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Sample records for human cutaneous melanoma

  1. Biology of Human Cutaneous Melanoma

    Directory of Open Access Journals (Sweden)

    Bhuvnesh K. Sharma

    2010-03-01

    Full Text Available A review of the natural behavior of cutaneous melanoma, clinical and pathological factors, prognostic indicators, some basic research and the present and possible futuristic strategies in the management of this disease are presented. While surgery remains to be the most effective therapeutic approach in the management of early primary lesions, there is no standard adjuvant therapy after surgical resection, or for metastatic disease.

  2. 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 to be in......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...

  3. Fluorescence in situ detection of human cutaneous melanoma: study of diagnostic parameters of the method

    National Research Council Canada - National Science Library

    Chwirot, B W; Chwirot, S; Sypniewska, N; Michniewicz, Z; Redzinski, J; Kurzawski, G; Ruka, W

    2001-01-01

    Multicenter study of the diagnostic parameters was conducted by three groups in Poland to determine if in situ fluorescence detection of human cutaneous melanoma based on digital imaging of spectrally...

  4. Fluorescence in situ detection of human cutaneous melanoma: study of diagnostic parameters of the method.

    Science.gov (United States)

    Chwirot, B W; Chwirot, S; Sypniewska, N; Michniewicz, Z; Redzinski, J; Kurzawski, G; Ruka, W

    2001-12-01

    Multicenter study of the diagnostic parameters was conducted by three groups in Poland to determine if in situ fluorescence detection of human cutaneous melanoma based on digital imaging of spectrally resolved autofluorescence can be used as a tool for a preliminary selection of patients at increased risk of the disease. Fluorescence examinations were performed for 7228 pigmented lesions in 4079 subjects. Histopathologic examinations showed 56 cases of melanoma. A sensitivity of fluorescence detection of melanoma was 82.7% in agreement with 82.5% found in earlier work. Using as a reference only the results of histopathologic examinations obtained for 568 cases we found a specificity of 59.9% and a positive predictive value of 17.5% (melanomas versus all pigmented lesions) or 24% (melanomas versus common and dysplastic naevi). The specificity and positive predictive value found in this work are significantly lower than reported earlier but still comparable with those reported for typical screening programs. In conclusion, the fluorescence method of in situ detection of melanoma can be used in screening large populations of patients for a selection of patients who should be examined by specialists.

  5. Melanoma inhibitory activity in Brazilian patients with cutaneous melanoma*

    OpenAIRE

    Odashiro, Macanori; Hans Filho, Gunter; Pereira,Patricia Rusa; Castro, Ana Rita Coimbra Motta de; Stief, Alcione Cavalheiro; Pontes, Elenir Rose Jardim Cury; Odashiro, Alexandre Nakao

    2015-01-01

    Abstract BACKGROUND: Melanoma inhibitory activity is a protein secreted by melanoma cells and has been used as a tumor marker. Increased Melanoma inhibitory activity serum levels are related to metastatic disease or tumor recurrence. Currently there are no studies on Melanoma inhibitory activity and cutaneous melanoma involving Brazilian patients. OBJECTIVE: To evaluate the performance and feasibility of measuring Melanoma inhibitory activity levels in Brazilian patients with cutaneous melano...

  6. Cutaneous melanoma in women

    Directory of Open Access Journals (Sweden)

    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.

  7. 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

  8. N-ras mutations in human cutaneous melanoma from sun-exposed body sites

    NARCIS (Netherlands)

    van 't Veer, L. J.; Burgering, B. M.; Versteeg, R.; Boot, A. J.; Ruiter, D. J.; Osanto, S.; Schrier, P. I.; Bos, J. L.

    1989-01-01

    In 7 of 37 patients with cutaneous melanoma, mutations in the N-ras gene were found. The primary tumors of these seven patients were exclusively localized on body sites continuously exposed to sunlight. Moreover, the ras mutations were all at or near dipyrimidine sites known to be targets of UV

  9. [Diagnosis tools for cutaneous melanoma].

    Science.gov (United States)

    Guitera-Rovel, P; Vestergaard, M-E

    2008-12-01

    A number of new tools have been developed in the last ten years to improve the diagnosis of cutaneous melanoma. To review the value of diagnostic tools for cutaneous melanoma in a clinical setting. Review of multiple databases from 1987 to 2007 and classification of publications in terms of level of evidence according to "The Australian Cancer Network". Dermoscopy has superior specificity and sensitivity to naked-eye examination according to a meta-analysis of nine level-2 studies. Sequential digital dermoscopic imaging allowed detection of melanoma in the absence of dermoscopic evidence of melanoma in four level-2 studies. Total body photography, generally performed for high-risk patients, seems to be equally valuable but has the additional advantage of allowing self-examination by patients themselves. Dermographic photographs with computer-assisted diagnosis of primary melanoma appear to have equivalent diagnostic capacity to experts but very few studies have been performed in a clinical setting. Optical methods still under development yield in vivo information that is closely correlated with histopathology data and may avoid unnecessary excision while providing improved control of excision margins. They will doubtless be used as a second-line method after clinical detection of suspect lesions and history-taking, which will continue to be primordial regardless of the other tools available.

  10. Lessons from Cancer Immunoediting in Cutaneous Melanoma

    Directory of Open Access Journals (Sweden)

    Mariana Aris

    2012-01-01

    Full Text Available We will revisit the dual role of the immune system in controlling and enabling tumor progression, known as cancer immunoediting. We will go through the different phases of this phenomenon, exposing the most relevant evidences obtained from experimental models and human clinical data, with special focus on Cutaneous Melanoma, an immunogenic tumor per excellence. We will describe the different immunotherapeutic strategies employed and consider current models accounting for tumor heterogeneity. And finally, we will propose a rational discussion of the progress made and the future challenges in the therapeutics of Cutaneous Melanoma, taking into consideration that tumor evolution is the resulting from a continuous feedback between tumor cells and their environment, and that different combinatorial therapeutic approaches can be implemented according to the tumor stage.

  11. Clinicopathological and molecular aspects of cutaneous Melanoma

    NARCIS (Netherlands)

    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

  12. Selenium for the prevention of cutaneous melanoma.

    Science.gov (United States)

    Cassidy, Pamela B; Fain, Heidi D; Cassidy, James P; Tran, Sally M; Moos, Philip J; Boucher, Kenneth M; Gerads, Russell; Florell, Scott R; Grossman, Douglas; Leachman, Sancy A

    2013-03-07

    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.

  13. Selenium for the Prevention of Cutaneous Melanoma

    Directory of Open Access Journals (Sweden)

    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.

  14. Molecular Profiling in Cutaneous Melanoma.

    Science.gov (United States)

    Ji, Andrew L; Bichakjian, Christopher K; Swetter, Susan M

    2016-04-01

    Molecular profiling of malignant tumors is gaining increasing interest in oncology. In recent years, several molecular techniques have been studied in melanoma, with the goal to improve upon the diagnostic and prognostic abilities of currently available clinical and histopathologic parameters. Reliable tests performed early in the diagnosis and management of melanoma could lead to decreased morbidity and mortality by selecting appropriate patients for more-aggressive therapy and sparing those for whom it is not indicated. This article reviews the molecular diagnostic and prognostic techniques currently available for melanoma and evaluates their potential role in clinical practice. Copyright © 2016 by the National Comprehensive Cancer Network.

  15. 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

  16. Molecular Bases of Cutaneous and Uveal Melanomas

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    Sudeep Gaudi

    2011-01-01

    Full Text Available Intensive research in recent years has begun to unlock the mysteries surrounding the molecular pathogenesis of melanoma, the deadliest of skin cancers. The high-penetrance, low-frequency susceptibility gene CDKN2A produces tumor suppressor proteins that function in concert with p53 and retinoblastoma protein to thwart melanomagenesis. Aberrant CDKN2A gene products have been implicated in a great many cases of familial cutaneous melanoma. Sporadic cases, on the other hand, often involve constitutive signal transduction along the mitogen-activated protein kinase (MAPK pathway, with particular focus falling upon mutated RAS and RAF protooncogenes. The proliferative effects of the MAPK pathway may be complemented by the antiapoptotic signals of the PI3K/AKT pathway. After skin, melanoma most commonly affects the eye. Data for the constitutive activation of the MAPK pathway in uveal melanoma exists as well, however, not through mutations of RAS and RAF. Rather, evidence implicates the proto-oncogene GNAQ. In the following discussion, we review the major molecular pathways implicated in both familial and sporadic cutaneous melanomagenesis, the former accounting for approximately 10% of cases. Additionally, we discuss the molecular pathways for which preliminary evidence suggests a role in uveal melanomagenesis.

  17. Cutaneous Complications of Targeted Melanoma Therapy.

    Science.gov (United States)

    de Golian, Emily; Kwong, Bernice Y; Swetter, Susan M; Pugliese, Silvina B

    2016-11-01

    The landscape of advanced and metastatic melanoma therapy has shifted dramatically in recent years. Since 2011, eight drugs (ipilimumab, vemurafenib, dabrafenib, trametinib, cometinib, pembrolizumab, nivolumab, and talimogene laherparepvec) have received FDA approval for the treatment of advanced or metastatic melanoma, including combination regimens of both small molecule kinase and immune checkpoint inhibitors. These therapies have revolutionized the management of unresectable regional nodal and distant melanoma, providing hope of extended survival to patients. As the use of novel agents has increased, so have the cutaneous toxicities associated with these medications. While most skin reactions are low-grade and can be managed conservatively with topical therapies, malignant lesions and more serious or life-threatening drug reactions can arise during therapy, requiring prompt dermatologic recognition and treatment in order to improve patient outcome. Given the survival benefit attributed to these new agents, treating skin toxicity and maintaining patient quality of life is of paramount importance. Oncologists should be aware of the common cutaneous toxicities associated with these medications and should be encouraged to involve dermatologists in the collaborative care of advanced melanoma patients. Close communication between oncologists and dermatologists can help to avoid unnecessary dose reduction or treatment discontinuation and identify situations when treatment cessation is truly warranted.

  18. Genetic study of familial uveal melanoma: association of uveal and cutaneous melanoma with cutaneous and ocular nevi.

    Science.gov (United States)

    Smith, Jennifer H; Padnick-Silver, Lissa; Newlin, Anna; Rhodes, Katrina; Rubinstein, Wendy S

    2007-04-01

    To evaluate a kindred with familial uveal and cutaneous melanoma and to identify potential genetic and environmental factors that may predispose individuals to develop uveal melanoma. Family-based case report with detailed clinical and genetic evaluation. Ten siblings in a single nuclear family. Evaluation of a large sibship via family history, complete eye and skin examinations, environmental risk factor questionnaire, and genetic testing, as well as a MEDLINE search of familial uveal melanoma kindreds. Cutaneous and ocular nevi, benign and malignant neoplasms of skin and other sites, brief skin cancer risk assessment tool risk classification for cutaneous melanoma, DNA sequencing of p16INK4a and p14ARF genes, and citations on familial uveal melanoma. The proband and his mother had uveal melanoma, 3 cutaneous melanomas occurred among 2 siblings, and 2 other siblings had basal cell carcinomas. No germline mutations were detected in the melanoma-associated tumor suppressor genes p16INK4a and p14ARF. Seven out of 10 siblings had a history of cutaneous and/or ocular nevi. Of the 3 subjects without nevi, 2 had histories of eye or skin malignancies (1 uveal melanoma, 1 basal cell carcinoma). Three of the 10 siblings had relevant ocular findings (2 choroidal nevi, 1 uveal melanoma). Six were also found to be in the "high-risk" classification for cutaneous malignancies based on scores from a previously validated risk assessment tool. This family, combined with the 91 previously reported familial uveal melanoma kindreds, brings to 92 the total number thus far recorded. Our results strengthen the association between uveal melanoma, atypical nevi, and cutaneous melanoma. This relationship supports the recommendation that individuals with a personal or family history of uveal melanoma, particularly in combination with atypical nevi, should be regularly screened for uveal and cutaneous melanoma.

  19. Primary cutaneous melanoma: an 18-year study

    Directory of Open Access Journals (Sweden)

    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. Surgical excision margins for primary cutaneous melanoma.

    Science.gov (United States)

    Sladden, Michael J; Balch, Charles; Barzilai, David A; Berg, Daniel; Freiman, Anatoli; Handiside, Teenah; Hollis, Sally; Lens, Marko B; Thompson, John F

    2009-10-07

    Cutaneous melanoma accounts for 75% of skin cancer deaths. Standard treatment is surgical excision with a safety margin some distance from the borders of the primary tumour. The purpose of the safety margin is to remove both the complete primary tumour and any melanoma cells that might have spread into the surrounding skin.Excision margins are important because there could be trade-off between a better cosmetic result but poorer long-term survival if margins become too narrow. The optimal width of excision margins remains unclear. This uncertainty warrants systematic review. To assess the effects of different excision margins for primary cutaneous melanoma. In August 2009 we searched for relevant randomised trials in the Cochrane Skin Group Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 3, 2009), MEDLINE, EMBASE, LILACS, and other databases including Ongoing Trials Registers. We considered all randomised controlled trials (RCTs) of surgical excision of melanoma comparing different width excision margins. We assessed trial quality, and extracted and analysed data on survival and recurrence. We collected adverse effects information from included trials. We identified five trials. There were 1633 participants in the narrow excision margin group and 1664 in the wide excision margin group. Narrow margin definition ranged from 1 to 2 cm; wide margins ranged from 3 to 5 cm. Median follow-up ranged from 5 to 16 years. This systematic review summarises the evidence regarding width of excision margins for primary cutaneous melanoma. None of the five published trials, nor our meta-analysis, showed a statistically significant difference in overall survival between narrow or wide excision.The summary estimate for overall survival favoured wide excision by a small degree [Hazard Ratio 1.04; 95% confidence interval 0.95 to 1.15; P = 0.40], but the result was not significantly different. This result is compatible

  1. Genetics of uveal melanoma and cutaneous melanoma: two of a kind?

    NARCIS (Netherlands)

    T. van den Bosch (Thomas); E. Kiliç (Emine); A.D.A. Paridaens (Dion); J.E.M.M. de Klein (Annelies)

    2010-01-01

    textabstractCutaneous melanoma and uveal melanoma both derive from melanocytes but show remarkable differences in tumorigenesis, mode of metastatic spread, genetic alterations, and therapeutic response. In this review we discuss the differences and similarities along with the genetic research

  2. Sun behaviour after cutaneous malignant melanoma

    DEFF Research Database (Denmark)

    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...

  3. Ocular metastasis of cutaneous malignant melanoma.

    Science.gov (United States)

    Ullah, Tehseena; Gurwood, Andrew S; Myers, Marc D

    2009-10-01

    Metastatic melanoma to the eye and orbit are rare. Patients at greatest risk often have disseminated metastases in the setting of advanced disease. Because the prognosis for orbital metastatic disease is poor, emphasis must be placed on early detection and prevention. Although cutaneous malignancies include basal cell carcinoma, squamous cell carcinoma, sebaceous cell carcinoma, and malignant melanoma, the majority of cases that result in metastasis, ocular morbidity, and mortality are from sebaceous cell carcinoma and malignant melanoma. A 72-year-old white woman presented emergently with a chief complaint of sudden, painless vision loss in her left eye of 2 weeks' duration. Her best-corrected visual acuities measured 20/30 in the right eye and 20/400 in the left eye with no improvement on refraction. Her systemic medical history was significant for the diagnosis of a cutaneous malignant melanoma. Examination of the left eye found grade II disc edema with all other posterior pole and peripheral structures intact and unremarkable. Magnetic resonance imaging confirmed the diagnosis of metastatic lesions involving structures of the left orbit ultimately causing reduced visual ability. The patient opted to avoid aggressive care and "hope for the best." Denying significant medical intervention, the woman lived in hospice where she died 6 months later. The primary care optometric setting, by the way a patient's visual symptoms present or the appearance of fundus abnormalities, can offer the capability of first detection and referral for the discovery of metastatic lesions. Although orbital metastasis is considered a terminal finding in these cases, timely diagnosis enables, while limited, the best options for management.

  4. Pitfalls in Cutaneous Melanoma Lymphatic Drainage.

    Science.gov (United States)

    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.

  5. Sonography of the Primary Cutaneous Melanoma: A Review

    Directory of Open Access Journals (Sweden)

    Ximena Wortsman

    2012-01-01

    Full Text Available The diagnosis and management of primary cutaneous melanoma have traditionally relied on clinical and histological characteristics. Nevertheless, in recent years there has been a significant growth in the usage of ultrasound for studying the cutaneous layers. Thus, the present paper focuses on the primary lesion, its sonographic characteristics, the potential benefits of early imaging, and the new developments on the ultrasound field applied to cutaneous melanoma.

  6. Minichromosome maintenance protein expression in benign nevi, dysplastic nevi, melanoma, and cutaneous melanoma metastases.

    Science.gov (United States)

    Boyd, Alan S; Shakhtour, Bashar; Shyr, Yu

    2008-05-01

    Minichromosome maintenance (MCM) proteins are a recently elucidated group of polypeptides intimately involved in DNA replication and appreciable only in cycling cells. In other organ systems their expression has proven more prognostically useful than cell proliferation markers such as Ki-67 and proliferating cell nuclear antigen. To date, the evaluation of MCM proteins in melanocytic neoplasms has not been undertaken. We sought to determine whether MCM protein 2 (the most extensively evaluated of the MCM protein family) is present in melanocytes from benign nevi, dysplastic nevi, primary cutaneous melanomas, and cutaneous melanoma metastases and, if so, whether there exists a significant difference in expression among the 3 groups. Immunohistochemical staining for MCM 2 was performed on tissue sections from 10 benign nevi, dysplastic nevi, and primary cutaneous melanomas and from 5 cutaneous melanoma metastases. Approximately 200 cells were evaluated microscopically in 5 separate fields for each specimen and the number of positively staining nuclei was counted. After a percentage was calculated for each lesion, the data were pooled and statistically analyzed. Melanocyte nuclear staining was readily visible microscopically. The percentage of positively staining nuclei in benign nevi (1.2%), dysplastic nevi (6.1%), primary cutaneous melanomas (49.1%), and cutaneous melanoma metastases (40.9%) was significantly different (P benign nevi and melanoma, dysplastic nevi and melanoma, benign nevi and cutaneous melanoma metastases, and dysplastic nevi and cutaneous melanoma metastases. There was no statistically significant difference between cutaneous melanoma metastases and primary cutaneous melanoma. This is a small pilot study without blinded evaluation of the tissue sections and lacking correlation with patient clinical outcome or accepted histologic prognostic factors. MCM protein expression appears to differ significantly in melanocytic neoplasms and potentially

  7. 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

  8. 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

  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. 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

  11. Metastatic Tumor Dormancy in Cutaneous Melanoma: Does Surgery Induce Escape?

    Energy Technology Data Exchange (ETDEWEB)

    Tseng, William W. [Department of Surgery, University of California at San Francisco, 513 Parnassus Avenue, Room S-321, San Francisco, CA 94143 (United States); Fadaki, Niloofar; Leong, Stanley P., E-mail: leongsx@cpmcri.org [Department of Surgery and Center for Melanoma Research and Treatment, California Pacific Medical Center and Research Institute, 2340 Clay Street, 2nd floor, San Francisco, CA 94115 (United States)

    2011-02-21

    According to the concept of tumor dormancy, tumor cells may exist as single cells or microscopic clusters of cells that are clinically undetectable, but remain viable and have the potential for malignant outgrowth. At metastatic sites, escape from tumor dormancy under more favorable local microenvironmental conditions or through other, yet undefined stimuli, may account for distant recurrence after supposed “cure” following surgical treatment of the primary tumor. The vast majority of evidence to date in support of the concept of tumor dormancy originates from animal studies; however, extensive epidemiologic data from breast cancer strongly suggests that this process does occur in human disease. In this review, we aim to demonstrate that metastatic tumor dormancy does exist in cutaneous melanoma based on evidence from mouse models and clinical observations of late recurrence and occult transmission by organ transplantation. Experimental data underscores the critical role of impaired angiogenesis and immune regulation as major mechanisms for maintenance of tumor dormancy. Finally, we examine evidence for the role of surgery in promoting escape from tumor dormancy at metastatic sites in cutaneous melanoma.

  12. Metastatic Tumor Dormancy in Cutaneous Melanoma: Does Surgery Induce Escape?

    Directory of Open Access Journals (Sweden)

    William W. Tseng

    2011-02-01

    Full Text Available According to the concept of tumor dormancy, tumor cells may exist as single cells or microscopic clusters of cells that are clinically undetectable, but remain viable and have the potential for malignant outgrowth. At metastatic sites, escape from tumor dormancy under more favorable local microenvironmental conditions or through other, yet undefined stimuli, may account for distant recurrence after supposed “cure” following surgical treatment of the primary tumor. The vast majority of evidence to date in support of the concept of tumor dormancy originates from animal studies; however, extensive epidemiologic data from breast cancer strongly suggests that this process does occur in human disease. In this review, we aim to demonstrate that metastatic tumor dormancy does exist in cutaneous melanoma based on evidence from mouse models and clinical observations of late recurrence and occult transmission by organ transplantation. Experimental data underscores the critical role of impaired angiogenesis and immune regulation as major mechanisms for maintenance of tumor dormancy. Finally, we examine evidence for the role of surgery in promoting escape from tumor dormancy at metastatic sites in cutaneous melanoma.

  13. POLE mutations in families predisposed to cutaneous melanoma

    DEFF Research Database (Denmark)

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

    2015-01-01

    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......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...... variants in the exonuclease domain of POLE. Although this frequency is not significantly higher than that in unselected Caucasian controls, we observed multiple cancer types in the melanoma families, suggesting that some germline POLE mutations may predispose to a broad spectrum of cancers, including...

  14. Epidemiological aspects of cutaneous malignant melanoma (review).

    Science.gov (United States)

    Serraino, D; Fratino, L; Gianni, W; Campisi, C; Pietropaolo, M; Trimarco, G; Marigliano, V

    1998-01-01

    There is an increasing interest in the etiology of cutaneous malignant melanoma (CMM). Once considered a rare tumour, CMM is now the fourth commonest cancer in Australia and New Zeland, the tenth in the Usa, Canada and Scandinavia and the eighteenth in Great Britain. The growing scientific concern on the urgent need to highlight the cause/s of CMM is well documented by the large number of well-designed and well-conducted epidemiological studies reported in the last two decades. Such studies facilitated testing of many etiological hypotheses derived from earlier descriptive investigations and contributed to significant progress in understanding the etiology of such disease. The quantification of the extent to which the increases in CMM incidence and mortality rates are related to new lifestyles and to new patterns of exposure to potential carcinogenetic agents is essential in order to establish an appropriate preventive strategy. In population of mainly European origin a substantial proportion of the increased incidence of CMM is attributable to steady change from predominantly occupational to predominantly recreational exposure to solar radiation. Therefore the present review puts particular emphasis on exposure to sunlight as well as to artificial ultraviolet light, as modifiable causes of CMM. Incidence and mortality data and other potential risk factors for the development of CMM will also be briefly reviewed.

  15. Tumor-associated B cells in cutaneous primary melanoma and improved clinical outcome.

    Science.gov (United States)

    Garg, Kanika; Maurer, Margarita; Griss, Johannes; Brüggen, Marie-Charlotte; Wolf, Ingrid H; Wagner, Christine; Willi, Niels; Mertz, Kirsten D; Wagner, Stephan N

    2016-08-01

    B cells often infiltrate the microenvironment of human tumors. B cells can both positively and negatively regulate antitumor immune responses. In several human cancers, higher numbers of CD20(+) TAB are associated with a favorable prognosis, whereas in human primary melanomas, this association is contentious. In this study, we determined the association of TAB numbers in cutaneous primary melanoma tissue samples and patients' overall survival. The CD20 immunohistochemistry on archival nonmetastasized and metastasized cutaneous primary melanoma tissues from 2 independent patient cohorts was performed. One cohort was used in class comparison for metastasis, the most important prognostic factor for overall survival, and the other cohort for a subsequent survival analysis. Survival association was further validated with RNA data from a third independent cohort. Whole tissue sections were read automatically via quantitative digital imaging and analysis. Survival data were analyzed by Cox proportional hazard modeling. We discovered that cutaneous primary melanomas without metastasis contain significantly more TAB than primary melanomas that had metastasized. At time of first diagnosis, a higher number of TAB is associated with a significantly better overall survival in patients with cutaneous primary melanomas of >1 mm Breslow depth. Also, higher CD20/CD19 tumor mRNA levels are correlated with a significantly better overall survival. Thus, our data support TAB numbers as a prognostic biomarker in cutaneous primary melanoma patients with a tumor of >1 mm Breslow depth. For a survey in larger studies, whole tissue section analysis seems to be key to accurate assessment of TAB numbers. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. POLE mutations in families predisposed to cutaneous melanoma.

    Science.gov (United States)

    Aoude, Lauren G; Heitzer, Ellen; Johansson, Peter; Gartside, Michael; Wadt, Karin; Pritchard, Antonia L; Palmer, Jane M; Symmons, Judith; Gerdes, Anne-Marie; Montgomery, Grant W; Martin, Nicholas G; Tomlinson, Ian; Kearsey, Stephen; Hayward, Nicholas K

    2015-12-01

    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 variants in the exonuclease domain of POLE. Although this frequency is not significantly higher than that in unselected Caucasian controls, we observed multiple cancer types in the melanoma families, suggesting that some germline POLE mutations may predispose to a broad spectrum of cancers, including melanoma. In addition, we found the first mutation outside the exonuclease domain, p.(Gln520Arg), in a family with an extensive history of colorectal cancer.

  17. DMBT1 expression distinguishes anorectal from cutaneous melanoma

    DEFF Research Database (Denmark)

    Helmke, Burkhard Maria; Renner, Marcus; Poustka, Annemarie

    2009-01-01

    AIMS: Anorectal melanoma (AM) forms a rare but highly malignant subset of mucosal melanoma with an extremely poor prognosis. Although AMs display histological and immunohistochemical features very similar to cutaneous melanoma (CM), no association exists either with exposure to ultraviolet light...... tumours 1 (DMBT1) in cases of primary anorectal malignant melanoma and CM. METHODS AND RESULTS: Expression analyses of classical immunohistochemical markers (S100, HMB45, Melan A and MiTF) and of the protein DMBT1 were carried out in 27 cases of primary anorectal malignant melanoma and 26 cases of CM. All...... AM cases analysed showed expression of at least three of the classical markers for melanoma. However, immunohistochemistry showed 19 out of 27 AM to be positive for DMBT1, which represented a statistically significant difference (P = 0.0009) compared with CM (six out of 26), which more commonly...

  18. 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.

  19. On the clinical significance of cutaneous melanoma's precursors

    Science.gov (United States)

    Noto, Giuseppe

    2012-01-01

    We can identify three main groups of cutaneous pigmented lesions that could be represented as melanoma precursors: (a) congenital melanocytic nevi, (b) dysplastic or atypical nevi, and (c) acquired melanocytic nevi. The occurrence of melanoma in small and intermediate congenital melanocytic nevi is very uncommon, but there is a high risk in large congenital melanocytic nevi, in particular those arising in the so-called “bathing trunk” distribution. It is very important to distinguish the familial dysplastic nevus syndrome, which is a strong risk factor for cutaneous melanoma, from not familial (sporadic) dysplastic nevus, in which the risk for melanoma would depend on the total number of melanocytic nevi, phototype, and on the relationship to environmental factors. PMID:23130279

  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. Cutaneous melanoma in solid organ transplant patients.

    Science.gov (United States)

    Russo, I; Piaserico, S; Belloni-Fortina, A; Alaibac, M

    2014-08-01

    Solid organ transplant patients are at greatly increased risk of developing a wide variety of skin cancers, particularly epithelial skin cancers. On the other hand, it is well known that an intact immune system limits the development of benign melanocytic lesions. The eruptive nevi phenomenon, which we can observe in solid organ transplant recipients, is indicative of the relationship between melanocyte proliferation and immune system. Regression of melanocytic nevi after restoration of complete immune responsiveness is a further clinical example the role of immunosurveillance on melanocyte proliferation. However, melanoma incidence in organ transplant recipients appears only 2-3 folds higher than in general population. To this regard, organ transplant recipients who develop de novo melanomas thicker than 2mm seem to have a significantly worse outcome with a greatly increased risk of dying of metastatic melanoma, whereas those who develop a ≤2 mm thickness melanoma seem to have a prognosis similar to that of the general population. Furthermore, there is no evidence supporting an increased risk of melanoma recurrences after transplant in patients with a history of low-risk melanoma. Melanoma is also one of the most frequent and lethal donor-derived malignancies suggesting that a history of invasive melanoma should be considered an absolute contraindication to donation. The aim of this review is to investigate the relationship between immunosuppression and melanoma and to discuss its clinical implications for the management of transplant-associated melanoma.

  2. 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

  3. Geometric cutaneous melanoma: a helpful clinical sign of malignancy?

    Science.gov (United States)

    Morris, Andrew D; Gee, Bruce C; Millard, Leslie G

    2003-08-01

    Malignant melanomas change shape in a random pattern, with ovoid, crescentic, or nodular shapes seen most frequently. We have observed a number of malignant melanomas that have presented with a geometric, angular shape and have noted that pigmented lesions with this configuration are often found to be malignant. We present 20 patients with malignant melanoma whose lesion displayed a geometric, angular shape. Before excision for formal histopathology, all lesions were scored using the seven-point checklist and ABCDE systems and were divided into low-risk or significant risk of melanoma. Five different geometric shapes were observed. Depending on the scoring system employed, 20% to 40% of the geometric melanomas were considered to be of low risk of malignancy. The development of geometrical angular patterns in a malignant melanoma may represent a morphologic growth pattern that can be used as a clinical risk sign. Even apparently benign low-risk lesions with a geometric shape may pose a significant risk of malignant melanoma. By definition, the majority of lesions that are morphologically geometric are symmetrical in shape, which is more in favor of a benign diagnosis. This may increase the likelihood that early cutaneous melanomas with a geometric shape may be missed. Any pigmented lesion with a geometric configuration should raise the clinician's suspicion of malignancy even if considered otherwise to be of low risk by the standard melanoma checklists.

  4. 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 BRAFV600E 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.

  5. 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.

  6. Follow-up in patients with localised primary cutaneous melanoma

    NARCIS (Netherlands)

    Francken, AB; Bastiaannet, E; Hoekstra, HJ

    Follow-up services for patients with localised cutaneous melanoma are widely discussed but there is no international consensus. Our aim was to discuss frequency and duration of follow-up, type of health professional involved, optimum intensity of routine investigation, and patients' satisfaction

  7. 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...

  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. Selected benign cutaneous lesions that may simulate melanoma histologically.

    Science.gov (United States)

    Wick, Mark R

    2016-07-01

    As cutaneous melanomas manifest a wide spectrum of clinical and pathologic presentations, several other lesions enter into their differential diagnosis. This article considers those entities, including melanocytic hyperplasia, cellular nodules in congenital nevi, atypical lentiginous melanocytic proliferations, "special site" nevi, epithelioid histiocytoma, neurothekeoma, cellular schwannoma, and proliferating scars. Copyright © 2016. Published by Elsevier Inc.

