baccard, M.; Barrazza, V.; Havard, S.; Verrier, A.; Wechsler, J.

    2006-01-01

    Introduction: Melanoma remains an important public health problem because of its increasing incidence and its responsibility for the deaths of young individuals. A first study was carried out by the P.E.T.R.I. association in 1994 to estimate the incidence of melanoma in the Paris region. A second one was carried out in 2004, with the same methodology, to estimate the increase of melanoma incidence in the Paris region and the main clinical and histological characteristics of these cancers, comparing to 1994 data. Methodology: Every pathologist of the region has been contacted to fill a questionnaire for each primary cutaneous melanoma excised between January 1. and December 31. 2004, from patients living in the Paris region (departments 75, 77, 91, 92, 93, 94, 95). The information requested included melanoma characteristics (localisation, type, Breslow thickness, Clark level, regression signs, pre existence of a nevus) and demographic data (age, sex, zip code of residence). Results: 98 % of pathologists in the region agree to participate in the study. They send 1453 questionnaires, among them 160 were excluded (double, non cutaneous melanoma, secondary lesion, non resident in the region, diagnoses out of the inclusion dates, biopsy followed by exeresis). The analyse included 1293 lesions in 1269 patients. More than 2/3 of diagnoses were confirmed by 2 laboratories and 10 laboratories (on 98) reported 86 % of the diagnoses. Incidence:The crude incidence of melanoma in the Paris region during 2004 was 11.4 cases per 100 000 inhabitants, by sex:11.1 per 100 000 males and 12.4 cases per 100 000 females. The sex ratio men/women was 0.82. The crude incidence of invasive melanoma (Clark 2 to 5) was 8,9 cases per 100 000 inhabitants, 9,2 per 100 000 women and 8,6 per 100 000 men, with a sex ratio men/women of 0,93. Demographic characteristics: Melanoma diagnosis was more often in women (54.9 %) than in men (45.1 %). The patients mean age was 59.3 years (S.D.: 17.3). The

  3. Development of a tridimensional microvascularized human skin substitute to study melanoma biology.

    Science.gov (United States)

    Gibot, Laure; Galbraith, Todd; Huot, Jacques; Auger, François A

    2013-01-01

    Cutaneous malignant melanomas represent an important clinical problem because they are highly invasive, they can metastasize to distant sites and are typically resistant to available therapy. The precise molecular determinants responsible for melanoma progression and chemo-resistance are not yet known, in part due to lack of pertinent experimental models that mimic human melanoma progression. Accordingly, we developed a complex human microvascularized reconstructed skin substitute in which the organized three-dimensional (3D) architecture of the native skin is reproduced. Human melanoma cell lines derived from primary and metastatic sites were added to this 3D model. Our results demonstrate that histological features and behavior of melanoma cells applied in our skin substitute model are specific to their site of origin. In particular, the ability of melanoma cells to cross the dermal-epidermal junction correlates with their metastatic potential. In addition, a potent angiogenic effect was detected for an aggressive metastatic cell line that produces VEGF. The presence of a microvascular network within this model will allow studying a crucial step of the metastatic process. We conclude that such an in vitro human tumor microvascularized reconstructed skin substitute promises to be a versatile and efficient model to investigate skin cancer progression and to screen new anticancer drugs to improve currents clinical treatments.

  4. Regulatory and Functional Connection of Microphthalmia-Associated Transcription Factor and Anti-Metastatic Pigment Epithelium Derived Factor in Melanoma

    Directory of Open Access Journals (Sweden)

    Asunción Fernández-Barral

    2014-06-01

    Full Text Available Pigment epithelium-derived factor (PEDF, a member of the serine protease inhibitor superfamily, has potent anti-metastatic effects in cutaneous melanoma through its direct actions on endothelial and melanoma cells. Here we show that PEDF expression positively correlates with microphthalmia-associated transcription factor (MITF in melanoma cell lines and human samples. High PEDF and MITF expression is characteristic of low aggressive melanomas classified according to molecular and pathological criteria, whereas both factors are decreased in senescent melanocytes and naevi. Importantly, MITF silencing down-regulates PEDF expression in melanoma cell lines and primary melanocytes, suggesting that the correlation in the expression reflects a causal relationship. In agreement, analysis of Chromatin immunoprecipitation coupled to high throughput sequencing (ChIP-seq data sets revealed three MITF binding regions within the first intron of SERPINF1, and reporter assays demonstrated that the binding of MITF to these regions is sufficient to drive transcription. Finally, we demonstrate that exogenous PEDF expression efficiently halts in vitro migration and invasion, as well as in vivo dissemination of melanoma cells induced by MITF silencing. In summary, these results identify PEDF as a novel transcriptional target of MITF and support a relevant functional role for the MITF-PEDF axis in the biology of melanoma.

  5. Melanoma of unknown origin: a case series.

    LENUS (Irish Health Repository)

    Kelly, J

    2010-12-01

    The natural history of metastatic melanoma involving lymph nodes, in the absence of a known primary site (cutaneous, ocular or mucosal) has, to date, been poorly defined; and the optimal management of this rare subtype of disease is therefore unclear. Melanomas of unknown primary site (MUP) are estimated to comprise between 3.7 and 6% of all melanomas (Anbari et al. in Cancer 79:1861-1821, 1997).

  6. Giant hanging melanoma of the eyelid skin

    Directory of Open Access Journals (Sweden)

    Pai Radha

    2008-01-01

    Full Text Available Cutaneous melanoma of the eyelid is a rare entity. We present a 53-year-old male who had a nevus on the left upper eyelid skin since childhood, which transformed into a huge ulcerated hanging mass in the same region. Excision of the mass was done and histopathology confirmed the diagnosis of nodular malignant melanoma. A small preauricular lymph node showed metastatic melanoma on fine needle aspiration cytology.

  7. Genetic alterations and markers of melanoma

    Directory of Open Access Journals (Sweden)

    N. N. Mazurenko

    2014-01-01

    Full Text Available Melanoma remains the most deadly form of malignant skin disease with high risk of metastases. Metastatic melanoma is prognostic highly unfavorable and resistant to traditional chemotherapy and biologic treatment. There is a great progress in understanding of the molecular mechanisms underlying melanoma initiation and progression. The external (ultraviolet irradiation and internal (genetic factors are involved in melanoma genesis. 5–14 % of melanoma cases occur in familial context due to genetic predisposition risk factors. Among them rare germinal mutations in the cell cycle genes regulators CDKN2A and CDK4 and in the master gene of melanocyte homeostasis MITF, as well as single nucleotide polymorphisms of several low-penetrated genes, namely MC1R, have been identified. The main cell signaling pathways and oncogene driver mutations are involved in melanoma pathogenesis. RAS / RAF / MEK / ERK cascade is hyperactivated in 75 % of cutaneous melanoma cases. Activation of PI3K / AKT / mTOR signaling pathway is important for melanoma progression. Recent studies revealed that melanomas are genetically and phenotypically heterogeneous tumors. Spectrum of chromosomal alterations and activating mutations corresponding to tumor molecular portraits varies in melanomas of different location. Most of cutaneous melanomas contain BRAF (50 % or NRAS (20 % mutations, and NRAS mutations occur on chronically sun-exposed skin. Activating KIT mutations have been reported in approximately 20–30 % of certain subtypes of melanoma, including acral and mucosal, and melanoma that develop on photodamaged skin. Cutaneous metastatic melanoma derive from preexisting nevi in 25 % of cases, molecular mechanisms of nevi malignization are discussed. Deepsequencing approaches of melanoma samples of different melanoma types highlighted new melanoma driver genes, that are damaged due to tumorigenic effects of ultraviolet: PPP6C, RAC1, SNX31, TACC1 and STK19. The

  8. Canine oral melanoma.

    Science.gov (United States)

    Bergman, Philip J

    2007-05-01

    Melanoma is the most common oral malignancy in the dog. Oral and/or mucosal melanoma has been routinely considered an extremely malignant tumor with a high degree of local invasiveness and high metastatic propensity. Primary tumor size has been found to be extremely prognostic. The World Health Organization staging scheme for dogs with oral melanoma is based on size, with stage I = or = 4cm tumor and/or lymph node metastasis, and stage IV = distant metastasis. Median survival times for dogs with oral melanoma treated with surgery are approximately 17 to 18, 5 to 6, and 3 months with stage I, II, and III disease, respectively. Significant negative prognostic factors include stage, size, evidence of metastasis, and a variety of histologic criteria. Standardized treatments such as surgery, coarse-fractionation radiation therapy, and chemotherapy have afforded minimal to modest stage-dependent clinical benefits and death is usually due to systemic metastasis. Numerous immunotherapeutic strategies have been employed to date with limited clinical efficacy; however, the use of xenogeneic DNA vaccines may represent a leap forward in clinical efficacy. Oral melanoma is a spontaneous syngeneic cancer occurring in outbred, immunocompetent dogs and appears to be a more clinically faithful therapeutic model for human melanoma; further use of canine melanoma as a therapeutic model for human melanoma is strongly encouraged. In addition, the development of an expanded but clinically relevant staging system incorporating the aforementioned prognostic factors is also strongly encouraged.

  9. Melanoma continues to rise throughout the world

    African Journals Online (AJOL)

    Review Article: Melanoma continues to rise throughout the world. 530 ... of melanoma. The radiation in the ultraviolet B range is said to be the critical component. Generally, worldwide, the incidence of melanoma in white people4,5 correlates inversely with .... lymphocytes, mitotic rate, regression, angiolymphatic invasion ...

  10. Metastatic Malignant Melanoma Presenting as an Appendiceal Mucocele

    Directory of Open Access Journals (Sweden)

    A. A. Alduaij

    2011-01-01

    Full Text Available Melanoma metastatic to the appendix is extremely rare. Here we describe a case of a 31-year-old female from Bolivia with a remote history of metastatic malignant melanoma first diagnosed as a cutaneous malignant melanoma ten years prior to this presentation. The patient was being followed for a mucocele which on resection was found to be metastatic melanoma. “Mucocele” is a generic diagnosis that warrants further characterization and treatment.

  11. UVB: suscetibilidade no melanoma maligno UVB: susceptibility in malignant melanoma

    Directory of Open Access Journals (Sweden)

    Nilton Nasser

    2010-12-01

    Full Text Available FUNDAMENTOS: Está bem definido que a radiação ultravioleta provoca depleção imunológica na pele, permitindo o desenvolvimento de tumores cutâneos malignos. A maioria dos pacientes de cânceres da pele não melanomas são considerados UVB-suscetíveis. OBJETIVOS: Estudar a UVB-suscetibilidade nos pacientes com melanoma maligno e se este é um fator de risco para o desenvolvimento desse câncer. MÉTODOS: Foram selecionados 88 voluntários divididos em dois grupos: grupo-controle saudável (n=61 e grupo de portadores de melanoma (n=27, todos identificados de acordo com os critérios: tipo histológico, nível de invasão, fotótipos de pele, sexo e idade. A suscetibilidade à radiação ultravioleta B (UVB foi medida pela reação de hipersensibilidade ao contato com o difenciprone nos voluntários sensibilizados em áreas previamente irradiadas. RESULTADOS: A suscetibilidade à radiação UVB foi de 81,5% nos pacientes com melanoma maligno e de 31,2% no grupo-controle. O risco de um indivíduo desenvolver o melanoma maligno foi 9,7 vezes maior do que nos indivíduos UVB-resistentes. CONCLUSÕES: A UVB-suscetibilidade pode ser considerada um fator de risco importante para o desenvolvimento do melanoma maligno.BACKGROUND: It is well established that UV radiation provokes an immunological depletion in the skin, enabling the development of malignant cutaneous tumors. Most nonmelanoma skin cancer patients are considered to be UVB-susceptible. OBJECTIVE: To study the behavior of UVB- susceptibility in malignant melanoma (MM patients and whether this is a risk factor to the development of MM. METHODS: Eighty-eight volunteers were selected and divided into two groups: healthy control group (n = 61 and MM group (n = 27, which were identified according to the following clinical criteria: histopathological type, level of invasion, skin phototype, sex and age. Susceptibility to ultraviolet B (UVB radiation was measured by the onset of a contact

  12. Basal cell carcinoma, squamous cell carcinoma and melanoma of the head and face.

    Science.gov (United States)

    Feller, L; Khammissa, R A G; Kramer, B; Altini, M; Lemmer, J

    2016-02-05

    Ultraviolet light (UV) is an important risk factor for cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin. These cancers most commonly affect persons with fair skin and blue eyes who sunburn rather than suntan. However, each of these cancers appears to be associated with a different pattern of UV exposure and to be mediated by different intracellular molecular pathways.Some melanocortin 1 receptor (MC1R) gene variants play a direct role in the pathogenesis of cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma apart from their role in determining a cancer-prone pigmentory phenotype (fair skin, red hair, blue eyes) through their interactions with other genes regulating immuno-inflammatory responses, DNA repair or apoptosis.In this short review we focus on the aetiological role of UV in cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin, and on some associated biopathological events.