  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 melanoma – guidelines for diagnostics and therapy in 2016

    Directory of Open Access Journals (Sweden)

    Piotr Rutkowski

    2016-02-01

    Full Text Available Dermoscopy is currently the standard method for clinical differential diagnosis of cutaneous melanoma and for qualifying a lesion for excisional biopsy. Full thickness excisional biopsy of suspicious melanomatous skin lesions likely to be diagnosed as early melanomas is crucial in establishing the diagnosis and defining prognostic factors. Early diagnosis and surgical removal of cutaneous melanoma not only improves patients’ prognosis but is also associated with approximately 90% likelihood of cure. The next steps in the therapeutic management of cutaneous melanoma following excisional biopsy are radical scar excision with adequate margins and sentinel lymph node biopsy. Radical lymph node dissection is recommended in the case of regional lymph node metastases. High-risk patients (lymph node involvement and/or ulcerated primary lesion should be advised to participate in prospective clinical trials on adjuvant therapy. Melanoma patients with distant metastases are still characterized by poor outcomes. In patients with metastatic disease testing for the presence of BRAF gene mutation is mandatory. Patients with metastatic disease should be considered for participation in clinical trials. Long-term survival is confined to a selected group of patients undergoing resection of isolated metastatic lesions. In systemic – mainly first-line – therapy of patients with BRAF V600 mutation the BRAF inhibitor vemurafenib or dabrafenib (preferentially in combination with a MEK inhibitor may be employed and independently of mutational status immunotherapy with anti-PD-1 antibodies (nivolumab or pembrolizumab and eventually ipilimumab (anti-CTLA4 antibody may be used.

  12. 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

  13. Role of obesity on the thickness of primary cutaneous melanoma.

    Science.gov (United States)

    Skowron, F; Bérard, F; Balme, B; Maucort-Boulch, D

    2015-02-01

    Thick primary cutaneous melanoma (PCM) is associated with older age, male sex, being single, a low educational level, self-detection and general practice detection, nodular melanoma (NM) and acral lentiginous melanoma (ALM) types; and are found in the head-neck and lower limb locations. Obesity plays a direct role on melanoma tumour growth, as it has been shown in animal models, but its role in the thickness of PCM remains unknown. We investigated the impact of obesity on the thickness of invasive PCM. A cross-sectional study was performed in a prospective cohort for which we collected several clinical and histological data already known to be associated with thick PCM and the Body Mass Index from new cases of invasive PCM which were referred to the dermatology department in Valence. Four hundred and twenty-seven patients were studied. In an univariate analysis, thick PCM was associated with low educational level, obesity, identification by the patient or the general practitioner (GP), location on the cephalic extremity, in a non-visible area of the body, the NM and ALM type, and an ulceration. In a multivariate analysis, NM, ulceration, topography of the melanoma and identification of the melanoma by the patient or GP were significantly associated with thick melanoma. When including only clinical features in the model, low educational level, mode of melanoma identification and obesity were significantly associated with a risk of thick melanoma. Obesity is a clinical independent risk factor of thick PCM. For health policies, governments should pay greater attention to detect melanoma in obese patients. Our results encourage the basic research on tumoural growth mechanisms due to obesity in melanoma. © 2014 European Academy of Dermatology and Venereology.

  14. Vitamin D status and risk for malignant cutaneous melanoma: recent advances.

    Science.gov (United States)

    Ombra, Maria N; Paliogiannis, Panagiotis; Doneddu, Valentina; Sini, Maria C; Colombino, Maria; Rozzo, Carla; Stanganelli, Ignazio; Tanda, Francesco; Cossu, Antonio; Palmieri, Giuseppe

    2017-11-01

    Cutaneous malignant melanoma, whose incidence is increasing steadily worldwide, is the result of complex interactions between individual genetic factors and environmental risk factors. Ultraviolet radiation represents the most important environmental risk factor for the development of skin cancers, including melanoma. Sun exposure and early sunburn during childhood are the principal causes of cutaneous melanoma insurgence in adults, with double the risk relative to a nonexposed population. Consequently, ultraviolet protection has long been recognized as an important measure to prevent such a malignancy. Biological and epidemiological data suggest that vitamin D status could affect the risk of cancer and play a role in cancer prevention by exerting antiproliferative effects. Solar radiations are critical for vitamin D synthesis in humans; however, uncontrolled and intensive sun exposure is dangerous to skin health and may contribute toward the development of cutaneous malignant melanoma. An optimum balance between sun protection and exposure is thus advocated. Additional research is required to confirm the preventive role of vitamin D in melanoma incidence or a positive influence on patient outcome.

  15. Sentinel lymph node biopsy in cutaneous melanoma.

    Science.gov (United States)

    Ribero, Simone; Sportoletti Baduel, Eugenio; Osella-Abate, Simona; Dika, Emi; Quaglino, Pietro; Picciotto, Franco; Macripò, Giuseppe; Bataille, Veronique

    2017-08-01

    The management of melanoma is constantly evolving. New therapies and surgical advances have changed the landscape over the last years. Since being introduced by Dr Donald Morton, the role of sentinel lymph node has been debated. In many melanoma centers, sentinel node biopsy is not a standard of care for melanoma above 1 mm in thickness. The results of the MSLT-II Trial are not available for a while and in the meantime, this procedure is offered as a prognostic indicator as it has been shown to be very useful for assessing risk of relapse. The biology of lymph node spread in melanoma is a complex field and there are many factors which influence it such as age, melanoma body site, thickness but other factors such as regression, ulceration and gender need further evaluation. In this review, we address the clinical value of sentinel lymph node biopsy and how its indication has changed over the years especially recently with the setup of many adjuvant trials which are offered to stage 3 melanomas.

  16. Penetration of dacarbazine and its active metabolite 5-aminoimidazole-4-carboxamide into cutaneous metastases of human malignant melanoma.

    Science.gov (United States)

    Joukhadar, C; Klein, N; Mader, R M; Schrolnberger, C; Rizovski, B; Heere-Ress, E; Pehamberger, H; Strauchmann, N; Jansen, B; Müller, M

    2001-10-15

    Dacarbazine has been on the market for approximately 3 decades but remains the most effective single agent available for the therapy of metastatic malignant melanoma (MMM). Most MMMs, however, respond poorly to dacarbazine therapy. Apart from tumor resistance at a molecular level, several studies support the notion that therapeutic failure in tumor therapy also might be attributed to an impaired transcapillary drug transfer. On the basis of this hypothesis, the authors measured intratumor transcapillary transfer rates of dacarbazine and its active metabolite 5-aminoimidazole-4-carboxamide (AIC) by in vivo microdialysis after intravenous administration of dacarbazine at doses of 200 mg/m(2) to 1000 mg/m(2) (n = 7) in patients suffering from MMM. For all doses, area under the concentration curve (AUC) values for dacarbazine and AIC were not significantly different between plasma and tumor interstitium with AUC(tumor)/AUC(plasma) ratios of 0.97 +/- 0.08 (mean +/- standard error of the mean) for dacarbazine and 0.76 +/- 0.22 for AIC. AUC(0-240) values for dacarbazine and AIC measured in plasma correlated closely with corresponding AUC(0-240)values measured in the interstitium of MMMs with values of r(s) = 0.82 (P = 0.042) and r(s) = 0.90 (P = 0.037), respectively. The results of this study indicate favorable tumor penetration characteristics of dacarbazine and its active metabolite AIC. The relative lack of response to antineoplastic therapy with dacarbazine, thus might be explained by resistance of melanoma cells at a molecular level rather than by an inability of dacarbazine and AIC to penetrate into the interstitium of MMM. Copyright 2001 American Cancer Society.

  17. Caffeine Intake, Coffee Consumption, and Risk of Cutaneous Malignant Melanoma.

    Science.gov (United States)

    Wu, Shaowei; Han, Jiali; Song, Fengju; Cho, Eunyoung; Gao, Xiang; Hunter, David J; Qureshi, Abrar A

    2015-11-01

    Caffeine has been shown to prevent ultraviolet radiation-induced carcinogenesis and to inhibit growth of melanoma cells in experimental studies. We evaluated the association among caffeine intake, coffee consumption, and melanoma risk among three large cohort studies. The analysis used data from 89,220 women in the Nurses' Health Study II (1991-2009), 74,666 women in the Nurses' Health Study (1980-2008), and 39,424 men in the Health Professionals Follow-up Study (1986-2008). We used Cox proportional hazards models to estimate the hazard ratios (HR) with 95% confidence intervals (CIs) of melanoma associated with dietary intakes. We documented 2,254 melanoma cases over 4 million person-years of follow-up. After adjustment for other risk factors, higher total caffeine intake was associated with a lower risk of melanoma (≥393 mg/day vs. caffeinated coffee consumption, whereas no association was found for decaffeinated coffee consumption and melanoma risk. Increasing caffeine intake and caffeinated coffee consumption is associated with decreased risk of cutaneous malignant melanomas.

  18. Cutaneous Malignant Melanoma in a Cat

    OpenAIRE

    Karakurum, Mehmet Çağrı; Pekcan, Zeynep; Özmen, Özlem

    2009-01-01

    Melanomlar melanosit ve melanoblastların benign veya malign tümörleridir. Malign melanom kedilerde oldukça nadir gözlenen bir tümördür. Bu vaka takdiminde 16 yaşlı bir kedide kutanöz malign melonoma’nın klinik ve histopatolojik bulguları bildirilmiştir. Bu, aynı zamanda, Türkiye’de bir kedide bildirilen ilk kutanöz malign melanoma vakasıdır. Melanomas are neoplasia of melanocytes and melanoblasts which may in benign or malign character. Malign melanoma is typically considered as a rare neo...

  19. Data Set for Pathology Reporting of Cutaneous Invasive Melanoma

    Science.gov (United States)

    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

  20. Cutaneous Spitzoid melanoma in a very young girl of Asian descent

    OpenAIRE

    Miranda, Suzette G; Kashani-Sabet, Mohammed; Zedek, Daniel; McCalmont, Timothy H.; Leong, Stanley P L

    2011-01-01

    Cutaneous melanoma is extremely uncommon in children. Further, Asian-Americans appear to be at decreased risk for cutaneous melanoma. The authors present the case of a prepubescent Asian girl who presents with the rare spitzoid variant of cutaneous melanoma. The patient is a 4-year-old girl of Chinese descent who presented with a red, raised nodule, which increased in size over a 3-month period. She underwent wide local excision with sentinel lymph node dissection. On histopathologic analysis...

  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. Cost of Cutaneous Melanoma by Tumor Stage: A Descriptive Analysis.

    Science.gov (United States)

    Serra-Arbeloa, P; Rabines-Juárez, Á O; Álvarez-Ruiz, M S; Guillén-Grima, F

    2017-04-01

    The basis for optimal resource allocation is an understanding of requirements during the diagnostic and treatment phases. Costs associated with the rising incidence of cutaneous melanoma are considerable. We undertook an up-to-date analysis of the cost of diagnosis, treatment, and follow-up according to tumor stage. We constructed descriptive tables following a theoretical model of direct costs based on amounts published in directives for the Spanish national health system and in international guidelines for managing cutaneous melanoma according to stage at diagnosis and clinical course. The tables allowed us to calculate the cost of treating individual patients as well as the expected cost for all patients with tumors in the same stage. Individual patients would generate costs ranging from €1689 (for a stage I tumor) to €88, 268 (stage IV). The largest differences were between stages IA and IB-IIA and between stages III and IV. Costs differed greatly between patients with early-stage tumors and favorable outcomes and those with recurring tumors, which cost 50-fold more in the first year and 20-fold more after 10 years of follow-up. The high cost of diagnosing advanced-stage cutaneous melanoma calls attention to the need to promote primary prevention and early detection. Our findings provide the knowledge base for cost-effectiveness studies in this disease. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Kinetics of three lymphoscintigraphic agents in patients with cutaneous melanoma.

    Science.gov (United States)

    Glass, E C; Essner, R; Morton, D L

    1998-07-01

    Although lymphoscintigraphy is commonly used for the preoperative evaluation of patients with cutaneous melanoma and for intraoperative identification of sentinel lymph nodes, there is no consensus regarding the most useful radiopharmaceuticals or imaging times. Fifty-one consecutive patients with clinical American Joint Committee on Cancer Stage I or II melanoma were assigned to one of three groups of 17 for lymphoscintigraphy with one of three radiopharmaceuticals: 99mTc-albumin colloid (AC), 99mTc-human serum albumin (HSA) or 99mTc-sulfur colloid (SC). Colloidal agents were filtered through 0.2 microm filters. After injecting 18.5-30 MBq (500-800 microCi) of the radiopharmaceutical, dynamic monitoring over injection sites and node basins was performed to identify draining lymphatic channels and sentinel nodes. In addition, static digital and analog images were acquired from the injection site and draining node basins immediately after injection and at 30 min (early) and 2 to 4 hr (delayed) after injection. Dynamic and static images were analyzed to determine transit times to the sentinel node, the number of nodes visualized in early and delayed images, the quality of lymph node and lymph channel visualization, the sentinel-to-nonsentinel uptake ratios and the washout rates from injection sites. Early images with all three agents provided reliable identification of sentinel lymph nodes. Technetium-99m-HSA demonstrated faster washout rates from injection sites and better definition of lymph channels than either particulate agent, whereas particulate agents were retained longer in nodes and demonstrated more nodes in delayed images than in early images. All agents demonstrated lymph channels better in early images than in delayed images. In general, variations between patients exceeded differences between agents. Sentinel nodes could not be distinguished reliably from nonsentinel nodes in delayed images alone. All three agents are acceptable for cutaneous

  4. 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.

  5. Regression in primary cutaneous melanoma: etiopathogenesis and clinical significance.

    Science.gov (United States)

    Aung, Phyu P; Nagarajan, Priyadharsini; Prieto, Victor G

    2017-02-27

    Though not required currently for staging, regression is a histopathologic parameter typically reported upon diagnosis of an invasive primary cutaneous melanoma. The studies examining the prognostic significance of regression in patient outcome have yielded controversial findings; likely because the definition and assessment of regression have not been consistent, in addition to subjectivity of pathologists' interpretation. Regression is histologically characterized by variable decrease in the number of melanoma cells accompanied by the presence of a host response consisting of dermal fibrosis, inflammatory infiltrate, melanophages, ectatic blood vessels, epidermal attenuation, and/or apoptosis of keratinocytes or melanocytes; the relative extent of these features depends on the stage of the regression. However, the magnitudes to which these individual changes must be present to meet the threshold of histologic regression have not been well defined or agreed upon, and thus, the definition and classification of histologic regression in melanoma varies considerably among institutions and even among individual pathologists. In order to determine the clinical significance of histologic analysis of regression, there is a compelling need for a universal scheme to objectively define and assess histologic regression in primary cutaneous melanoma, so that the biologic and prognostic significance of this process may be completely understood.Laboratory Investigation advance online publication, 27 February 2017; doi:10.1038/labinvest.2017.8.

  6. The miRNA machinery in primary cutaneous malignant melanoma, cutaneous malignant melanoma metastases and benign melanocytic nevi.

    Science.gov (United States)

    Sand, Michael; Skrygan, Marina; Georgas, Dimitrios; Sand, Daniel; Gambichler, Thilo; Altmeyer, Peter; Bechara, Falk G

    2012-10-01

    Although several studies have shown a dysregulation of microRNA (miRNA) expression profiles in cutaneous melanoma, there has been little research on the miRNA machinery itself. In this study, we investigated the mRNA expression profiles of different miRNA machinery components in primary cutaneous malignant melanoma (PCMM), cutaneous malignant melanoma metastases (CMMM) and benign melanocytic nevi (BMN). Patients with PCMM (n = 7), CMMM (n = 6) and BMN (n = 7) were included in the study. Punch biopsies were harvested from the centers of tumors (lesional) and from BMN (control). In contrast to previous reports exploring specific clusters of miRNAs in PCMM, the present study investigates mRNA expression levels of Dicer, Drosha, Exp5, DGCR8 and the RISC components PACT, argonaute-1, argonaute-2, TARBP1, TARBP2, MTDH and SND1, which were detected by TaqMan real-time reverse transcription polymerase chain reaction (RT-PCR). Argonaute-1, TARBP2 and SND1 expression levels were significantly higher in BMN compared to PCMM (p  0.05). The results of this study show that the miRNA machinery components argonaute-1, TARBP2 and SND1 are dysregulated in PCMM and CMMM compared to BMN and may play a role in the process of malignant transformation.

  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. Variability of cutaneous lymphatic flow rates in melanoma patients.

    Science.gov (United States)

    Uren, R F; Howman-Giles, R B; Thompson, J F; Roberts, J; Bernard, E

    1998-06-01

    Preoperative lymphoscintigraphy was performed in 198 consecutive patients with cutaneous melanoma prior to their definitive surgical treatment. After intradermal injection of antimony sulphide colloid labelled with technetium-99m, lymphatic flow rates were measured in each patient and found to vary according to the location of the primary tumour. The fastest flow rates occurred from melanoma sites on the distal limbs, particularly the lower limbs. The slowest flow rates were from the head and neck region and the proximal limbs, especially the upper arms and shoulders. Lack of flow in the early dynamic images occurred most commonly for tumours on the upper arms and shoulders. These results can be used to optimize the timing of blue dye injection prior to surgery and may influence the sentinel node biopsy method to be used in individuals who show no early drainage.

  10. 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......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...... to the control or intervention group. Patients in the intervention group were offered six weekly sessions of 2 hours of psychoeducation, consisting of health education, enhancement of problem-solving skills, stress management, and psychological support. The participants were assessed at baseline before random...

  11. University Hospital Waterford: 5-year experience of cutaneous melanoma.

    Science.gov (United States)

    Sehgal, R; Cheung, C X; Alradadi, R; Healy, D A; Landers, R; O'Donoghue, G T

    2017-05-01

    The incidence of cutaneous melanoma (CM) continues to rise in Ireland. Despite significant advances in melanoma molecular therapy, surgery remains the mainstay of treatment for CM. The University Hospital Waterford (UHW) prospectively maintained CM registry was established in 2010. To summarize 5-year experience (2010-2015) of primary CM presenting to UHW. Data were retrospectively obtained from a central electronic pathology and radiology repository augmented by HIPE data and theatre logs. Data collected included patient demographics and clinico-pathological characteristics, specimen number, size, anatomical location, melanoma subtype, Breslow thickness, Clark's level, ulceration, and mitosis. 592 CMs were managed in UHW during the study period. Overall, females comprised the majority of cases with mean age at presentation 60.78 ± 18.29 years. The most commonly affected anatomical location was the lower limb (26.7%) followed by the back (15.1%), upper limb (15.07%), and face (14.40%). Superficial spreading and lentigo maligna were the most common histological subtype accounting for 19.8 and 20%, respectively. Overall, the mean Breslow depth was 2.4 ± 3.7 mm with corresponding Clark's Level III. Sentinel lymph node positivity was 39/103 (37.89%) most commonly located in the axilla (53.8%) and groin (30.7%). There has been a steady increase in the number of cutaneous melanoma presentations over the past 5-years to the South East Cancer Centre. Patients are managed best by prompt surgical excision and multidisciplinary management. Our results are in keeping with international standards and work continues in determining overall 5-year survival and recurrence rates.

  12. BRAF mutations distinguish anorectal from cutaneous melanoma at the molecular level

    DEFF Research Database (Denmark)

    Helmke, Burkhard M; Mollenhauer, Jan; Herold-Mende, Christel

    2004-01-01

    BACKGROUND & AIMS: Anorectal melanoma (AM) is a rare but highly malignant tumor, displaying histologic and immunohistochemical features very similar to cutaneous melanoma (CM). Because BRAF mutations were recently identified in the majority of CM and nevi, we investigated AM for BRAF mutations an......599E BRAF mutations, AM significantly differs from CM (P melanoma at the molecular level.......BACKGROUND & AIMS: Anorectal melanoma (AM) is a rare but highly malignant tumor, displaying histologic and immunohistochemical features very similar to cutaneous melanoma (CM). Because BRAF mutations were recently identified in the majority of CM and nevi, we investigated AM for BRAF mutations...

  13. Increased incidence of brain metastases in cutaneous head and neck melanoma

    NARCIS (Netherlands)

    Daryanani, D; Plukker, JT; de Jong, MA; Haaxma-Reiche, H; Nap, R; Kuiper, H; Hoekstra, HJ

    The incidence of cutaneous melanoma is increasing, and 10-20% of these melanomas are located in the head and neck region. The incidence of brain metastases, risk factors and outcome were analysed for melanomas originating in the head and neck region. During the period 1965-2000, 324 patients [12

  14. Prognostic significance of vascularity in cutaneous melanoma: pilot study using in vivo confocal scanning laser microscopy.

    Science.gov (United States)

    Humphrey, Shannon; Walsh, Noreen M; Delaney, Laura; Propperova, Iva; Langley, Richard G B

    2006-01-01

    Tumor vascularity may be of strong prognostic significance in cutaneous melanoma. We are the first to use a novel, noninvasive, in vivo confocal scanning laser microscope (CSLM) to evaluate vascularity in cutaneous melanoma. Our purpose was to apply a CSLM to assess vascularity in melanoma and to evaluate the prognostic significance of these findings. Patients with a suspicious pigmented lesion were prospectively recruited to undergo CSLM prior to skin biopsy, and those diagnosed with melanoma were included in this study. A blinded observer graded tumor vascularity from still digital CSLM images. The CSLM vascularity grading was correlated to tumor thickness and ulceration as a proxy for clinical prognosis. Sixty-six patients and 67 lesions underwent imaging with CSLM. Eleven patients were diagnosed with melanoma, including six in situ and five invasive melanomas. Prominent vascularity was observed in all advanced melanomas. There was an overall increase in mean tumor thickness between the absent (x = 0.315 mm) to prominent (x = 1.51 mm) categories. In this pilot study, vascularity was readily detected in cutaneous melanomas using CSLM. Prominent vascularity was observed in patients with advanced cutaneous melanomas. Our preliminary results are encouraging and indicate potential for the use of CSLM to assess vascularity in cutaneous melanoma, with potential prognostic and therapeutic implications.

  15. Immunomodulatory Monoclonal Antibodies in Combined Immunotherapy Trials for Cutaneous Melanoma

    Directory of Open Access Journals (Sweden)

    Mariana Aris

    2017-08-01

    Full Text Available In the last few years, there has been a twist in cancer treatment toward immunotherapy thanks to the impressive results seen in advanced patients from several tumor pathologies. Cutaneous melanoma is a highly mutated and immunogenic tumor that has been a test field for the development of immunotherapy. However, there is still a way on the road to achieving complete and long-lasting responses in most patients. It is desirable that immunotherapeutic strategies induce diverse immune reactivity specific to tumor antigens, including the so-called neoantigens, as well as the blockade of immunosuppressive mechanisms. In this review, we will go through the role of promising monoclonal antibodies in cancer immunotherapy with immunomodulatory function, especially blocking of the inhibitory immune checkpoints CTLA-4 and PD-1, in combination with different immunotherapeutic strategies such as vaccines. We will discuss the rational basis for these combinatorial approaches as well as different schemes currently under study for cutaneous melanoma in the clinical trials arena. In this way, the combination of “push and release” immunomodulatory therapies can contribute to achieving a more robust and durable antitumor immune response in patients.

  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. 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 < 0.001). Additionally lower ALCAM immunoreactivity in nodal metastatic foci was significantly statistically correlated with deeper melanoma invasion in the primary tumor according to Clark scale (P = 0.032). It was also found that decreased ALCAM expression (IRS <8) in nodal metastases shows a trend related with a correlation with shorter cancer specific overall survival (P = 0.083). Statistically significant correlations were also demonstrated between the presence of ulceration and decreased intensity of lymphocytic inflammatory infiltration and a high percentage of ALCAM-positive cells (P = 0.035, P = 0.01, respectively). High ALCAM expression in melanoma cells of the primary tumor can be used as a marker of negative

  19. Blue Nevus-Like Metastasis of a Cutaneous Melanoma Identified by Fluorescence In Situ Hybridization.

    Science.gov (United States)

    Campa, Molly; Patel, Mahir; Aubert, Pamela; Hosler, Gregory; Witheiler, Daniel

    2016-09-01

    A blue nevus-like melanoma is a rare melanoma variant arising from or histologically similar to a blue nevus. It can be challenging to distinguish a cellular blue nevus from a blue nevus-like melanoma, particularly in cases of blue nevus-like melanoma lacking a transition from a clearly benign component. We present a case of a 78-year-old man who refused treatment for a previously existing melanoma and subsequently developed a gray nodule near the site of the previous melanoma. After fluorescence in situ hybridization revealed copy number gains in RREB1, this was diagnosed as a blue nevus-like metastatic melanoma. Blue nevus-like metastatic melanoma is most commonly seen near the site of the primary cutaneous melanoma. This entity should be considered in a patient with a history of melanoma and a new blue nevus-like lesion.

  20. The MeLiM Minipig: An Original Spontaneous Model to Explore Cutaneous Melanoma Genetic Basis

    Directory of Open Access Journals (Sweden)

    Emmanuelle Bourneuf

    2017-10-01

    Full Text Available Melanoma is the deadliest skin cancer and is a major public health concern with a growing incidence worldwide. As for other complex diseases, animal models are needed in order to better understand the mechanisms leading to pathology, identify potential biomarkers to be used in the clinics, and eventually molecular targets for therapeutic solutions. Cutaneous melanoma, arising from skin melanocytes, is mainly caused by environmental factors such as UV radiation; however a significant genetic component participates in the etiology of the disease. The pig is a recognized model for spontaneous development of melanoma with features similar to the human ones, followed by a complete regression and a vitiligo-like depigmentation. Three different pig models (MeLiM, Sinclair, and MMS-Troll have been maintained through the last decades, and different genetic studies have evidenced a complex inheritance of the disease. As in humans, pigmentation seems to play a prominent role, notably through MC1R and MITF signaling. Conversely, cell cycle genes as CDKN2A and CDK4 have been excluded as predisposing for melanoma in MeLiM. So far, only sparse studies have focused on somatic changes occurring during oncogenesis, and have revealed major cytological changes and a potential dysfunction of the telomere maintenance system. Finally, the spontaneous tumor progression and regression occurring in these models could shed light on the interplay between endogenous retroviruses, melanomagenesis, and adaptive immune response.

  1. 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

  2. Non-invasive tools for the diagnosis of cutaneous melanoma.

    Science.gov (United States)

    Fink, C; Haenssle, H A

    2017-08-01

    While the excisional biopsy and histological examination of suspicious lesions remains the current gold standard for diagnosing cutaneous melanoma (CM), there is a demand for more objective and non-invasive examination methods that may support clinicians in their decision when to biopsy or not. This review is based on publications and guidelines retrieved by a selective search in PubMed and MEDLINE and focused on non-invasive diagnostic strategies for detecting melanoma. Ten different non-invasive techniques were compared with regard to applicability, status of development, and resources necessary for introduction into clinical routine (dermoscopy, sequential digital dermoscopy, total body photography, computer-aided multispectral digital analysis, electrical impedance spectroscopy, Raman spectroscopy, reflectance confocal microscopy, multiphoton tomography, stepwise two-photon-laser spectroscopy, quantitative dynamic infrared imaging). In an effort to create a classification based on our analyses, we suggest to differentiate i) tools for screening of patients in daily clinical routine, ii) tools for examination of a restricted number of preselected lesions that produce an automated diagnostic score, iii) tools for examination of a restricted number of preselected lesions at specialized centers requiring extensive training, iv) devices at an experimental stage of development. None of the discussed examination techniques is able to provide a definite and final diagnosis or to completely replace the histopathological examination. Up to date, the need for fully automated devices offering a complete skin cancer screening has not been satisfied. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. 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

  4. [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.

  5. Comprehensive DNA methylation study identifies novel progression-related and prognostic markers for cutaneous melanoma.

    Science.gov (United States)

    Wouters, Jasper; Vizoso, Miguel; Martinez-Cardus, Anna; Carmona, F Javier; Govaere, Olivier; Laguna, Teresa; Joseph, Jesuchristopher; Dynoodt, Peter; Aura, Claudia; Foth, Mona; Cloots, Roy; van den Hurk, Karin; Balint, Balazs; Murphy, Ian G; McDermott, Enda W; Sheahan, Kieran; Jirström, Karin; Nodin, Bjorn; Mallya-Udupi, Girish; van den Oord, Joost J; Gallagher, William M; Esteller, Manel

    2017-06-05

    Cutaneous melanoma is the deadliest skin cancer, with an increasing incidence and mortality rate. Currently, staging of patients with primary melanoma is performed using histological biomarkers such as tumor thickness and ulceration. As disruption of the epigenomic landscape is recognized as a widespread feature inherent in tumor development and progression, we aimed to identify novel biomarkers providing additional clinical information over current factors using unbiased genome-wide DNA methylation analyses. We performed a comprehensive DNA methylation analysis during all progression stages of melanoma using Infinium HumanMethylation450 BeadChips on a discovery cohort of benign nevi (n = 14) and malignant melanoma from both primary (n = 33) and metastatic (n = 28) sites, integrating the DNA methylome with gene expression data. We validated the discovered biomarkers in three independent validation cohorts by pyrosequencing and immunohistochemistry. We identified and validated biomarkers for, and pathways involved in, melanoma development (e.g., HOXA9 DNA methylation) and tumor progression (e.g., TBC1D16 DNA methylation). In addition, we determined a prognostic signature with potential clinical applicability and validated PON3 DNA methylation and OVOL1 protein expression as biomarkers with prognostic information independent of tumor thickness and ulceration. Our data underscores the importance of epigenomic regulation in triggering metastatic dissemination through the inactivation of central cancer-related pathways. Inactivation of cell-adhesion and differentiation unleashes dissemination, and subsequent activation of inflammatory and immune system programs impairs anti-tumoral defense pathways. Moreover, we identify several markers of tumor development and progression previously unrelated to melanoma, and determined a prognostic signature with potential clinical utility.

  6. Comparative microarray analysis of microRNA expression profiles in primary cutaneous malignant melanoma, cutaneous malignant melanoma metastases, and benign melanocytic nevi.

    Science.gov (United States)

    Sand, Michael; Skrygan, Marina; Sand, Daniel; Georgas, Dimitrios; Gambichler, Thilo; Hahn, Stephan A; Altmeyer, Peter; Bechara, Falk G

    2013-01-01

    Perturbations in microRNA (miRNA) expression profiles have been reported for cutaneous malignant melanoma (CMM) predominantly when examined in cell lines. Despite the rapidly growing number of newly discovered human miRNA sequences, the availability of up-to-date miRNA expression profiles for clinical samples of primary cutaneous malignant melanoma (PCMM), cutaneous malignant melanoma metastases (CMMM), and benign melanocytic nevi (BMN) is limited. Specimens excised from the center of tumors (lesional) from patients with PCMM (n=9), CMMM (n=4), or BMN (n=8) were obtained during surgery. An exploratory microarray analysis was performed by miRNA expression profiling based on Agilent platform screening for 1205 human miRNAs. The results from the microarray analysis were validated by TaqMan quantitative real-time polymerase chain reaction. In addition to several miRNAs previously known to be associated with CMM, 19 unidentified miRNA candidates were found to be dysregulated in CMM patient samples. Among the 19 novel miRNA candidates, the genes hsa-miR-22, hsa-miR-130b, hsa-miR-146b-5p, hsa-miR-223, hsa-miR-301a, hsa-miR-484, hsa-miR-663, hsa-miR-720, hsa-miR-1260, hsa-miR-1274a, hsa-miR-1274b, hsa-miR-3663-3p, hsa-miR-4281, and hsa-miR-4286 were upregulated, and the genes hsa-miR-24-1*, hsa-miR-26a, hsa-miR-4291, hsa-miR-4317, and hsa-miR-4324 were downregulated. The results of this study partially confirm previous CMM miRNA profiling studies identifying miRNAs that are dysregulated in CMM. However, we report several novel miRNA candidates in CMM tumors; these miRNA sequences require further validation and functional analysis to evaluate whether they play a role in the pathogenesis of CMM.

  7. Molecular characterisation of cutaneous melanoma: creating a framework for targeted and immune therapies.

    Science.gov (United States)

    Rajkumar, Shivshankari; Watson, Ian R

    2016-07-12

    Large-scale genomic analyses of cutaneous melanoma have revealed insights into the aetiology and heterogeneity of this disease, as well as opportunities to further personalise treatment for patients with targeted and immune therapies. Herein, we review the proposed genomic classification of cutaneous melanoma from large-scale next-generation sequencing studies, including the largest integrative analysis of melanoma from The Cancer Genome Atlas (TCGA) Network. We examine studies that have identified molecular features of melanomas linked to immune checkpoint inhibitor response. In addition, we draw attention to low-frequency actionable mutations and highlight frequent non-coding mutations in melanoma where little is known about their biological function that may provide novel avenues for the development of treatment strategies for melanoma patients.

  8. 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...

  9. Genome-wide promoter methylation analysis identifies epigenetic silencing of MAPK13 in primary cutaneous melanoma

    NARCIS (Netherlands)

    Gao, L.; Smit, Matthijs; Oord, J.J. van den; Goeman, J.J.; Verdegaal, E.M.; Burg, S.H. van der; Stas, M.; Beck, S.; Gruis, N.A.; Tensen, C.P.; Willemze, R.; Peeper, D.S.; Doorn, R. van

    2013-01-01

    The involvement of epigenetic alterations in the pathogenesis of melanoma is increasingly recognized. Here, we performed genome-wide DNA methylation analysis of primary cutaneous melanoma and benign melanocytic nevus interrogating 14 495 genes using BeadChip technology. This genome-wide view of

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

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    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.

  11. 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...

  12. 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

  13. Analysis of the Antitumor Activity of Clotrimazole on A375 Human Melanoma Cells

    DEFF Research Database (Denmark)

    Adinolfi, Barbara; Carpi, Sara; Romanini, Antonella

    2015-01-01

    AIM: The current study was designed to characterize the anticancer effects of clotrimazole on human cutaneous melanoma cells. MATERIALS AND METHODS: The v-raf murine sarcoma viral oncogene homolog B1 V600E mutant melanoma cell line A375 was used as an in vitro model. Characterization tools included...

  14. The epidemiology of cutaneous malignant melanoma in Nova Scotia

    Science.gov (United States)

    Howlett, Andrew L; Dewar, Ron AD; Morris, Steven F

    2006-01-01

    BACKGROUND: Since 1993, the annual increase in cutaneous malignant melanoma (MM) incidence has been one of the highest for all cancers registered in Canada, with the leading rate in Nova Scotia (NS). The purpose of the present study was to document the pathological and epidemiological data on MM cases found in NS. PATIENTS AND METHODS: All MM cases identified by the Nova Scotia Cancer Registry from January 1998 to December 2002 were evaluated. The five-year survival outlook, by major prognostic factors, was also determined. In addition, the annual incidence and mortality rates from 1972 to 2002 were computed. RESULTS: Between 1998 and 2002, 925 MM cases were recorded. The age-standardized incidence rate for males and females in this period was 19.2 and 16.1 per 100,000 respectively. Men 65 years of age or older had the highest age-specific rate. The most common MM had a Breslow’s depth of less than 1.0 mm (61.9%) and was Clark’s level II (34.9%). There was no significant seasonal variation noted in the time of diagnosis. Survival analyses indicated that sex, age, tumour location and thickness were significant independent predictors. Despite the increase in incidence, there have only been modest changes in the annual mortality rate. CONCLUSION: The incidence of MM in NS increases with age, and is nearly double for men 65 years of age or older, compared with women in the same age group. Thin melanomas on the extremities of young females have the best prognosis in NS, which is similar to other parts of the world. Incidence appears to be unrelated to season. Public health interventions are necessary to reduce the burden of this disease. PMID:19554137

  15. 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...

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

    DEFF Research Database (Denmark)

    Glud, Martin; Rossing, Maria; Hother, Christoffer

    2010-01-01

    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...... 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...

  17. Prognosis of sentinel node staged patients with primary cutaneous melanoma.

    Directory of Open Access Journals (Sweden)

    Otmar Elsaesser

    Full Text Available BACKGROUND: This study investigated survival probabilities and prognostic factors in sentinel lymph node biopsy (SLNB staged patients with cutaneous melanoma (CM with the aim of defining subgroups of patients who are at higher risk for recurrences and who should be considered for adjuvant clinical trials. METHODS: Patients with primary CM who underwent SLNB in the Department of Dermatology, University of Tuebingen, Germany, between 1996 and 2009 were included into this study. Survival probabilities and prognostic factors were evaluated by Kaplan-Meier and multivariate Cox proportional hazard models. RESULTS: 1909 SLNB staged patients were evaluated. Median follow-up time was 44 months. Median tumor thickness was 1.8 mm, ulceration was present in 31.8% of cases. The 5-year Overall Survival (OS was 90.3% in SLNB negative patients (IB 96.2%, IIA 87.0%, IIB 78.1%, IIC 72.6%. Patients with micrometastases (stage IIIA/B had a 5-year OS rate of 70.9% which was clearly less favorable than for stages I-II. Multivariate analysis revealed tumor thickness, ulceration, body site, histopathologic subtype and SLNB status as independent significant prognostic factors. CONCLUSION: Survival rates of patients with primary CM in stages I-II were shown to be much more favorable than previously reported from non sentinel node staged collectives. For future clinical trials, sample size calculations should be adapted using survival probabilities based on sentinel node staging.

  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 history of NMSC or 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 History of NMSC was associated with higher odds of malignancies of the bladder, brain, breast, colon, oesophagus, kidney, lung, lymphoma, 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 history of NMSC or 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. Cutaneous melanoma in Latin America: a population-based descriptive study.

    Science.gov (United States)

    Sortino-Rachou, Ana Maria; Curado, Maria Paula; Cancela, Marianna de Camargo

    2011-03-01

    Cutaneous melanoma incidences vary between geographic regions and are a health concern for Caucasians and for all ethnic populations. In Latin America, data from population-based cancer registries of cutaneous melanoma incidence rates have rarely been reported. We searched the Cancer Incidence in Five Continents volume IX (CI5-IX) database for cutaneous melanoma and select cases by topography (C43) from 11 population-based cancer registries in Latin America. Between 1998 and 2002, a total of 4,465 cutaneous melanoma cases were reported in Latin America. The average age-standardized incidence rates (per 100,000 persons-year) was 4.6 (male) and 4.3 (female). This study presents an overview of cutaneous melanoma incidence in Latin America, highlighting the need to enhance coverage of population-based cancer registries in Latin America, to allow for a better understanding of this neoplasm in the region. Thus it can help in implementing primary prevention programs for the whole Latino population. At this point in time, early detection messages should target young women and older men in Latin America.

  20. 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.

  1. Correlations Between Cutaneous Malignant Melanoma and Other Cancers: An Ecological Study in Forty European Countries.

    Science.gov (United States)

    Serrano, Pablo Fernandez-Crehuet; Serrano, Jose Luis Fernandez-Crehuet; Allam, Mohamed Farouk; Navajas, Rafael Fernandez-Crehuet

    2016-01-01

    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. 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. 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]). These correlations call to conduct new studies about the epidemiology of cancer in general and cutaneous malignant melanoma risk factors in particular.

  2. Cutaneous melanoma in Latin America: a population-based descriptive study

    Directory of Open Access Journals (Sweden)

    Ana Maria Sortino-Rachou

    2011-03-01

    Full Text Available Cutaneous melanoma incidences vary between geographic regions and are a health concern for Caucasians and for all ethnic populations. In Latin America, data from population-based cancer registries of cutaneous melanoma incidence rates have rarely been reported. We searched the Cancer Incidence in Five Continents volume IX (CI5-IX database for cutaneous melanoma and select cases by topography (C43 from 11 population-based cancer registries in Latin America. Between 1998 and 2002, a total of 4,465 cutaneous melanoma cases were reported in Latin America. The average age-standardized incidence rates (per 100,000 persons-year was 4.6 (male and 4.3 (female. This study presents an overview of cutaneous melanoma incidence in Latin America, highlighting the need to enhance coverage of population-based cancer registries in Latin America, to allow for a better understanding of this neoplasm in the region. Thus it can help in implementing primary prevention programs for the whole Latino population. At this point in time, early detection messages should target young women and older men in Latin America.

  3. 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.

  4. Periodic acid Schiff loops and blood lakes associated with metastasis in cutaneous melanoma.

    Science.gov (United States)

    van Beurden, Anne; Schmitz, Roderick F; van Dijk, Cornelis M; Baeten, Coen I M

    2012-12-01

    Aggressive melanoma cells are able to form alternative routes for angiogenesis. The formation of extracellular matrix-rich vasculogenic-like networks [periodic acid Schiff (PAS) loops] and expression of endothelial-associated genes [allowing direct contact of erythrocytes (blood lakes)] are forms of vasculogenic mimicry (VM). The detection of these alternative routes may be used as an additional staging factor for cutaneous melanoma and predicts the route of metastasis in melanoma. We studied the association of the presence of VM with metastasis (lymphogenous and/or haematogenous) in patients diagnosed with cutaneous malignant melanoma in het Groene Hart Hospital, the Netherlands, between 1995 and 2000. Tumour tissue samples of 123 patients were assessed on PAS loops and blood lakes and correlated to clinical data. VM was detected in 42 (34%) and proven metastasis developed in 23 patients (18.7%). VM was associated with shorter survival (Pmetastasis (P=0.062 and 0.013). In 20 tumours, blood lakes were detected and correlated with haematogenous metastasis (Pmetastasis (Pmetastasis of cutaneous melanoma and were an independent determinant for survival. These interesting findings need further investigation, although we believe that implementation of this detection can directly lead to better staging of cutaneous melanoma.

  5. A donor cornea with metastatic cells from a cutaneous malignant melanoma.

    Science.gov (United States)

    Campanelli, Marino; Mistò, Raffaela; Limongelli, Anna; Valente, Maria G; Cuttin, Maria S; D'Amato Tóthová, Jana

    2013-12-01

    To describe the case of a donor cornea that showed hematogenous metastatic spread of cutaneous melanoma to the sclerocorneal limbus. Corneal tissue obtained from a donor with cutaneous malignant melanoma was evaluated for endothelial cell density, corneal transparency, and epithelial morphology. Subsequently, hematoxylin and eosin staining and immunohistochemical characterization using S100, HMB45, Melan-A, and CD34 antibodies were performed on the corneal sections. The corneal tissue was transparent with high endothelial cell density; it was graded as being suitable for transplantation according to the current eye bank criteria. However, the aggressiveness of the donor's cancer and the diffuse melanosis of the sclera led to the suspicion of malignant melanoma metastasis to the cornea. Histochemical analysis of the corneoscleral rim showed small aggregates rich in pigmented cells that were localized in cleft-like structures in the sclera, at the sclerocorneal interface and in the peripheral avascular portion of the cornea. The aggregates were positive for the melanocytic tumor markers S100, HMB45, and Melan-A; the rims of the clefts expressed the panvascular CD34 antigen, which was suggestive of neovascularization. Corneal tissue from a donor with malignant cutaneous melanoma displayed neoplastic lesions of melanocytic origin that had spread from a primitive melanoma through hematogenous routes to the sclerocorneal limbus. On the basis of this finding, we believe that having a metastatic cutaneous malignant melanoma could in some cases be reviewed as an exclusionary criterion for undergoing cornea transplantation.

  6. Interval Sentinel Lymph Nodes: An Unusual Localization in Patients with Cutaneous Melanoma

    Directory of Open Access Journals (Sweden)

    A. M. Manganoni

    2011-01-01

    Full Text Available Background. Recent studies have demonstrated that there exists a great variation in the lymphatic drainage in patients with malignant melanoma. Some patients have drainage to lymph nodes outside of conventional nodal basins. The lymph nodes that exist between a primary melanoma and its regional nodal basin are defined “interval nodes”. Interval node occurs in a small minority of patients with forearm melanoma. We report our experience of the Melanoma Unit of University Hospital Spedali Civili Brescia, Italy. Methods. Lymphatic mapping using cutaneous lymphoscintigraphy (LS has become a standard preoperative diagnostic procedure to locate the sentinel lymph nodes (SLNs in cutaneous melanoma. We used LS to identify sentinel lymph nodes biopsy (SLNB in 480 patients. Results. From over 2100 patients affected by cutaneous melanoma, we identified 2 interval nodes in 480 patients with SLNB . The melanomas were both located in the left forearm. The interval nodes were also both located in the left arm. Conclusion. The combination of preoperative LS and intraoperative hand-held gamma detecting probe plays a remarkable role in identifying these uncommon lymph node locations. Knowledge of the unusual drainage patterns will help to ensure the accuracy and the completeness of sentinel nodes identification.

  7. A Synopsis of Serum Biomarkers in Cutaneous Melanoma Patients

    OpenAIRE

    Pierre Vereecken; Frank Cornelis; Nicolas van Baren; Valérie Vandersleyen; Jean-François Baurain

    2012-01-01

    Many serum biomarkers have been evaluated in melanoma but their clinical significance remains a matter of debate. In this paper, a review of the serum biomarkers for melanoma will be detailed and will be discussed from the point of view of their practical usefulness. The expression of biomarkers can be detected intracellularly or on the cell membrane of melanoma cells or noncancer cells in association with the melanoma. Some of these molecules can then be released extracellularly and be found...

  8. Epidemiología del melanoma cutáneo Epidemiology of cutaneous melanoma

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    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.

  9. 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.

  10. Prognostic significance of thymidylate synthase (TS) expression in cutaneous malignant melanoma.

    Science.gov (United States)

    Shimizu, A; Kaira, K; Yasuda, M; Asao, T; Ishikawa, O

    2016-01-01

    Thymidylate synthase (TS) plays an essential role in the pathogenesis and development of cancer, and TS-targeting agents have been widely used against different types of cancers. However, it remains still unclear whether or not TS is expressed in malignant melanoma. We conducted the clinicopathological study to investigate the prognostic significance of TS expression in cutaneous malignant melanoma. Ninety-nine patients with surgically resected cutaneous malignant melanoma were assessed. Tumor sections were stained by immunohistochemistry for TS, Ki-67, and microvessel density (MVD) determined by CD34. TS was positively expressed in 26% (26 out of 99). The expression of TS was significantly associated with T factor, cell proliferation (Ki-67) and MVD (CD34). By Spearman's rank test, TS expression was significantly correlated with Ki67 and CD34. By univariate analysis, ulceration, disease stage, TS, Ki-67 and CD34 had a significant relationship with survival. Multivariate analysis confirmed that TS was an independent prognostic factor for poor prognosis of cutaneous malignant melanoma. The positive expression of TS could be a useful marker for predicting poor prognosis in patients with cutaneous malignant melanoma, and TS-targeting agents may be worth trying for the treatment of this dismal disease.

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

    DEFF Research Database (Denmark)

    Glud, Martin; Rossing, Maria; Hother, Christoffer

    2010-01-01

    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...

  12. Serum Fatty Acids and Risk of Cutaneous Melanoma: A Population-Based Case-Control Study

    Directory of Open Access Journals (Sweden)

    Marco Vinceti

    2013-01-01

    Full Text Available Background. Some observational studies have suggested that excess dietary intake of polyunsaturated fatty acids such as linoleic acid increases cutaneous melanoma risk. We aimed at examining the association between serum fatty acids and melanoma risk by conducting a population-based case-control study in a northern Italy community. Methods. The percentage composition of 12 fatty acids was determined in 51 newly diagnosed melanoma patients and 51 age- and sex-matched population controls by extracting total lipids from serum samples using thin layer and gas chromatography. Conditional logistic regression was used to estimate the relative risk of melanoma associated with tertiles of percentage composition of each fatty acid as well as groupings including saturated, monounsaturated, and polyunsaturated fatty acids. Results. We found a slightly increased melanoma risk for stearic and arachidic acids proportion, with and without adjustment for potential confounders. For an n-3 polyunsaturated fatty acid, docosapentaenoic acid, we found a male-specific direct association with melanoma risk. No other associations emerged for the other saturated, monounsaturated, and polyunsaturated fatty acids, individually or grouped by type. Conclusions. These findings do not suggest a major role of fatty acids, including linoleic acid, on risk of cutaneous melanoma, though their evaluation is limited by the small sample size.

  13. Surgery and radiotherapy in the treatment of cutaneous melanoma

    DEFF Research Database (Denmark)

    Testori, A; Rutkowski, P; Marsden, J

    2009-01-01

    Adequate surgical management of primary melanoma and regional lymph node metastasis, and rarely distant metastasis, is the only established curative treatment. Surgical management of primary melanomas consists of excisions with 1-2 cm margins and primary closure. The recommended method of biopsy...... 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....

  14. Talimogene Laherparepvec and Pembrolizumab in Treating Patients With Stage III-IV Melanoma

    Science.gov (United States)

    2017-11-06

    Recurrent 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

  15. High-resolution ultrasonography assists the differential diagnosis of blue naevi and cutaneous metastases of melanoma.

    Science.gov (United States)

    Samimi, M; Perrinaud, A; Naouri, M; Maruani, A; Perrodeau, E; Vaillant, L; Machet, L

    2010-09-01

    Metastases of cutaneous melanoma may simulate benign blue naevi clinically. To investigate the value of ultrasonography in the differential diagnosis of lesions that look similar clinically, i.e. blue naevi and cutaneous metastases of melanoma. Participants were invited for inclusion in the study if they had a cutaneous blue lesion clinically suggestive of a blue naevus or cutaneous metastasis of melanoma. After obtaining signed consent, the lesion was photographed and studied using dermoscopy and high-resolution ultrasonography before being removed for histological examination. Clinical, dermoscopic and ultrasonographic images were reviewed anonymously by four dermatologists to assign the diagnosis of blue naevus or metastasis of melanoma. The diagnostic performance of clinical examination, dermoscopy and sonography was assessed for the ability of each to differentiate between metastases of melanoma and blue naevi with reference to the histological diagnosis. Moreover, experts undertook a semeiological description of each ultrasonographic image according to seven items: location of the lesion, echogenicity, homogeneity, shape of the lesion, definition of margins, posterior acoustic shadow and increased posterior echogenicity.   Twenty-eight patients were included with a total of 39 blue skin lesions, and 17 of the 28 patients had a previous history of melanoma. Interobserver agreement in the semeiological description of the sonographic images was good (κ≥0·6) for five of seven items. Sonography was more specific (94%) than clinical examination (77%) and dermoscopy (74%). The sonographic features contributing to the differential diagnosis were: location of the lesion (P=0·027), shape of the lesion (Pmelanoma. A blue naevus is a homogeneous, hypoechoic, 'dish-shaped' lesion, located in the superficial dermis, whereas metastases of melanoma are 'potato-shaped', hypoechoic, heterogeneous lesions, located in the hypodermis. © 2010 The Authors. Journal

  16. 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...... of these 16 patients (75%) died of disseminated melanoma. We conclude that thin head and neck melanomas do not necessarily carry an excellent prognosis. Prognosis is not dependent upon tumour thickness when less than 1.00 mm....

  17. 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

  18. 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.

  19. Prognosis and determinants of outcome following locoregional or distant recurrence in patients with cutaneous melanoma

    NARCIS (Netherlands)

    Francken, Anne Brecht; Accortt, Neil A.; Shaw, Helen M.; Wiener, Martin; Soong, Seng-jaw; Hoekstra, Harald J.; Thompson, John F.

    Objective: Information on prognosis for patients with cutaneous melanoma after locoregional or distant recurrence is sparse and controversial. The aim of this study was to analyze factors influencing outcome after the development of a first relapse. Methods: Information was extracted from the Sydney

  20. ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma.

    NARCIS (Netherlands)

    Gudbjartsson, D.F.; Sulem, P.; Stacey, S.N.; Goldstein, A.M.; Rafnar, T.; Sigurgeirsson, B.; Benediktsdottir, K.R.; Thorisdottir, K.; Ragnarsson, R.; Sveinsdottir, S.G.; Magnusson, V.; Lindblom, A.; Kostulas, K.; Botella-Estrada, R.; Soriano, V.; Juberias, P.; Grasa, M.; Saez, B.; Andres, R.; Scherer, D.; Rudnai, P.; Gurzau, E; Koppova, K.; Kiemeney, L.A.L.M.; Jakobsdottir, M.; Steinberg, S.; Helgason, A.; Gretarsdottir, S.; Tucker, M.A.; Mayordomo, J.I.; Nagore, E.; Kumar, R.; Hansson, J.; Olafsson, J.H.; Gulcher, J.R.; Kong, A.; Thorsteinsdottir, U.; Stefansson, K.

    2008-01-01

    Fair color increases risk of cutaneous melanoma (CM) and basal cell carcinoma (BCC). Recent genome-wide association studies have identified variants affecting hair, eye and skin pigmentation in Europeans. Here, we assess the effect of these variants on risk of CM and BCC in European populations

  1. Morbidity after axillary sentinel lymph node biopsy in patients with cutaneous melanoma

    NARCIS (Netherlands)

    de Vries, M; Vonkeman, WG; van Ginkel, RJ; Hoekstra, HJ

    Aim: In this study, the short-term and tong-term morbidity was assesed after axillary sentinel lymph node biopsy (SLNB) with or without completion axillary lymph node dissection (SLNB/ALND) in patients with cutaneous melanoma. Methods: Between 1995 and 2003, 119 axillary SLNBs were performed for

  2. Positron emission tomography in the follow-up of cutaneous malignant melanoma patients

    DEFF Research Database (Denmark)

    Danielsen, Maria; Højgaard, Liselotte; Kjær, Andreas

    2014-01-01

    Cutaneous malignant melanoma (CMM) has a high risk of dissemination to regional lymph nodes and visceral organs. Recurrences are most frequently seen within the first 2-3 years after initial treatment, but these patients have a life-long risk of relapse. The prognosis is highly dependent on lymph...

  3. 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.

  4. 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.

  5. 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

    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......: 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. RESULTS: 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...

  6. Risk factors for positive or equivocal margins after wide local excision of 1345 cutaneous melanomas.

    Science.gov (United States)

    Miller, Christopher J; Shin, Thuzar M; Sobanko, Joseph F; Sharkey, John M; Grunyk, John W; Elenitsas, Rosalie; Chu, Emily Y; Capell, Brian C; Ming, Michael E; Etzkorn, Jeremy R

    2017-08-01

    Positive or equivocal margins after wide local excision (WLE) complicate surgical management of cutaneous melanoma. To identify the frequency of and risk factors for positive or equivocal margins after WLE of cutaneous melanoma. Retrospective, single-center, cross-sectional study of 1345 consecutive melanomas treated with WLE. The overall frequency of positive or equivocal margins was 4.2% (56/1345), ranging from 2.2% to 22.6%, depending on the size of the surgical margins, patient characteristics, biopsy history, and the clinicopathology of the melanoma. In descending order, independent risk factors associated with the greatest odds for positive or equivocal margins after multivariate analysis were noncompliance with recommended surgical margins (odds ratio [OR] 5.57, P = .002); anatomic location on the head, neck, hands, feet, genitals, or pretibial leg (OR 5.07, P < .001); histologic regression (OR 2.78, P = .007); in situ melanoma (OR 2.27, P = .011); multiple biopsies at the tumor site before WLE (OR 1.92 [per biopsy], P = .004); and increasing age (OR 1.049 [per year], P < .001). This was a single-site, retrospective observational study. Clinicopathologic factors, especially location in cosmetically or functionally sensitive areas and noncompliance with recommended surgical margins, identified melanomas at increased risk for positive or equivocal margins after WLE. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  7. [Cutaneous malignant melanoma; diagnostic procedures and their evaluation in diagnosing and mapping sentinel nodes].

    Science.gov (United States)

    Valsamaki, Pipitsa; Zanglis, Antonios; Gerali, Sophia

    2009-01-01

    Cutaneous malignant melanoma represents 4% of all the malignant neoplasms. Nevertheless, 79% of the fatal malignant skin diseases are attributed to melanoma. In melanoma patients, the most important prognostic factor is the regional lymph node invasion. The present article describes the classical diagnostic, staging and therapeutic strategies in melanoma patients. In the realm of cutaneous melanoma, pre-operative lymphoscintigraphy and the intra-operative gamma-probe detection, removal and biopsy of the sentinel lymph node(s), comprise convenient, procedures, virtually lacking morbidity. The definition of sentinel includes the first lymph node or nodes, draining the lymph from the primary lesion, thereby attributed with the highest probability of harbouring migrating metastatic cells. A sentinel lymph node negative for malignancy accurately "predicts" the absence of melanoma cell invasion in all the rest regional and distant lymphatic basins. The method aims in the best discrimination of high-risk patients, as candidates for selective lymphadenectomy, with or without adjunctive treatment. Radionuclide-guided lymphatic mapping and surgery is based on the phagocytosis of colloidal-based radiopharmaceuticals by the macrophages encountered in functional tumour-infiltrated sentinel nodes. The nuclear methods successfully add to the staging and the potential surgical treatment of the disease.

  8. A Synopsis of Serum Biomarkers in Cutaneous Melanoma Patients

    Directory of Open Access Journals (Sweden)

    Pierre Vereecken

    2012-01-01

    Full Text Available Many serum biomarkers have been evaluated in melanoma but their clinical significance remains a matter of debate. In this paper, a review of the serum biomarkers for melanoma will be detailed and will be discussed from the point of view of their practical usefulness. The expression of biomarkers can be detected intracellularly or on the cell membrane of melanoma cells or noncancer cells in association with the melanoma. Some of these molecules can then be released extracellularly and be found in body fluids such as the serum. Actually, with the emergence of new targeted therapies for cancer and the increasing range of therapeutic options, the challenge for the clinician is to assess the unique risk/response ratio and the prognosis for each patient. New serum biomarkers of melanoma progression and metastatic disease are still awaited in order to provide efficient rationale for followup and treatment choices. LDH as well as S100B levels have been correlated with poor prognosis in AJCC stage III/IV melanoma patients. However, the poor sensitivity and specificity of those markers and many other molecules are serious limitations for their routine use in both early (AJCC stage I and II and advanced stages of melanoma (AJCC stage III and IV. Microarray technology and proteomic research will surely provide new candidates in the near future allowing more accurate definition of the individual prognosis and prediction of the therapeutic outcome and select patients for early adjuvant strategies.

  9. A synopsis of serum biomarkers in cutaneous melanoma patients.

    Science.gov (United States)

    Vereecken, Pierre; Cornelis, Frank; Van Baren, Nicolas; Vandersleyen, Valérie; Baurain, Jean-François

    2012-01-01

    Many serum biomarkers have been evaluated in melanoma but their clinical significance remains a matter of debate. In this paper, a review of the serum biomarkers for melanoma will be detailed and will be discussed from the point of view of their practical usefulness. The expression of biomarkers can be detected intracellularly or on the cell membrane of melanoma cells or noncancer cells in association with the melanoma. Some of these molecules can then be released extracellularly and be found in body fluids such as the serum. Actually, with the emergence of new targeted therapies for cancer and the increasing range of therapeutic options, the challenge for the clinician is to assess the unique risk/response ratio and the prognosis for each patient. New serum biomarkers of melanoma progression and metastatic disease are still awaited in order to provide efficient rationale for followup and treatment choices. LDH as well as S100B levels have been correlated with poor prognosis in AJCC stage III/IV melanoma patients. However, the poor sensitivity and specificity of those markers and many other molecules are serious limitations for their routine use in both early (AJCC stage I and II) and advanced stages of melanoma (AJCC stage III and IV). Microarray technology and proteomic research will surely provide new candidates in the near future allowing more accurate definition of the individual prognosis and prediction of the therapeutic outcome and select patients for early adjuvant strategies.

  10. 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.

  11. Time trends and latitude dependence of uveal and cutaneous malignant melanoma induced by solar radiation

    Energy Technology Data Exchange (ETDEWEB)

    Moan, J.; Setlow, R.; Cicarma, E.; Porojnicu, A. C.; Grant, W. B.; Juzeniene, A.

    2010-01-01

    In order to evaluate the role of solar radiation in uveal melanoma etiology, the time and latitude dependency of the incidence rates of this melanoma type were studied in comparison with those of cutaneous malignant melanoma (CMM). Norway and several other countries with Caucasian populations were included. There is a marked north - south gradient of the incidence rates of CMM in Norway, with three times higher rates in the south than in the north. No such gradient is found for uveal melanoma. Similar findings have been published for CMM in other Caucasian populations, with the exception of Europe as a whole. In most populations the ratios of uveal melanoma incidence rates to those of CMM tend to decrease with increasing CMM rates. This is also true for Europe, in spite of the fact that in this region there is an inverse latitude gradient of CMM, with higher rates in the north than in the south. In Norway the incidence rates of CMM have increased until about 1990 but have been constant, or even decreased (for young people) after that time, indicating constant or decreasing sun exposure. The uveal melanoma rates have been increasing after 1990. In most other populations the incidence rates of CMM have been increasing until recently while those of uveal melanoma have been decreasing. These data generally support the assumption that uveal melanomas are not generated by ultraviolet (UV) radiation and that solar UV, via its role in vitamin D photosynthesis, may have a protective effect.

  12. Risk prediction models for incident primary cutaneous melanoma: a systematic review.

    Science.gov (United States)

    Vuong, Kylie; McGeechan, Kevin; Armstrong, Bruce K; Cust, Anne E

    2014-04-01

    Currently, there is no comprehensive assessment of melanoma risk prediction models. To systematically review published studies reporting multivariable risk prediction models for incident primary cutaneous melanoma for adults. EMBASE, MEDLINE, PREMEDLINE, and Cochrane databases were searched to April 30, 2013. Eligible studies were hand searched and citation tracked. Two independent reviewers extracted information. Nineteen studies reporting 28 melanoma prediction models were included. The number of predictors in the final models ranged from 2 to 13; the most common were nevi, skin type, freckle density, age, hair color, and sunburn history. There was limited reporting and substantial variation among the studies in model development and performance. Discrimination (the ability of the model to differentiate between patients with and without melanoma) was reported in 9 studies and ranged from fair to very good (area under the receiver operating characteristic curve, 0.62-0.86). Few studies assessed internal or external validity of the models or their use in clinical and public health practice. Of the published melanoma risk prediction models, the risk prediction tool developed by Fears and colleagues, which was designed for the US population, appears to be the most clinically useful and may also assist in identifying high-risk groups for melanoma prevention strategies. Few melanoma risk prediction models have been comprehensively developed and assessed. More external validation and prospective evaluation will help translate melanoma risk prediction models into useful tools for clinical and public health practice.

  13. 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

  14. Prognostic Impact of Autophagy Biomarkers for Cutaneous Melanoma.

    Science.gov (United States)

    Tang, Diana Y L; Ellis, Robert A; Lovat, Penny E

    2016-01-01

    Prognosis and survival for malignant melanoma is highly dependent on early diagnosis and treatment. While the American Joint Committee on Cancer (AJCC) criterion provides a means of staging melanomas and guiding treatment approaches, it is unable to identify the risk of disease progression of early stage tumors 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 personalized/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 tumors. Conversely, loss of AMBRA1 in the epidermis overlying primary melanomas defines a novel prognostic biomarker for AJCC stage I tumors. Collectively, the definition of AMBRA1 and p62 as prognostic biomarkers for early stage melanomas provides novel and accurate means through which to identify tumors at risk of disease progression, facilitating earlier patient therapeutic

  15. 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

  16. Quality of life patient-reported outcomes for locally advanced cutaneous melanoma.

    Science.gov (United States)

    Weitman, Evan S; Perez, Matthew; Thompson, John F; Andtbacka, Robert H I; Dalton, Jo; Martin, Mona L; Miller, Talia; Gwaltney, Chad; Sarson, David; Wachter, Eric; Zager, Jonathan S

    2017-12-19

    Locally advanced cutaneous melanoma has marked quality-of-life implications; however, the patient experience of symptom management and subsequent impact on quality of life has not been well described. This study aims to address the impact on patients of advanced cutaneous melanoma through qualitative interviews. Adults with stage IIIB, IIIC, or IV (M1a) cutaneous melanoma were recruited from two cancer centers in the USA and one in Australia. Telephone interviews were conducted to assess how locoregionally advanced cutaneous melanoma impacted everyday life. Interviews were recorded, transcribed, and coded for qualitative analysis. Twenty-two melanoma patients were interviewed, mean age 69.7 years (range: 52-83), 64% male. The study included stage IIIB (36%), stage IIIC (59%), and stage IV M1a (5%) patients. Emotional health/self-perception issues were the most commonly identified (41% of patient impact expressions), including worry, concern, embarrassment, self-consciousness, fear, and thoughts of death. Limitations of lifestyle and activities were also identified (28% of expressions) including leisure and social activities, physical functioning, general functioning, and personal care. Coping strategies such as modified clothing choices, increased use of pain and/or anti-inflammatory medications, and avoidance/protection from the sun represented 20% of all impact expressions. Ratings of the degree of difficulty patients experienced (using an 11-point numerical rating scale) ranged from 0.0 to 10.0 (mean 5.7, SD 2.9). Condition-related and treatment-related factors were well characterized in patients with locally advanced cutaneous melanoma. This provides a strong foundation for assessment of how cutaneous melanoma impacts quality of life.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly

  17. 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.