  13. Oral mucosal melanoma: A case report

    Directory of Open Access Journals (Sweden)

    Ramlal Gantala

    2017-01-01

    Full Text Available Malignant melanoma is most deadly of all primary skin cancers. Over 90% of melanomas occur on the skin. Half of such melanomas occur in the oral cavity, followed by nasal cavity (44% and sinuses (8%. In the oral cavity, the most frequent sites of occurrence are hard palate and maxillary gingiva. Mucosal melanomas represent a diagnostic challenge than the more common cutaneous melanomas because oral melanomas demonstrate significant heterogeneity in morphological features, developmental process, and biological behaviour. This case report highlights an exophytic, lobulated oral malignant melanoma involving maxillary gingiva and is presented to reemphasize the fact that any pigmented lesion in the oral cavity should be examined with suspicion; proper investigation should be carried out to rule out any untoward experiences later.

  14. Melanoma maligno cutâneo: sistema de pontos (scoring system para auxílio no diagnóstico histopatológico Cutaneous malignant melanoma: scoring system to assist in the histopathologic diagnosis

    Directory of Open Access Journals (Sweden)

    Luiz Alberto Veronese

    2006-10-01

    Full Text Available INTRODUÇÃO: O diagnóstico histopatológico de algumas lesões melanocíticas pode ser muito difícil, mesmo para especialistas, mas há casos em que a dificuldade surge pela inadequada e subjetiva aplicação dos critérios diagnósticos. OBJETIVO: O objetivo deste estudo é desenvolver um método de aplicação sistemática desses critérios, atribuindo valores para os mais importantes. MATERIAL E MÉTODOS: Selecionaram-se os critérios mais relevantes para o diagnóstico de melanoma, atribuindo valores de 1 a 5 de acordo com sua importância. Foram escolhidos 101 casos de melanomas de tipo extensivo-superficial com menos de 2mm de espessura para análise comparativa com 33 lesões melanocíticas benignas (13 nevos de Spitz, seis de Reed, seis displásicos, três congênitos, três adquiridos, um combinado e um recorrente. RESULTADOS: A soma dos valores dados aos critérios (score apresentou diferença significativa entre lesões malignas e benignas, mostrando que esse método pode ser útil ao patologista cirúrgico generalista em sua rotina diária. CONCLUSÃO: A aplicação objetiva e sistemática dos critérios histopatológicos pelo sistema de pontos (scoring system pode ajudar o diagnóstico diferencial entre maligno e benigno em muitas lesões, porém não tendo o efeito desejado nas lesões melanocíticas de comportamento biológico indeterminado.INTRODUCTION: The histopathological diagnosis of melanocytic lesions may be very difficult, even by experts within the field. The challenge can come from inaccurate and/or subjective application of the diagnosis criteria. AIM: The goal of this study was to develop a method of systematic application of histopathological criteria as a result of the most relevant microscopic characteristics. MATERIAL AND METHODS: The most important criteria to diagnosing melanoma on histopathological bases were selected and given points ranging from 1 to 5 according to their relevance to the melanoma diagnosis

  15. Avaliação de 496 laudos anatomopatológicos de melanoma diagnosticados no município de Florianópolis, Santa Catarina, Brasil Assessment of 496 pathological reports of melanoma diagnosed in the city of Florianopolis, SC, Brazil

    Directory of Open Access Journals (Sweden)

    Ariana Lebsa Weber

    2007-06-01

    metastasis. RESULTS - A total of 186 in situ, 210 invasive and 100 metastatic melanomas were observed. The most common histological type was superficial spreading melanoma (60%. The mean Breslow thickness of malignant lentigo and superficial spreading melanomas was 1.829 mm, and of nodular and acral melanoma was 5.035 mm (p<0.0001. The main metastasis sites were skin and subcutaneous tissue, lymph nodes and brain. CONCLUSIONS - In this study, the histopathological profile was superficial spreading, invasive, 1.25-mm Breslow thickness, with inflammatory infiltrate and free margin cutaneous melanomas.

  16. Successful Use of Posaconazole to Treat Invasive Cutaneous Fungal Infection in a Liver Transplant Patient on Sirolimus

    Directory of Open Access Journals (Sweden)

    Randah Dahlan

    2012-01-01

    Full Text Available Fungi are an important and common cause of cutaneous infections affecting solid organ transplant recipients. These infections can represent a primary site of infection with the potential for dissemination, or a manifestation of metastatic infection. The high morbidity and mortality associated with these infections necessitates urgent therapy with antifungal drugs; however, the interaction between these drugs and immunosuppressive therapies can be a major limitation because of drug toxicity. A case of soft tissue infection of the toe caused by Fusarium chlamydosporum and Candida guilliermondii in a liver transplant patient on sirolimus, who was successfully treated with the new antifungal agent posaconazole, is described. The pharmacokinetic interactions of sirolimus and the new triazoles, and their impact on treatment choices are briefly discussed.

  17. Dysplastic vs. Common Naevus-associated vs. De novo Melanomas: An Observational Retrospective Study of 1,021 Patients.

    Science.gov (United States)

    Martin-Gorgojo, Alejandro; Requena, Celia; Garcia-Casado, Zaida; Traves, Victor; Kumar, Rajiv; Nagore, Eduardo

    2018-02-13

    The aim of this case-case study was to determine the differences between dysplastic and common naevus-associated melanomas (NAM) and de novo melanomas. A total of 1,021 prospectively collected patients with invasive cutaneous melanoma from an oncology referral centre were included in the study. Of these, 75.51% had de novo melanomas, 12.93% dysplastic NAM, and 11.56% common NAM. Dysplastic NAM, compared with de novo melanomas, were associated with intermittently photo-exposed sites, atypical melanocytic naevi, decreased tumour thickness, and presence of MC1R non-synonymous variants. Common NAM were more frequent on the trunk and of superficial spreading type. Comparison of dysplastic with common NAM showed significant difference only with regard to mitoses. Both subtypes of NAM shared less aggressive traits than de novo melanomas, albeit with no significant differences in survival after multivariate adjustment. In conclusion, NAM present with less aggressive traits, mostly due to a greater awareness among patients of changing moles than due to their intrinsic biological characteristics.

  18. In-depth characterization of microRNA transcriptome in melanoma.

    Directory of Open Access Journals (Sweden)

    James Kozubek

    Full Text Available The full repertoire of human microRNAs (miRNAs that could distinguish common (benign nevi from cutaneous (malignant melanomas remains to be established. In an effort to gain further insight into the role of miRNAs in melanoma, we applied Illumina next-generation sequencing (NGS platform to carry out an in-depth analysis of miRNA transcriptome in biopsies of nevi, thick primary (>4.0 mm and metastatic melanomas with matched normal skin in parallel to melanocytes and melanoma cell lines (both primary and metastatic (n=28. From this data representing 698 known miRNAs, we defined a set of top-40 list, which properly classified normal from cancer; also confirming 23 (58% previously discovered miRNAs while introducing an additional 17 (42% known and top-15 putative novel candidate miRNAs deregulated during melanoma progression. Surprisingly, the miRNA signature distinguishing specimens of melanoma from nevus was significantly different than that of melanoma cell lines from melanocytes. Among the top list, miR-203, miR-204-5p, miR-205-5p, miR-211-5p, miR-23b-3p, miR-26a-5p and miR-26b-5p were decreased in melanomas vs. nevi. In a validation cohort (n=101, we verified the NGS results by qRT-PCR and showed that receiver-operating characteristic curves for miR-211-5p expression accurately discriminated invasive melanoma (AUC=0.933, melanoma in situ (AUC=0.933 and dysplastic (atypical nevi (AUC=0.951 from common nevi. Target prediction analysis of co-transcribed miRNAs showed a cooperative regulation of key elements in the MAPK signaling pathway. Furthermore, we found extensive sequence variations (isomiRs and other non-coding small RNAs revealing a complex melanoma transcriptome. Deep-sequencing small RNAs directly from clinically defined specimens provides a robust strategy to improve melanoma diagnostics.

  19. Melanoma-associated spongiform scleropathy: biochemical changes and possible relation to tumour extension

    DEFF Research Database (Denmark)

    Alyahya, Ghassan Ayish Jabur; Ribel-Madsen, S.; Heegaard, S.

    2003-01-01

    ophthalmology, melanoma-associated spongiform acleropathy (MASS), malignant melanoma, glycosaminoglycans (GAGs), collagen amino acids, tumour invasiveness, tumour extension, collagen degradation......ophthalmology, melanoma-associated spongiform acleropathy (MASS), malignant melanoma, glycosaminoglycans (GAGs), collagen amino acids, tumour invasiveness, tumour extension, collagen degradation...

  20. Superficial melanomas of oral mucous membranes.

    Science.gov (United States)

    Regezi, J A; Hayward, J R; Pickens, T N

    1978-05-01

    In accordance with microscopic and clinical criteria established for superficial melanomas of the skin (superficial spreading melanoma, lentigo maligna melanoma, acral-lentiginous melanoma), three oral lesions have been evaluated. The literature on oral melanomas has also been reviewed, with special attention given to those cases that had pre-existing melanosis. One patient with a diagnosis of superficial spreading melanoma eventually died of his untreated lesion 11 years after its first appearance. Two patients had lesions diagnosed as acral-lentiginous melanoma (a group which also includes volar and subungual melanomas) that exhibited aggressive, recurrent behavior. These lesions had microsocpic features similar to lentigo maligna melanoma but did not behave in a manner consistent with that diagnosis. Electron microscopic study of one acral-lentiginous melanoma demonstrated malenosomes and premelanosomes that were like those seen in normal melanocytes and nevus cells. The superficial or radial growth phase of many oral melanomas has apparently gone unrecognized. Melanosis has been reported to be a common feature of invasive oral melanomas but has not generally been related to the natural history of these lesions. Oral lesions with a prolonged intra-epithelial or radial growth phase would be expected to have a better prognosis than nodular melanomas, but meaningful survival data are not available because of the infrequency with which oral melanomas have been subclassified.

  1. Semi-automated non-invasive diagnostics method for melanoma differentiation from nevi and pigmented basal cell carcinomas

    Science.gov (United States)

    Lihacova, I.; Bolocko, K.; Lihachev, A.

    2017-12-01

    The incidence of skin cancer is still increasing mostly in in industrialized countries with light- skinned people. Late tumour detection is the main reason of the high mortality associated with skin cancer. The accessibility of early diagnostics of skin cancer in Latvia is limited by several factors, such as high cost of dermatology services, long queues on state funded oncologist examinations, as well as inaccessibility of oncologists in the countryside regions - this is an actual clinical problem. The new strategies and guidelines for skin cancer early detection and post-surgical follow-up intend to realize the full body examination (FBE) by primary care physicians (general practitioners, interns) in combination with classical dermoscopy. To implement this approach, a semi- automated method was established. Developed software analyses the combination of 3 optical density images at 540 nm, 650 nm, and 950 nm from pigmented skin malformations and classifies them into three groups- nevi, pigmented basal cell carcinoma or melanoma.