  18. Prognostic survival model for people diagnosed with invasive cutaneous melanoma.

    Science.gov (United States)

    Baade, Peter D; Royston, Patrick; Youl, Philipa H; Weinstock, Martin A; Geller, Alan; Aitken, Joanne F

    2015-01-31

    The ability of medical practitioners to communicate risk estimates effectively to patients diagnosed with melanoma relies on accurate information about prognostic factors and their impact on survival. This study reports the development of one of the few melanoma prognostic models, called the Melanoma Severity Index (MSI), based on population-based cancer registry data. Data from the Queensland Cancer Registry for people (20-89 years) diagnosed with a single invasive melanoma between 1995 and 2008 (n = 28,654; 1,700 melanoma deaths). Additional clinical information about metastasis, ulceration and positive lymph nodes was manually extracted from pathology forms. Flexible parametric survival models were combined with multivariable fractional polynomial for selecting variables and transformations of continuous variables. Multiple imputation was used for missing covariate values. The MSI contained the variables thickness (transformed, explained 40.6% of variation in survival), body site (additional 1.9% in variation), metastasis (1.8%), positive nodes (0.7%), ulceration (1.3%), age (1.1%). Royston and Sauerbrei's D statistic (measure of discrimination) was 1.50 (95% CI = 1.44, 1.56) and the corresponding RD2 (measure of explained variation) was 0.47 (0.45, 0.49), demonstrating strong explanatory performance. The Harrell-C statistic was 0.88 (0.88, 0.89). Lacking an external validation dataset, we applied internal-external cross validation to demonstrate the consistency of the prognostic information across geographically-defined subsets of the cohort. The MSI provides good ability to predict survival for melanoma patients. Beyond the immediate clinical use, the MSI may have important public health and research applications for evaluations of public health interventions aimed at reducing deaths from melanoma.

  19. 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.

  20. Clear cell melanoma: a cutaneous clear cell malignancy.

    Science.gov (United States)

    Pletneva, Maria A; Andea, Aleodor; Palanisamy, Nallasivam; Betz, Bryan L; Carskadon, Shannon; Wang, Min; Patel, Rajiv M; Fullen, Douglas R; Harms, Paul W

    2014-10-01

    Clear cell melanoma is a rare clear cell malignancy. Accurate diagnosis of clear cell melanoma requires integration of immunohistochemical and morphologic findings, with molecular studies to rule out clear cell sarcoma. The differential diagnosis includes melanoma, carcinoma, perivascular epithelioid cell tumor, and epidermotropic clear cell sarcoma. We use a case of a lesion on the helix of an 86-year-old man as an example. Histologic examination revealed an ulcerated clear cell malignant tumor. Tumor cell cytoplasm contained periodic acid-Schiff-positive, diastase-sensitive glycogen. Tumor cells showed positive labeling for S100, HMB-45, and Melan-A, and negative labeling for cytokeratins, p63, and smooth muscle actin. Molecular studies demonstrated BRAF V600E mutation, copy gains at the 6p25 (RREB1) and 11q13 (CCND1) loci, and absence of EWSR1-ATF1 fusion. These findings supported a diagnosis of clear cell melanoma. The rare pure clear cell morphology occurs due to accumulation of intracytoplasmic glycogen. We review the differential diagnosis of clear cell melanoma and describe the utility of immunohistochemical and molecular studies in confirming this diagnosis.

  1. Activating mutations of the oncogene EZH2 in cutaneous melanoma revealed by next generation sequencing

    Directory of Open Access Journals (Sweden)

    Paul W. Harms

    2014-06-01

    Full Text Available Enhancer of zeste homolog 2 (EZH2 is a histone methyltransferase that promotes tumorigenesis by epigenetic repression of tumor suppressor genes. Although EZH2 is overexpressed in many malignancies, activating EZH2 mutations have been described predominantly in follicular lymphoma and diffuse large B-cell lymphoma. EZH2 activating mutations in melanoma are not well described. Here, we report a case of cutaneous melanoma that displayed an EZH2 (Y641S activating mutation detected by transcriptome sequencing as well as BRAF (V600K. The patient had concurrent follicular lymphoma that lacked both the EZH2 (Y641 and BRAF (V600K mutations present in the patient's melanoma. Further, we screened publicly available sequence data and identified four additional melanoma cases harboring activating EZH2 mutation. Our findings provide additional evidence that activating recurrent EZH2 mutations occur in cutaneous melanoma, to our knowledge the first solid tumor shown to harbor such mutations. These tumors may be amenable to EZH2 inhibitor therapy.

  2. Metastatic Melanoma to the Urinary Bladder of Ocular Origin Accompanied with Primary Cutaneous Melanoma: Diagnostic Challenge—A Report of a Case

    Directory of Open Access Journals (Sweden)

    Constantine Theocharides

    2017-01-01

    Full Text Available Metastases of melanoma to the urinary bladder are infrequent. Even rarer are metastases to the urinary bladder from uveal melanoma, with only 3 cases published in the literature so far. Herein we present a case of a 77-year-old male patient who presented with metastatic melanoma to the urinary bladder. The patient’s history included the diagnoses of uveal melanoma treated with radiation 25 years ago, as well as that of cutaneous melanoma diagnosed 7 years ago. The molecular study of the urinary bladder tumor specimen identified mutation of the GNAQ gene, which has been suggested to be an early molecular event in the pathogenetic course of over 80% of uveal melanomas. Therefore, the diagnosis of uveal melanoma metastatic to the urinary bladder was made.

  3. Serous Retinopathy Associated with Mitogen-Activated Protein Kinase Kinase Inhibition (Binimetinib) for Metastatic Cutaneous and Uveal Melanoma

    NARCIS (Netherlands)

    Dijk, E.H. van; Herpen, C.M.L. van; Marinkovic, M.; Haanen, J.B.; Amundson, D.; Luyten, G.P.M.; Jager, M.J. de; Kapiteijn, E.H.; Keunen, J.E.E.; Adamus, G.; Boon, C.J.F.

    2015-01-01

    PURPOSE: To analyze the clinical characteristics of a serous retinopathy associated with mitogen-activated protein kinase kinase (MEK) inhibition with binimetinib treatment for metastatic cutaneous melanoma (CM) and uveal melanoma (UM), and to determine possible pathogenetic mechanisms that may lead

  4. Detection of first relapse in cutaneous melanoma patients : Implications for the formulation of evidence-based follow-up guidelines

    NARCIS (Netherlands)

    Francken, Anne Brecht; Shaw, Helen M.; Accortt, Neil A.; Soong, Seng-Jaw; Hoekstra, Harald J.; Thompson, John F.

    Background: The value of follow-up surveillance for patients with cutaneous melanoma remains uncertain. In this prospective study the frequency of detection of first melanoma recurrence (FMR) by patient or doctor was analyzed to assist in the future design of evidence-based follow-up guidelines.

  5. Morbidity after inguinal sentinel lymph node biopsy and completion lymph node dissection in patients with cutaneous melanoma

    NARCIS (Netherlands)

    de Vries, M.; Vonkeman, W. G.; van Ginkel, R. J.; Hoekstra, H. J.

    Background: Aim of the study was to assess the short-term and long-term morbidity after inguinal sentinel lymph node biopsy (SLNB) with or without completion groin dissection (GD) in patients with cutaneous melanoma. Methods: Between 1995 and 2003, 127 inguinal SLNBs were performed for cutaneous

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

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt

    1989-01-01

    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......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...... a favorable prognosis. No significant differences in vV could be demonstrated among different noninvasive tumor types. Two-dimensional estimates only distinguished benign from malignant tumors with considerable overlap and with significantly varying influence from other factors among different benign lesional...

  7. Primary cutaneous melanoma of the scalp: Patterns of recurrence.

    Science.gov (United States)

    Sparks, David S; Read, Tavis; Lonne, Michael; Barbour, Andrew P; Wagels, Michael; Bayley, Gerard J; Smithers, B Mark

    2017-03-01

    Patients with primary melanoma of the scalp have been reported to have worse disease-related outcomes compared with other anatomical regions. There are few studies in the literature specifically addressing recurrence patterns and treatment outcomes for primary scalp melanoma as a discrete anatomical sub-region. We sought to identify key features adversely influencing disease control and survival and to clarify the role of resection plane, margin, and method of reconstruction in the management of this disease process. A retrospective clinical study of medical records was performed evaluating all patients with primary melanoma of the scalp treated at two hospitals in southeast Queensland between 2004 and 2014. A total of 107 patients were eligible for analysis. There were 46 recurrences in 38 patients in the cohort accounting for a recurrence rate of 35.5%. The local recurrence rate was 15.9% with 12 in-transit metastases after diagnosis. Regional and distant recurrence rates were 12.1% and 15%, respectively. At a median follow up of 30.5 months, disease-free survival was 47% and overall survival was also 47%. On multi-variate analysis, the deeper resection plane (sub-galeal) had a lower disease-free survival rate compared with the supra-galeal resection plane (P = 0.032). Our results support the hypothesis that primary scalp melanoma represents a unique aggressive subcategory with high rates of in-transit disease and poor disease-related and survival outcomes. There is a need for robust prospective comparative studies to address the significance of resection plane in the management of patients with scalp melanoma. © 2016 Wiley Periodicals, Inc.

  8. Biologic and Therapeutic Significance of MYB Expression in Human Melanoma

    Science.gov (United States)

    Hijiya, Nobuko; Zhang, Jin; Ratajczak, Mariusz Z.; Kant, Jeffrey A.; Deriel, Kim; Herlyn, Meenhard; Zon, Gerald; Gewirtz, Alan M.

    1994-05-01

    We investigated the therapeutic potential of employing antisense oligodeoxynucleotides to target the disruption of MYB, a gene which has been postulated to play a pathogenetic role in cutaneous melanoma. We found that MYB was expressed at low levels in several human melanoma cell lines. Also, growth of representative lines in vitro was inhibited in a dose- and sequence-dependent manner by targeting the MYB gene with unmodified or phosphorothioate-modified antisense oligodeoxynucleotides. Inhibition of cell growth correlated with specific decrease of MYB mRNA. In SCID mice bearing human melanoma tumors, infusion of MYB antisense transiently suppressed MYB gene expression but effected long-term growth suppression of transplanted tumor cells. Toxicity of the oligodeoxynucleotides was minimal in mice, even when targeted to the murine Myb gene. These results suggest that the MYB gene may play an important, though undefined, role in the growth of at least some human melanomas. Inhibition of MYB expression might be of use in the treatment of this disease.

  9. Coffee consumption and the risk of cutaneous melanoma: a meta-analysis.

    Science.gov (United States)

    Wang, Jia; Li, Xutong; Zhang, Dongfeng

    2016-06-01

    Results from epidemiologic studies on coffee consumption and the risk of cutaneous melanoma are inconsistent. We conducted a meta-analysis to assess the associations between the consumption of total coffee, caffeinated coffee and decaffeinated coffee and the risk of cutaneous melanoma, respectively. A literature search was performed in PubMed, Web of Science and EMBASE for relevant articles published up to August 2015. Pooled relative risks (RRs) with 95 % confidence intervals (CIs) were calculated with a random-effects model. Dose-response relationship was assessed by restricted cubic spline. Twelve studies involving 832,956 participants for total coffee consumption, 5 studies involving 717,151 participants for caffeinated coffee consumption and 6 studies involving 718,231 participants for decaffeinated coffee consumption were included in this meta-analysis. Compared with the lowest level of consumption, the pooled RRs were 0.80 (95 % CI 0.69-0.93, I (2) = 53.5 %), 0.85 (95 % CI 0.71-1.01, I (2) = 65.0 %) and 0.92 (95 % CI 0.81-1.05, I (2) = 0.0 %) for the consumption of total coffee, caffeinated coffee and decaffeinated coffee, respectively. In subgroup analysis by study design, the pooled RRs in cohort studies and case-control studies were 0.83 (95 % CI 0.72-0.97) and 0.74 (95 % CI 0.51-1.07) for total coffee consumption, respectively. Dose-response analysis suggested cutaneous melanoma risk decreased by 3 % [0.97 (0.93-1.00)] and 4 % [0.96 (0.92-1.01)] for 1 cup/day increment of total coffee and caffeinated coffee consumption, respectively. This meta-analysis suggests that coffee consumption may reduce the risk of cutaneous melanoma.

  10. Epidemiological Profile of Patients with Cutaneous Melanoma in a Region of Southern Brazil

    OpenAIRE

    Marcelo Moreno; Ricardo Ludwig Schmitt; Maria Gabriela Lang; Vanessa Gheno

    2012-01-01

    Cutaneous melanoma (CM) is responsible for 75% of deaths from malignant skin cancer. The incidence of CM in the southern region of Brazil, particularly in the western region of Santa Catarina, is possibly higher than estimated. In this study, the clinical and epidemiological profile of patients with CM treated in the western region of Santa Catarina was examined. A cross-sectional study was performed with patients diagnosed with CM from January 2002 to December 2009, from 78 counties of the w...

  11. Analysis of sentinel node positivity in primary cutaneous melanoma: an 8-year single institution experience.

    Science.gov (United States)

    Joyce, K M; McInerney, N M; Piggott, R P; Martin, F; Jones, D M; Hussey, A J; Kerin, M J; Kelly, J L; Regan, P J

    2017-11-01

    Sentinel lymph node biopsy (SLNB) is a standard method for determining the pathologic status of the regional lymph nodes. The aim of our study was to determine the incidence and clinicopathologic factors predictive of SLN positivity, and to evaluate the prognostic importance of SLNB in patients with cutaneous melanoma. We performed a retrospective analysis of a prospectively maintained database of all patients who underwent SLNB for primary melanoma at our institution from 2005 to 2012. Statistical analysis was performed using χ 2 and Fischer exact test. In total, 318 patients underwent SLNB, of which 65 were for thin melanoma (≤1 mm). There were 36 positive SLNB, 278 negative SLNB and in four cases the SLN was not located. The incidence rate for SLNB was 11.3% overall and 1.5% in thin melanomas alone. Statistical analysis identified Breslow thickness >1 mm (P = 0.006), Clark level ≥ IV (P = 0.004) and age <75 years (P = 0.035) as the strongest predictors of SLN positivity. Our overall false negativity rate was 20% (9/45) with one case of false-negative SLNB in thin melanomas. Breslow thickness of the primary tumour remains the strongest predictor of SLN positivity. Our findings point to a possible limited role for SLNB in thin melanoma due to its low positivity rate, associated false-negative rate and related morbidity.

  12. Modelling the Future: System Dynamics in the Cutaneous Malignant Melanoma Care Pathway.

    Science.gov (United States)

    Claeson, Magdalena; Hallberg, Stefan; Holmström, Paul; Wennberg, Ann-Marie; Gonzalez, Helena; Paoli, John

    2016-02-01

    Incidence rates for cutaneous malignant melanoma are increasing worldwide. Estimates of the future number of melanoma cases are important for strategic planning of the care pathway. The aim of this study was to use system dynamics modelling to evaluate the long-term effects of changes in incidence, population growth and preventive interventions. Historical data on invasive melanoma cases in Western Sweden from 1990 to 2006 were obtained. Using computer simulation software, a model estimating the accumulated number of melanoma cases for 2014 to 2023 was developed. Five future scenarios were designed: stable incidence, business-as-usual, 25% reduced patient's delay, 50% reduced doctor's delay, and a combination of the last two, called improved overall secondary prevention. After 10 years, improved overall secondary prevention would have resulted in a 42% decrease in melanomas > 4 mm and a 10% increase in melanomas ≤ 1 mm, compared with business-as-usual. System dynamics is a valuable tool, which can help policymakers choose the preventive interventions with the greatest impact.

  13. 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.

  14. Various Dermatoses What the Patients with Cutaneous Melanoma Had Anxiety for the Recurrence during Postoperative Surveillance.

    Science.gov (United States)

    Lee, Hyun-Joo; Jin, Hyunju; You, Hyang-Suk; Shim, Woo-Haing; Kim, Jeong-Min; Kim, Gun-Wook; Mun, Je-Ho; Kim, Hoon-Soo; Ko, Hyun-Chang; Kim, Byung-Soo; Kim, Moon-Bum

    2017-08-01

    The incidence and mortality rates associated with cutaneous melanoma (CM) have steadily increased over the last 20 years. Even with successful treatment, melanoma patients usually experience substantial anxiety regarding the development of terrible recurrence. To date, few studies have investigated various dermatoses what the patients with CM had anxiety for the recurrence during postoperative surveillance (Dw). To describe various Dw and to evaluate the risk of subsequent malignant skin disease in patients with CM. We performed a prospective study between August 2002 and August 2015. Fifty-six patients presented with a total of 68 Dw. Among them, melanocytic nevus was the most common (n=27), followed by seborrheic keratosis (n=9) and CM recurrence (n=7). Approximately 5.6% of the lesions were diagnosed as malignant skin diseases. This was a single-center study, so the prevalence of malignant skin diseases following primary melanoma may not represent that of all patients with CM. The results of this study can be referred by dermatologists dealing with melanoma especially when CM patients have too excessive or unrealistic anxiety for melanoma recurrence during postoperative surveillance of CM. However, the importance of postoperative surveillance must still be emphasized because of real risk of melanoma recurrence and other malignant skin.

  15. Increased NY-ESO-1 Expression and Reduced Infiltrating CD3+ T Cells in Cutaneous Melanoma

    Directory of Open Access Journals (Sweden)

    Mara Giavina-Bianchi

    2015-01-01

    Full Text Available 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<0.02. NY-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.

  16. 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.

  17. Influence of fast lymphatic drainage on metastatic spread in cutaneous malignant melanoma: a prospective feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Maza, Sofiane; Valencia, Ray; Geworski, Lilli; Sandrock, Dirk; Zander, Andreas; Munz, Dieter L. [Clinic for Nuclear Medicine, University Hospital Charite, Humboldt University of Berlin, Schumannstrasse 20-21, 10117, Berlin (Germany); Audring, Heike [Division of Dermatopathology, University Hospital Charite, Humboldt University of Berlin, Berlin (Germany); Draeger, Erik; Winter, Helmut; Sterry, Wolfram [Clinic for Dermatology, Venereology and Allergology, University Hospital Charite, Humboldt University of Berlin, Berlin (Germany)

    2003-04-01

    The concept of sentinel lymph node biopsy in cutaneous malignant melanoma is widely established. Preoperative cutaneous lymphoscintigraphic mapping is a reliable method for identifying the nodal basins at risk of metastases in melanomas. In this prospective study we investigated the correlation between the scintigraphic appearance time and the metastatic involvement of sentinel lymph nodes. In 276 malignant melanoma patients (137 women, 139 men; age 16-93 years), dynamic and static lymphoscintigraphy was performed after strict intracutaneous application of technetium-99m nanocolloid (40-150 MBq; 0.05 ml/deposit) around the tumour or biopsy scar. Analysis of dynamic scans primarily focussed on the appearance time of sentinel lymph nodes. Sentinel lymph node visualisation {<=}20 min post injection was defined as fast drainage, and visualisation >20 min as slow drainage. Fast lymphatic drainage was found in 236 patients, of whom 34 (14.4%) had sentinel lymph node metastases. Twenty-two patients showed hybrid (fast and slow) lymphatic drainage, and eight (36.4%) of them had sentinel lymph node metastases. Seven of the latter demonstrated fast lymphatic drainage, while one showed one positive sentinel lymph node with fast and another with slow drainage. The melanomas of 18 patients demonstrated exclusively slow lymphatic drainage, in all cases without sentinel lymph node metastases. This prospective study indicates that the scintigraphic appearance time of sentinel lymph nodes seems to be a clinically relevant factor for prediction of metastatic spread of cutaneous malignant melanoma. Larger numbers of patients need to be examined to truly assess the benefit of the scintigraphic appearance time compared with other predictors of sentinel lymph node tumour positivity. (orig.)

  18. Basic and clinical aspects of malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Nathanson, L. (Health Sciences Center, State Univ. of New York at Stony Brook, Stony Brook, NY (US))

    1987-01-01

    This book contains the following 10 chapters: The role of oncogenes in the pathogenesis of malignant melanoma; Laminin and fibronectin modulate the metastatic activity of melanoma cells; Structure, function and biosynthesis of ganglioside antigens associated with human tumors derived from the neuroectoderm; Epidemiology of ocular melanoma; Malignant melanoma: Prognostic factors; Endocrine influences on the natural history of human malignant melanoma; Psychosocial factors associated with prognostic indicators, progression, psychophysiology, and tumor-host response in cutaneous malignant melanoma; Central nervous system metastases in malignant melanoma; Interferon trials in the management of malignant melanoma and other neoplasms: an overview; and The treatment of malignant melanoma by fast neutrons.

  19. Clinical and epidemiological profile of cutaneous malignant melanomas in two referral institutions in the city of Manaus, Brazil.

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    Chiba, Fabiano Bandeira; Schettini, Antonio Pedro Mendes; Delfino, Ana Carolina Guimaraes; Chirano, Carlos Alberto; Damasceno, Silvana de Albuquerque Silva

    2011-01-01

    Knowledge on the frequency and clinical and pathological characteristics of cutaneous melanoma in the different geographical regions of Brazil is important in evaluating the magnitude of the problem and in directing healthcare actions appropriately. The present study reviewed data from 55 cases of cutaneous melanoma in patients treated at two healthcare institutions in the city of Manaus, Amazonas, Brazil. Rates were higher in brown-skinned males and in individuals of 70-80 years of age. Lesions were most commonly located on the lower limbs, were of the acral lentiginous melanoma type and at advanced stages of the disease, with Breslow thickness > 1 mm and Clark level V.

  20. Gene expression profiling for molecular staging of cutaneous melanoma in patients undergoing sentinel lymph node biopsy.

    Science.gov (United States)

    Gerami, Pedram; Cook, Robert W; Russell, Maria C; Wilkinson, Jeff; Amaria, Rodabe N; Gonzalez, Rene; Lyle, Stephen; Jackson, Gilchrist L; Greisinger, Anthony J; Johnson, Clare E; Oelschlager, Kristen M; Stone, John F; Maetzold, Derek J; Ferris, Laura K; Wayne, Jeffrey D; Cooper, Chelsea; Obregon, Roxana; Delman, Keith A; Lawson, David

    2015-05-01

    A gene expression profile (GEP) test able to accurately identify risk of metastasis for patients with cutaneous melanoma has been clinically validated. We aimed for assessment of the prognostic accuracy of GEP and sentinel lymph node biopsy (SLNB) tests, independently and in combination, in a multicenter cohort of 217 patients. Reverse transcription polymerase chain reaction (RT-PCR) was performed to assess the expression of 31 genes from primary melanoma tumors, and SLNB outcome was determined from clinical data. Prognostic accuracy of each test was determined using Kaplan-Meier and Cox regression analysis of disease-free, distant metastasis-free, and overall survivals. GEP outcome was a more significant and better predictor of each end point in univariate and multivariate regression analysis, compared with SLNB (P melanoma. In this study cohort, GEP was an objective tool that accurately predicted metastatic risk in SLNB-eligible patients. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  1. Mayo Clinic consensus recommendations for the depth of excision in primary cutaneous melanoma.

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    Grotz, Travis E; Markovic, Svetomir N; Erickson, Lori A; Harmsen, William S; Huebner, Marianne; Farley, David R; Pockaj, Barbara A; Donohue, John H; Sim, Franklin H; Grant, Clive S; Bagaria, Sanjay P; Shives, Thomas C; Balch, Charles M; Jakub, James W

    2011-06-01

    Currently, no data from randomized controlled clinical trials are available to guide the depth of resection for intermediate-thickness primary cutaneous melanoma. Thus, we hypothesized that substantial variability exists in this aspect of surgical care. We have summarized the literature regarding depth of resection and report the results of our survey of surgeons who treat melanoma. Most of the 320 respondents resected down to, but did not include, the muscular fascia (extremity, 71%; trunk, 66%; and head and neck, 62%). However, significant variation exists. We identified variability in our own practice and have elected to standardize this common aspect of routine surgical care across our institution. In light of the lack of evidence to support resection of the deep muscular fascia, we have elected to preserve the muscular fascia as a matter of routine, except when a deep primary melanoma or thin subcutaneous tissue dictates otherwise.

  2. Surgical management of sentinel lymph node biopsy outside major nodal basin in patients with cutaneous melanoma.

    Science.gov (United States)

    Caracò, Corrado; Marone, Ugo; Di Monta, Gianluca; Aloj, Luigi; Caracò, Corradina; Anniciello, Annamaria; Lastoria, Secondo; Botti, Gerardo; Mozzillo, Nicola

    2014-01-01

    To assess the incidence of nonmajor lymphatic basin sentinel nodes in patients with cutaneous melanoma in order to propose a correct nomenclature and inform appropriate surgical management. This was a retrospective review of 1,045 consecutive patients with cutaneous melanoma who underwent sentinel lymph node biopsy and dynamic lymphoscintigraphy to identify sentinel node site. Nonmajor drainage sites were classified as uncommon (located in a minor lymphatic basin along the lymphatic drainage to a major classical nodal basin) or interval (located anywhere along the lymphatics between the primary tumor site and the nearest lymphatic basin) sentinel nodes. Nonclassical sentinel nodes were identified in 32 patients (3.0 %). Uncommon sentinel nodes were identified in 3.2 % (n = 17) of trunk melanoma primary disease and in 1.5 % (n = 7) of upper and lower extremity sites. Interval sentinel nodes were identified in 1.3 % (n = 7) of trunk primary lesions, with none from upper and lower extremities melanomas. The incidence of tumor-positive sentinel nodes was 24.1 % (245 of 1,013) in classical sites and 12.5 % (4 of 32) in uncommon/interval sites. The definition of uncommon and interval sentinel nodes allows the identification of different lymphatic pathways and inform appropriate surgical treatment. Wider experience with uncommon/interval sentinel nodes will better clarify the clinical implications and surgical management to be adopted in the management of uncommon and interval sentinel node sites.

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

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    Hieken, Tina J.; Hernández-Irizarry, Roberto; Boll, Julia M.; Jones Coleman, Jamie E.

    2013-01-01

    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. PMID:24102023

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

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    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.

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

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    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.

  6. Impact of Time Between Diagnosis and SLNB on Outcomes in Cutaneous Melanoma.

    Science.gov (United States)

    Nelson, Daniel W; Stern, Stacey; Elashoff, David E; Elashoff, Robert; Thompson, John F; Mozzillo, Nicola; Nieweg, Omgo E; Hoekstra, Harald J; Cochran, Alistair J; Faries, Mark B

    2017-08-01

    Hypothetically, delay between melanoma diagnosis and SLNB could affect outcomes, either adversely by allowing growth and dissemination of metastases, or beneficially by allowing development of an anti-melanoma immune response. Available data are conflicting about the effect of SLNB delay on patient survival. Our objective was to determine whether delay between initial diagnosis and SLNB affects outcomes in patients with cutaneous melanoma. We performed query and analysis of a large prospectively maintained database of patients with primary cutaneous melanomas undergoing SLNB. An independent dataset from MSLT-1 (Multicenter Selective Lymphadenectomy Trial-1) was used for validation. Primary outcomes included disease-free survival and melanoma-specific survival. Early and delayed SLNB were defined as less than 30 and 30 or more days from initial diagnosis, respectively. There were 2,483 patients that met inclusion criteria. Positive sentinel lymph nodes were identified in 17.4% (n = 432). Among all patients, 42% had SLNB 30 or more days after diagnosis and 37% of positive sentinel lymph nodes were at 30 or more days. No differences in sex, anatomic site, or histopathologic features were identified between the 2 groups. There was no difference in melanoma-specific survival or disease-free survival between those undergoing early or delayed SLNB. Examination of MSLT-1 trial data similarly demonstrated no difference in survival outcomes. This, the largest study on this subject to date, found no adverse impact on long-term clinical outcomes of patients due to delay of SLNB beyond 30 days. The MSLT-1 data confirm this result. Patients can be reassured that if the operation is performed 30 or more days after diagnosis, it will not cause harm. Copyright © 2017. Published by Elsevier Inc.

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

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    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.

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

    Science.gov (United States)

    Pellegrini, Cristina; Fargnoli, Maria Concetta; Suppa, Mariano; Peris, Ketty

    2012-09-14

    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. 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. 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.

  9. Multispectral autofluorescence diagnosis of non-melanoma cutaneous tumors

    Science.gov (United States)

    Borisova, Ekaterina; Dogandjiiska, Daniela; Bliznakova, Irina; Avramov, Latchezar; Pavlova, Elmira; Troyanova, Petranka

    2009-07-01

    Fluorescent analysis of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), keratoacanthoma and benign cutaneous lesions is carried out under initial phase of clinical trial in the National Oncological Center - Sofia. Excitation sources with maximum of emission at 365, 380, 405, 450 and 630 nm are applied for better differentiation between nonmelanoma malignant cutaneous lesions fluorescence and spectral discrimination from the benign pathologies. Major spectral features are addressed and diagnostic discrimination algorithms based on lesions' emission properties are proposed. The diagnostic algorithms and evaluation procedures found will be applied for development of an optical biopsy clinical system for skin cancer detection in the frames of National Oncological Center and other university hospital dermatological departments in our country.

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

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    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

  11. Melanoma cutáneo asociado a nevo previo Cutaneous melanoma associated with previous nevus

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    María P. Gutiérrez

    2009-10-01

    Full Text Available El melanoma maligno es una neoplasia originada en los melanocitos de la piel y otras localizaciones. No existe información en nuestro país acerca de su incidencia y prevalecencia, sí se sabe cuáles son los factores de riesgo más importantes. El melanoma puede originarse de novo o a partir de lesiones melanocíticas previas. La noción de que un nevo melanocítico pueda servir como lesión precursora es sustentada por evidencias clínicas e histológicas. Realizamos en el Hospital Privado de Córdoba un estudio observacional, retrospectivo y analítico. El objetivo de este trabajo fue conocer cuál es la frecuencia de asociación de melanomas malignos que se desarrollan sobre nevos previos. Fueron analizados un total de 134 melanomas. En 32 pacientes (24%, los melanomas estuvieron histológicamente asociados con nevos, con espesores de Breslow mayores de 1 mm el porcentaje de asociación fue de 16.3%, y con Breslow menores de 1 mm, 38.1%. Al evaluar los melanomas en relación a la clasificación de Breslow y Clark, se objetivó que el grupo de melanomas asociados a nevos presentó un espesor de Breslow y niveles de Clark bajos y en el análisis estadístico fueron predictores significativos en la probabilidad de hallar esta asociación (p The malignant melanoma is a neoplasia originated from the melanocytes located in the skin and other locations. Even though there is not information regarding its incidence and prevalence in our country, its most important risk factors are known. The melanoma can originate de novo or from previous melanocytic lesions. The concept that a melanocytic nevus can serve as a precursor lesion is supported by clinical and histological evidence. An observational, retrospective and analytical study was carried out in the Hospital Privado de Córdoba. The objective was to determine which is the frequency of association of malignant melanomas that develop on previous nevus. A total of 134 melanomas were analyzed. In 32

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

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    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

  13. Cutaneous Manifestations of Human and Murine Leishmaniasis

    Science.gov (United States)

    Scorza, Breanna M.; Carvalho, Edgar M.; Wilson, Mary E.

    2017-01-01

    The leishmaniases are diseases caused by pathogenic protozoan parasites of the genus Leishmania. Infections are initiated when a sand fly vector inoculates Leishmania parasites into the skin of a mammalian host. Leishmania causes a spectrum of inflammatory cutaneous disease manifestations. The type of cutaneous pathology is determined in part by the infecting Leishmania species, but also by a combination of inflammatory and anti-inflammatory host immune response factors resulting in different clinical outcomes. This review discusses the distinct cutaneous syndromes described in humans, and current knowledge of the inflammatory responses associated with divergent cutaneous pathologic responses to different Leishmania species. The contribution of key hematopoietic cells in experimental cutaneous leishmaniasis in mouse models are also reviewed and compared with those observed during human infection. We hypothesize that local skin events influence the ensuing adaptive immune response to Leishmania spp. infections, and that the balance between inflammatory and regulatory factors induced by infection are critical for determining cutaneous pathology and outcome of infection. PMID:28629171

  14. Cutaneous Manifestations of Human and Murine Leishmaniasis

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    Breanna M. Scorza

    2017-06-01

    Full Text Available The leishmaniases are diseases caused by pathogenic protozoan parasites of the genus Leishmania. Infections are initiated when a sand fly vector inoculates Leishmania parasites into the skin of a mammalian host. Leishmania causes a spectrum of inflammatory cutaneous disease manifestations. The type of cutaneous pathology is determined in part by the infecting Leishmania species, but also by a combination of inflammatory and anti-inflammatory host immune response factors resulting in different clinical outcomes. This review discusses the distinct cutaneous syndromes described in humans, and current knowledge of the inflammatory responses associated with divergent cutaneous pathologic responses to different Leishmania species. The contribution of key hematopoietic cells in experimental cutaneous leishmaniasis in mouse models are also reviewed and compared with those observed during human infection. We hypothesize that local skin events influence the ensuing adaptive immune response to Leishmania spp. infections, and that the balance between inflammatory and regulatory factors induced by infection are critical for determining cutaneous pathology and outcome of infection.

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

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    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.

  16. Radiosensitivity of Human Melanoma Cell Lines

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    Bergoc, R. M.; Medina, V.; Cricco, G.; Mohamed, N.; Martin, G.; Nunez, M.; Croci, M.; Crescenti, E. J.; Rivera, E. S.

    2004-07-01

    Cutaneous melanoma is a skin cancer resulting from the malign transformation of skin-pigment cells, the melanocytes. The radiotherapy, alone or in combination with other treatment, is an important therapy for this disease. the objective of this paper was to determine in vitro the radiosensitivity of two human melanoma cell lines with different metastatic capability: WM35 and MI/15, and to study the effect of drugs on radiobiological parameters. The Survival Curves were adjusted to the mathematical Linear-quadratic model using GrapsPad Prism software. Cells were seeded in RPMI medium (3000-3500 cells/flask), in triplicate and irradiated 24 h later. The irradiation was performed using an IBL 437C H Type equipment (189 TBq, 7.7 Gy/min) calibrated with a TLD 700 dosimeter. The range of Doses covered from 0 to 10 Gy and the colonies formed were counted at day 7th post-irradiation. Results obtained were: for WM35, {alpha}=0.37{+-}0.07 Gy''-1 and {beta}=0.06{+-}0.02 Gy''-2, for M1/15m {alpha}=0.47{+-}0.03 Gy''-1 and {beta}=0.06{+-}0.01 Gy''-2. The {alpha}/{beta} values WM35: {alpha}/{beta} values WM35: {alpha}/{beta}=6.07 Gy and M1/15: {alpha}/{beta}{sub 7}.33 Gy were similar, independently of their metastatic capabillity and indicate that both lines exhibit high radioresistance. Microscopic observation of irradiated cells showed multinuclear cells with few morphologic changes non-compatible with apoptosis. By means of specific fluorescent dyes and flow cytometry analysis we determined the intracellular levels of the radicals superoxide and hydrogen peroxide and their modulation in response to ionizing radiation. The results showed a marked decreased in H{sub 2}O{sub 2} intracellular levels with a simultaneous increase in superoxide that will be part of a mechanism responsible for induction of cell radioresistance. This response triggered by irradiated cells could not be abrogated by different treatments like histamine or the

  17. 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.

  18. Lymphoscintigraphy Defines New Lymphatic Pathways from Cutaneous Melanoma Site: Clinical Implications and Surgical Management

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    Ugo Marone

    2011-01-01

    Full Text Available Sentinel lymph node biopsy is commonly applied as staging procedure of regional lymph nodes in patients with cutaneous melanoma. Dynamic lymphoscintigraphy defines the lymphatic pathways from a primary melanoma site and allows to identify the node receiving lymphatic drainage from the primary tumor, which is the sentinel lymph node. In rare cases, lymphoscintigraphy shows sites of lymphatic drainage in nonclassical basins never described in the past when lymphatic drainage was considered only according to the anatomical proximity of the tumor primary site. These peculiar sentinel nodes, so-called “uncommon/interval” nodes, must be surgically removed because they may contain micrometastatic disease and may be the only site of nodal involvement.

  19. Immunosuppression is an independent prognostic factor associated with aggressive tumor behavior in cutaneous melanoma.

    Science.gov (United States)

    Donahue, Tracy; Lee, Christina Y; Sanghvi, Asmi; Obregon, Roxana; Sidiropoulos, Michael; Cooper, Chelsea; Merkel, Emily A; Yélamos, Oriol; Ferris, Laura; Gerami, Pedram

    2015-09-01

    A number of factors other than those identified by the American Joint Committee on Cancer (AJCC) may have prognostic significance in the evaluation of melanoma. We sought to evaluate commonly recorded clinical features potentially associated with aggressive melanoma. We conducted a retrospective case-control study. We included patients given a diagnosis of cutaneous melanoma with at least 5 years of follow-up or documented metastases. Patients were divided into nonaggressive and aggressive groups. Univariate and multivariate statistical analyses were performed to evaluate the association of multiple clinical and histologic parameters and metastases. We included 141 patients. Significant prognostic factors in univariate analysis associated with nonaggressive disease included history of dysplastic nevus syndrome and ABCDE criteria. Significant factors in univariate analysis associated with aggressive disease included age and immunosuppression. Only age and immunosuppression remained significant in multivariate analysis when controlled across statistically significant histologic variables from AJCC. The study is retrospective and has a small sample size. Older patients and those with a history of immunosuppression may be at higher risk for aggressive disease and should be closely monitored after an initial diagnosis of melanoma. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  20. CDKN2A and MC1R variants found in Cypriot patients diagnosed with cutaneous melanoma.

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    Koulermou, Georgia; Shammas, Christos; Vassiliou, Andreas; Kyriakides, Tassos C; Costi, Constantina; Neocleous, Vassos; Phylactou, Leonidas A; Pantelidou, Maria

    2017-03-01

    The prevalence of genetic variants associated to cutaneous melanoma (CM) has never been determined within Cypriot melanomas. This study evaluates the frequency of variants in cyclin-dependent kinase inhibitor 2A (CDKN2A) and melanocortin-1 receptor (MC1R) in 32 patients diagnosed with CM. Other characteristics and risk factors were also assessed. CDKN2A p.Ala148Thr was detected in three of 32 patients, while the control group revealed no variations within CDKN2A. MC1R screening in 32 patients revealed the following variations: p.Val60Leu in 11 patients, p.Arg142His in four patients, p.Thr314Thr in one patient, p.Arg160Trp in one patient, p.Val92Met/p.Thr314Thr in one patient and p.Val92Met/p.Arg142His/p.Thr314Thr in one patient. The control group revealed only p.Val60Leu (in 10 of 45 individuals), which is frequently found in general populations. Two unrelated patients carried CDKN2A p.Ala148Thr in combination with MC1R p.Arg142His, suggesting digenic inheritance that may provide evidence of different gene variants acting synergistically to contribute for CM development. This study confirms the presence of CDKN2A and MC1R variants among Cypriot melanomas and supports existing evidence of a role for these variants in susceptibility to melanoma.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Early diagnosis of malignant melanoma: Proposal of a working formulation for the management of cutaneous pigmented lesions from the Melanoma Cooperative Group.

    Science.gov (United States)

    Ascierto, Paolo A; Palmieri, Giuseppe; Botti, Gerardo; Satriano, Rocco A; Stanganelli, Ignazio; Bono, Riccardo; Testori, Alessandro; Bosco, Leonardo; Daponte, Antonio; Caracò, Corrado; Chiofalo, Maria Grazia; Melucci, Maria Teresa; Calignano, Rosario; Tatangelo, Fabiana; Cochran, Alistair J; Castello, Giuseppe

    2003-06-01

    Epiluminescence microscopy (ELM) strongly improves the separation of different types of cutaneous pigmented lesions (CPL) and facilitates the early diagnosis of cutaneous melanoma (CM). ELM alone is not 100% accurate in routine diagnosis, and should not be considered the only criterion in the diagnosis of high-risk skin lesions. We have however, demonstrated close agreement between ELM classification criteria and histology in 2,731 cutaneous lesions. In the past five years, our Melanoma Cooperative Group has evaluated 61,000 skin lesions from 30,000 individuals and identified 478 cutaneous melanomas. Most newly diagnosed patients had very early stage melanoma [299 (62%) were Stage I (203 Stage IA and 96 Stage IB), by the American Joint Committee on Cancer (AJCC) criteria]. We have compared data from the patient histories and clinical evaluations with ELM-based morphological patterns to better characterize skin lesions and minimize interpretative problems. From these comparisons, we propose new guidelines for the management of CPL to provide a standard diagnostic and therapeutic approaches and to foster the early identification of lesions at risk for malignant transformation.

  3. 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...... as paraganglioma, breast cancer, and suspected mesothelioma cases in the family. Bioinformatic analysis and splicing assays demonstrated that this mutation creates a strong cryptic splice donor, resulting in aberrant splicing and a truncating frameshift of the BAP1 transcript. Somatic loss of the wild-type allele...

  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. 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.......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....

  6. The human melanoma side population displays molecular and functional characteristics of enriched chemoresistance and tumorigenesis.

    Science.gov (United States)

    Wouters, Jasper; Stas, Marguerite; Gremeaux, Lies; Govaere, Olivier; Van den Broeck, Anke; Maes, Hannelore; Agostinis, Patrizia; Roskams, Tania; van den Oord, Joost J; Vankelecom, Hugo

    2013-01-01

    Melanoma remains the most lethal skin cancer, mainly because of high resistance to therapy. Side population (SP) cells are found in many types of cancer and are usually enriched in therapy-resistant as well as tumorigenic cells. Here, we identified a Hoechst dye-effluxing SP in a large series of human melanoma samples representing different progression phases. The SP size did not change with disease stage but was correlated with the prognostic "Breslow's depth" in the primary (cutaneous) tumors. When injected into immunodeficient mice, the SP generated larger tumors than the bulk "main population" (MP) melanoma cells in two consecutive generations, and showed tumorigenic capacity at lower cell numbers than the MP. In addition, the SP reconstituted the heterogeneous composition of the human A375 melanoma cell line, and its clonogenic activity was 2.5-fold higher than that of the MP. Gene-expression analysis revealed upregulated expression in the melanoma SP (versus the MP) of genes associated with chemoresistance and anti-apoptosis. Consistent with these molecular characteristics, the SP increased in proportion when A375 cells were exposed to the melanoma standard chemotherapeutic agent dacarbazine, and to the aggravating condition of hypoxia. In addition, the SP showed enhanced expression of genes related to cell invasion and migration, as well as to putative (melanoma) cancer stem cells (CSC) including ABCB1 and JARID1B. ABCB1 immunoreactivity was detected in a number of tumor cells in human melanomas, and in particular in clusters at the invasive front of the primary tumors. Together, our findings support that the human melanoma SP is enriched in tumorigenic and chemoresistant capacity, considered key characteristics of CSC. The melanoma SP may therefore represent an interesting therapeutic target.

  7. Expression of lumican, a small leucine-rich proteoglycan with antitumour activity, in human malignant melanoma.

    Science.gov (United States)

    Brézillon, S; Venteo, L; Ramont, L; D'Onofrio, M-F; Perreau, C; Pluot, M; Maquart, F-X; Wegrowski, Y

    2007-07-01

    The family of small leucine-rich proteoglycans (SLRPs), which includes decorin, lumican, biglycan and fibromodulin, constitutes an abundant component of the skin extracellular matrix. We previously demonstrated that human lumican inhibits melanoma growth and progression in a mouse experimental model, by regulating cell migration, proliferation and apoptosis. The aim of this study was to investigate the expression of lumican and decorin in human malignant melanoma and adjacent peritumoral tissue, to understand better their role in the control of growth and invasion of human melanoma. Expression of both proteoglycans was studied by immunohistochemistry using specific antibodies in 34 malignant melanomas, 12 Hutchinson's melanotic freckles and 4 cutaneous metastatic melanomas. We showed that lumican and decorin are located in the dermis and in the peritumoral stroma of malignant melanoma, but are not found in melanoma cells or dense tumour tissue. In the healthy dermis, distant from the tumour, the increasing ratio of lumican to decorin was inversely correlated with the proliferation of the tumour cells (P = 0.035). The comparison of the level of expression of lumican protein in superficial vs. nodular subtypes of malignant melanomas showed a decrease of lumican but not decorin in the peritumoral stroma of nodular subtypes. In the peritumoral stroma, the level of expression of lumican but not decorin decreased significantly (P = 0.016) with increasing Clark levels. In addition, immunocytochemical and reverse transcription PCR analyses of malignant melanoma cell lines (A-375, HT-144) and of MRC-5 and dermal fibroblasts from healthy donors in vitro confirmed that dermal fibroblasts are responsible for lumican and decorin synthesis in skin. CONCLUSIONS. Lumican may regulate vertical progression of human malignant melanoma, but further study is necessary to clarify the antitumour mechanism and the downstream signal transduction pathways involved.

  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. Feasibility of Postoperative Radiotherapy Using Conventional Fractionation for Lymph Node Metastasis from Cutaneous Melanoma.

    Science.gov (United States)

    Kim, Yeon Joo; Song, Si Yeol; Kim, Wanlim; Jeong, Seong-Yun; Choi, Wonsik; Je, Hyoung Uk; Lee, Jong-Seok; Choi, Eun Kyung

    2017-08-01

    In the present study we assessed if postoperative radiotherapy (PORT) using conventional fractionation confers a benefit in cutaneous melanoma patients with lymph node (LN) metastasis. Sixty-two patients with axillary or inguinal LN metastasis were retrospectively reviewed. Twenty-eight patients received PORT. The median RT dose was 50 Gy in 25 fractions. The high-risk group was defined by the presence of any of the following: ≥3 LNs, size ≥3 cm, extranodal extension. The median follow-up time was 34 months. PORT showed a significant benefit on 5-year axilla-inguinal recurrence-free survival (RFS) in high-risk patients (RT 100% vs. No-RT 37%, p=0.001). There was also a benefit of RT on 5-year out-field RFS in the high-risk population (RT 93% vs. No-RT 29%, p=0.002). There were no ≥grade 2 lymphedemas after RT. PORT using conventional fractionation for high-risk LN metastasis from cutaneous melanoma is feasible with comparable regional control and minimal toxicity. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  10. Clinical genetic aspects of cutaneous malignant melanoma: I. Prevalence, familial study, genetic heterogeneity

    Energy Technology Data Exchange (ETDEWEB)

    Gar`kavtseva, R.F.; Sitnikova, T.S.; Kazubskaya, T.P. [Institute of Clinical Oncology, Moscow (Russian Federation)] [and others

    1995-11-01

    Epidemiological and clinical genetic data on cutaneous malignant melanoma (CMM) are presented. CMM morbidity in Moscow from 1983 to 1987 was analyzed. Cumulative incidence (cumulative risk) of CMM was calculated for various life periods on the basis of estimates for various age groups, which were used as population frequencies. By the age of 85, these frequencies were 0.35% for males and 0.38% for females. Among relatives of patients, the incidence of CMM was 1.420{plus_minus}0.498% for males and 1. 110{plus_minus} 0.348% for females; i.e., it exceeded the population frequency by a factor of 3 or 4. As a whole, the familial frequency of cancer was equal to 13.3% for male probands and 14.2% for female probands, i.e., more than three times higher than the population frequency. The data obtained formed the basis for the development of CMM classification. Hereditary and nonhereditary variants of cutaneous melanoma were identified. Familial cases and CMM that occurred against the background of inherited diseases or syndromes were classified as hereditary variants of CMM; taken together, they accounted for 38.8%. The data provided grounds for identification of families at increased risk for the development of CMM. 10 refs., 2 tabs.

  11. 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.

  12. Genetic variants of PDGF signaling pathway genes predict cutaneous melanoma survival.

    Science.gov (United States)

    Li, Hong; Wang, Yanru; Liu, Hongliang; Shi, Qiong; Li, Hongyu; Wu, Wenting; Zhu, Dakai; Amos, Christopher I; Fang, Shenying; Lee, Jeffrey E; Li, Yi; Han, Jiali; Wei, Qingyi

    2017-09-26

    To investigate whether genetic variants of platelet-derived growth factor (PDGF) signaling pathway genes are associated with survival of cutaneous melanoma (CM) patients, we assessed associations of single-nucleotide polymorphisms in PDGF pathway with melanoma-specific survival in 858 CM patients of M.D. Anderson Cancer Center (MDACC). Additional data of 409 cases from Harvard University were also included for further analysis. We identified 13 SNPs in four genes (COL6A3, NCK2, COL5A1 and PRKCD) with a nominal P Harvard datasets, there were two SNPs associated with poor survival of CM patients: rs6707820 C>T in NCK2 (HR = 1.87, 95% CI = 1.35-2.59, Pmeta= 1.53E-5); and rs2306574 T>C in PRKCD (HR = 1.73, 95% CI = 1.33-2.24, Pmeta= 4.56E-6). Moreover, CM patients in MDACC with combined risk genotypes of these two loci had markedly poorer survival (HR = 2.47, 95% CI = 1.58-3.84, P T in NCK2 and rs2306574 T>C in PRKCD of the PDGF signaling pathway may be biomarkers for melanoma survival.

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. [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.

  16. [Role of high-definition and high frequency ultrasonography in determining tumor thickness in cutaneous malignant melanoma].

    Science.gov (United States)

    Solivetti, F M; Thorel, M F; Di Luca Sidozzi, A; Bucher, S; Donati, P; Panichelli, V

    1998-12-01

    We investigated the predictive capabilities of high frequency, high resolution ultrasound (US) in the preoperative assessment of tumor thickness in cutaneous malignant melanomas. This evaluation is a valuable help for correct surgical planning. December 1997 to August 1998, we studied with US over 120 pigmented skin lesions and collected the data, including the final histologic diagnosis, of 78 of them, which make our series. Sixty-six of 78 lesions were histologically defined as cutaneous malignant melanomas with superficial spread and the other 12 as melanocytic nevi. All examinations were carried out with an Esaotebiomedica AU 5 Harmonic scanner equipped with a 20-MHz annular array probe and a linear 13-MHz probe; B-mode, color and power Doppler images were always acquired. The statistical analysis of the comparative US and histologic measurements of tumor thickness showed very good agreement, with a high Pearson's coefficient (R: .93). However, US frequently underestimated the actual thickness relative to histology, which is in contradiction with previous literature reports. We could study with US the melanoma in situ, which has never been described before. Last but not least, low-thickness melanomas had very few color and power Doppler signals. US is the correct tool for the preoperative assessment of the thickness of cutaneous malignant melanomas because it provides high agreement with histologic data even in lesions thinner than 1 mm.

  17. Epidemiology, management and survival outcomes of primary cutaneous melanoma: a ten-year overview.

    Science.gov (United States)

    Aubuchon, M M F; Bolt, L J J; Janssen-Heijnen, M L G; Verleisdonk-Bolhaar, S T H P; van Marion, A; van Berlo, C L H

    2017-02-01

    Malignant melanoma (MM) is the most aggressive type of skin cancer, accounting for 90% of all the skin cancer mortality. The objective of this study was providing an overview of current patient- and tumour characteristics, treatment strategies, complications and survival in patients with MM over the past ten years. Hereby, an up-to-date view of every day clinical practice is obtained. Files of patients treated for primary cutaneous melanoma (n = 686) in the VieCuri Medical Centre in the Netherlands between January 2002 and December 2013 were retrospectively reviewed. Relevant patient features, tumour characteristics, and (surgical) outcomes were evaluated. The majority of all the patients presented thin tumours (59.1% stage 1A/in situ melanoma). Men showed more ulceration (17.7% vs. 8.4%, p < .01) and a significantly higher Breslow thickness than women (1.2 mm vs. 0.9 mm, p < .01). 14.6% (40/273) underwent sentinel lymph node biopsy (SLNB); 10/40 (25%) showed nodal metastasis, 50 patients (7.3%) developed distant metastases (M: 10.6%, F: 5%, p < .01). One-, 5- and 10- year disease specific survival rates were 96%, 86% and 84%, respectively. Median survival for stage 4 MM was 3 months. Extensive surgery was uncommon (n = 3). Patients generally presented with thin melanomas. Lymph node disease and distant metastases remained infrequently observed during following years, and general 1- and 5-year overall disease-specific survival rates exceeded 85%. Small numbers of rescue surgery and palliative medical treatment warrant further centralisation and investigation.

  18. Birth outcome in women with breast cancer, cutaneous malignant melanoma, or Hodgkin's disease: a review

    Directory of Open Access Journals (Sweden)

    Vivian Langagergaard

    2010-12-01

    Full Text Available Vivian LangagergaardDepartment of Clinical Epidemiology, Aarhus University Hospital, Aarhus, DenmarkBackground: Data on birth outcome in women diagnosed with cancer before, during, or shortly after pregnancy are very sparse. The purpose of this review was to summarize the existing epidemiologic evidence of the adverse effect of breast cancer, cutaneous malignant melanoma, and Hodgkin's disease on birth outcome.Methods: The MEDLINE database was used to review the literature systematically. Studies that examined the following outcomes were included: preterm birth, low birth weight, low birth weight at term, stillbirths, congenital abnormalities, male proportion of newborns, and mean birth weight. Studies were grouped according to whether the woman had been diagnosed with the specific cancer before, during, or shortly after pregnancy.Results: Few data exist on birth outcome in women with breast cancer, melanoma, or Hodgkin's disease. The overall results from the limited number of studies, which included a comparison group for birth outcome, were reassuring. However, for women diagnosed with breast cancer before pregnancy, the only 2 studies that included comparison groups for birth outcome had conflicting results regarding the risk of preterm birth and congenital abnormalities. Furthermore, a recent cohort study of birth outcome in women who were diagnosed with Hodgkin's disease before pregnancy indicated a slightly increased risk of congenital abnormalities among the newborns.Conclusion: Overall, the existing studies offer reassuring results concerning the risks of adverse birth outcome for women diagnosed with breast cancer, melanoma, or Hodgkin's disease before, during or shortly after pregnancy. A limitation of most studies was the imprecise risk estimates caused by the small number of adverse birth outcomes and the lack of results stratified by treatment. Therefore, international collaboration is necessary in the future, to obtain more precise

  19. Multispectral imaging approach in the diagnosis of cutaneous melanoma: potentiality and limits

    Energy Technology Data Exchange (ETDEWEB)

    Farina, B.; Bartoli, C.; Bono, A.; Colombo, A.; Lualdi, M.; Tragni, G.; Marchesini, R. [Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan (Italy)

    2000-05-01

    In an attempt to overcome the subjectiveness of clinical observation in the diagnosis of cutaneous melanoma, a computerized method is proposed. Reflectance images of 237 pigmented lesions (67 melanomas and 170 non-melanomas) were analysed using a telespectrophotometric technique. This device consists of a CCD camera with 17 interference filters. Images were acquired at selected wavelengths, from 420 to 1040 nm. Morphological and reflectance related parameters were extracted from the wavelength-dependent images of the lesions. The most significant features in the comparison between benign and malignant lesions were: lesion dimension (P < 10{sup -8} at 578 nm); mean value (P < 10{sup -7} at 940 nm) and standard deviation (P < 10{sup -4} at 904 nm) of lesion reflectance; lesion roundness (P < 10{sup -5} at 461 nm); and border irregularity (P < 10{sup -4} at461 nm). Based on these parameters, a discriminant function between the two populations of lesions (naevi and melanomas) was obtained. By using the results of the analysis of the recruited lesions as 'training data', discriminant functions enabled the assignment of a score, or a 'risk probability', to each studied lesion. By imposing a sensitivity of 80% (a figure that mimics the diagnostic capability of an experienced clinician), entering or not entering the lesion dimension as input data in the discriminant analysis led to a specificity of 51% or 46% respectively. The high number of false-positive cases, which is a consequence of the selection criteria of the lesions, is, at present, the major limitation of the current technique. Nevertheless, our results suggest that an imaging-based computer-assisted device could be capable of discriminating malignant lesions mainly by evaluation of reflectance, especially in the infrared region, and shape properties. The dimension of a lesion should not be essential in the diagnosis of melanoma and, in our opinion, small melanomas should be recognized by a

  20. Meta-analysis of the performance of {sup 18}F-FDG PET in cutaneous melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez-Requena, Felisa; Perez-Vazquez, Jose M. [Hospital General Universitario Gregorio Maranon, Nuclear Medicine Department, Madrid (Spain); Delgado-Bolton, Roberto C.; Carreras-Delgado, Jose L. [Hospital Clinico San Carlos, Nuclear Medicine Department, Madrid (Spain); Fernandez-Perez, Cristina [Hospital Clinico San Carlos, Research Unit, Madrid (Spain); Gambhir, Sanjiv S. [Stanford University School of Medicine, Department of Radiology, James H. Clark Center, Stanford, CA (United States); Schwimmer, Judy [David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, Los Angeles, CA (United States)

    2010-02-15

    The aim of this study was to perform a systematic review of the literature to evaluate the accuracy of FDG-PET in staging and restaging of cutaneous melanoma. Systematic methods were used to identify, select, and evaluate the methodologic quality of the studies as well as to summarize the overall findings of sensitivity and specificity. The search strategy consisted of identifying studies published between 2000 and 2006. Inclusion criteria were studies that evaluated the diagnostic performance of FDG-PET in staging/restaging of cutaneous melanoma. The results were compared and pooled with a meta-analysis published previously that included studies published until 1999. The meta-analysis included 95% confidence intervals (CI) of sensitivity, specificity, likelihood-ratio (LR), and diagnostic-odds-ratio (DOR). The quantitative meta-analysis included 24 studies that were analysed in two groups: eight studies were included only in the regional staging analysis (group I), 13 studies were included only in the detection of distant metastases analysis (group II), and three studies were included in both analyses. Compliance with the methodologic-quality criteria was acceptable. We analysed the results of data presented in patients, lesions, basins, lymph-nodes, areas, and scans. Regarding the performance of FDG-PET in the detection of metastases, the pooled studies presented homogeneity for the negative-LR (0.15; 95% CI, 0.10-0.22) when analyzing lesions. When analyzing scans, there was global homogeneity for specificity (0.86; 95% CI, 0.77-0.92), positive-LR (5.86; 95% CI, 3.64-9.43), and DOR (37.89; 95% CI, 15.80-90.86). The pooled studies presented heterogeneity for the other items analysed. Regarding the detection of regional metastases, when analyzing lymph-nodes there was global homogeneity for specificity (0.99; 95% CI, 0.97-0.99; P = 0.101). The meta-regression evidenced that the variable that most influenced the DOR of the different studies and that can explain the

  1. Risk of subsequent cutaneous malignancy in patients with prior melanoma: a systematic review and meta-analysis.

    Science.gov (United States)

    van der Leest, R J T; Flohil, S C; Arends, L R; de Vries, E; Nijsten, T

    2015-06-01

    Melanoma patients are known to be at risk of developing multiple cutaneous (pre-) malignancies, however, the exact dimensions of these risks are unknown. In this meta-analysis, risks of developing a melanoma, basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) after a melanoma were investigated. An extensive systematic literature search was conducted (last performed on 18 January 2012). Studies reporting risks, i.e. proportions, standardized incidence ratios (SIR) and cumulative risks (CRs) were included. Fifty, of 233 fully read articles, met selection criteria. Two independent reviewers extracted data on study characteristics and risks measurements. Random-effects meta-analyses were used to pool the risk estimates for the three tumour combinations. In melanoma patients, pooled proportions for a subsequent melanoma, BCC or SCC were respectively 3.8% (n = 47), 2.8% (n = 5) and 1.0% (n = 6). The pooled SIRs for a subsequent melanoma, BCC or SCC in melanoma patients were respectively 10.4 (n = 12), 4.6 (n = 2) and 2.8 (n = 2). Mean 20-year CRs of a subsequent melanoma, BCC or SCC in melanoma patients were respectively 5.4% (n = 3), 14.0% (n = 1) and 4.0% (n = 1). Subgroup analyses showed substantial differences in reported risks between continents and study design. In conclusion, a history of a prior melanoma is a strong predictor for development of a subsequent melanoma (approximately 10-fold increased risk) and to a lesser extent BCC or SCC. This information could serve as information for health care systems. Further, secondary prevention seems pivotal in this patient group. © 2014 European Academy of Dermatology and Venereology.

  2. Comparação dos casos de melanoma cutâneo diagnosticados por diferentes especialistas A comparison of cutaneous melanoma cases diagnosed by different medical specialists

    Directory of Open Access Journals (Sweden)

    Ariana Lebsa Weber

    2007-08-01

    Full Text Available FUNDAMENTOS: A importância do diagnóstico e intervenção precoces nos casos de melanoma cutâneo é vital para o prognóstico do paciente. OBJETIVO: Comparar os casos de melanoma cutâneo diagnosticados primariamente por diferentes especialidades médicas no município de Florianópolis, SC, Brasil. MÉTODO: Analisados 396 laudos de 332 pacientes com diagnóstico histopatológico de melanoma, de dois centros de serviços de Anatomia Patológica, em Florianópolis, entre 1º de janeiro de 1999 e 31 de dezembro de 2004. O protocolo, com base no questionário do Grupo Brasileiro de Melanoma, incluiu sexo, idade, localização, especialidade requisitante e espessura do tumor (índice de Breslow. RESULTADOS: Foram observados 186 melanomas in situ e 210 invasivos, predominantemente em mulheres (56%. O pico etário ocorreu entre a quinta e a sexta décadas. O índice de Breslow foi semelhante nos grupos masculino e feminino (p = 0,424, mas apontou diferença entre a dermatologia (1,852mm e demais especialidades médicas (4,383mm, com p = 0,037. Número maior de ulcerações foi encontrado no grupo diagnosticado pelos cirurgiões gerais (p = 0,05. Os dermatologistas diagnosticaram 217 melanomas cutâneos (54%, e a maioria dos tipos clínicopatológicos, exceto o acral. CONCLUSÃO: O papel do dermatologista é fundamental para o diagnóstico precoce do melanoma cutâneo, que permite modificar o curso natural da doença.BACKGROUND: Early diagnosis and intervention in melanoma cases are crucial for prognosis. OBJECTIVE: To compare the results of cutaneous melanoma cases diagnosed by different medical specialists, in the city of Florianopolis, Brazil. METHOD: A total of 396 reports of 332 patients with histopathological diagnosis of melanoma were analyzed. The reports were collected from two laboratories in Florianopolis from January 1st, 1999 to December 31st, 2004. The protocol was based on the questionnaire of the Brazilian Group of Melanoma

  3. 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.