  2. Uveal melanoma: From diagnosis to treatment and the science in between.

    Science.gov (United States)

    Chattopadhyay, Chandrani; Kim, Dae Won; Gombos, Dan S; Oba, Junna; Qin, Yong; Williams, Michelle D; Esmaeli, Bita; Grimm, Elizabeth A; Wargo, Jennifer A; Woodman, Scott E; Patel, Sapna P

    2016-08-01

    Melanomas of the choroid, ciliary body, and iris of the eye are collectively known as uveal melanomas. These cancers represent 5% of all melanoma diagnoses in the United States, and their age-adjusted risk is 5 per 1 million population. These less frequent melanomas are dissimilar to their more common cutaneous melanoma relative, with differing risk factors, primary treatment, anatomic spread, molecular changes, and responses to systemic therapy. Once uveal melanoma becomes metastatic, therapy options are limited and are often extrapolated from cutaneous melanoma therapies despite the routine exclusion of patients with uveal melanoma from clinical trials. Clinical trials directed at uveal melanoma have been completed or are in progress, and data from these well designed investigations will help guide future directions in this orphan disease. Cancer 2016;122:2299-2312. © 2016 American Cancer Society. © 2016 American Cancer Society.

  3. Melanoma-specific marker expression in skin biopsy tissues as a tool to facilitate melanoma diagnosis.

    Science.gov (United States)

    Alexandrescu, Doru T; Kauffman, C Lisa; Jatkoe, Timothy A; Hartmann, Dan P; Vener, Tatiana; Wang, Haiying; Derecho, Carlo; Rajpurohit, Yashoda; Wang, Yixin; Palma, John F

    2010-07-01

    Diagnosis of cutaneous melanoma requires accurate differentiation of true malignant tumors from highly atypical lesions, which lack the capacity to develop uncontrolled proliferation and to metastasize. We used melanoma markers from previous work to differentiate benign and atypical lesions from melanoma using paraffin-embedded tissue. This critical step in diagnosis generates the most uncertainty and discrepancy between dermatopathologists. A total of 193 biopsy tissues were selected: 47 melanomas, 48 benign nevi, and 98 atypical/suspicious, including 48 atypical nevi and 50 melanomas as later assigned by expert dermatopathologists. Performance for SILV, GDF15, and L1CAM normalized to TYR in unequivocal melanoma versus benign nevi resulted in an area under the curve (AUC) of 0.94, 0.67, and 0.5, respectively. SILV also differentiated atypical cases classified as melanoma from atypical nevi with an AUC=0.74. Furthermore, SILV showed a significant difference between suspicious melanoma and each suspicious atypia group: melanoma versus severe atypia and melanoma versus moderate atypia had P-values of 0.0077 and 0.0009, respectively. SILV showed clear discrimination between melanoma and benign unequivocal cases as well as between different atypia subgroups in the group of suspicious samples. The role and potential utility of this molecular assay as an adjunct to the morphological diagnosis of melanoma are discussed.

  4. Toxicity and morbility after isolated lower limb perfusion in 242 chemo-hyperthermal treatments for cutaneous melanoma: The experience of the Tuscan Reference Centre

    Directory of Open Access Journals (Sweden)

    Bechi Paolo

    2008-11-01

    Full Text Available Abstract Background The aim of this retrospective study was to assess the results concerning the regional and systemic toxicity and complications in 242 chemo-hyperthermal treatments (HILPs for lower limb melanoma. Patients and methods 60 HILPs (G-A were performed with mild HT plus L-PAM (10 mg/lt ± D-actimomycin; 74 HILPs (G-B with true HT (40–41.8°C plus L-PAM (10 mg/lt ± D-act; 108 HILPs (G-C with true HT plus L-PAM (10 mg/lt ± D-act plus L-PAM (5 mg/lt additional bolus. Results Limb toxicity was very low in G-A and in G-B; increasing toxicity (grade III = 37% in G-C; no grade IV statistical difference was registered in all three groups, with percentage values among 1.6% and 2.7%. Systemic toxicity showed itself only in the haemopoietic parameters. No differences were registered in G-B vs G-A group. In G-C vs G-B a significative increase of systemic toxicity was seen in grade 3 (p Conclusion These data suggested that the technical implementations reduced the occurrence and the severity of the side effects and complications. The essential requirement for HILP is the quality assurance of the procedures. Although higher regional and systemic toxicity were observed in the G-C group caused by L-PAM additional bolus, the safeness of the procedures under the true hyperthermal regimen and the time increase of the high L-PAM concentration have assured the treatment reliability along with the increased clinical efficacy expectations of the treatments.

  5. Primary cutaneous malignancies in the Northern Cape Province of ...

    African Journals Online (AJOL)

    Results. A total of 4 270 biopsies (13 cutaneous malignancies) were identified. The commonest was squamous cell carcinoma (SCC), followed by basal cell carcinoma, Kaposi's sarcoma (KS), cutaneous malignant melanoma (CMM) and basosquamous carcinoma, in descending order. The odds of a white male developing ...

  6. Current Research and Development of Chemotherapeutic Agents for Melanoma

    Directory of Open Access Journals (Sweden)

    Kyaw Minn Hsan

    2010-04-01

    Full Text Available Cutaneous malignant melanoma is the most lethal form of skin cancer and an increasingly common disease worldwide. It remains one of the most treatment-refractory malignancies. The current treatment options for patients with metastatic melanoma are limited and in most cases non-curative. This review focuses on conventional chemotherapeutic drugs for melanoma treatment, by a single or combinational agent approach, but also summarizes some potential novel phytoagents discovered from dietary vegetables or traditional herbal medicines as alternative options or future medicine for melanoma prevention. We explore the mode of actions of these natural phytoagents against metastatic melanoma.

  7. Primary malignant melanoma of the nasal cavity.

    Science.gov (United States)

    Uysal, Ismail Önder; Misir, Mustafa; Polat, Kerem; Altuntaş, Emine Elif; Atalar, Mehmet Haydar; Tuncer, Ersin; Müderris, Suphi

    2012-01-01

    Primary malignant melanoma of the nose and paranasal sinus mucosa is a rare disease and seen in less than 1% among all melanomas. Malignant melanomas have 2 origins: cutaneous and mucosal. The mucosal form has a worse prognosis because of its aggressiveness compared with that of the cutaneous form. Mucosal melanomas often occur at a rate of 2% to 3% among all melanomas and are typically found in the nasal cavity and paranasal sinuses. Generally, it is more common in males and in those older than 50 years. In this study, 4 patients were observed at the Cumhuriyet University Faculty of Medicine; 2 of them were a 64-year-old man and an 82-year-old woman who had a malignant melanoma originating from the nasal septal mucosa, 1 patient was a 72-year-old woman whose malignant melanoma originated from the inferior turbinate, and 1 patient was a 77-year-old woman with a sinonasally located melanoma. The conditions of these patients were discussed under the light of literature instructions.

  8. Congenital uveal melanoma?

    Science.gov (United States)

    Singh, Arun D; Schoenfield, Lynn A; Bastian, Boris C; Aziz, Hassan A; Marino, Meghan J; Biscotti, Charles V

    2016-01-01

    A 3-month-old infant with a white mother and Asian father presented with discoloration and prominence of the left eye since birth. Examination revealed a normal right eye. The left eye had hyperchromic heterochromia and an enlarged cornea (diameter, 13.0 mm) with intraocular pressure of 26 mm Hg. There were multiple areas of subconjunctival nodular pigmentation that extended posteriorly into the superior fornix. Fundus examination showed a large ciliochoroidal pigmented mass extending from 10:30 to 3:00 o'clock position involving the superior half of the choroid and adjacent ciliary body. The eye was enucleated, confirming the diagnosis of diffuse uveal melanoma with extraocular extension. Systemic surveillance (hepatic panel and ultrasonography of the liver) performed every 6 months for 5 years was has been negative for metastases. The tumor was investigated intensively for the panel of genes (BAP1, BRAF, NRAS12, NRAS61, GNAQ, Kit 9,11,13,17,18) implicated in pathogenesis of blue nevus, cutaneous melanoma, and mucosal melanomas with negative results. Moreover, germline BAP1 mutation could not be identified. This case possibly represents as yet unidentified uveal melanocytic proliferation rather than a true variant of uveal melanoma. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Extracutaneous melanomas: a primer for the radiologist

    OpenAIRE

    Keraliya, Abhishek R.; Krajewski, Katherine M.; Braschi-Amirfarzan, Marta; Tirumani, Sree Harsha; Shinagare, Atul B.; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.

    2015-01-01

    Objective: The purpose of this article is to provide a comprehensive review of the imaging features of extracutaneous melanomas. Conclusion: Extracutaneous melanomas are clinically and biologically distinct from their more common cutaneous counterpart with higher frequency of metastatic disease and poorer overall prognosis. Complete surgical excision is the treatment of choice whenever possible; systemic therapy in the form of conventional chemotherapeutic agents as well as novel targeted age...

  10. A minimally invasive human in vivo cutaneous wound model for the evaluation of innate skin reactivity and healing status.

    Science.gov (United States)

    Varol, Alexandra L; Anderson, Chris D

    2010-07-01

    Individual variability in skin reactivity and healing capacity after trauma are important clinical issues. The aims were to develop an in vivo, human wound model based on a standardised minimal skin injury and to demonstrate therapeutic effect of simple wound therapies in terms of morphological wound outcome with changes in skin blood perfusion as a quantified indicator of wound healing. In a series of experiments, wounds were induced on the normal forearm skin of volunteers using a blood collection lancet. This was well tolerated. Wounds were assessed by naked eye examination or laser Doppler perfusion imaging (LDPI) at baseline and at up to 6 further time points up to 96 h in control wounds and wounds treated by commonly used occlusive dressing options. Assessment by clinical observation with 10x magnification showed over 96 h a progression of erythema, surface crust, a new keratinisation layer and finally healed areas. LDPI quantifying wound erythema showed a peak at 24 h and near normal levels at 96 h. Inter-individual variability was evident but intra-individual variability was much less pronounced. Wounds treated with occlusion showed a statistically significant more rapid return to baseline blood perfusion as measured by LDPI compared to controls supported by favourable healing parameters in the clinical assessment. The paper exemplifies use of non-invasive, bioengineering technique for quantification of individual innate variability in skin reactivity, wound healing capacity and therapeutic effect in a well-tolerated in vivo, human, minimal skin trauma model.

  11. Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy

    DEFF Research Database (Denmark)

    Eggermont, Alexander M M; Chiarion-Sileni, Vanna; Grob, Jean-Jacques

    2016-01-01

    undergone complete resection of stage III melanoma. Methods After patients had undergone complete resection of stage III cutaneous melanoma, we randomly assigned them to receive ipilimumab at a dose of 10 mg per kilogram (475 patients) or placebo (476) every 3 weeks for four doses, then every 3 months...

  12. Cutaneous leishmaniasis

    OpenAIRE

    Ramesh V; Kumar Joginder

    2006-01-01

    ABSTRACTLeishmaniasis is considered to be zoonotic disease, caused by a protozoan parasite of the genus Leishmania, and transmitted by a bite of infected female sandfly. Primary cutaneous leishmaniasis is not common disease in Nepal, however, there were cases reported from Terai region of Nepal. The patients with cutaneous leishmaniasis present with a papule or nodule at the site of inoculation, followed by formation of crusts. Differential diagnoses of cutaneous leishmaniasis include variety...

  13. [Acute dyspnea in malignant melanoma].

    Science.gov (United States)

    Franzen, A M; Günzel, T

    2011-09-01

    Metastases to the larynx are rare. The current article presents the case of a 75-year-old patient with a history of shortness of breath due to a supraglottic exophytic lesion that was identified as a metastasis of a cutaneous melanoma treated 2.5 years previously. As a result of our medline analysis we found approximately 30 cases of metastatic melanoma to the larynx published to date. Primary tumors are always cutaneous in origin and spread over the whole integument of trunk and extremities. The time interval between diagnosis of the primary and the laryngeal metastasis is often several years. In most reports a supraglottic exophytic, red coloured lesion is described. Diagnosis can only be proven by histological examination. Laryngeal metastasis is usually an indication of tumor dissemination and always has a fatal prognosis.

  14. Recombinant Interleukin-15 in Treating Patients With Advanced Melanoma, Kidney Cancer, Non-small Cell Lung Cancer, or Squamous Cell Head and Neck Cancer

    Science.gov (United States)

    2017-09-14

    Head and Neck Squamous Cell Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Skin Carcinoma; Stage III Renal Cell Cancer; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IV Renal Cell Cancer

  15. Factors Predictive of the Status of Sentinel Lymph Nodes in Melanoma Patients from a Large Multicenter Database

    NARCIS (Netherlands)

    White, Richard L.; Ayers, Gregory D.; Stell, Virginia H.; Ding, Shouluan; Gershenwald, Jeffrey E.; Salo, Jonathan C.; Pockaj, Barbara A.; Essner, Richard; Faries, Mark; Charney, Kim James; Avisar, Eli; Hauschild, Axel; Egberts, Friederike; Averbook, Bruce J.; Garberoglio, Carlos A.; Vetto, John T.; Ross, Merrick I.; Chu, David; Trisal, Vijay; Hoekstra, Harald; Whitman, Eric; Wanebo, Harold J.; DeBonis, Daniel; Vezeridis, Michael; Chevinsky, Aaron; Kashani-Sabet, Mohammed; Shyr, Yu; Berry, Lynne; Zhao, Zhiguo; Soong, Seng-jaw; Leong, Stanley P. L.

    2011-01-01

    Numerous predictive factors for cutaneous melanoma metastases to sentinel lymph nodes have been identified; however, few have been found to be reproducibly significant. This study investigated the significance of factors for predicting regional nodal disease in cutaneous melanoma using a large

  16. Cutaneous Porphyrias

    DEFF Research Database (Denmark)

    Lindegaard Christiansen, Anne; Aagaard, Lise; Krag, Aleksander

    2016-01-01

    and a flowchart for the diagnosis of cutaneous porphyrias, with recommendations for monitoring and an update of treatment options. From the Danish Porphyria Register, we present the incidences and approximate prevalences of cutaneous porphyrias within the last 25 years. A total of 650 patients with porphyria...

  17. Feasibility study of a non-invasive eye fixation and monitoring device using a right-angle prism mirror for intensity-modulated radiotherapy for choroidal melanoma.

    Science.gov (United States)

    Inoue, Toshihiko; Masai, Norihisa; Shiomi, Hiroya; Oh, Ryoong-Jin; Uemoto, Kenji; Hashida, Noriyasu

    2017-05-01

    We aimed to describe the feasibility and efficacy of a novel non-invasive fixation and monitoring (F-M) device for the eyeballs (which uses a right-angle prism mirror as the optic axis guide) in three consecutive patients with choroidal melanoma who were treated with intensity-modulated radiotherapy (IMRT). The device consists of an immobilization shell, a right-angle prism mirror, a high magnification optical zoom video camera, a guide lamp, a digital voice recorder, a personal computer, and a National Television System Committee standard analog video cable. Using the right-angle prism mirror, the antero-posterior axis was determined coincident with the optic axis connecting the centers of the cornea and pupil. The axis was then connected to the guide light and video camera installed on the couch top on the distal side. Repositioning accuracy improved using this method. Furthermore, the positional error of the lens was markedly reduced from ±1.16, ±1.68 and ±1.11 mm to ±0.23, ±0.58 and ±0.26 mm in the horizontal direction, and from ±1.50, ±1.03 and ±0.48 mm to ±0.29, ±0.30 and ±0.24 mm in the vertical direction (Patient #1, #2 and #3, respectively). Accordingly, the F-M device method decreased the planning target volume size and improved the dose-volume histogram parameters of the organ-at-risk via IMRT inverse planning. Importantly, the treatment method was well tolerated. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  18. Detection of desmoplastic melanoma with dermoscopy and reflectance confocal microscopy.

    Science.gov (United States)

    Maher, N G; Solinas, A; Scolyer, R A; Puig, S; Pellacani, G; Guitera, P

    2017-12-01

    Desmoplastic melanoma (DM) is frequently misdiagnosed clinically and often associated with melanoma in situ (MIS). To improve the detection of DM using dermoscopy and reflectance confocal microscopy (RCM). A descriptive analysis of DM dermoscopy features and a case-control study within a melanoma population for RCM feature evaluation was performed blindly, using data obtained between 2005 and 2015. After retrospectively identifying all DM cases with RCM data over the study period (n = 16), a control group of non-DM melanoma patients with RCM data, in a ratio of at least 3 : 1, was selected. The control group was matched by age and primary tumour site location, divided into non-DM invasive melanomas (n = 27) and MIS (n = 27). Invasive melanomas were selected according to the melanoma subtypes associated with the DM cases. The main outcomes were the frequency of melanoma-specific features on dermoscopy for DM; and the odds ratios of RCM features to distinguish DM from MIS and/or other invasive melanomas; or MIS from the combined invasive melanoma group. At least one of the 14 melanoma-specific features evaluated on dermoscopy was found in 100% of DMs (n = 15 DM with dermoscopy). Known RCM melanoma predictors were commonly found in the DMs, such as pagetoid cells (100%) and cell atypia (100%). The RCM feature of spindle cells in the superficial dermis was more common in DM compared with the entire melanoma control group (OR 3.82, 95% CI 1.01-14.90), and particularly compared to MIS (OR 5.48, 95% CI 1.11-32.36). Nucleated cells in the dermis and the RCM correlate of dermal inflammation were also significant RCM features favouring DM over MIS, as well as invasive melanoma over MIS. Dermoscopy and RCM may be useful tools for the identification of DM. Certain RCM features may help distinguish DM from MIS and other invasive melanomas. Larger studies are warranted. © 2017 European Academy of Dermatology and Venereology.

  19. Comprehensive histopathological comparison of epidermotropic/dermal metastatic melanoma and primary nodular melanoma.

    Science.gov (United States)

    Skala, Stephanie L; Arps, David P; Zhao, Lili; Cha, Kelly B; Wang, Min; Harms, Paul W; Andea, Aleodor A; Fullen, Douglas R; Chan, May P

    2018-02-01

    Metastatic melanoma involving the epidermis and/or upper dermis may show significant histological overlap with primary cutaneous melanoma, especially the nodular subtype. Proper histopathological classification is crucial to appropriate staging and management, but is often challenging. The aim of this study was to identify helpful histopathological features for differentiating epidermotropic/dermal metastatic melanoma (EDMM) and primary nodular melanoma (PNM). A cohort of EDMMs (n = 74) and PNMs (n = 75) was retrospectively reviewed for various histopathological features, and the data were compared between groups by the use of univariate analysis. Features significantly associated with EDMM included a tumour size of 10 mm, ulceration, epidermal collarettes, a higher mitotic rate, necrosis, multiple phenotypes, significant pleomorphism, and lichenoid inflammation. In multivariate analysis, a logistic regression model including large tumour size, ulceration, prominent TIPs, lichenoid inflammation and epidermal collarettes was highly predictive of PNM. Six (8%) EDMMs from three patients showed an 'epidermal-only' or 'epidermal-predominant' pattern closely simulating in-situ or microinvasive melanoma. Two of these cases were tested by fluorescence in-situ hybridisation, which confirmed clonal relationships with their corresponding primary melanomas. This is the first comprehensive histopathological comparison of EDMM and PNM. Recognition of the above histopathological associations should aid in the correct classification and staging of cutaneous melanoma. Epidermotropic metastatic melanomas may occasionally show an epidermal-only/epidermal-predominant pattern; accurate diagnosis requires prudent clinical correlation and, when necessary, ancillary molecular tests. © 2017 John Wiley & Sons Ltd.

  20. Cathepsin B inhibition interferes with metastatic potential of human melanoma: an in vitro and in vivo study

    Directory of Open Access Journals (Sweden)

    Matarrese Paola

    2010-08-01

    Full Text Available Abstract Background Cathepsins represent a group of proteases involved in determining the metastatic potential of cancer cells. Among these are cysteinyl- (e.g. cathepsin B and cathepsin L and aspartyl-proteases (e.g. cathepsin D, normally present inside the lysosomes as inactive proenzymes. Once released in the extracellular space, cathepsins contribute to metastatic potential by facilitating cell migration and invasiveness. Results In the present work we first evaluated, by in vitro procedures, the role of cathepsins B, L and D, in the remodeling, spreading and invasiveness of eight different cell lines: four primary and four metastatic melanoma cell lines. Among these, we considered two cell lines derived from a primary cutaneous melanoma and from a supraclavicular lymph node metastasis of the same patient. To this purpose, the effects of specific chemical inhibitors of these proteases, i.e. CA-074 and CA-074Me for cathepsin B, Cathepsin inhibitor II for cathepsin L, and Pepstatin A for cathepsin D, were evaluated. In addition, we also analyzed the effects of the biological inhibitors of these cathepsins, i.e. specific antibodies, on cell invasiveness. We found that i cathepsin B, but not cathepsins L and D, was highly expressed at the surface of metastatic but not of primary melanoma cell lines and that ii CA-074, or specific antibodies to cathepsin B, hindered metastatic cell spreading and dissemination, whereas neither chemical nor biological inhibitors of cathepsins D and L had significant effects. Accordingly, in vivo studies, i.e. in murine xenografts, demonstrated that CA-074 significantly reduced human melanoma growth and the number of artificial lung metastases. Conclusions These results suggest a reappraisal of the use of cathepsin B inhibitors (either chemical or biological as innovative strategy in the management of metastatic melanoma disease.

  1. A new understanding in the epidemiology of melanoma.

    Science.gov (United States)

    Erdei, Esther; Torres, Salina M

    2010-11-01

    The incidence of melanoma is continuing to increase worldwide. UV exposure is a known risk factor for melanoma. Geographic location is known to influence UV exposure and the distribution of the incidence of melanoma. Furthermore, epidemiologic data suggest that gender and genetics may influence the distribution of melanoma on the body surface and histopathologic characteristics of the lesion. This article describes what is known about the impact of gender, ethnicity and geography on the progression of melanoma. Advanced-stage cutaneous melanoma has a median survival time of less than 1 year. Surgical removal, radiotherapy, chemotherapy, targeted therapies and a variety of immunotherapies have been utilized in the treatment of melanoma. Current treatment strategies and the results of recent clinical trials are also discussed in this article.

  2. The biology of melanoma prognostic factors.

    NARCIS (Netherlands)

    Spatz, A.; Stock, N.; Batist, G.; Kempen, L.C.L.T. van

    2010-01-01

    Cutaneous melanoma still represents a paradox among all solid tumors. It is the cancer for which the best prognostic markers ever identified in solid tumors are available, yet there is very little understanding of their biological significance. This review focuses on recent biological data that shed

  3. Gender Differences in Melanoma Progression and Survival

    NARCIS (Netherlands)

    A. Joosse (Arjen)

    2014-01-01

    markdownabstract__Abstract__ Cutaneous melanoma is developing into a major public health problem worldwide. Incidence differs greatly across the world with high incidence rates in the Unites states, Europe and especially in Australia and New Zealand, but relatively low incidence rates

  4. Immunohistochemical Expression of MCAM/CD146 in Canine Melanoma.

    Science.gov (United States)

    Abou Asa, S

    2017-07-01

    MCAM/CD146 (melanoma cell adhesion molecule/CD146) is a transmembrane immunoglobulin superfamily cell adhesion molecule involved in transendothelial migration and signal transduction. It is expressed in melanoma, squamous cell carcinoma, prostatic, ovarian, cervical and endometrial cancers and promotes tumour growth, angiogenesis and metastasis. Melanoma is the most common malignant oral tumour of dogs and also arises in the skin, nail bed and footpad. The aim of this study was to investigate the immunohistochemical expression of MCAM/CD146 in 51 canine melanomas, including oral, cutaneous and ocular tumours. Seventeen of the 51 (33.3%) cases were negative, eight (15.7%) were weakly positive, seven (13.7%) were moderately positive and 19 (37.3%) were strongly positive. MCAM/CD146 was expressed by both oral and cutaneous melanomas; however, the intensity and the extent of the immunoreactivity was higher in oral (P = 0.009) than in cutaneous tumours (P = 0.058). Most ocular melanomas did not express MCAM/CD146 (P = 0.256). Expression of MCAM/CD146 by canine melanomas may suggest the molecule as a target for treatment, especially in oral melanomas. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Melanoma epidemiology, prognosis and trends in Latvia.