  4. 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...... skin type participated in the study. Exposure to UVR was assessed the first and second summers (n = 20) and the first and third summers (n = 22) after diagnosis. Data from 40 participants were analyzed. MAIN OUTCOMES AND MEASURES Exposure to UVR was assessed by personal electronic UVR dosimeters...... 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...

  5. 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 < .05). DSS was significantly different among regions (P < .0066). The East (5 years: 89.4%, 10 years: 84.1%) had the highest DSS rate, and the South (5 years: 87.0%, 10 years: 81.8%) had the lowest DSS rate. The Midwest (5 years: 88.4%, 10 years: 84.3%) and West (5 years: 88.3%, 10 years: 83.5%) had intermediate DSS. On multivariate analysis, the South had an elevated hazard ratio (1.17, 95% confidence interval: 1.05-1.30) when compared to the West. Geographic 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.

  6. Cytotoxic Activity of Oleocanthal Isolated from Virgin Olive Oil on Human Melanoma Cells.

    Science.gov (United States)

    Fogli, Stefano; Arena, Chiara; Carpi, Sara; Polini, Beatrice; Bertini, Simone; Digiacomo, Maria; Gado, Francesca; Saba, Alessandro; Saccomanni, Giuseppe; Breschi, Maria Cristina; Nieri, Paola; Manera, Clementina; Macchia, Marco

    2016-07-01

    Oleocanthal is one of the phenolic compounds of extra virgin olive oil with important anti-inflammatory properties. Although its potential anticancer activity has been reported, only limited evidence has been provided in cutaneous malignant melanoma. The present study is aimed at investigating the selective in vitro antiproliferative activity of oleocanthal against human malignant melanoma cells. Since oleocanthal is not commercially available, it was obtained as a pure standard by direct extraction and purification from extra virgin olive oil. Cell viability experiments carried out by WST-1 assay demonstrated that oleocanthal had a remarkable and selective activity for human melanoma cells versus normal dermal fibroblasts with IC50s in the low micromolar range of concentrations. Such an effect was paralleled by a significant inhibition of ERK1/2 and AKT phosphorylation and downregulation of Bcl-2 expression. These findings may suggest that extra virgin olive oil phenolic extract enriched in oleocanthal deserves further investigation in skin cancer.

  7. 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

    OpenAIRE

    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; Howard L. Kaufman

    2016-01-01

    Abstract Background 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). Methods Retrospective review of OPTiM identified patients with cutaneous head a...

  8. Dermoscopic features of cutaneous melanoma are associated with clinical characteristics of patients and tumours and with MC1R genotype.

    Science.gov (United States)

    Fargnoli, M C; Sera, F; Suppa, M; Piccolo, D; Landi, M T; Chiarugi, A; Pellegrini, C; Seidenari, S; Peris, K

    2014-12-01

    Several algorithms are available for the dermoscopic diagnosis of pigmented skin lesions. The MC1R gene is a key determinant of pigmentation characteristics that are established host-related melanoma risk factors. To investigate the association of dermoscopic features of sporadic cutaneous melanomas with clinical characteristics of patients and corresponding tumours and with genetic changes in the MC1R and BRAF genes. A total of 64 dermoscopic images of 62 patients were scored by ABCD rule and modified pattern analysis. Detailed patients' and melanomas' characteristics were collected. Patients were screened for germline MC1R variants and related melanomas for somatic V600 BRAF mutations. A lower total dermoscopic score (TDS) was observed in melanomas of patients with red hair (P = 0.019), due to reduced dermoscopic structures (P MC1R R carriers showed lower TDS value (P = 0.037), reduced dermoscopic structures (P = 0.001) and lower prevalence of atypical pigment network (P = 0.001). No differences were identified between BRAF-mutated or wild-type melanomas. We suggest a phenotypic/MC1R profile for melanoma patients and their tumours. Melanomas of MC1R R carriers show a significant lower TDS value, with reduced dermoscopic structures, and a lower prevalence of an atypical pigment network. Non-carriers of MC1R R variants develop melanomas dermoscopically characterized by an atypical pigment network which is prevalent in superficial spreading melanomas, in patients with dark complexion and less frequent in red-haired individuals. © 2014 European Academy of Dermatology and Venereology.

  9. Epidemiological profile of patients with cutaneous melanoma in a region of southern Brazil.

    Science.gov (United States)

    Moreno, Marcelo; Schmitt, Ricardo Ludwig; Lang, Maria Gabriela; Gheno, Vanessa

    2012-01-01

    Cutaneous melanoma (CM) is responsible for 75% of deaths from malignant skin cancer. The incidence of CM in the southern region of Brazil, particularly in the western region of Santa Catarina, is possibly higher than estimated. In this study, the clinical and epidemiological profile of patients with CM treated in the western region of Santa Catarina was examined. A cross-sectional study was performed with patients diagnosed with CM from January 2002 to December 2009, from 78 counties of the western region of the state of Santa Catarina. Data were collected using a protocol adapted from the Brazilian Melanoma Group and 503 patients were evaluated. The incidence and prevalence of CM found in this region are much higher than those found elsewhere in the country. This fact is most likely due to the phenotypic characteristics of the population and the high incidence of UV radiation in this region due to its location in southern Brazil, as is the case in the countries of Oceania.

  10. Human Papillomaviruses and Non-Melanoma Skin Cancer: Basic Virology and Clinical Manifestations

    Directory of Open Access Journals (Sweden)

    Ingo Nindl

    2007-01-01

    Full Text Available Human papillomaviruses (HPV infect cutaneous and mucosal epithelia and induce benign and malignant lesions. Non-melanoma skin cancer (NMSC, encompassing basal cell carcinoma and squamous cell carcinoma (SCC, is the most frequent cancer in the Caucasian population, and the incidence has increased dramatically worldwide. Ultraviolet (UV radiation is a major risk factor for NMSC, and cutaneous HPV is also considered to play an active role during the pathogenesis of these cancers. The first evidence for the involvement of HPV in NMSC was reported in patients with Epidermodysplasia verruciformis (EV. HPV types detected in skin tumours of these patients are referred to as EV/cutaneous HPV types belonging to the beta- and gamma-papillomaviruses (PV. Epidemiological studies have shown a higher risk of several EV/cutaneous HPV types for NMSC. Furthermore, in vitro and animal models show transforming properties of some PV types. The anti-apoptotic activities, and the delay of DNA repair mechanism caused by some EV/cutaneous HPV E6 proteins in response to UV-induced mutations, may lead to the persistence of DNA-damaged keratinocytes. Thus, specific EV/cutaneous HPV types as co-factors in association with UV-radiation and the immune system seem to be involved in the early pathogenesis of cutaneous SCC.

  11. Trends in incidence and survival of cutaneous malignant melanoma in Estonia: a population-based study.

    Science.gov (United States)

    Padrik, Peeter; Valter, Ann; Valter, Epp; Baburin, Aleksei; Innos, Kaire

    2017-01-01

    Previous studies have shown an increase in the incidence of cutaneous melanoma (CM) in Estonia, but also poor survival in international comparisons, with a significant survival gap between the sexes. The aim of this study was to analyze the time trends in CM incidence and relative survival by age, TNM stage and anatomical subsite among men and women in Estonia. Data from the Estonian Cancer Registry were used to calculate age-standardized (World) and age-specific incidence of CM in 1995-2013, and five-year relative survival ratios (RSR) for cases diagnosed in 1995-2012 and followed through in 2014. Period hybrid analysis was used to calculate the most recent survival estimates for 2010-2014. Between 1995 and 2013, the age-standardized incidence of CM increased significantly in Estonia among both sexes, at a rate of around 4% per year. Among women, the proportion of trunk melanomas increased from 26% in 1995-1999 to 39% in 2010-2012 and became the most common site. The proportion of stage I cases and T1 tumors increased considerably. Women had more favorable stage distribution and thinner tumors than men. The age-adjusted five-year RSR increased significantly, from 64% in 1995-1999 to 81% in 2010-2014. The latest age-adjusted RSRs were 76% among men and 84% among women. Survival gains were the largest in patients below 50 years, those with head and neck or trunk melanomas, and stage III cancer. The proportion of stage I and T1 cases is lower in Estonia compared with the Scandinavian data and is likely a major contributor to the persisting overall survival deficit in Estonia. The apparent deficit in stage II survival also warrants further investigation. A public health program is necessary in Estonia to raise awareness of CM and to significantly increase early stage diagnosis.

  12. 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

  13. 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 ...

  14. 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 i...

  15. 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.

  16. 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 31st 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.

  17. Does patients' place of residence affect the type of physician performing primary excision of cutaneous melanoma in northern Scotland?

    Science.gov (United States)

    Green, Joanna; Murchie, Peter; Lee, Amanda J

    2013-08-01

    Rural residence may adversely affect cancer outcomes, perhaps because rural cancer patients are managed differently. Current UK guidelines recommend all patients with suspected melanoma be referred urgently for specialist excision biopsy; however, up to 20% of patients receive their biopsy in primary care. This project explored if rural dwellers with melanoma were more likely to have their primary biopsy in primary care. A clinical database of all primary cutaneous melanomas diagnosed in Northern Scotland between January 1991 and July 2007 was analyzed for patient demographics, clinical variables, and intermediate outcomes. Significant findings on univariate analysis were then included in a binary logistic regression model to adjust for confounders. On univariate analysis patients living in rural areas were significantly more likely to have their melanomas excised in primary care compared with those living in the city (26.3% compared with 17.7%, P small towns were significantly more likely to be treated contrary to current UK melanoma guidelines compared to those in cities. In Northern Scotland patients living in suburban areas and remote small towns are significantly more likely to have an initial melanoma excision in primary care, contrary to current UK guidelines. This geographical contrast signposts the way to further in-depth research into the interplay between place of residence and how the cancer journey is experienced. © 2013 National Rural Health Association.

  18. Linkage of cutaneous malignant melanoma/dysplastic Nevi to chromosome 9p, and evidence for genetic heterogeneity

    Energy Technology Data Exchange (ETDEWEB)

    Goldstein, A.M.; Fraser, M.C.; Tucker, M.A.; Dracopoli, N.C.; Engelstein, M. (Massachusetts Institute of Technology, Cambridge, MA (United States)); Clark, W.H. Jr. (Univ. of Pennyslvania School of Medicine, Philadelphia, PA (United States))

    1994-03-01

    The authors examined the relationship between cutaneous malignant melanoma/dysplastic nevi (CMM/DN) and chromosome 9p in 13 pedigrees with two or more living cases of invasive melanoma. They used two highly informative (CA)[sub n] repeats, D9S126 and IFNA, previously implicated in familial malignant melanoma (MLM), to conduct linkage analysis. Three analyses were performed: (1) CMM alone - all individuals without either confirmed melanoma or borderline lesions were considered unaffected (model A); (2) CMM/DN with both variable age at onset and sporadics (model B); and (3) CMM affecteds only - all individuals either without confirmed melanoma or with borderline lesions were designated unknown' (model C). There was significant evidence for linkage to IFNA in all three models. For CMM along, the maximum lod score (Z[sub max]) was 4.36 at 0 = .10 for model A and 3.39 at 0 = .10 for model C. For CMM/DN (model B), Z[sub max] = 3.05 at 0 = .20. There was no significant evidence for heterogeneity when a homogeneity test allowing for linkage to chromosome 9p or chromosome 1p or neither region was used. These results suggest that there is an MLM susceptibility locus on chromosome 9p but that familial melanoma is heterogeneous and not all families with CMM/DN are linked to a locus in this region. 30 refs., 1 fig., 5 tabs.

  19. 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

  20. Cutaneous melanoma follow-up: appropriateness of requests for ultrasound tests--the S.Gallicano National Referral Centre Experience.

    Science.gov (United States)

    Solivetti, Francesco M; Elia, Fulvia; Guerrisi, Antonino; Desiderio, Flora; Santaguida, Maria; Sperduti, Isabella; Cavallotti, Claudia; Di Carlo, Aldo

    2013-10-09

    Cutaneous melanoma is a malignant neoplasm with a constantly increasing incidence, the prognosis of which is largely dependent on early diagnosis. The appropriateness of requests for ultrasound (US) tests during melanoma follow-up of patients referred to our institute was evaluated. The requests for US tests of all patients referred to our institute over a four-month period were assessed. In order to correctly evaluate the appropriateness of requests, patients were split into two groups on the basis of melanoma thickness: > 1 mm (Group A) and request. In our study, more than 30% of the requests for US tests were found to be inappropriate, to the detriment of those with a real need for diagnostic testing. This lengthens waiting lists and it may also increase public healthcare costs. Therefore, it is mandatory to adopt new, widely accepted and easily applicable guidelines.

  1. Cutaneous human myiasis due to Dermatobia hominis.

    Science.gov (United States)

    Suite, M; Polson, K

    2007-10-01

    This is a case report of cutaneous myiasis due to Dermatobia hominis in a female physician who had travelled to Belize. Cutaneous myiasis is endemic in Central and South America but is seldom reported from the Caribbean islands.

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

    Directory of Open Access Journals (Sweden)

    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

  3. 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.

  4. Predictive factors for loco regional recurrence and distant metastasis following primary surgical treatment of cutaneous melanoma

    Directory of Open Access Journals (Sweden)

    Vijayalakshmi Deshmane

    2014-01-01

    Full Text Available Background: Cutaneous melanoma (CM has a high propensity for regional and systemic spread. This is one of the largest series of CM reported from India. Aims: To predict factors for loco regional recurrence (LRR and distant metastasis in patients with CM primarily treated with surgery. Study Design: Retrospective analysis of patient database at a tertiary care cancer center with evaluation of factors for LRR and distant metastasis for CM. Materials and Methods: Data from 68 patients treated for CM between January 2006 and December 2010 were reviewed. Data recorded included age, sex, symptoms, investigations, treatment given, histopathology, recurrence and follow-up. Patient factors, tumor factors, pathologic variables, and adjuvant treatment were investigated as predictors′ of LRR and distant metastasis. Results: Mean age of patients was 54 years. Melanoma was more common in males (44. Tumor thickness > 4 mm was found in 43 patients. Lymph node involvement was found in 43 patients. Adjuvant radiotherapy was given in seven patients. At mean follow-up of 16.5 months, LRR was seen in 34 patients and distant metastasis in 28 patients. LRR and distant metastasis were more commonly found in females, age > 40 years, Clark′s level IV and V, Breslow′s depth > 4 mm, patients with lymph node involvement and extra-capsular spread. Conclusion: The age, sex, site, thickness of lesion, involvement of lymph node, and extra-capsular spread were important factors in predicting LRR and distant metastasis. Distant metastasis was also more commonly found in patients with LRR.

  5. A multigene support vector machine predictor for metastasis of cutaneous melanoma.

    Science.gov (United States)

    Wei, Dong

    2018-02-01

    Gene expression profiles of cutaneous melanoma were analyzed to identify critical genes associated with metastasis. Two gene expression datasets were downloaded from Gene Expression Omnibus (GEO) and another dataset was obtained from The Cancer Genome Atlas (TCGA). Differentially expression genes (DEGs) between metastatic and non‑metastatic melanoma were identified by meta‑analysis. A protein‑protein interaction (PPI) network was constructed for the DEGs using information from BioGRID, HPRD and DIP. Betweenness centrality (BC) was calculated for each node in the network and the top feature genes ranked by BC were selected to construct the support vector machine (SVM) classifier using the training set. The SVM classifier was then validated in another independent dataset. Pathway enrichment analysis was performed for the feature genes using Fisher's exact test. A total of 798 DEGs were identified and a PPI network including 337 nodes and 466 edges was then constructed. Top 110 feature genes ranked by BC were included in the SVM classifier. The prediction accuracies for the three datasets were 96.8, 100 and 94.4%, respectively. A total of 11 KEGG pathways and 13 GO biological pathways were significantly over‑represented in the 110 feature genes, including endometrial cancer, regulation of actin cytoskeleton, focal adhesion, ubiquitin mediated proteolysis, regulation of apoptosis and regulation of cell proliferation. A SVM classifier of high prediction accuracy was acquired. Several critical genes implicated in melanoms metastasis were also revealed. These results may advance understanding of the molecular mechanisms underlying metastasis, and also provide potential therapeutic targets.

  6. Inoculation site from a cutaneous melanoma patient treated with an allogeneic therapeutic vaccine: a case report

    Directory of Open Access Journals (Sweden)

    Mariana eAris

    2015-03-01

    Full Text Available We have developed a therapeutic vaccine consisting of a mixture of lethally-irradiated allogeneic cutaneous melanoma cell lines with BCG and GM-CSF as adjuvants. The CSF-470 vaccine is currently being assayed in a Phase II-III trial against medium-dose IFN-a2b. All vaccinated patients immunized intradermally developed large edematous erythema reactions, which then transformed into subcutaneous nodules active for several months. However, vaccine injection sites were not routinely biopsied. We describe the case of a female patient, previously classified as stage III, but who, due to the simultaneous discovery of bone metastases, only received one vaccination, was withdrawn from the study and continued her treatment elsewhere. Patient #1 developed a post-vaccination nodule which was surgically removed 7 weeks later, and allowed to analyze the reactivity and immune profiling of the inoculation site. An inflammatory reaction with zones of fibrosis, high irrigation and brisk lymphoid infiltration, primarily composed of CD8+ and CD20+ lymphocytes, was observed. There were no remaining BCG bacilli, and scarce CD4+ and Foxp3+ T cells were observed. MART-1 Ag was found throughout the vaccination site. CD11c+ Ag presenting cells were either dispersed or forming dense nests. Some CD11c+ cells proliferated; most of them contained intracellular MART-1 Ag, and some interacted with CD8+ lymphocytes. These observations suggest a potent, long-lasting local inflammatory response with recruitment of Ag-presenting cells that incorporate melanoma Ags, probably leading to Ag presentation to naïve T cells.

  7. Detection of Melanoma Metastases in Resected Human Lymph Nodes by Noninvasive Multispectral Photoacoustic Imaging

    Directory of Open Access Journals (Sweden)

    Gerrit Cornelis Langhout

    2014-01-01

    Full Text Available Objective. Sentinel node biopsy in patients with cutaneous melanoma improves staging, provides prognostic information, and leads to an increased survival in node-positive patients. However, frozen section analysis of the sentinel node is not reliable and definitive histopathology evaluation requires days, preventing intraoperative decision-making and immediate therapy. Photoacoustic imaging can evaluate intact lymph nodes, but specificity can be hampered by other absorbers such as hemoglobin. Near infrared multispectral photoacoustic imaging is a new approach that has the potential to selectively detect melanin. The purpose of the present study is to examine the potential of multispectral photoacoustic imaging to identify melanoma metastasis in human lymph nodes. Methods. Three metastatic and nine benign lymph nodes from eight melanoma patients were scanned ex vivo using a Vevo LAZR© multispectral photoacoustic imager and were spectrally analyzed per pixel. The results were compared to histopathology as gold standard. Results. The nodal volume could be scanned within 20 minutes. An unmixing procedure was proposed to identify melanoma metastases with multispectral photoacoustic imaging. Ultrasound overlay enabled anatomical correlation. The penetration depth of the photoacoustic signal was up to 2 cm. Conclusion. Multispectral three-dimensional photoacoustic imaging allowed for selective identification of melanoma metastases in human lymph nodes.

  8. 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.

  9. [Initial evaluation, diagnosis, staging, treatment, and follow-up of patients with primary cutaneous malignant melanoma. Consensus statement of the Network of Catalan and Balearic Melanoma Centers].

    Science.gov (United States)

    Mangas, C; Paradelo, C; Puig, S; Gallardo, F; Marcoval, J; Azon, A; Bartralot, R; Bel, S; Bigatà, X; Curcó, N; Dalmau, J; del Pozo, L J; Ferrándiz, C; Formigón, M; González, A; Just, M; Llambrich, A; Llistosella, E; Malvehy, J; Martí, R M; Nogués, M E; Pedragosa, R; Rocamora, V; Sàbat, M; Salleras, M

    2010-03-01

    The consensus statement on the management of primary cutaneous melanoma that we present here was based on selection, discussion, review, and comparison of recent literature (including national and international guidelines). The protocols for the diagnosis, treatment, and follow-up used in the hospital centers throughout Catalonia and the Balearic Isles belonging to the Network of Catalan and Balearic Melanoma Centers were also considered. The main objective of this statement was to present the overall management of melanoma patients typically used in our region at the present time. As such, the statement was not designed to be an obligatory protocol for health professionals caring for this group of patients, and neither can it nor should it be used for this purpose. Professionals reading the statement should not therefore consider it binding on their practice, and in no case can this text be used to guarantee or seek responsibility for a given medical opinion. The group of dermatologists who have signed this statement was created 3 years ago with the aim of making our authorities aware of the importance of this complex tumor, which, in comparison with other types of cancer, we believe does not receive sufficient attention in Spain. In addition, the regular meetings of the group have produced interesting proposals for collaboration in various epidemiological, clinical, and basic applied research projects on the subject of malignant melanoma in our society.

  10. Electron Paramagnetic Resonance Spectrometry and Imaging in Melanomas: Comparison between Pigmented and Nonpigmented Human Malignant Melanomas

    Directory of Open Access Journals (Sweden)

    Quentin Godechal

    2013-06-01

    Full Text Available It has been known for a long time that the melanin pigments present in normal skin, hair, and most of malignant melanomas can be detected by electron paramagnetic resonance (EPR spectrometry. In this study, we used EPR imaging as a tool to map the concentration of melanin inside ex vivo human pigmented and nonpigmented melanomas and correlated this cartography with anatomopathology. We obtained accurate mappings of the melanin inside pigmented human melanoma samples. The signal intensity observed on the EPR images correlated with the concentration of melanin within the tumors, visible on the histologic sections. In contrast, no EPR signal coming from melanin was observed from nonpigmented melanomas, therefore demonstrating the absence of EPR-detectable pigments inside these particular cases of skin cancer and the importance of pigmentation for further EPR imaging studies on melanoma.

  11. Clinicopathological features and clinical outcomes associated with TP53 and BRAFNon-V600 mutations 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

    BRAFV600 , NRAS, TP53, and BRAFNon-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 BRAFV600 and NRAS mutations, limited data are available regarding the correlates and significance of TP53 and BRAFNon-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 BRAFV600 , NRAS, TP53, and BRAFNon-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). BRAFNon-V600 mutations were associated with older age (P = .005) but not with primary tumor features or OS from stage IV. Neither TP53 nor BRAFNon-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 BRAFNon-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 BRAFNon-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.

  12. 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

  13. Lock-in thermal imaging for the early-stage detection of cutaneous melanoma: a feasibility study.

    Science.gov (United States)

    Bonmarin, Mathias; Le Gal, Frédérique-Anne

    2014-04-01

    This paper theoretically evaluates lock-in thermal imaging for the early-stage detection of cutaneous melanoma. Lock-in thermal imaging is based on the periodic thermal excitation of the specimen under test. Resulting surface temperature oscillations are recorded with an infrared camera and allow the detection of variations of the sample's thermophysical properties under the surface. In this paper, the steady-state and transient skin surface temperatures are numerically derived for a different stage of development of the melanoma lesion using a two-dimensional axisymmetric multilayer heat-transfer model. The transient skin surface temperature signals are demodulated according to the digital lock-in principle to compute both a phase and an amplitude image of the lesions. The phase image can be advantageously used to accurately detect cutaneous melanoma at an early stage of development while the maximal phase shift can give precious information about the lesion invasion depth. The ability of lock-in thermal imaging to suppress disturbing subcutaneous thermal signals is demonstrated. The method is compared with the previously proposed pulse-based approaches, and the influence of the modulation frequency is further discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Non-compliance with the re-excision guidelines for cutaneous melanoma in The Netherlands does not influence survival.

    Science.gov (United States)

    Haniff, J; de Vries, E; Claassen, A T P M; Looman, C W N; van Berlo, Ch; Coebergh, J W W

    2006-02-01

    To evaluate causes and consequences of not adhering to the clinical practice guideline for cutaneous malignant melanoma. We conducted a retrospective cohort study of the clinical records of 454 subjects whose pathological reports were obtained from a population-based cancer registry to assess determinants and effects of non-compliance of physicians with the excision policy and the related clinical practice guideline for patients with primary localized cutaneous malignant melanoma (CMM). A comparative analysis was performed of patients who did and did not undergo re-excision (compliance versus non-compliance with the guideline). Subjects diagnosed in 1988, 1993 and 1997, just 1 year after publication of the (adapted) guideline, were followed until death due to any cause or until July 1st 2003. Old age was the most important determinant of non-compliance. After adjusting for age at diagnosis, gender, subsite and Breslow thickness there was no significant difference in overall survival between the compliance group and the non-compliance group. Non-compliance to the guideline is more common in older patients and in patients with melanoma in the head and neck region. After adjusting for confounders, a significant effect of complying with the guidelines on overall survival could not be observed.

  15. A Bayesian destructive weighted Poisson cure rate model and an application to a cutaneous melanoma data.

    Science.gov (United States)

    Rodrigues, Josemar; Cancho, Vicente G; de Castro, Mário; Balakrishnan, N

    2012-12-01

    In this article, we propose a new Bayesian flexible cure rate survival model, which generalises the stochastic model of Klebanov et al. [Klebanov LB, Rachev ST and Yakovlev AY. A stochastic-model of radiation carcinogenesis--latent time distributions and their properties. Math Biosci 1993; 113: 51-75], and has much in common with the destructive model formulated by Rodrigues et al. [Rodrigues J, de Castro M, Balakrishnan N and Cancho VG. Destructive weighted Poisson cure rate models. Technical Report, Universidade Federal de São Carlos, São Carlos-SP. Brazil, 2009 (accepted in Lifetime Data Analysis)]. In our approach, the accumulated number of lesions or altered cells follows a compound weighted Poisson distribution. This model is more flexible than the promotion time cure model in terms of dispersion. Moreover, it possesses an interesting and realistic interpretation of the biological mechanism of the occurrence of the event of interest as it includes a destructive process of tumour cells after an initial treatment or the capacity of an individual exposed to irradiation to repair altered cells that results in cancer induction. In other words, what is recorded is only the damaged portion of the original number of altered cells not eliminated by the treatment or repaired by the repair system of an individual. Markov Chain Monte Carlo (MCMC) methods are then used to develop Bayesian inference for the proposed model. Also, some discussions on the model selection and an illustration with a cutaneous melanoma data set analysed by Rodrigues et al. [Rodrigues J, de Castro M, Balakrishnan N and Cancho VG. Destructive weighted Poisson cure rate models. Technical Report, Universidade Federal de São Carlos, São Carlos-SP. Brazil, 2009 (accepted in Lifetime Data Analysis)] are presented.

  16. Influence of having a home garden on personal UVR exposure behavior and risk of cutaneous malignant melanoma in Denmark

    DEFF Research Database (Denmark)

    Idorn, Luise Winkel; Thieden, Elisabeth; Philipsen, Peter Alshede

    2013-01-01

    There is a need for more knowledge concerning the association of higher socioeconomic status (SES) with cutaneous malignant melanoma (CMM). Having a home garden is associated with a higher SES. We aimed to study the influence of having a home garden on UVR exposure behavior and risk of CMM....... Register study: We collected information from Danish national registers about gender, age, type of home and CMM among persons aged 16-75 in 2002-2006. A total of 5,118 CMM cases were identified. Risk of CMM of the trunk was increased by 46% (p ... of the extremities by 34% (p personal electronic UVR dosimeters measuring time-stamped UVR doses...

  17. 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.

  18. 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)

    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.

    2016-01-01

    Abstract Background 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). Methods 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. Results 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. Conclusion 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 PMID:27407058

  19. 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/mm2 (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.

  20. NF-kB signalling is attenuated by the E7 protein from cutaneous human papillomaviruses

    DEFF Research Database (Denmark)

    Byg, Luise M; Stensson, Jessica; Vasiljevic, Natasa

    2012-01-01

    -¿B pathway leading to an attenuation of the activity. There is a possible link between development of non melanoma skin cancer and cutaneous Beta-papillomavirus but if these HPV types attenuate the NF-¿B pathway is unclear. Seven different E7 proteins, representing four out of the five different species....... In addition, E7 proteins from the cutaneous HPV types demonstrated interaction with IKKa but not with IKKß. The deregulation of the NF-¿B pathway by cutaneous HPVs might contribute to the pathogenesis of non-melanoma skin cancers and its precursors....

  1. Hypothesis: Is frequent, commercial jet travel by the general public a risk factor for developing cutaneous melanoma? [version 1; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Harvey Arbesman

    2015-08-01

    Full Text Available Melanoma incidence has been increasing worldwide over the past 50 years and various risk factors have been identified. Interestingly, multiple studies have shown a multifold increased risk of developing melanoma in jet pilots and airline crew. There has also been a dramatic increase in the availability and frequency of jet travel by the general population during this time period.. Therefore, it is hypothesized that frequent commercial jet travel may represent an additional risk factor for the development of cutaneous melanoma in susceptible individuals of the general public.

  2. Ultrasound-guided core needle biopsy of superficial lymph nodes: an alternative to fine-needle aspiration cytology for the diagnosis of lymph node metastasis in cutaneous melanoma.

    Science.gov (United States)

    Bohelay, Gérôme; Battistella, Maxime; Pagès, Cécile; de Margerie-Mellon, Constance; Basset-Seguin, Nicole; Viguier, Manuelle; Kerob, Delphine; Madjlessi, Nika; Baccard, Michel; Archimbaud, Alain; Comte, Christelle; Mourah, Samia; Porcher, Raphael; Bagot, Martine; Janin, Anne; De Kerviler, Eric; Lebbé, Céleste

    2015-12-01

    To investigate the diagnostic value of ultrasound-guided core needle biopsy (US-CNB) in suspected cases of lymph node metastasis from cutaneous melanoma. All patients with cutaneous melanoma followed in Saint-Louis Hospital between 2006 and 2010 who underwent US-CNB for suspicion of melanoma lymph node metastasis were reviewed retrospectively. Histopathological results of US-CNB samples were classified as melanoma, other malignancy, suspicious, inadequate, or benign. The diagnostic accuracy of US-CNB was assessed by comparison with two reference standards: histopathological examination of the radical lymph node dissection or, when this was not available, clinical and radiological follow-up. The data from 72 US-CNB were analyzed. Forty-four melanomas, 22 benign, three other malignancies, three inadequate samples, and no inconclusive specimens were diagnosed. Seventy-one US-CNB results were confirmed (98.6%). US-CNB achieved high sensitivity, specificity, and positive predictive value (respectively, 97.9, 100, and 100%). No adverse events were reported after the procedure. US-CNB provided a mean tissue volume of 16.7 mm per lymphadenopathy. US-CNB has diagnostic value similar to that of fine-needle aspiration cytology. It represents a reliable alternative method in melanoma lymph node metastasis to avoid surgery in patients who will not benefit from it. US-CNB provides relatively large samples of tissue suitable for comprehensive genomic analyses currently needed for research and personalized care of melanoma patients.

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

    Directory of Open Access Journals (Sweden)

    Amrita Dasgupta

    2015-08-01

    Full Text Available 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.

  4. 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.