    Science.gov (United States)

    Azarjana, K; Ozola, A; Ruklisa, D; Cema, I; Rivosh, A; Azaryan, A; Pjanova, D

    2013-11-01

    Melanoma incidence and mortality rates are increasing worldwide within the white population. Clinical and histological factors have been usually used for the prognosis and assessment of the risk for melanoma. The aim of the study was to describe the clinical and histopathological features of the cutaneous melanoma (CM) in the Latvian population, to test the association between melanoma features and patient survival, and to assess the time trends for melanoma incidence. We undertook a descriptive, retrospective analysis of archive data of 984 melanoma patients treated at the largest oncological hospital of Latvia, Riga East University Hospital Latvian Oncology Centre (LOC), between 1998 and 2008. Cox proportional hazards model was used to analyse patient survival and autoregressive models were applied to detect trends in melanoma incidence over time for various categories of melanoma. The study showed a significant ascending trend in melanoma incidence in Latvia during the time period from 1998 to 2008 (ß = 1.83, 95% CI = 1.15-2.91, P = 0.011). Nodular melanoma was the most common tumour subtype with a frequency of 39.2%. Ulceration was present in 45.2% of melanomas. The mean Breslow thickness was 6.0 mm (6.8 mm) and no significant decline in median Breslow thickness was observed during the study period (P = 0.609). A better overall prognosis was detected for females in comparison with males (HR = 1.49; 95% CI = 1.22-1.81; P Latvia with the majority of melanomas diagnosed at late stages with poor prognosis for survival. © 2012 The Authors Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

  6. Cutaneous leishmaniasis

    Directory of Open Access Journals (Sweden)

    Ram Chandra Adhikari

    2017-09-01

    Full Text Available ABSTRACTLeishmaniasis is considered to be zoonotic disease, caused by a protozoan parasite of the genus Leishmania, and transmitted by a bite of infected female sandfly. Primary cutaneous leishmaniasis is not common disease in Nepal, however, there were cases reported from Terai region of Nepal. The patients with cutaneous leishmaniasis present with a papule or nodule at the site of inoculation, followed by formation of crusts. Differential diagnoses of cutaneous leishmaniasis include variety of skin diseases, inflammatory like impetigo, eczema, or granulomatous like sarcoidosis, lupus vulgaris, to skin tumor like basal cell carcinoma & squamous cell carcinoma. There are various procedures and laboratory techniques used to diagnose leishmaniasis. Punch skin biopsy is widely used & popular technique to diagnose cutaneous leishmaniasis. Different drugs like sodium stibogluconate, sodium antimony gluconate, Amphotericin B and Miltefosine: are used for its treatment. No vaccines are available for prevention. 

  7. Cutaneous Angiosarcoma

    Directory of Open Access Journals (Sweden)

    Heloisa Rampinelli

    2018-03-01

    Full Text Available Cutaneous angiosarcoma is a rare malignant tumor showing blood or lymphatic vessel differentiation, corresponding to < 2% of all sarcomas. It preferably affects elderly, with predilection for the head and neck. Diagnosis is frequently late due to the early interpretation by the patient as a benign lesion similar to ecchymosis, which explains its aggressiveness with high metastasis and recurrence rates. We report the case of an elderly man whose histopathologic diagnosis confirmed the clinical suspicion of cutaneous angiosarcoma.

  8. Ocular Melanoma

    Science.gov (United States)

    ... also occur on the conjunctiva . Because most eye melanomas form in the part of the eye you can’t see when looking in a mirror, they can be difficult to detect. Also, eye melanoma typically doesn’t cause early signs or symptoms . ...

  9. Acetylsalicylic acid regulates MMP-2 activity and inhibits colorectal invasion of murine B16F0 melanoma cells in C57BL/6J mice: effects of prostaglandin F(2)alpha.

    Science.gov (United States)

    Tsai, Chin-Shaw Stella; Luo, Shue-Fen; Ning, Chung-Chu; Lin, Chien-Liang; Jiang, Ming-Chung; Liao, Ching-Fong

    2009-08-01

    Epidemiological studies indicate that acetylsalicylic acid may reduce the risk of mortality due to colon cancers. Metastasis is the major cause of cancer death. Matrix metalloproteinases (MMPs) play important roles in tumor invasion regulation, and prostaglandin F(2)alpha (PGF(2)alpha) is a key stimulator of MMP production. Thus, we investigated whether acetylsalicylic acid regulated MMP activity and the invasion of cancer cells and whether PGF(2)alpha attenuated acetylsalicylic acid-inhibited invasion of cancer cells. Gelatin-based zymography assays showed that acetylsalicylic acid inhibited the MMP-2 activity of B16F0 melanoma cells. Matrigel-based chemoinvasion assays showed that acetylsalicylic acid inhibited the invasion of B16F0 cells. Acetylsalicylic acid can inhibit PGF(2)alpha synthesis and PGF(2)alpha is a key stimulator of MMP-2 production. Our data showed that PGF(2)alpha treatment attenuated the acetylsalicylic acid-inhibited invasion of B16F0 cells. In animal experiments, acetylsalicylic acid reduced colorectal metastasis of B16F0 cells in C57BL/6J mice by 44%. Our results suggest that PGF(2)alpha is a therapeutic target for metastasis inhibition and acetylsalicylic acid may possess anti-metastasis ability.

  10. Risk Factors for Invasive Fungal Infection among Thai Oncologic Patients with Febrile Neutropenia and Cutaneous Presentation: A 5-Year Retrospective Study in Southern Thailand

    Science.gov (United States)

    Aiempanakit, Kumpol; Naorungroj, Surarit; Chiratikarnwong, Kanokphorn; Auepemkiate, Sauvarat; Apinantriyo, Benjawan

    2017-12-29

    Background: Febrile neutropenia (FNP) is a condition defined by fever and neutropenia. There are current only limited data on related cutaneous manifestations. This study aimed to assess cutaneous lesions and their etiologies in a Thai group of FNP patients. Methods: A retrospective analysis was conducted on 43 non-transplant febrile neutropenic patients with concurrent cutaneous lesions, as determined by dermatopathologic studies at Songklanagarind Hospital in Thailand over a five-year period. Results: The mean age was 39 years (SD: 18.8). Approximately 60% were male. The most common underlying disease was a hematologic neoplasm. Twenty-one of the participants had developed FNP within 7.5±8.7 days after presenting with skin lesions. Twenty-two participants had skin lesions 9.0±11.1 days after FNP diagnosis. Cutaneous manifestations were mostly in the form of multiple lesions (67.4%), of which the most common were nodular skin lesions (37.2%) presenting on the lower extremities of the body (58.1%). The dermatopathologic diagnoses included infections which were almost all fungal and leukemia cutis. The development of skin lesions after FNP proved to be a statistically significant risk factor for fungal infection (OR 8.13, P = 0.009), whereas age (over 40 years) proved to be a statistically significant protective factor (OR 0.20, P = 0.04). Conclusions: There are a variety of cutaneous manifestations in FNP, of which the most common were cutaneous nodular skin lesions in the lower extremities. The most frequent infection was fungal in patients under 40 who had developed skin lesions after FNP. Creative Commons Attribution License

  11. Emerging targeted therapies for melanoma.

    Science.gov (United States)

    Johnson, Douglas B; Pollack, Megan H; Sosman, Jeffrey A

    2016-06-01

    Melanoma is an aggressive cutaneous malignancy associated with poor response to traditional therapies. Recent regulatory approval for immune checkpoint inhibitors and agents targeting mutated BRAF has led to a tremendous expansion of effective treatment options for patients with advanced melanoma. Unfortunately, primary or acquired resistance develops in most patients, highlighting the need for additional therapies. Numerous genetic and other molecular features of this disease may provide effective targets for therapy development. This article reviews available melanoma treatments, including immune and molecularly-targeted therapies. We then discuss agents in development, with a focus on targeted (rather than immune) therapies. In particular, we discuss agents that block mitogen-activated protein kinase (MAPK) signaling, as well as other emerging approaches such as antibody-drug conjugates, cell-cycle targeting, and novel genetically-informed clinical trials. Despite the incredible advances in melanoma therapeutics over the last several years, a clear need to develop more effective therapies remains. Molecularly-targeted therapy approaches will likely remain a cornerstone of melanoma treatment in parallel to immune therapy strategies.

  12. Transplantable Melanomas in Hamsters and Gerbils as Models for Human Melanoma. Sensitization in Melanoma Radiotherapy—From Animal Models to Clinical Trials

    Directory of Open Access Journals (Sweden)

    Martyna Śniegocka

    2018-04-01

    Full Text Available The focus of the present review is to investigate the role of melanin in the radioprotection of melanoma and attempts to sensitize tumors to radiation by inhibiting melanogenesis. Early studies showed radical scavenging, oxygen consumption and adsorption as mechanisms of melanin radioprotection. Experimental models of melanoma in hamsters and in gerbils are described as well as their use in biochemical and radiobiological studies, including a spontaneously metastasizing ocular model. Some results from in vitro studies on the inhibition of melanogenesis are presented as well as radio-chelation therapy in experimental and clinical settings. In contrast to cutaneous melanoma, uveal melanoma is very successfully treated with radiation, both using photon and proton beams. We point out that the presence or lack of melanin pigmentation should be considered, when choosing therapeutic options, and that both the experimental and clinical data suggest that melanin could be a target for radiosensitizing melanoma cells to increase efficacy of radiotherapy against melanoma.

  13. Metastatic melanoma masquerading as a furuncle

    Directory of Open Access Journals (Sweden)

    Imran Aslam

    2017-10-01

    Full Text Available Melanoma metastasizes to the skin in about 10-17% of patients. Although there are reports of metastatic melanoma masquerading as panniculitis and erysipelas, it is very uncommon for it to present as an inflammatory skin lesion. When malignant melanoma cells invade the superficial dermal lymphatic vessels it can result in erythema, edema and induration of the overlying skin. This presentation can be problematic for clinicians if they do not suspect melanoma and choose not to biopsy the lesion. We report a case of an elderly man with a history of invasive melanoma who presented with a furuncle-like lesion that was found to be in-transit metastatic melanoma.

  14. Associations between childhood height and morphologically different variants of melanoma in adulthood

    DEFF Research Database (Denmark)

    Meyle, Kathrine Damm; Gamborg, Michael Orland; Hølmich, Lisbet Rosenkrantz

    2016-01-01

    .5% nodular melanoma (NM), and 2% lentigo maligna melanoma (LMM). The remaining rare melanoma forms were not analysed. Childhood height was positively and significantly associated with SSM, melanoma NOS, and NM, but not LMM, in adulthood. Per height z-score at age 13 years, the hazard ratios were 1.20 (95......AIM OF THE STUDY: Melanoma subtypes have different aetiological characteristics. Child height is positively associated with adult melanoma; however, a clarification of associations with specific melanoma variants is necessary for an improved understanding of risk factors underlying the histologic...... entities. This study investigated associations between childhood height and future development of cutaneous melanoma variants. METHOD: A cohort study of 316,193 individuals from the Copenhagen School Health Records Register, with measured heights at ages 7-13 years who were born from 1930 to 1989. Melanoma...

  15. Long-term effects of laser-imiquimod combination in the treatment of late-stage melanoma patients

    Science.gov (United States)

    Naylor, Mark F.; Le, Henry; Li, Xiaosong; Nordquist, Robert E.; Hode, Tomas; Liu, Hong; Chen, Wei R.

    2012-03-01

    Topical application of a potent immunological modulator, imiquimod, followed by laser irradiation has been used for the treatment of late-stage melanoma patients. This novel approach, laser-assisted laser immunotherapy (LIT), targets the root course of melanoma, a highly metastatic cancer. We started a phase I clinical trial in 2006 with promising initial outcomes. The laser-imiquimod combination showed significant palliative effects for these patients with multiple treatment cycles. For the returning patients, we found that the recurrent tumors were less aggressive than usually seen in untreated patients. The current protocol uses a light-absorbing dye for selective laser photothermal interaction with a non-invasive treatment mode. It has limitations for patient treatment, particularly for large, deeper tumors, and for patients with dark pigmented skins. This study provides some information on the treated patients (both stage IV and stage IV) during the past several years. We also discuss the future directions of LIT, particularly in the area of photothermal treatment mode with a new approach of interstitial irradiation. The current results in melanoma treatment using LIT indicate that the combination of photothermal therapy and immunological stimulation may hold the key for the treatment of late-stage, metastatic cancers, not only for cutaneous cancers such as melanoma and breast cancer, but also for deep and internal tumors using different operations modes such as interstitial laser irradiation.

  16. T-cell Landscape in a Primary Melanoma Predicts the Survival of Patients with Metastatic Disease after Their Treatment with Dendritic Cell Vaccines

    NARCIS (Netherlands)

    Vasaturo, Angela; Halilovic, Altuna; Bol, Kalijn F.; Verweij, Dagmar I.; Blokx, Willeke A. M.; Punt, Cornelis J. A.; Groenen, Patricia J. T. A.; van Krieken, J. Han J. M.; Textor, Johannes; de Vries, I. Jolanda M.; Figdor, Carl G.

    2016-01-01

    Tumor-infiltrating lymphocytes appear to be a predictor of survival in many cancers, including cutaneous melanoma. We applied automated multispectral imaging to determine whether density and distribution of T cells within primary cutaneous melanoma tissue correlate with survival of metastatic

  17. Subungual melanoma: Management in the modern era.

    Science.gov (United States)

    Reilly, D J; Aksakal, G; Gilmour, R F; Gyorki, D E; Chauhan, A; Webb, A; Henderson, M A

    2017-12-01

    Subungual melanoma is a rare subtype of cutaneous melanoma that arises from the structures of the nail apparatus. It presents most commonly in older patients and at an advanced stage. A retrospective review of all patients with subungual melanoma in a single institution over a 15-year period was performed. In total, 54 patients were included (26 males, average age 62.9 years), of which 28 cases involved the upper limb. Median tumour thickness was 4.5 mm. Eighteen patients had lymph node metastasis at diagnosis, including 11 of 36 patients with positive sentinel lymph node biopsy. Median survival was 4.6 years. Subungual melanoma has a poor prognosis that is strongly associated with presence of nodal disease at diagnosis. Sentinel lymph node biopsy should be considered to determine stage and prognosis. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  18. Cutaneous Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Mehmet Harman

    2015-12-01

    Full Text Available Leishmaniasis is used to describe a spectrum of diseases caused by the parasitic protozoa leishmania spp. and transmitted by infected female sandflies. There are three main forms of the disease; cutaneous, mucocutaneous, and visceral. According to the World Health Organization, almost 12 million people from 98 countries worldwide are currently infected with leishmaniasis, while 350 million people are at risk. It was reported that 2 million new cases are diagnosed every year, with three-fourth are cutaneous leishmaniasis (CL cases. The scientific and medical communities have learnt a lot about CL during the 20th and early 21st centuries. However, the management and control of the disease remains a difficult task. This article was focused on the most common form of the disease, cutaneous leishmaniasis, and especially its epidemiological aspects and treatment.

  19. Isolation and Molecular Characterization of Circulating Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Xi Luo

    2014-05-01

    Full Text Available Melanoma is an invasive malignancy with a high frequency of blood-borne metastases, but circulating tumor cells (CTCs have not been readily isolated. We adapted microfluidic CTC capture to a tamoxifen-driven B-RAF/PTEN mouse melanoma model. CTCs were detected in all tumor-bearing mice and rapidly declined after B-RAF inhibitor treatment. CTCs were shed early from localized tumors, and a short course of B-RAF inhibition following surgical resection was sufficient to dramatically suppress distant metastases. The large number of CTCs in melanoma-bearing mice enabled a comparison of RNA-sequencing profiles with matched primary tumors. A mouse melanoma CTC-derived signature correlated with invasiveness and cellular motility in human melanoma. CTCs were detected in smaller numbers in patients with metastatic melanoma and declined with successful B-RAF-targeted therapy. Together, the capture and molecular characterization of CTCs provide insight into the hematogenous spread of melanoma.

  20. Efficient adenovector CD40 ligand immunotherapy of canine malignant melanoma.

    Science.gov (United States)

    von Euler, Henrik; Sadeghi, Arian; Carlsson, Björn; Rivera, Patricio; Loskog, Angelica; Segall, Thomas; Korsgren, Olle; Tötterman, Thomas H

    2008-05-01

    Cutaneous canine melanomas are usually benign in contrast to human malignant melanoma. However, the canine oropharyngeal, uveal, and mucocutaneous neoplasms are aggressive and have metastatic potential. Surgery and to a lesser extent radiotherapy and chemotherapy are widely adopted treatments but are seldom curative in advanced stages. The similarities between human and canine melanoma make spontaneous canine melanoma an excellent disease model for exploring novel therapies. Herein, we report the first 2 adenovector CD40L immunogene (AdCD40L) treatments of aggressive canine malignant melanoma. Case no. 1 was an advanced stage III oral melanoma that was cured from malignant melanoma with 2 intratumor AdCD40L injections before cytoreductive surgery. After treatment, the tumor tissue was infiltrated with T lymphocytes and B lymphocytes suggesting immune activation. This dog survived 401 days after the first round of gene therapy and was free of melanoma at autopsy. Case no. 2 had a conjunctival malignant melanoma with a rapid progression. This case was treated with 6 AdCD40L injections over 60 days. One hundred and twenty days after start of gene therapy and 60 days after the last injection, the tumor had regressed dramatically, and the dog had a minimal tumor mass and no signs of progression or metastasis. Our results indicate that AdCD40L immunogene therapy is beneficial in canine malignant melanoma and could be considered for human malignant melanoma as well.

  1. Ocular melanoma: an overview of the current status

    Science.gov (United States)

    Jovanovic, Predrag; Mihajlovic, Marija; Djordjevic-Jocic, Jasmina; Vlajkovic, Slobodan; Cekic, Sonja; Stefanovic, Vladisav

    2013-01-01

    Ocular melanoma is the second most common type of melanoma after cutaneous and the most common primary intraocular malignant tumor in adults. Large majority of ocular melanomas originate from uvea, while conjunctival melanomas are far less frequent. Incidence of uveal melanoma has remained stable over last three decades. Diagnosis is in most cases established by clinical examination with great accuracy. Local treatment of uveal melanoma has improved, with increased use of conservative methods and preservation of the eye, but survival rates have remained unchanged. Recent advances in cytogenetics and genetics enhanced prognostication and enabled to determine tumors with high metastatic potential. However, due to lack of effective systemic therapy, prognosis of patients with metastasis remains poor and metastatic disease remains the leading cause of death among patients with uveal melanoma. Conjunctival melanoma is rare, but its incidence is increasing. It mostly occurs among white adults. In majority of cases it originates from preceding primary acquired melanosis. Current standard treatment for conjunctival melanoma is wide local excision with adjuvant therapy, including brachytherapy, cryotherapy and topical application of chemotherapeutic agent. Rarity of this tumor limits conduction of controlled trials to define the best treatment modality. As well as for uveal melanoma, prognosis of patients with metastasis is poor because there is no effective systemic therapy. Better understanding of underlying genetic and molecular abnormalities implicated in development and progression of ocular melanomas provides a great opportunity for development of targeted therapy, which will hopefully improve prognosis of patients with metastatic disease. PMID:23826405

  2. Sarcoidosis in Melanoma Patients: Case Report and Literature Review

    Energy Technology Data Exchange (ETDEWEB)

    Beutler, Bryce D., E-mail: brycebeutler@hotmail.com [School of Allied Health Sciences, University of Nevada, Las Vegas, 1060 Wiegand Road, Encinitas, CA 92024 (United States); Cohen, Philip R., E-mail: brycebeutler@hotmail.com [Department of Dermatology, University of California San Diego, 10991 Twinleaf Court, San Diego, CA 92131 (United States)

    2015-06-15

    Sarcoidosis is a systemic inflammatory disease characterized by the development of noncaseating granulomas in multiple organ systems. Many hematologic malignancies and solid tumors, including melanoma, have been associated with sarcoidosis. We describe the clinical and pathologic findings of a 54-year-old man with melanoma-associated sarcoidosis. In addition, we not only review the literature describing characteristics of other melanoma patients with sarcoidosis, but also the features of melanoma patients with antineoplastic therapy-associated sarcoidosis. Sarcoidosis has been described in 80 melanoma patients; sufficient information for analysis was provided in 39 of these individuals. In 43.6% of individuals (17 out of 39), sarcoidosis was directly associated with melanoma; in 56.4% of oncologic patients (22 out of 39), sarcoidosis was induced by antineoplastic therapy that had been administered for the treatment of their metastatic melanoma. The discovery of melanoma preceded the development of sarcoidosis in 12 of the 17 (70.5%) individuals who did not receive systemic treatment. Pulmonary and/or cutaneous manifestations of sarcoidosis were common among both groups of patients. Most patients did not require treatment for sarcoidosis. Melanoma patients—either following antineoplastic therapy or without systemic treatment—may be at an increased risk to develop sarcoidosis. In antineoplastic therapy naive melanoma patients, a common etiologic factor—such as exposure to ultraviolet light—may play a role in their developing melanoma and sarcoidosis.

  3. The contribution of nodular subtype to melanoma mortality in the United States, 1978 to 2007.

    Science.gov (United States)

    Shaikh, Waqas R; Xiong, Michael; Weinstock, Martin A

    2012-01-01

    To gain insight into reducing melanoma mortality by examining epidemiologic trends by subtype with emphasis on the contribution of each subtype to melanoma-related death. Retrospective population-based cohort study. Original 9 registries of the Surveillance, Epidemiology, and End Results Program from 1978 to 2007. A total of 111,478 patients with histologically confirmed invasive melanoma. Proportion of ultimately fatal melanomas by subtype. Among melanomas of known subtype, superficial spreading melanoma comprised 66% of incident melanomas and 46% of ultimately fatal melanomas; nodular melanoma comprised 14% of incident melanomas and 37% of ultimately fatal melanomas. For superficial spreading melanoma, overall incidence per 100,000 per year increased (from 4.28 to 6.63), ultimately fatal incidence remained stable (at 0.56 to 0.51), and 10-year relative survival increased (from 90.6% to 96.5%) when comparing successive 5-year intervals. In contrast, for nodular melanoma, the overall incidence (1.30-1.32), ultimately fatal incidence (0.46-0.44), and 10-year relative survival rate (61.8%-61.5%) remained stable. Epidemiologic trends of melanoma, not otherwise specified, were similar to superficial spreading melanoma. There was a strong negative correlation between the proportion of melanoma, not otherwise specified, among all melanomas, and the proportion of superficial spreading melanoma, among melanomas of known subtype (r = -0.80; P = .01), across the registries. Superficial spreading and nodular melanoma constitute similar proportions of ultimately fatal melanomas. Although incidence of and survival from superficial spreading melanoma have increased from 1978 to 2007, neither the incidence of nor survival from nodular melanoma has changed. Public health efforts should include a focus on nodular melanoma for maximum reduction of melanoma mortality.