  5. Melanoma genetics

    DEFF Research Database (Denmark)

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

    2015-01-01

    in melanoma families at rates greater than expected by chance. The most extensively documented association is between CDKN2A germ line mutations and pancreatic cancer, and a cancer syndrome including cutaneous melanoma, uveal melanoma and mesothelioma has been proposed for BAP1 germ line mutations. Other...

  6. {sup 123}I-N-(2-diethylaminoethyl)-2-iodobenzamide: a potential imaging agent for cutaneous melanoma staging

    Energy Technology Data Exchange (ETDEWEB)

    Moins, Nicole; Labarre, Pierre; Moreau, Marie-France; Noirault, Elisabeth; Papon, Janine; Bayle, Martine; Madelmont, Jean-Claude [UMR 484 INSERM-Universite d' Auvergne, Centre Jean Perrin, Rue Montalembert, BP 184, 63005 Clermont-Ferrand (France); D' Incan, Michel; Souteyrand, Pierre [Department of Dermatology, CHU, Clermont-Ferrand (France); Bonafous, Jacques; Veyre, Annie [UMR 484 INSERM-Universite d' Auvergne, Centre Jean Perrin, Rue Montalembert, BP 184, 63005 Clermont-Ferrand (France); Department of Nuclear Medicine, Centre Jean Perrin, Clermont-Ferrand (France); Bacin, Franck [Department of Ophtalmology, CHU, Clermont-Ferrand (France); Mestas, Daniele [Department of Nuclear Medicine, Centre Jean Perrin, Clermont-Ferrand (France); Chossat, Florence; Berthommier, Eric [CIS bio international, Gif-sur-yvette (France)

    2002-11-01

    Melanoma is a neoplasia of dramatically increasing incidence that has a propensity to spread rapidly. Early detection is fundamental and patient management requires reliable, sensitive and reproducible staging methods, such as a single examination by planar scintigraphy or single-photon emission tomography (SPET) using a radiopharmaceutical with selectivity for melanoma tissue. Among iodobenzamides reported to possess an affinity for melanoma, a new compound, N-(2-diethylaminoethyl)-2-iodobenzamide (BZA{sub 2}), was selected for a clinical trial in view of its pharmacokinetic experimental profile in melanoma-bearing mice. Planar whole-body scintigraphy using {sup 123}I-BZA{sub 2} was performed in 25 patients with histologically proven cutaneous melanoma. Performance was evaluated in two groups of patients with one or more documented secondary lesions (n=13) or with no known secondary lesions (n=12), and results were compared with those of conventional investigation techniques. No adverse clinical or biological events were recorded. Lesions were imaged by increased tracer uptake, and good quality images were obtained 4 h after administration. After a follow-up of more than 1 year, the overall results of {sup 123}I-BZA{sub 2} scintigraphy on a per patient basis showed a sensitivity of 100%, a specificity of 95%, a positive predictive value of 86% and a negative predictive value of 100%. The proven secondary lesions were imaged with a sensitivity of 100% and a specificity of 91%. In seven patients with suspected metastases, the absence of {sup 123}I-BZA{sub 2} uptake was confirmed as true negative, and in one patient without suspected metastases, {sup 123}I-BZA{sub 2} scintigraphy revealed a gastric lesion. Hence eight diagnoses would have been modified by {sup 123}I-BZA{sub 2} scintigraphy data. {sup 123}I-BZA{sub 2} allowed discrimination between benign and malignant lesions and, in the case of malignancies, between those of melanomatous origin and others. This

  7. Time Course and Pattern of Metastasis of Cutaneous Melanoma Differ between Men and Women

    Science.gov (United States)

    Mervic, Liljana

    2012-01-01

    Background This study identified sex differences in progression of cutaneous melanoma. Methodology/Principal Findings Of 7,338 patients who were diagnosed as an invasive primary CM without clinically detectable metastases from 1976 to 2008 at the University of Tuebingen in Germany, 1,078 developed subsequent metastases during follow up. The metastatic pathways were defined in these patients and analyzed using the Kaplan-Meier method. Multivariate survival analysis was performed using Cox modeling. In 18.7% of men and 29.2% of women (Pmetastasis following diagnosis of primary tumor was locoregional as satellite/in-transit metastasis. The majority of men (54.0%) and women (47.6%, P = 0.035) exhibited direct regional lymph node metastasis. Direct distant metastasis from the stage of the primary tumor was observed in 27.3% of men and 23.2% of women (P = 0.13). Site of first metastasis was the most important prognostic factor of survival after recurrence in multivariate analysis (HR:1.3; 95% CI: 1.0–1.6 for metastasis to the regional lymph nodes vs. satellite/in-transit recurrence, and HR:5.5; 95% CI: 4.2–7.1 for distant metastasis vs. satellite/in-transit recurrence, Pmetastasis was 40.5 months (IQR, 58.75) in women and 33 months (IQR, 44.25) in men (P = 0.002). Five-year survival after distant recurrence probability was 5.2% (95% CI: 1.4–2.5) for men compared with 15.3% (95% CI: 11.1–19.5; P = 0.008) for women. Conclusions/Significance Both, the pattern of metastatic spread with more locoregional metastasis in women, and the time course with retracted metastasis in women contributed to the more favorable outcome of women. Furthermore, the total rate of metastasis is increased in men. Interestingly, there is also a much more favorable long term survival of women after development of distant metastasis. It remains a matter of debate and of future research, whether hormonal or immunologic factors may be responsible for these sex differences. PMID

  8. Genetic variants in the integrin signaling pathway genes predict cutaneous melanoma survival.

    Science.gov (United States)

    Li, Hongyu; Wang, Yanru; Liu, Hongliang; Shi, Qiong; Xu, Yinghui; Wu, Wenting; Zhu, Dakai; Amos, Christopher I; Fang, Shenying; Lee, Jeffrey E; Han, Jiali; Wei, Qingyi

    2017-03-15

    To identify genetic variants involved in prognosis of cutaneous melanoma (CM), we investigated associations of single nucleotide polymorphisms (SNPs) of genes in the integrin signaling pathway with CM survival by re-analyzing a published genome-wide association study (GWAS) from The University of Texas M.D. Anderson Cancer Center (MDACC) and then validated significant SNPs in another GWAS from Harvard University. In the MDACC study, 1,148 SNPs were significantly associated with CM-specific survival (CMSS) (p ≤ 0.050 and false-positive report probability ≤ 0.20), and nine SNPs were validated in the Harvard study (p ≤ 0.050). Among these, three independent SNPs (i.e., DOCK1 rs11018104 T > A, rs35748949 C > T and PAK2 rs1718404 C > T) showed a predictive role in CMSS, with an effect-allele attributed adjusted hazards ratio [adjHR of 1.50 (95% confidence interval (CI) = 1.18-1.90, p = 7.46E-04), 1.53 (1.18-1.97, 1.18E-03) and 0.58 (0.45-0.76, 5.60E-05), respectively]. Haplotype analysis revealed that a haplotype carrying two risk alleles A-T in DOCK1 was associated with the poorest survival in both MDACC (adjHR = 1.73, 95% CI = 1.19-2.50, p = 0.004) and Harvard (adjHR = 1.95, 95% CI = 1.14-3.33, p = 0.010) studies. In addition, patients with an increasing number of unfavorable genotypes (NUGs) for these three SNPs had a poorer survival. Incorporating NUGs with clinical variables showed a significantly improved ability to classify CMSS (AUC increased from 86.8% to 88.6%, p = 0.031). Genetic variants in the integrin signaling pathway may independently or jointly modulate the survival of CM patients. Further large, prospective studies are needed to validate these findings. © 2016 UICC.

  9. Time course and pattern of metastasis of cutaneous melanoma differ between men and women.

    Directory of Open Access Journals (Sweden)

    Liljana Mervic

    Full Text Available BACKGROUND: This study identified sex differences in progression of cutaneous melanoma. METHODOLOGY/PRINCIPAL FINDINGS: Of 7,338 patients who were diagnosed as an invasive primary CM without clinically detectable metastases from 1976 to 2008 at the University of Tuebingen in Germany, 1,078 developed subsequent metastases during follow up. The metastatic pathways were defined in these patients and analyzed using the Kaplan-Meier method. Multivariate survival analysis was performed using Cox modeling. In 18.7% of men and 29.2% of women (P<0.001 the first metastasis following diagnosis of primary tumor was locoregional as satellite/in-transit metastasis. The majority of men (54.0% and women (47.6%, P = 0.035 exhibited direct regional lymph node metastasis. Direct distant metastasis from the stage of the primary tumor was observed in 27.3% of men and 23.2% of women (P = 0.13. Site of first metastasis was the most important prognostic factor of survival after recurrence in multivariate analysis (HR:1.3; 95% CI: 1.0-1.6 for metastasis to the regional lymph nodes vs. satellite/in-transit recurrence, and HR:5.5; 95% CI: 4.2-7.1 for distant metastasis vs. satellite/in-transit recurrence, P<0.001. Median time to distant metastasis was 40.5 months (IQR, 58.75 in women and 33 months (IQR, 44.25 in men (P = 0.002. Five-year survival after distant recurrence probability was 5.2% (95% CI: 1.4-2.5 for men compared with 15.3% (95% CI: 11.1-19.5; P = 0.008 for women. CONCLUSIONS/SIGNIFICANCE: Both, the pattern of metastatic spread with more locoregional metastasis in women, and the time course with retracted metastasis in women contributed to the more favorable outcome of women. Furthermore, the total rate of metastasis is increased in men. Interestingly, there is also a much more favorable long term survival of women after development of distant metastasis. It remains a matter of debate and of future research, whether hormonal or immunologic

  10. 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...

  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

    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. A systematic review of health-related quality of life in cutaneous melanoma.

    NARCIS (Netherlands)

    D. Cornish; C. Holterhues (Cynthia); L.V. van de Poll-Franse (Lonneke); J.W.W. Coebergh (Jan Willem); T.E.C. Nijsten (Tamar)

    2009-01-01

    textabstractMelanoma can be considered an emerging chronic disease that may considerably affect patients' lives. The authors systematically reviewed the available literature on health-related quality of life (HRQOL) and melanoma. Of reviews and the selected studies, reference lists were

  13. Recent advances in cutaneous melanoma: towards a molecular model and targeted treatment.

    Science.gov (United States)

    Read, Jazlyn

    2013-08-01

    Melanoma is an aggressive disease process, with a heterogeneous aetiology linked to environmental and genetic risk factor profiles. Overall prognosis for advanced disease remains poor, and a lack of effective systemic therapies has prompted investigation into alternative strategies. The identification of novel mutations that instigate and perpetuate melanocyte transformation has offered insight into new treatment approaches, and the subsequent development of targeted treatments appears to be integral to improving melanoma survival. This article reviews the mechanisms of melanoma oncogenesis and classic molecular signalling pathways, targeted treatment approaches based on the molecular model and immunotherapy, and the advent of next-generation sequencing technologies in understanding the complexity of the melanoma pathogenome. In addition to the known somatic activating mutations BRAF and NRAS, exome sequencing has recently identified RAC1, a novel UV-signature gain-of-function mutation. Germline mutations associated with familial melanoma have added a further dimension to the molecular underpinnings of melanoma, implicating BAP1 and MITF as melanoma predisposition genes. Advances in understanding melanoma and implementing targeted treatment strategies will be of increasing importance in this era of personalised medicine. © 2013 The Author Australasian Journal of Dermatology © 2013 The Australasian College of Dermatologists.

  14. The Impact of Smoking on Sentinel Node Metastasis of Primary Cutaneous Melanoma

    NARCIS (Netherlands)

    Jones, Maris S.; Jones, Peter C.; Stern, Stacey L.; Elashoff, David; Hoon, Dave S. B.; Thompson, John; Mozzillo, Nicola; Nieweg, Omgo E.; Noyes, Dirk; Hoekstra, Harald J.; Zager, Jonathan S.; Roses, Daniel F.; Testori, Alessandro; Coventry, Brendon J.; Smithers, Mark B.; Andtbacka, Robert; Agnese, Doreen; Schultz, Erwin; Hsueh, Eddy C.; Kelley, Mark; Schneebaum, Schlomo; Jacobs, Lisa; Bowles, Tawnya; Kashani-Sabet, Mohammed; Johnson, Douglas; Faries, Mark B.

    Background. Although a well-established causative relationship exists between smoking and several epithelial cancers, the association of smoking with metastatic progression in melanoma is not well studied. We hypothesized that smokers would be at increased risk for melanoma metastasis as assessed by

  15. Merlin is a negative regulator of human melanoma growth.

    Science.gov (United States)

    Murray, Lucas B; Lau, Ying-Ka Ingar; Yu, Qin

    2012-01-01

    Merlin is encoded by the neurofibromatosis type 2 (NF2) gene and is a member of the Band 4.1 protein family. This protein acts as a linker that connects cell surface proteins to the actin cytoskeleton. Defects caused by mutations of the NF2 gene give rise to NF2 disease, which is generally characterized by the formation of bilateral vestibular schwannomas and, to a lesser extent, meningiomas and ependymomas. In addition to these tumor types, NF2 is mutated and/or merlin expression is reduced or lost in numerous non-NF2 associated tumors, including melanoma. However, the role of merlin in human melanoma growth and the mechanism underlying its effect are currently unknown. In the present study, we show that merlin knockdown enhances melanoma cell proliferation, migration, and invasion in vitro and that decreased merlin expression promotes subcutaneous melanoma growth in immunocompromised mice. Concordantly, we find that increased expression of merlin in a metastatic melanoma cell line reduced their in vitro migration and proliferation, and diminished their ability to grow in an anchorage independent manner. Increased merlin expression also inhibits in vivo growth of these melanoma cells. Lastly, we demonstrate that higher merlin levels in human melanoma cells promote the H(2)O(2)-induced activation of MST1/2 Ser/Thr kinases, which are known tumor suppressors in the Hippo signaling pathway. Taken together, these results provide for the first time evidence that merlin negatively regulates human melanoma growth, and that loss of merlin, or impaired merlin function, results in an opposite effect. In addition, we show that increased merlin expression leads to enhanced activation of the MTS1/2 kinases, implying the potential roles of MST1/2 in mediating the anti-melanoma effects of merlin.

  16. Melanin content of hamster tissues, human tissues, and various melanomas

    Energy Technology Data Exchange (ETDEWEB)

    Watts, K.P.; Fairchild, R.G.; Slatkin, D.N.; Greenberg, D.; Packer, S.; Atkins, H.L.; Hannon, S.J.

    1981-02-01

    Melanin content (percentage by weight) was determined in both pigmented and nonpigmented tissues of Syrian golden hamsters bearing Greene melanoma. Melanin content was also measured in various other melanoma models (B-16 in C57 mice, Harding-Passey in BALB/c mice, and KHDD in C3H mice) and in nine human melanomas, as well as in selected normal tissues. The purpose was to evaluate the possible efficacy of chlorpromazine, which is known to bind to melanin, as a vehicle for boron transport in neutron capture therapy. Successful therapy would depend upon selective uptake and absolute concentration of borated compounds in tumors; these parameters will in turn depend upon melanin concentration in melanomas and nonpigmented ''background'' tissues. Hamster whole eyes, hamster melanomas, and other well-pigmented animal melanomas were found to contain 0.3 to 0.8% melanin by weight, whereas human melanomas varied from 0.1 to 0.9% (average, 0.35%). Other tissues, with the exception of skin, were lower in content by a factor of greater than or equal to30. Melanin pigment was extracted from tissues, and the melanin content was determined spectrophotometrically. Measurements were found to be sensitive to the presence of other proteins. Previous procedures for isolating and quantifying melanin often neglected the importance of removing proteins and other interfering nonmelanic substances.

  17. [Loco-regional treatments of the metastatic sites for patients with pauci-metastatic cutaneous melanoma (without brain metastasis): French national guidelines].

    Science.gov (United States)

    Sassolas, Bruno; Mourrégot, Anne; Thariat, Juliette; Tiffet, Olivier; Dygai-Cochet, Inna; Mirabel, Xavier; Truc, Gilles; Cupissol, Didier; Modiano, Philippe; Combemale, Patrick; Bedane, Christophe; Derrey, Stéphane; Lamant, Laurence; Lubrano, Vincent; Siegrist, Sophie; Rougé-Bugat, Marie-Ève; Mazeau-Woynar, Valérie; Verdoni, Laëtitia; Planchamp, François; Leccia, Marie-Thérèse

    2014-01-01

    The last years are marked by the emergence of new molecules for the treatment of metastatic cutaneous melanoma with a significant benefit on the survival. Besides, some techniques are in development for the loco-regional treatment of the metastatic sites, bringing new therapeutic perspectives. However, their respective use and place in the therapeutic strategy are debated by healthcare professionals. The French National Cancer Institute leads a national clinical practice guidelines project since 2008. It realized a review of these modalities of treatment and developed recommendations. The clinical practice guidelines development process is based on systematic literature review and critical appraisal by a multidisciplinary expert workgroup. The recommendations are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines are reviewed by independent practitioners in cancer care delivery. This article presents recommendations for loco-regional treatments of the pulmonary, bone, cutaneous, hepatic and digestive metastatic sites for patients with pauci-metastatic cutaneous melanoma.

  18. Utility of a Noninvasive 2-Gene Molecular Assay for Cutaneous Melanoma and Effect on the Decision to Biopsy.

    Science.gov (United States)

    Ferris, Laura K; Jansen, Burkhard; Ho, Jonhan; Busam, Klaus J; Gross, Kenneth; Hansen, Doyle D; Alsobrook, John P; Yao, Zuxu; Peck, Gary L; Gerami, Pedram

    2017-07-01

    Expression of long intergenic non-protein coding RNA 518 (LINC00518) and preferentially expressed antigen in melanoma (PRAME) genes, obtained via noninvasive adhesive patch biopsy, is a sensitive and specific method for detection of cutaneous melanoma. However, the utility of this test in biopsy decisions made by dermatologists has not been evaluated. To determine the utility of the pigmented lesion assay (PLA) for LINC00518/PRAME expression in decisions to biopsy a series of pigmented skin lesions. In this secure web-based, multiple-reader-multiple-case study, 45 board-certified dermatologists each evaluated 60 clinical and dermoscopic images of clinically atypical pigmented lesions, first without and then with PLA gene expression information and were asked whether the lesions should be biopsied. Data were collected from March 24, 2014, through November 13, 2015. Participants were given a report for each lesion, which included the results of an assay for expression of LINC00518/PRAME and a PLA score with data on the predictive values of the information provided. Biopsy sensitivity and specificity with vs without PLA data. Forty-five dermatologists (29 male and 16 female) performed the evaluation. After incorporating the PLA into their decision as to whether to biopsy a pigmented lesion suggestive of melanoma, dermatologists improved their mean biopsy sensitivity from 95.0% to 98.6% (P = .01); specificity increased from 32.1% to 56.9% (P biopsy specificity while maintaining or improving sensitivity. This result may increase the number of early melanomas biopsied and reduce the number of benign lesions biopsied, thereby improving patient outcomes and reducing health care costs.

  19. Phase II Study of Adjuvant Immunotherapy with the CSF-470 Vaccine Plus Bacillus Calmette–Guerin Plus Recombinant Human Granulocyte Macrophage-Colony Stimulating Factor vs Medium-Dose Interferon Alpha 2B in Stages IIB, IIC, and III Cutaneous Melanoma Patients: A Single Institution, Randomized Study

    Directory of Open Access Journals (Sweden)

    José Mordoh

    2017-05-01

    Full Text Available The irradiated, allogeneic, cellular CSF-470 vaccine plus Bacillus Calmette–Guerin (BCG and recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF is being tested against medium-dose IFN-α2b in stages IIB–III cutaneous melanoma (CM patients (pts after surgery in an open, randomized, Phase II/III study. We present the results of the Phase II part of the ongoing CASVAC-0401 study (ClinicalTrials.gov: NCT01729663. Thirty-one pts were randomized to the CSF-470 vaccine (n = 20 or to the IFN-α2b arm (n = 11. During the 2-year treatment, immunized pts should receive 13 vaccinations. On day 1 of each visit, 1.6 × 107 irradiated CSF-470 cells plus 106 colony-forming units BCG plus 100 µg rhGM-CSF were administered intradermally, followed on days 2–4 by 100 µg rhGM-CSF. IFN-α2b pts should receive 10 million units (MU/day/5 days a week for 4 weeks; then 5 MU thrice weekly for 23 months. Toxicity and quality of life (QOL were evaluated at each visit. With a mean and a maximum follow-up of 39.4 and 83 months, respectively, a significant benefit in the distant metastasis-free survival (DMFS for CSF-470 was observed (p = 0.022. Immune monitoring showed an increase in antitumoral cellular and humoral response in vaccinated pts. CSF-470 was well tolerated; 20/20 pts presented grades 1–2 dermic reactions at the vaccination site; 3/20 pts presented grade 3 allergic reactions. Other adverse events (AEs were grade 1. Pts in the IFN-α2b arm presented grades 2–3 hematological (7/11, hepatic (2/11, and cardiac (1/11 toxicity; AEs in 9/11 pts forced treatment interruptions. QOL was significantly superior in the vaccine arm (p < 0.0001. Our results suggest that CSF-470 vaccine plus BCG plus GM-CSF can significantly prolong, with lower toxicity, the DMFS of high-risk CM pts with respect to medium-dose IFN-α2b. The continuation of a Phase III part of the CASVAC-0401 study is encouraged.

  20. Development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma

    Science.gov (United States)

    Gerami, Pedram; Yao, Zuxu; Polsky, David; Jansen, Burkhard; Busam, Klaus; Ho, Jonhan; Martini, Mary; Ferris, Laura K.

    2017-01-01

    Background Clinical and histopathologic assessment of pigmented skin lesions remains challenging even for experts. Differentiated and accurate noninvasive diagnostic modalities are highly desirable. Objective We sought to provide clinicians with such a tool. Methods A 2-gene classification method based on LINC00518 and preferentially expressed antigen in melanoma (PRAME) gene expression was evaluated and validated in 555 pigmented lesions (157 training and 398 validation samples) obtained noninvasively via adhesive patch biopsy. Results were compared with standard histopathologic assessment in lesions with a consensus diagnosis among 3 experienced dermatopathologists. Results In 398 validation samples (87 melanomas and 311 nonmelanomas), LINC00518 and/or PRAME detection appropriately differentiated melanoma from nonmelanoma samples with a sensitivity of 91% and a specificity of 69%. We established LINC00518 and PRAME in both adhesive patch melanoma samples and underlying formalin fixed paraffin embedded (FFPE) samples of surgically excised primary melanomas and in melanoma lymph node metastases. Limitations This technology cannot be used on mucous membranes, palms of hands, and soles of feet. Conclusions This noninvasive 2-gene pigmented lesion assay classifies pigmented lesions into melanoma and nonmelanoma groups and may serve as a tool to help with diagnostic challenges that may be inherently linked to the visual image and pattern recognition approach. PMID:27707590

  1. Development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma.

    Science.gov (United States)

    Gerami, Pedram; Yao, Zuxu; Polsky, David; Jansen, Burkhard; Busam, Klaus; Ho, Jonhan; Martini, Mary; Ferris, Laura K

    2017-01-01

    Clinical and histopathologic assessment of pigmented skin lesions remains challenging even for experts. Differentiated and accurate noninvasive diagnostic modalities are highly desirable. We sought to provide clinicians with such a tool. A 2-gene classification method based on LINC00518 and preferentially expressed antigen in melanoma (PRAME) gene expression was evaluated and validated in 555 pigmented lesions (157 training and 398 validation samples) obtained noninvasively via adhesive patch biopsy. Results were compared with standard histopathologic assessment in lesions with a consensus diagnosis among 3 experienced dermatopathologists. In 398 validation samples (87 melanomas and 311 nonmelanomas), LINC00518 and/or PRAME detection appropriately differentiated melanoma from nonmelanoma samples with a sensitivity of 91% and a specificity of 69%. We established LINC00518 and PRAME in both adhesive patch melanoma samples and underlying formalin fixed paraffin embedded (FFPE) samples of surgically excised primary melanomas and in melanoma lymph node metastases. This technology cannot be used on mucous membranes, palms of hands, and soles of feet. This noninvasive 2-gene pigmented lesion assay classifies pigmented lesions into melanoma and nonmelanoma groups and may serve as a tool to help with diagnostic challenges that may be inherently linked to the visual image and pattern recognition approach. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  2. In vivo photoacoustic microscopy of human cutaneous microvasculature and a nevus

    Science.gov (United States)

    Favazza, Christopher P.; Jassim, Omar; Cornelius, Lynn A.; Wang, Lihong V.

    2011-01-01

    In several human volunteers, photoacoustic microscopy (PAM) has been utilized for noninvasive cutaneous imaging of the skin microvasculature and a melanocytic nevus. Microvascular networks in both acral and nonacral skin were imaged, and multiple features within the skin have been identified, including the stratum corneum, epidermal-dermal junction, and subpapillary vascular plexus. Several vascular and structural differences between acral and nonacral skin were also observed in the photoacoustic images. In addition, a nevus was photoacoustically imaged, excised, and histologically analyzed. The photoacoustic images allowed for in vivo measurement of tumor thickness, depth, and microvasculature-values confirmed by histologic examination. The presented images demonstrate the potential of PAM to aid in the study and evaluation of cutaneous microcirculation and analysis of pigmented lesions. Through its ability to three-dimensionally image the structure and function of the microvasculature and pigmented lesions, PAM can have a clinical impact in diagnosis and assessment of systemic diseases that affect the microvasculature such as diabetes and cardiovascular disease, cutaneous malignancies such as melanoma, and potentially other skin disorders.

  3. Intercellular crosstalk in human malignant melanoma

    Czech Academy of Sciences Publication Activity Database

    Dvořánková, Barbora; Szabo, Pavol; Kodet, O.; Strnad, Hynek; Kolář, Michal; Lacina, L.; Krejčí, E.; Nanka, O.; Sedo, A.; Smetana, K.

    2017-01-01

    Roč. 254, č. 3 (2017), s. 1143-1150 ISSN 0033-183X R&D Projects: GA ČR GA16-05534S; GA MŠk(CZ) LQ1604; GA MŠk(CZ) ED1.1.00/02.0109 Grant - others:GA MŠk(CZ) LM2015042 Institutional support: RVO:68378050 Keywords : Melanocyte * Melanoma cells * Melanoma ecosystem * cancer -associated fibroblast * Keratinocyte * Cytokine Impact factor: 2.870, year: 2016

  4. Modern non-invasive diagnostic techniques in the detection of early cutaneous melanoma.

    Science.gov (United States)

    Kardynal, Agnieszka; Olszewska, Malgorzata

    2014-03-31

    Over the past few years melanoma has grown into a disease of socio-economic importance due to the increasing incidence and persistently high mortality rates. Melanoma is a malignant tumor with a high tendency to metastasize. Therefore, an extremely important part of the therapeutic process is to identify the disease at an early stage: in situ or stage I. Many tools for early diagnosis of melanoma are available today, including dermoscopy, videodermoscopy and in vivo reflectance confocal microscopy. Other methods such as high frequency ultrasound, optical coherence tomography and electrical impedance spectroscopy may serve as additional diagnostic aids. Modern imaging techniques also allow the monitoring of melanocytic skin lesions over months or years to detect the moment of malignant transformation. This review summarizes the current knowledge about modern diagnostic techniques, which may aid early diagnosis of melanoma.

  5. First experiences of photoacoustic imaging for detection of melanoma metastases in resected human lymph nodes.

    Science.gov (United States)

    Grootendorst, D J; Jose, J; Wouters, M W; van Boven, H; Van der Hage, J; Van Leeuwen, T G; Steenbergen, W; Manohar, S; Ruers, T J M

    2012-09-01

    Excision and histological assessment of the first draining node (sentinel lymph node) is a frequently used method to assess metastatic lymph node involvement related to cutaneous melanoma. Due to the time required for accurate histological assessment, nodal status is not immediately available to the surgeon. Hence, in case histological examination shows metastases, the patient has to be recalled to perform additional lymphadenectomy. To overcome these drawbacks we studied the applicability of photoacoustic tomographic imaging as an intra-operative modality for examining the status of resected lymph nodes. In melanoma patients undergoing lymphadectomy for metastatic disease, six suspect lymph nodes were photoacoustically (PA) imaged using multiple wavelengths. Histopathologal examination showed three nodes without tumor cells (benign nodes) and three nodes with melanoma cells (malignant nodes). PA images were compared with histology and anatomical features were analyzed. In addition, PA spectral analysis was performed on areas of increased signal intensity. After correlation with histopathology, multiple areas containing melanoma cells could be identified in the PA images due to their increased response. Malignant nodes showed a higher PA response and responded differently to an increase in excitation wavelength than benign nodes. In addition, differences in anatomical features between the two groups were detected. Photoacoustic detection of melanoma metastases based on their melanin content proves to be possible in resected human lymph nodes. The amount of PA signal and several specific anatomical features seem to provide additional characteristics for nodal analysis. However, it is as yet preliminary to designate a highly accurate parameter to distinguish between malignant and benign nodes. We expect to improve the specificity of the technique with a future implementation of an adjusted illumination scheme and depth correction for photon fluence. Copyright © 2012

  6. Nonsynonymous somatic mitochondrial mutations occur in the majority of cutaneous melanomas.

    Science.gov (United States)

    Mithani, Suhail K; Smith, Ian M; Topalian, Suzanne L; Califano, Joseph A

    2008-06-01

    Earlier studies of mitochondrial mutations in melanoma have focused on analysis of selected mitochondrial genes and the displacement loop (D-loop) region using conventional sequencing. In this study we use data from a whole mitochondria-sequencing array, the MitoChip v2.0, to characterize the mutations that are present throughout the mitochondrial genome. The mitochondrial genome of DNA derived from 14 fresh melanoma specimens and two melanoma cell lines, and autologous lymphocytes or immortalized B cells, respectively, were sequenced using the MitoChip v2.0. Paired comparative sequence analysis was carried out to define somatic mutations. Somatic mitochondrial DNA mutations were identified in 12/16 (75%) melanomas, compared with germline lymphocyte DNA. One hundred mutations were present among these 12 melanomas. A disproportionate number of mutations occurred in the D-loop. Furthermore, 9/16 (56.3%) melanomas carried mutations, which resulted in amino acid substitutions in functional genes. In the 10 samples carrying nicotinamide adenine dinucleotide dehydrogenase (ND) complex mutations, multiple mutations were present at a rate significantly greater than the expected frequency based on the size of ND complex genes (P=0.028, Fisher's exact test). Mitochondrial mutation is a frequent occurrence in melanoma. The high rate of missense mutations and the propensity for the ND complex implicate a role for alterations in mitochondrial respiratory function in melanoma carcinogenesis. Mutations of the noncoding D-loop are of unclear significance, but may be associated with alterations in transcription or replication. Further studies are needed to delineate the timing and functional significance of these mutations, and their role in the pathogenesis of this disease.

  7. 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....

  8. Patterns of failure and predictors of outcome in cutaneous malignant melanoma of the scalp.

    Science.gov (United States)

    Terakedis, Breanne E; Anker, Christopher J; Leachman, Sancy A; Andtbacka, Robert H I; Bowen, Glen M; Sause, William T; Grossmann, Kenneth F; Bowles, Tawnya L; Noyes, R Dirk; Hitchcock, Ying J; Boucher, Kenneth M; Shrieve, Dennis C

    2014-03-01

    Patients with melanoma of the scalp may have higher failure (recurrence) rates than melanoma of other body sites. We sought to characterize survival and patterns of failure for patients with scalp melanoma. Between 1998 and 2010, 250 nonmetastatic patients underwent wide local excision of a primary scalp melanoma. Kaplan-Meier analyses were performed to evaluate overall survival, scalp control, regional neck control, distant metastases-free survival, and disease-free survival. Five-year overall survival was 86%, 57%, and 45% for stages I, II, and III, respectively, and 5-year scalp control rates were 92%, 75%, and 63%, respectively. Five-year distant metastases-free survival for these stages were 92%, 65%, and 45%, respectively. Of the 74 patients who recurred, the site of first recurrence included distant disease in 47%, although 31% recurred in the scalp alone. This is a retrospective review. Distant metastases-free survival and overall survival for stage II and III patients with scalp melanoma are poor, and stage III patients experience relatively high rates of scalp failure suggesting that these patients may benefit from additional adjuvant systemic and local therapy. Further research is needed to characterize the environmental, microenvironmental, and genetic causes of the increased aggressiveness of scalp melanoma and to identify more effective treatment and surveillance methods. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  9. Surgical treatment of metastases from cutaneous melanoma to the small intestine and the spleen. Case reports and review of the literature.