  4. Circulating melanoma cells and distant metastasis-free survival in stage III melanoma patients with or without adjuvant interferon treatment (EORTC 18991 side study)

    NARCIS (Netherlands)

    Fusi, Alberto; Collette, Sandra; Busse, Antonia; Suciu, Stefan; Rietz, Anika; Santinami, Mario; Kruit, Wim H. J.; Testori, Alessandro; Punt, Cornelis J. A.; Dalgleish, Angus G.; Spatz, Alan; Eggermont, Alexander M. M.; Keilholz, Ulrich

    2009-01-01

    To evaluate the prognostic and predictive importance of detection of melanoma cells in peripheral blood using reverse transcriptase polymerase chain reaction (RT-PCR) in stage III cutaneous melanoma patients after sentinel or regional lymph node dissection. Serial testing for tyrosinase and

  5. Study Suggests Smaller Melanoma Excision Margins May Be Option for Some Patients

    Science.gov (United States)

    A randomized controlled trial of patients with stage IIA–C cutaneous melanoma thicker than 2-mm found that a 2-cm surgical resection margin is sufficient and is as safe for patients as a 4-cm margin.

  6. Coffee, tea and melanoma risk : findings from the European Prospective Investigation into Cancer and Nutrition

    NARCIS (Netherlands)

    Caini, Saverio; Masala, Giovanna; Saieva, Calogero; Kvaskoff, Marina; Savoye, Isabelle; Sacerdote, Carlotta; Hemmingsson, Oskar; Hammer Bech, Bodil; Overvad, Kim; Tjønneland, Anne; Petersen, Kristina E N; Mancini, Francesca Romana; Boutron-Ruault, Marie Christine; Cervenka, Iris; Kaaks, Rudolf; Kühn, Tilman; Boeing, Heiner; Floegel, Anna; Trichopoulou, Antonia; Valanou, Elisavet; Kritikou, Maria; Tagliabue, Giovanna; Panico, Salvatore; Tumino, Rosario; Bueno-de-Mesquita, H. Bas; Peeters, Petra H.; Veierød, Marit B.; Ghiasvand, Reza; Lukic, Marko; Quirós, José Ramón; Chirlaque, Maria Dolores; Ardanaz, Eva; Salamanca Fernández, Elena; Larrañaga, Nerea; Zamora-Ros, Raul; Maria Nilsson, Lena; Ljuslinder, Ingrid; Jirström, Karin; Sonestedt, Emily; Key, Timothy J.; Wareham, Nick; Khaw, Kay Tee; Gunter, Marc; Huybrechts, Inge; Murphy, Neil; Tsilidis, Konstantinos K.; Weiderpass, Elisabete; Palli, Domenico

    2017-01-01

    In vitro and animal studies suggest that bioactive constituents of coffee and tea may have anticarcinogenic effects against cutaneous melanoma; however, epidemiological evidence is limited to date. We examined the relationships between coffee (total, caffeinated or decaffeinated) and tea consumption

  7. The presence of dysplastic nevus remnants in malignant melanomas. A population-based study of 551 malignant melanomas.

    Science.gov (United States)

    Hastrup, N; Osterlind, A; Drzewiecki, K T; Hou-Jensen, K

    1991-08-01

    We examined 512 malignant melanomas, representing all newly diagnosed cutaneous malignant melanomas, excluding lentigo maligna melanomas, from the period October 1, 1982 to March 31, 1985 occurring in the region of eastern Denmark in patients aged 20-79 years for the presence of dysplastic nevus remnants. Criteria for the diagnosis of a dysplastic nevus remnant include all the following changes (a) lentiginous or epithelioid melanocyte hyperplasia, (b) cytologic melanocyte atypia, (c) eosinophilic fibroplasia, (d) lamellar fibroplasia, and (e) lymphocytic infiltration in the dermis. Dysplastic nevus remnants were found in association with 34 (7%) of the evaluable 512 malignant melanomas. Fourteen (41%) of the remnants were of compound nevus type. In nine (27%) of the remnants, atypia was pronounced. Most (62%) dysplastic nevus remnants were contiguous to thin superficial spreading melanomas. We conclude from this population-based study that about 7% of malignant melanomas arise in prior dysplastic nevi.

  8. Stereological estimates of nuclear volume in thin malignant melanomas

    DEFF Research Database (Denmark)

    Björnhagen, V; Månsson-Brahme, E; Lindholm, J

    1998-01-01

    melanomas were individually compared with 33 thin non-metastasizing melanomas after individual matching of cases with one or two randomly chosen controls for site of primary tumour, tumour thickness, level of invasion, tumour regression and follow-up. Conditional logistic regression analysis showed......Stereological estimation of nuclear volume was performed in a case control study of 72 malignant melanomas, thickness melanomas due to too sparse cellularity. Thus, 21 thin metastasizing...... no significant differences in nuclear volume between metastasizing and non-metastasizing thin malignant melanomas....

  9. Acral lentiginous melanoma of the foot misdiagnosed as a traumatic ulcer. A cautionary case.

    Science.gov (United States)

    Gumaste, Priyanka; Penn, Lauren; Cohen, Nicole; Berman, Russell; Pavlick, Anna; Polsky, David

    2015-03-01

    The incidence of cutaneous melanoma is rising faster than that of almost any other cancer in the United States. Acral lentiginous melanoma is a subtype of melanoma that involves the palms, soles, and nail beds. Although it is one of the rarer types of melanoma, it has a poorer prognosis than other more common subtypes. We describe a case of plantar acral melanoma in a 66-year-old woman that was initially misdiagnosed as a traumatic foot ulcer. We highlight this case to emphasize the importance of close observation and biopsy of ulcerative lesions of the foot that have atypical features or are refractory to standard treatment.

  10. Naturally occurring melanomas in dogs as models for non-UV pathways of human melanomas.

    Science.gov (United States)

    Gillard, Marc; Cadieu, Edouard; De Brito, Clotilde; Abadie, Jérôme; Vergier, Béatrice; Devauchelle, Patrick; Degorce, Frédérique; Dréano, Stephane; Primot, Aline; Dorso, Laetitia; Lagadic, Marie; Galibert, Francis; Hédan, Benoit; Galibert, Marie-Dominique; André, Catherine

    2014-01-01

    Spontaneously occurring melanomas are frequent in dogs. They appear at the same localizations as in humans, i.e. skin, mucosal sites, nail matrix and eyes. They display variable behaviors: tumors at oral localizations are more frequent and aggressive than at other anatomical sites. Interestingly, dog melanomas are associated with strong breed predispositions and overrepresentation of black-coated dogs. Epidemiological analysis of 2350 affected dogs showed that poodles are at high risk of developing oral melanoma, while schnauzers or Beauce shepherds mostly developped cutaneous melanoma. Clinical and histopathological analyses were performed on a cohort of 153 cases with a 4-yr follow-up. Histopathological characterization showed that most canine tumors are intradermal and homologous to human rare morphological melanomas types - 'nevocytoid type' and 'animal type'-. Tumor cDNA sequencing data, obtained from 95 dogs for six genes, relevant to human melanoma classification, detected somatic mutations in oral melanoma, in NRAS and PTEN genes, at human hotspot sites, but not in BRAF. Altogether, these findings support the relevance of the dog model for comparative oncology of melanomas, especially for the elucidation of non-UV induced pathways. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Multiple cutaneous malignancies in xeroderma pigmentosum

    Directory of Open Access Journals (Sweden)

    Mohanty Prasenjeet

    2001-01-01

    Full Text Available A case of xeroderma pigmentosum with multiple cutaneous malignancies is being reported. The case presented with freckles, letigens, and keratosis, a non-tender ulcerated nodular lesion on the nose, a nodular ulcerated lesion on the right outer canthus of the conjunctiva, and a nodular growth which developed on the right cheek which on histopathology was found to be squamous cell cercinoma, basal cell carcinoma and malignant melanoma respectively.

  12. The MELFO-Study : Prospective, Randomized, Clinical Trial for the Evaluation of a Stage-adjusted Reduced Follow-up Schedule in Cutaneous Melanoma Patients-Results after 1 Year

    NARCIS (Netherlands)

    Damude, Samantha; Hoekstra-Weebers, Josette E. H. M.; Francken, Anne Brecht; ter Meulen, Sylvia; Bastiaannet, Esther; Hoekstra, Harald J.

    Guidelines for evidence-based follow-up in melanoma patients are not available. This study examined whether a reduced follow-up schedule affects: patient-reported outcome measures, detection of recurrences, and follow-up costs. This multicenter trial included 180 patients treated for AJCC stage

  13. A BAP1 Mutation in a Danish Family Predisposes to Uveal Melanoma and Other Cancers

    DEFF Research Database (Denmark)

    Aoude, Lauren G; Wadt, Karin; Bojesen, Anders

    2013-01-01

    with predominantly uveal melanoma but also a range of other tumor types including lung, neuroendocrine, stomach, and breast cancer; as well as pigmented skin lesions. Whole-exome sequencing identified a BAP1 splice mutation located at c.581-2A>G, which leads to a premature truncation of BAP1 in an individual...... with uveal melanoma. This mutation was carried by several other family members with melanoma or various cancers. The finding expands on the growing profile of BAP1 as an important uveal and cutaneous melanoma tumor suppressor gene and implicates its involvement in the development of lung, and stomach cancer.......Truncating germline mutations in the tumor suppressor gene BRCA-1 associated protein-1 (BAP1) have been reported in families predisposed to developing a wide range of different cancer types including uveal melanoma and cutaneous melanoma. There has also been an association between amelanotic tumor...

  14. Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Eshini Perera

    2013-12-01

    Full Text Available Melanomas are a major cause of premature death from cancer. The gradual decrease in rates of morbidity and mortality has occurred as a result of public health campaigns and improved rates of early diagnosis. Survival of melanoma has increased to over 90%. Management of melanoma involves a number of components: excision, tumor staging, re-excision with negative margins, adjuvant therapies (chemo, radiation or surgery, treatment of stage IV disease, follow-up examination for metastasis, lifestyle modification and counseling. Sentinel lymph node status is an important prognostic factor for survival in patients with a melanoma >1 mm. However, sentinel lymph node biopsies have received partial support due to the limited data regarding the survival advantage of complete lymph node dissection when a micrometastasis is detected in the lymph nodes. Functional mutations in the mitogen-activated pathways are commonly detected in melanomas and these influence the growth control. Therapies that target these pathways are rapidly emerging, and are being shown to increase survival rates in patients. Access to these newer agents can be gained by participation in clinical trials after referral to a multidisciplinary team for staging and re-excision of the scar.

  15. Targeting of the MAPK and AKT pathways in conjunctival melanoma shows potential synergy

    NARCIS (Netherlands)

    Cao, J. (Jinfeng); R.C. Heijkants (Renier C.); A.G. Jochemsen (Aart); M. Dogrusöz (Mehmet); de Lange, M.J. (Mark J.); P.A. van der Velden (Pieter); S.H. van der Burg (Sjoerd); M.J. Jager (Martine); R.M. Verdijk (Robert)

    2017-01-01

    textabstractPurpose: Conjunctival melanoma (CM) is a rare but lethal form of cancer. Similar to cutaneous melanoma, CM frequently carries activating mutations in BRAF and NRAS. We studied whether CM as well as conjunctival benign and premalignant melanocytic lesions express targets in the

  16. Uveal Melanoma

    International Nuclear Information System (INIS)

    Papastefanou, V. P.; Cohen, V. M. L.; Cohen, V. M. L.

    2011-01-01

    Uveal melanoma is the most common primary intraocular malignancy and the leading primary intraocular disease which can be fatal in adults. In this paper epidemiologic, pathogenetic, and clinical aspects of uveal melanoma are discussed. Despite the advance in local ocular treatments, there has been no change in patient survival for three decades. Development of metastases affects prognosis significantly. Current survival rates, factors predictive of metastatic potential and metastatic screening algorithms are discussed. Proposed and emerging treatments for uveal melanoma metastases are also overviewed. Current advances in genetics and cytogenetics have provided a significant insight in tumours with high metastatic potential and the molecular mechanisms that underlie their development. Biopsy of those lesions may prove to be important for prognostication and to allow further research into genetic mutations and potential new therapeutic targets in the future

  17. Cellular radiosensitivity of primary and metastatic human uveal melanoma cell lines

    OpenAIRE

    Aardweg, Gerard J. M.; Naus, Nicole; Verhoeven, A.C.; Klein, Annelies; Luyten, Gré

    2002-01-01

    textabstractPURPOSE: To investigate the radiosensitivity of uveal melanoma cell lines by a clonogenic survival assay, to improve the efficiency of the radiation regimen. METHODS: Four primary and four metastatic human uveal melanoma cell lines were cultured in the presence of conditioned medium. After single-dose irradiation (0-12 Gy), colonies were allowed to form for 6 to 14 days. Two cutaneous melanomas cell lines were also tested for comparison. The survival curves were analyzed by the li...

  18. Germline MC1R status influences somatic mutation burden in melanoma

    OpenAIRE

    Robles-Espinoza, Carla Daniela; Roberts, Nicola D.; Chen, Shuyang; Leacy, Finbarr P.; Alexandrov, Ludmil B.; Pornputtapong, Natapol; Halaban, Ruth; Krauthammer, Michael; Cui, Rutao; Timothy Bishop, D.; Adams, David J.

    2016-01-01

    The major genetic determinants of cutaneous melanoma risk in the general population are disruptive variants (R alleles) in the melanocortin 1 receptor (MC1R) gene. These alleles are also linked to red hair, freckling, and sun sensitivity, all of which are known melanoma phenotypic risk factors. Here we report that in melanomas and for somatic C>T mutations, a signature linked to sun exposure, the expected single-nucleotide variant count associated with the presence of an R allele is estimated...

  19. Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes in Advanced Melanoma Patients

    OpenAIRE

    Mélanie Saint-Jean; Anne-Chantal Knol; Christelle Volteau; Gaëlle Quéreux; Lucie Peuvrel; Anabelle Brocard; Marie-Christine Pandolfino; Soraya Saiagh; Jean-Michel Nguyen; Christophe Bedane; Nicole Basset-Seguin; Amir Khammari; Brigitte Dréno

    2018-01-01

    Immunotherapy for melanoma includes adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TILs). This monocenter retrospective study was undertaken to evaluate the efficacy and safety of this treatment of patients with advanced melanoma. All advanced melanoma patients treated with TILs using the same TIL expansion methodology and same treatment interleukin-2 (IL-2) regimen between 2009 and 2012 were included. After sterile intralesional excision of a cutaneous or subcutaneous ...

  20. Primary dermal melanoma: distinct immunohistochemical findings and clinical outcome compared with nodular and metastatic melanoma.

    Science.gov (United States)

    Cassarino, David S; Cabral, Erik S; Kartha, Reena V; Swetter, Susan M

    2008-01-01

    To provide an updated and expanded analysis of clinical outcome and immunohistochemical (IHC) findings unique to primary dermal melanoma (PDM) that may be used to differentiate this entity from primary nodular melanoma (PNM) and cutaneous metastatic melanoma (MM). Cohort analysis and extensive IHC panel comparing PDM with PNM and cutaneous MM. Melanoma clinics and pathology departments of academic and VA medical centers. Thirteen patients with a solitary dermal or subcutaneous nodule of histologically proven melanoma, prospectively followed through April 30, 2007. Clinical, pathologic, and IHC assessment of patients diagnosed as having PDM. Long-term clinical outcome and determination of unique clinical and IHC features in the study cohort compared with other melanoma subtypes. Histologically, there was no evidence of an overlying in situ component, ulceration, or regression, and there was no associated nevus in any cases. Clinical history and findings from workup, including imaging studies, skin examination, and sentinel lymph node biopsy, were negative for evidence of melanoma elsewhere. The mean Breslow depth was 9.6 mm. Two patients developed satellite or in-transit recurrences, 1 developed pulmonary metastasis, and another died of liver metastases. Overall, the cohort showed a 92% melanoma-specific survival rate at a mean duration of follow-up of 44 months. The IHC findings showed that PDM exhibited lower levels of staining for the antigens p53 (P = .02), Ki-67 (Mib-1) (P = .002), cyclin D1 (P = .001), and podoplanin (recognized by D2-40 antibody) lymphovascular staining (P <.001) compared with MM and PNM. All other markers were comparable. Patients with PDM have remarkably prolonged survival compared with patients with MM or PNM of similar thickness. Preliminary results suggest that PDM may be characterized by lower levels of p53, Ki-67, cyclin D1, and D2-40 compared with histologically similar MM and PNM.

  1. Differences in transcriptional activity of cutaneous human papillomaviruses

    DEFF Research Database (Denmark)

    Vasiljevic, Natasa; Nielsen, Lone; Doherty, Geoff

    2008-01-01

    The interaction between UV-B irradiation and cutaneous human papillomaviruses (HPV) has been suggested to be of relevance for the development of non-melanoma skin cancers. We investigated the activity within the upstream regulatory region (URR) of the HPV types 8, 38, 92, 93 and 96, as well...

  2. Prognostic Significance of Melanoma Differentiation and Trans-Differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Maddodi, Nityanand; Setaluri, Vijayasaradhi, E-mail: setaluri@wisc.edu [Department of Dermatology, University of Wisconsin School of Medicine and Public Health, 1300 University Avenue, B25, Madison WI 53706 (United States)

    2010-05-26

    Cutaneous malignant melanomas share a number of molecular attributes such as limitless replicative potential that define capabilities acquired by most malignancies. Accordingly, much effort has been focused on evaluating and validating protein markers related to these capabilities to function as melanoma prognostic markers. However, a few studies have also highlighted the prognostic value of markers that define melanocytic differentiation and the plasticity of melanoma cells to trans-differentiate along several other cellular pathways. Here, we provide a comprehensive review and evaluation of the prognostic significance of melanocyte-lineage markers such as MITF and melanogenic proteins, as well as markers of vascular epithelial and neuronal differentiation.

  3. Malignant Melanoma of the Foot

    Science.gov (United States)

    ... Javascript in your browser. Malignant Melanoma of the Foot What Is Malignant Melanoma? Melanoma is a cancer ... age groups, even the young. Melanoma in the Foot Melanoma that occurs in the foot or ankle ...

  4. Melanoma m (zero): diagnosis and therapy.

    Science.gov (United States)

    Rastrelli, Marco; Alaibac, Mauro; Stramare, Roberto; Chiarion Sileni, Vanna; Montesco, Maria Cristina; Vecchiato, Antonella; Campana, Luca Giovanni; Rossi, Carlo Riccardo

    2013-01-01

    This paper reviews the epidemiology, diagnosis, and treatment of M zero cutaneous melanoma including the most recent developments. This review also examined the main risk factors for melanoma. Tumor thickness measured according to Breslow, mitotic rate, ulceration, and growth phase has the greatest predictive value for survival and metastasis. Wide excision of the primary tumor is the only potentially curative treatment for primary melanoma. The sentinel node biopsy must be performed on all patients who have a primary melanoma with a Breslow thickness > 1 mm, or if the melanoma is from 0,75 mm to 1 mm thick but it is ulcerated and/or the mitotic index is ≥1. Total lymph node dissection consists in removing the residual lymph nodes in patients with positive sentinel node biopsy, or found positive on needle aspiration biopsy, without radiological evidence of spread. Isolated limb perfusion and isolated limb infusion are employed in patients within transit metastases with a rate of complete remission in around 50% and 38% of cases. Electrochemotherapy is mainly indicated for palliation in cases of metastatic disease, though it may sometimes be useful to complete isolated limb perfusion. The only agent found to affect survival as an adjuvant treatment is interferon alpha-2. Adjuvant radiotherapy improves local control of melanoma in patients at a high risk of recurrence after lymph node dissection.

  5. Nail apparatus melanoma: a diagnostic opportunity Melanoma do aparelho ungueal: uma oportunidade diagnóstica

    Directory of Open Access Journals (Sweden)

    Ana Maria Carreño

    2013-04-01

    Full Text Available Malignant Melanoma is a high mortality neoplasm. The involvement of the nail apparatus is rare, with only 2 out of 3 patients seeking medical attention as the result of recent nail melanocytic lesions. This results in late diagnosis and a prognosis worse than cutaneous melanoma. We report a female, presenting with ulcerative lesions with clinical and laboratory features compatible with leishmaniasis. On return after treatment initiation a longitudinal melanonychia was observed on her first right finger. Biopsy of the nail matrix was performed. Histopathology was compatible with melanoma in situ. Longitudinal melanonychia is not a specific sign for melanoma and it is important that the dermatologist should identify the suspect lesions correctly. The incidental diagnosis of nail melanoma in situ in our case significantly impacted the patient's survival.Melanoma Maligno é uma neoplasia de alta mortalidade, sendo raro o acometimento do aparelho ungueal. Apenas 2/3 dos pacientes procuram atendimento médico devido lesão melanocítica ungueal recente, tornando o diagnóstico tardio e com prognóstico pior que do melanoma cutâneo. Descreve-se um caso de paciente sexo feminino, apresentando lesões ulceradas com características clínico-laboratoriais compatíveis com leishmaniose tegumentar americana. No retorno após início do tratamento foi observada melanoníquia longitudinal no primeiro quirodáctilo direito. Realizada biópsia da matriz ungueal com histopatológico compatível com melanoma in situ. Melanoníquia longitudinal não é sinal específico de melanoma. A identificação das lesões suspeitas é importante tarefa dos dermatologistas. O diagnóstico incidental de melanoma ungueal in situ do caso relatado resultou em grande impacto na sobrevida da paciente.

  6. Malignant melanoma clinically masquerading vascular tumor: A diagnostic dilemma

    Directory of Open Access Journals (Sweden)

    Samiksha Pradhan

    2015-01-01

    Full Text Available Malignant melanoma is an invasive neoplasm of the skin, whose incidence is reported to be rising among Indians. We hereby present a unique case of unilateral, multiple, asymptomatic, pigmented, nodular lesions over the lower limb; resembling vascular tumor, revealing itself as malignant melanoma only on histopathology. To the best of our knowledge, such a unique presentation of malignant melanoma has not yet been reported from the Indian subcontinent.

  7. Metastatic disease from uveal melanoma: treatment options and future prospects.

    Science.gov (United States)

    Carvajal, Richard D; Schwartz, Gary K; Tezel, Tongalp; Marr, Brian; Francis, Jasmine H; Nathan, Paul D

    2017-01-01

    Uveal melanoma represents ∼85% of all ocular melanomas and up to 50% of patients develop metastatic disease. Metastases are most frequently localised to the liver and, as few patients are candidates for potentially curative surgery, this is associated with a poor prognosis. There is currently little published evidence for the optimal management and treatment of metastatic uveal melanoma and the lack of effective therapies in this setting has led to the widespread use of systemic treatments for patients with cutaneous melanoma. Uveal and cutaneous melanomas are intrinsically different diseases and so dedicated management strategies and therapies for uveal melanoma are much needed. This review explores the biology of uveal melanoma and how this relates to ongoing trials of targeted therapies in the metastatic disease setting. In addition, we consider the options to optimise patient management and care. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  8. Malignant melanoma of the oral cavity: A review of literature

    Directory of Open Access Journals (Sweden)

    Hashemi Pour M