    Science.gov (United States)

    Di Libero, Lorenzo; Sciascia, Valerio; Esposito, Daniela; Varriale, Roberto; Tartaglia, Ernesto; Santini, Luigi

    2011-01-01

    Cutaneous melanoma is found in the head and neck in 15% of patients, in the limbs in 22%, in the trunk in 40% and in occult sites in 16%. There is usually an interval of at least 3 years between the diagnosis of primary melanoma and the identification of metastases. Primary melanoma metastasizes most frequently to the lymph nodes (73.6% cases) and the lungs (71.3% cases). The small intestine and the spleen are the sites of 36.5% and 30.6% respectively of the gastrointestinal metastases from melanoma. The cases reported provide evidence of the effect radical resection in patients with gastrointestinal metastases can have on survival. The cases and a review of the literature suggest that a careful and multidisciplinary follow-up is of crucial importance since it is the only means of identifying metastases when they can be still cured with surgical treatment.

  10. 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...

  11. Cutaneous adverse events (AEs) of anti-programmed cell death (PD)-1 therapy in patients with metastatic melanoma: A single-institution cohort.

    Science.gov (United States)

    Hwang, Shelley Ji Eun; Carlos, Giuliana; Wakade, Deepal; Byth, Karen; Kong, Benjamin Y; Chou, Shaun; Carlino, Matteo S; Kefford, Richard; Fernandez-Penas, Pablo

    2016-03-01

    Anti-programmed cell death (PD)-1 therapy is emerging as the backbone of new standard of care immunotherapy for metastatic melanoma. Immune-related cutaneous events are observed in these patients. We sought to describe cutaneous adverse events observed in patients with metastatic melanoma on anti-PD-1 therapy. We reviewed the clinical and histologic information of all patients treated with single-agent anti-PD-1 therapy for metastatic melanoma at Westmead Hospital, Sydney, Australia, from May 2012 to February 2015. Of the 82 patients included in the study, 34 had dermatology assessments. Forty (49%) developed a form of anti-PD-1-associated cutaneous adverse events. In all, 17% developed lichenoid reactions and eczema, and 15% developed vitiligo. An estimated 25% of patients were expected to develop their first lichenoid reactions within 8.3 months, and eczema and vitiligo within 10.3 months of therapy. These adverse events tend to appear together in patients on anti-PD-1 therapy. The study was from a single center and clinical information was reviewed retrospectively in patients not referred to dermatology. Anti-PD-1 therapy is associated with the development of immune-related cutaneous events. Lichenoid reactions, eczema, and vitiligo are the 3 most prevalent lesions observed in our population. There is a tendency for lichenoid reactions and eczema to occur with vitiligo. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  12. A multicentre pilot study investigating high-definition optical coherence tomography in the differentiation of cutaneous melanoma and melanocytic naevi.

    Science.gov (United States)

    Gambichler, T; Schmid-Wendtner, M H; Plura, I; Kampilafkos, P; Stücker, M; Berking, C; Maier, T

    2015-03-01

    High-definition optical coherence tomography scanners have recently been developed. To assess the diagnostic performance of HD-OCT in the differentiation of benign melanocytic skin lesions (MSL) and cutaneous melanoma (CM). Patients with MSL were assessed by HD-OCT. All diagnoses were histopathologically confirmed. One blinded observer evaluated both slice and en-face HD-OCT images and diagnosed MLS on the basis of an algorithm adopted from reflectance confocal microscopy, recent HD-OCT reports, and conventional OCT. A total of 93 MSL were studied comprising 66 benign MSL and 27 CM. The sensitivity of HD-OCT was 74.1% [95% confidence interval (CI) 53.7-88.8%)], specificity was 92.4% (95% CI 83.2-97.5%). The positive predictive value was 80%, the negative predictive value 89.7%. The performance of HD-OCT depended on tumour thickness and the presence of borderline lesions indicated by high false negative rates in very thin melanomas and high false positive rates in dysplastic naevi. In the distinction of MSL, HD-OCT applied in an investigator blinded fashion has a moderate diagnostic performance. The diagnostic performance of HD-OCT of MSL should be reassessed in other clinical settings. © 2014 European Academy of Dermatology and Venereology.

  13. Cutaneous melanoma: an audit of management timeliness against New Zealand guidelines.

    Science.gov (United States)

    Brian, Tess; Adams, Brandon; Jameson, Michael

    2017-09-22

    The New Zealand Ministry of Health's "Faster Cancer Treatment" programme aims for timely care for patients with cancer, including melanoma. Melanoma care guidelines detail investigation and treatment timeliness standards. This audit assesses compliance with these. Patients admitted to Waikato Hospital for melanoma surgery during the year ending February 2016 were retrospectively identified. Time intervals between care events were calculated. Demographic, lesion, surgical and histopathological characteristics were analysed. For patients referred with skin lesions suspicious for melanoma, referral to first treatment (Standard 2.1), referral to diagnostic skin biopsy (Standards 2.2, 2.3), biopsy histology report to first treatment (Standard 2.4), referral to first treatment (Standards 2.2, 2.3, 2.4, 4.4) and biopsy to first treatment (Standards 2.4, 4.4) compliance was 0%, 17.6%, 21.7%, 9.3% and 21.7%, respectively. For patients referred with biopsy-confirmed melanomas, referral to first treatment (Standards 2.2, 2.4) and skin biopsy to first treatment (Standards 2.2, 2.4, 4.4) compliance was 42.2% and 42.9%, respectively. Compliance was low. Attention to logistical constraints in the department reviewed may improve this. Recommendation inconsistencies within and between suspicious-lesion and confirmed-diagnosis referral pathways suggest the investigation and treatment events selected and intervals mandated by the guidelines may usefully be reconsidered.

  14. MicroRNA and cutaneous melanoma: from discovery to prognosis and therapy

    Science.gov (United States)

    Hernando, Eva

    2012-01-01

    Melanoma incidence and associated mortality continue to increase worldwide. The lack of treatments with durable responses for stage IV melanoma may be due, at least in part, to an incomplete understanding of the molecular mechanisms that regulate tumor initiation and/or progression to metastasis. Recent evidence supports miRNA dysregulation in melanoma impacting several well-known pathways such as the PI3K/AKT or RAS/MAPK pathways, but also underexplored cellular processes like protein glycosylation and immune modulation. There is also increasing evidence that miRNA can improve patient prognostic classification over the classical staging system and provide new therapeutic opportunities. The integration of this recently acquired knowledge with known molecular alterations in protein coding genes characteristic of these tumors (i.e., BRAF and NRAS mutations, CDKN2A inactivation) is critical for a complete understanding of melanoma pathogenesis. Here, we compile the evidence of the functional roles of miRNAs in melanomagenesis and progression, and of their clinical utility as biomarkers, prognostic tools and potential therapeutic targets. Characterization of miRNA alterations in melanoma may provide new angles for therapeutic intervention, help to decipher mechanisms of drug resistance, and improve patient classification for disease surveillance and clinical benefit. PMID:22693259

  15. P-REX1 amplification promotes progression of cutaneous melanoma via the PAK1/P38/MMP-2 pathway.

    Science.gov (United States)

    Wang, Jinhua; Hirose, Hajime; Du, Guanhua; Chong, Kelly; Kiyohara, Eiji; Witz, Isaac P; Hoon, Dave S B

    2017-10-28

    P-REX1 (PIP3-dependent Rac exchange factor-1) is a guanine nucleotide exchange factor that activates Rac by catalyzing exchange of GDP for GTP bound to Rac. Aberrant up-regulation of P-REX1 expression has a role in metastasis however, copy number (CN) and function of P-REX1 in cutaneous melanoma are unclear. To explore the role of P-REX1 in melanoma, SNP 6.0 and Exon 1.0 ST microarrays were assessed. There was a higher CN (2.82-fold change) of P-REX1 in melanoma cells than in melanocytes, and P-REX1 expression was significantly correlated with P-REX1 CN. When P-REX1 was knocked down in cells by P-REX1 shRNA, proliferation, colony formation, 3D matrigel growth, and migration/invasiveness were inhibited. Loss of P-REX1 inhibited cell proliferation by inhibiting cyclin D1, blocking cell cycle, and increased cell apoptosis by reducing expression of the protein survivin. Knockdown of P-REX1 expression inhibited cell migration/invasiveness by disrupting P-REX1/RAC1/PAK1/p38/MMP-2 pathway. Assessment of patient tumors and disease outcome demonstrated lower distant metastasis-free survival among AJCC stage I/II/III patients with high P-REX1 expression compared to patients with low P-REX1 expression. These results suggest P-REX1 plays an important role in tumor progression and a potential theranostic target. Copyright © 2017. Published by Elsevier B.V.

  16. Oxidative stress inhibits distant metastasis by human melanoma cells.

    Science.gov (United States)

    Piskounova, Elena; Agathocleous, Michalis; Murphy, Malea M; Hu, Zeping; Huddlestun, Sara E; Zhao, Zhiyu; Leitch, A Marilyn; Johnson, Timothy M; DeBerardinis, Ralph J; Morrison, Sean J

    2015-11-12

    Solid cancer cells commonly enter the blood and disseminate systemically, but are highly inefficient at forming distant metastases for poorly understood reasons. Here we studied human melanomas that differed in their metastasis histories in patients and in their capacity to metastasize in NOD-SCID-Il2rg(-/-) (NSG) mice. We show that melanomas had high frequencies of cells that formed subcutaneous tumours, but much lower percentages of cells that formed tumours after intravenous or intrasplenic transplantation, particularly among inefficiently metastasizing melanomas. Melanoma cells in the blood and visceral organs experienced oxidative stress not observed in established subcutaneous tumours. Successfully metastasizing melanomas underwent reversible metabolic changes during metastasis that increased their capacity to withstand oxidative stress, including increased dependence on NADPH-generating enzymes in the folate pathway. Antioxidants promoted distant metastasis in NSG mice. Folate pathway inhibition using low-dose methotrexate, ALDH1L2 knockdown, or MTHFD1 knockdown inhibited distant metastasis without significantly affecting the growth of subcutaneous tumours in the same mice. Oxidative stress thus limits distant metastasis by melanoma cells in vivo.

  17. Human Melanoma-Derived Extracellular Vesicles Regulate Dendritic Cell Maturation.

    Science.gov (United States)

    Maus, Rachel L G; Jakub, James W; Nevala, Wendy K; Christensen, Trace A; Noble-Orcutt, Klara; Sachs, Zohar; Hieken, Tina J; Markovic, Svetomir N

    2017-01-01

    Evolution of melanoma from a primary tumor to widespread metastasis is crucially dependent on lymphatic spread. The mechanisms regulating the initial step in metastatic dissemination via regional lymph nodes remain largely unknown; however, evidence supporting the establishment of a pre-metastatic niche is evolving. We have previously described a dysfunctional immune profile including reduced expression of dendritic cell (DC) maturation markers in the first node draining from the primary tumor, the sentinel lymph node (SLN). Importantly, this phenotype is present prior to evidence of nodal metastasis. Herein, we evaluate melanoma-derived extracellular vesicles (EVs) as potential mediators of the premetastatic niche through cargo-specific polarization of DCs. DCs matured in vitro in the presence of melanoma EVs demonstrated significantly impaired expression of CD83 and CD86 as well as decreased expression of Th1 polarizing chemokines Flt3L and IL15 and migration chemokines MIP-1α and MIP-1β compared to liposome-treated DCs. Profiling of melanoma EV cargo identified shared proteomic and RNA signatures including S100A8 and S100A9 protein cargo, which in vitro compromised DC maturation similar to melanoma EVs. Early evidence demonstrates that similar EVs can be isolated from human afferent lymphatic fluid ex vivo. Taken together, here, we propose melanoma EV cargo as a mechanism by which DC maturation is compromised warranting further study to consider this as a potential mechanism enabled by the primary tumor to establish the premetastatic niche in tumor-draining SLNs of patients.

  18. Analytical and dimensional morphometry in early diagnosis cutaneous melanoma with dermoscopic images.

    Science.gov (United States)

    Ricco, Rosalia; Lettini, Teresa; Arpaia, Nicola; Valente, Tiziana; Ingravallo, Giuseppe; Vurro, Maria Lucia; De Pascalis, Raffaella; Delfino, Vittorio Pesce

    2011-08-01

    To give to the clinician an objective numerical assessment tool to evaluate melanomas so that a diagnosis can be reached with the assistance of computerized procedures. The approach adopted for differential diagnosis of melanomas and nevi considers diverse morphologic characteristics intrinsic to the lesions, that is, shape, size, and symmetry in total independence of pigmentation, and proposes that this information can be evaluated quantitatively and separately by morphometric procedures with statistically valid independent numeric variables that guarantee objectivity and, from a method point of view, consistency. The results show that the differential diagnosis on malignant and benign lesions is made on five variables, which all describe the fine irregularities of the contour and have a high significance in comparing melanomas to nevi. The multivariate discriminant analysis demonstrates the ability of the analytic variables to discriminate 88% of the lesions, rising to 90% if two-dimensional variables are included.

  19. Diagnosis and treatment of cutaneous melanoma: state of the art 2006.

    Science.gov (United States)

    Garbe, Claus; Eigentler, Thomas K

    2007-04-01

    Although the incidence of melanoma is still rising in Caucasian populations, the increase in mortality has leveled off. Improvements in early diagnosis, with more frequent diagnosis of low-risk patients (i.e. those with melanoma diagnosis when dermoscopy and digital dermoscopy were introduced, and computer algorithms have proved to be highly efficacious for automated melanoma diagnosis. Primary melanomas are now excised with narrower surgical margins of 1-2 cm. Sentinel-node biopsy is recommended as a nodal staging procedure in patients with tumor thickness of 1 mm and more, but the prognostic impact of this procedure has not yet been demonstrated. New imaging techniques, e.g. whole-body MRI and PET-CT, provide more accurate staging, particularly in patients with apparent metastasis, and facilitate decisions on surgical treatment strategies. Staging is now based on the 2001 TNM classification including tumor thickness and histopathologic ulceration in stages I and II and lymph node micro and macro-metastasis in stage III. A stage- and risk-adopted follow-up schedule is proposed for melanoma surveillance. Adjuvant therapy with interferon-alpha in high-risk patients offers a small benefit in terms of recurrence-free and overall survival; the optimal dosage and duration of this treatment are still to be defined. Almost no progress has been made in the medical treatment of disseminated metastasis of melanoma. Therapy with dacarbazine and a few other single agents remains the first-line treatment approach of choice. A number of new treatment modalities, including targeted molecules and immunologic approaches with monoclonal antibodies, are under development; hopefully, new treatment modalities will be available in the near future.

  20. 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

  1. Immunohistochemical expression of the glucose transporters Glut-1 and Glut-3 in human malignant melanomas and benign melanocytic lesions

    Directory of Open Access Journals (Sweden)

    Parente Paola

    2008-09-01

    Full Text Available Abstract Background Reported data indicate that cancer cells have increased rates of glucose metabolism, as determined by 18FDG-PET imaging in patients with malignancies. The results of many studies have demonstrated that the expression of glucose transporters, especially Glut-1, is increased in a variety of malignancies. This study was undertaken to assess the differential expression of Glut-1 and Glut-3 by benign and malignant melanocytic lesions. Methods Immunohistochemical staining for Glut-1 and Glut-3 was performed on paraffin-embedded tissue sections prepared from melanocytic nevi (12 cases, Spitz nevi (12 cases and primary cutaneous malignant melanomas (20 cases. Results We observed immunoreactivity for Glut-1 in all melanocytic nevi, 9 of the 12 Spitz nevi and in 9 of the 20 malignant melanomas, whereas Glut-3 was expressed in all the melanocytic lesions, both benign and malignant. Conclusion These findings indicate that the glucose transporters Glut-1 and Glut-3 play a role in the glucose metabolism of melanocytic cells. Glut-1 was present in the majority of benign nevi, whereas its expression was downregulated in 55% of malignant melanomas. Our results suggest that glucose transporter Glut-1 expression can significantly discriminate between human malignant melanoma and benign melanocytic nevi, and support the idea that additional mechanisms other than Glut-1 may contribute to glucose uptake in melanomas.

  2. Proteome profiling of human cutaneous leishmaniasis lesion.

    Science.gov (United States)

    da Silva Santos, Claire; Attarha, Sanaz; Saini, Ravi Kanth; Boaventura, Viviane; Costa, Jackson; Khouri, Ricardo; Barral-Netto, Manoel; Brodskyn, Cláudia Ida; Souchelnytskyi, Serhiy

    2015-02-01

    In this study, we used proteomics and biological network analysis to evaluate the potential biological processes and components present in the identified proteins of biopsies from cutaneous leishmaniasis (CL) patients infected by Leishmania braziliensis in comparison with normal skin. We identified 59 proteins differently expressed in samples from infected and normal skin. Biological network analysis employing identified proteins showed the presence of networks that may be involved in the cell death mediated by cytotoxic T lymphocytes. After immunohistochemical analyses, the expression of caspase-9, caspase-3, and granzyme B was validated in the tissue and positively correlated with the lesion size in CL patients. In conclusion, this work identified differentially expressed proteins in the inflammatory site of CL, revealed enhanced expression of caspase-9, and highlighted mechanisms associated with the progression of tissue damage observed in lesions.

  3. Proteome Profiling of Human Cutaneous Leishmaniasis Lesion

    Science.gov (United States)

    da Silva Santos, Claire; Attarha, Sanaz; Saini, Ravi Kanth; Boaventura, Viviane; Costa, Jackson; Khouri, Ricardo; Barral-Netto, Manoel; Brodskyn, Cláudia Ida; Souchelnytskyi, Serhiy

    2015-01-01

    In this study, we used proteomics and biological network analysis to evaluate the potential biological processes and components present in the identified proteins of biopsies from cutaneous leishmaniasis (CL) patients infected by Leishmania braziliensis in comparison with normal skin. We identified 59 proteins differently expressed in samples from infected and normal skin. Biological network analysis employing identified proteins showed the presence of networks that may be involved in the cell death mediated by cytotoxic T lymphocytes. After immunohistochemical analyses, the expression of caspase-9, caspase-3, and granzyme B was validated in the tissue and positively correlated with the lesion size in CL patients. In conclusion, this work identified differentially expressed proteins in the inflammatory site of CL, revealed enhanced expression of caspase-9, and highlighted mechanisms associated with the progression of tissue damage observed in lesions. PMID:25207817

  4. 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,

  5. Vaccines and vaccination strategies against human cutaneous leishmaniasis.

    Science.gov (United States)

    Okwor, Ifeoma; Uzonna, Jude

    2009-05-01

    One might think that the development of a vaccine against cutaneous leishmaniasis would be relatively straightforward because the type of immune response required for protection is known and natural immunity occurs following recovery from primary infection. However, there is as yet no effective vaccine against the disease in humans. Although vaccination in murine studies has yielded promising results, these vaccines have failed miserably when tested in primates or humans. The reasons behind these failures are unknown and remain a major hurdle for vaccine design and development against cutaneous leishmaniasis. In contrast, recovery from natural, deliberate or experimental infections results in development of long-lasting immunity to re-infection. This so called infection-induced resistance is the strongest anti-Leishmania immunity known. Here, we briefly review the different approaches to vaccination against cutaneous leishmaniasis and argue that vaccines composed of genetically modified (attenuated) parasites, which induce immunity akin to infection-induced resistance, may provide best protection against cutaneous leishmaniasis in humans.

  6. 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...

  7. A Pooled Analysis of Melanocytic Naevus Phenotype and the Risk of Cutaneous Melanoma at Different Latitudes

    Science.gov (United States)

    Chang, Yu-mei; Newton-Bishop, Julia A; Bishop, D Timothy; Armstrong, Bruce K; Bataille, Veronique; Bergman, Wilma; Berwick, Marianne; Bracci, Paige M; Elwood, J Mark; Ernstoff, Marc S; Green, Adèle C; Gruis, Nelleke A; Holly, Elizabeth A; Ingvar, Christian; Kanetsky, Peter A; Karagas, Margaret R; Le Marchand, Loïc; Mackie, Rona M; Olsson, Håkan; Østerlind, Anne; Rebbeck, Timothy R; Reich, Kristian; Sasieni, Peter; Siskind, Victor; Swerdlow, Anthony J; Titus-Ernstoff, Linda; Zens, Michael S; Ziegler, Andreas; Barrett, Jennifer H

    2008-01-01

    An abnormal naevus phenotype is associated with an increased risk of melanoma. We report a pooled analysis conducted using individual naevus data from 15 case-control studies (5,421 melanoma cases and 6,966 controls). The aims were to quantify better the risk, and to determine whether relative risk varied by latitude. Bayesian unconditional logistic random coefficients models were employed to study the risk associated with naevus characteristics. Participants with whole body naevus counts in the highest of four population-based categories had a greatly increased risk of melanoma compared with those in the lowest category (pooled odds ratio (pOR) 6.9 (95% confidence interval (CI): 4.4, 11.2) for those aged <50 years and pOR 5.1 (95% CI: 3.6, 7.5) for those aged ≥50). The pOR for presence compared with absence of any clinically atypical naevi was 4.0 (95% CI: 2.8, 5.8). The pORs for 1–2 and ≥3 large naevi on the body compared with none were 2.9 (95% CI: 1.9, 4.3) and 7.1 (95% CI: 4.7, 11.6), respectively. The relative heterogeneities among studies were small for most measures of naevus phenotype, except for the analysis of naevus counts on the arms, which may have been due to methodological differences among studies. The pooled analysis also suggested that an abnormal naevus phenotype is associated most with melanomas on intermittently sun-exposed sites. The presence of increased numbers of naevi, large naevi and clinically atypical naevi on the body are robust risk factors for melanoma showing little variation in relative risk among studies performed at different latitudes. PMID:18792098

  8. Effect of biopsy type on outcomes in the treatment of primary cutaneous melanoma.

    Science.gov (United States)

    Mills, Jane K; White, Ian; Diggs, Brian; Fortino, Jeanine; Vetto, John T

    2013-05-01

    Surgical excision remains the primary and only potentially curative treatment for melanoma. Although current guidelines recommend excisional biopsy as the technique of choice for evaluating lesions suspected of being primary melanomas, other biopsy types are commonly used. We sought to determine the impact of biopsy type (excisional, shave, or punch) on outcomes in melanoma. A prospectively collected, institutional review board-approved database of primary clinically node-negative melanomas (stages cT1-4N0) was reviewed to determine the impact of biopsy type on T-staging accuracy, wide local excision (WLE) area (cm(2)), sentinel lymph node biopsy (SLNB) identification rates and results, tumor recurrence, and patient survival. Seven hundred nine patients were diagnosed by punch biopsy (23%), shave biopsy (34%), and excisional biopsy (43%). Shave biopsy results showed significantly more positive deep margins (P biopsies (P = .030), and this result was sustained on multivariate analysis. SLNB accuracy was 98.5% and was not affected by biopsy type. Similarly, biopsy type did not confer survival advantage or impact tumor recurrence; the finding of residual tumor in the WLE impacted survival on univariate but not multivariate analysis. Both shave and punch biopsies demonstrated a significant risk of finding residual tumor in the WLE, with pathologic upstaging of the WLE. Punch biopsy also led to a larger mean WLE area compared with other biopsy types. However, biopsy type did not impact SLNB accuracy or results, tumor recurrence, or disease-specific survival (DSS). Punch and shave biopsies, when used appropriately, should not be discouraged for the diagnosis of melanoma. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Incorporating clinical metadata with digital image features for automated identification of cutaneous melanoma.

    Science.gov (United States)

    Liu, Z; Sun, J; Smith, M; Smith, L; Warr, R

    2013-11-01

    Computer-assisted diagnosis (CAD) of malignant melanoma (MM) has been advocated to help clinicians to achieve a more objective and reliable assessment. However, conventional CAD systems examine only the features extracted from digital photographs of lesions. Failure to incorporate patients' personal information constrains the applicability in clinical settings. To develop a new CAD system to improve the performance of automatic diagnosis of melanoma, which, for the first time, incorporates digital features of lesions with important patient metadata into a learning process. Thirty-two features were extracted from digital photographs to characterize skin lesions. Patients' personal information, such as age, gender and, lesion site, and their combinations, was quantified as metadata. The integration of digital features and metadata was realized through an extended Laplacian eigenmap, a dimensionality-reduction method grouping lesions with similar digital features and metadata into the same classes. The diagnosis reached 82.1% sensitivity and 86.1% specificity when only multidimensional digital features were used, but improved to 95.2% sensitivity and 91.0% specificity after metadata were incorporated appropriately. The proposed system achieves a level of sensitivity comparable with experienced dermatologists aided by conventional dermoscopes. This demonstrates the potential of our method for assisting clinicians in diagnosing melanoma, and the benefit it could provide to patients and hospitals by greatly reducing unnecessary excisions of benign naevi. This paper proposes an enhanced CAD system incorporating clinical metadata into the learning process for automatic classification of melanoma. Results demonstrate that the additional metadata and the mechanism to incorporate them are useful for improving CAD of melanoma. © 2013 British Association of Dermatologists.

  10. Tratamiento de los melanomas cutáneos de la cabeza y el cuello: Estado actual The current state of treatment for cutaneous melanoma of the head and neck

    Directory of Open Access Journals (Sweden)

    P.M. Villarreal Renedo

    2005-08-01

    Full Text Available Objetivo. Demostrar nuestra experiencia en el tratamiento del melanoma cutáneo de cabeza y cuello, así como en el estadiaje ganglionar regional a través de la detección y biopsia de los ganglios centinelas cervicofaciales. Métodos. Analizamos los casos de melanoma de cabeza y cuello tratados a lo largo de los últimos 3 años. Los pacientes que nos fueron enviados con metástasis cervicofaciales fueron tratados mediante linfadenectomías cervicales acompañadas de parotidectomías si existían ganglios peri o intraparotídeos afectos. En los pacientes enviados sin resecar el tumor primario, tras la biopsia preoperatoria y el estudio de extensión, se realizó la identificación y exéresis de los ganglios centinelas cervicofaciales, la resección del primario y la reconstrucción del defecto creado mediante colgajos locorregionales. Resultados. El melanoma se asocia con un excelente pronóstico a largo plazo si se detecta y trata en estadios precoces. La técnica de la identificación y exéresis de los ganglios centinelas cervicofaciales es factible en los melanomas de cabeza y cuello. Conclusión. La técnica de detección y biopsia de los ganglios centinelas regionales se considera el procedimiento de elección para realizar el estadiaje ganglionar regional en el melanoma de cabeza y cuello. Permite aumentar la eficacia y sensibilidad del estudio histopatológico, al seleccionar los ganglios linfáticos cervicofaciales con mayor probabilidad de encontrar focos metastásicos.Objective. To demonstrate our experience in the treatment of head and neck cutaneous melanoma and the regional lymph nodes staging, by the sentinel lymph nodes biopsy technique. Methods. We analyze the cases of head and neck cutaneous melanoma treated during the last 3 years. Patients with cervical and/or facial metastases were treated by neck dissection plus parotidectomy if peripheral or intra-parotid nodes were affected. In the patients with primary tumours, a

  11. Dual-energy computed tomography in patients with cutaneous malignant melanoma: Comparison of noise-optimized and traditional virtual monoenergetic imaging.

    Science.gov (United States)

    Martin, Simon S; Wichmann, Julian L; Weyer, Hendrik; Albrecht, Moritz H; D'Angelo, Tommaso; Leithner, Doris; Lenga, Lukas; Booz, Christian; Scholtz, Jan-Erik; Bodelle, Boris; Vogl, Thomas J; Hammerstingl, Renate

    2017-10-01

    The aim of this study was to investigate the impact of noise-optimized virtual monoenergetic imaging (VMI+) reconstructions on quantitative and qualitative image parameters in patients with cutaneous malignant melanoma at thoracoabdominal dual-energy computed tomography (DECT). Seventy-six patients (48 men; 66.6±13.8years) with metastatic cutaneous malignant melanoma underwent DECT of the thorax and abdomen. Images were post-processed with standard linear blending (M_0.6), traditional virtual monoenergetic (VMI), and VMI+ technique. VMI and VMI+ images were reconstructed in 10-keV intervals from 40 to 100keV. Attenuation measurements were performed in cutaneous melanoma lesions, as well as in regional lymph node, subcutaneous and in-transit metastases to calculate objective signal-to-noise (SNR) and contrast-to-noise (CNR) ratios. Five-point scales were used to evaluate overall image quality and lesion delineation by three radiologists with different levels of experience. Objective indices SNR and CNR were highest at 40-keV VMI+ series (5.6±2.6 and 12.4±3.4), significantly superior to all other reconstructions (all P<0.001). Qualitative image parameters showed highest values for 50-keV and 60-keV VMI+ reconstructions (median 5, respectively; P≤0.019) regarding overall image quality. Moreover, qualitative assessment of lesion delineation peaked in 40-keV VMI+ (median 5) and 50-keV VMI+ (median 4; P=0.055), significantly superior to all other reconstructions (all P<0.001). Low-keV noise-optimized VMI+ reconstructions substantially increase quantitative and qualitative image parameters, as well as subjective lesion delineation compared to standard image reconstruction and traditional VMI in patients with cutaneous malignant melanoma at thoracoabdominal DECT. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. SKI knockdown inhibits human melanoma tumor growth in vivo.

    Science.gov (United States)

    Chen, Dahu; Lin, Qiushi; Box, Neil; Roop, Dennis; Ishii, Shunsuke; Matsuzaki, Koichi; Fan, Tao; Hornyak, Thomas J; Reed, Jon A; Stavnezer, Ed; Timchenko, Nikolai A; Medrano, Estela E

    2009-12-01

    The SKI protein represses the TGF-beta tumor suppressor pathway by associating with the Smad transcription factors. SKI is upregulated in human malignant melanoma tumors in a disease-progression manner and its overexpression promotes proliferation and migration of melanoma cells in vitro. The mechanisms by which SKI antagonizes TGF-beta signaling in vivo have not been fully elucidated. Here we show that human melanoma cells in which endogenous SKI expression was knocked down by RNAi produced minimal orthotopic tumor xenograft nodules that displayed low mitotic rate and prominent apoptosis. These minute tumors exhibited critical signatures of active TGF-beta signaling including high levels of nuclear Smad3 and p21(Waf-1), which are not found in the parental melanomas. To understand how SKI promotes tumor growth we used gain- and loss-of-function approaches and found that simultaneously to blocking the TGF-beta-growth inhibitory pathway, SKI promotes the switch of Smad3 from tumor suppression to oncogenesis by favoring phosphorylations of the Smad3 linker region in melanoma cells but not in normal human melanocytes. In this context, SKI is required for preventing TGF-beta-mediated downregulation of the oncogenic protein c-MYC, and for inducing the plasminogen activator inhibitor-1, a mediator of tumor growth and angiogenesis. Together, the results indicate that SKI exploits multiple regulatory levels of the TGF-beta pathway and its deficiency restores TGF-beta tumor suppressor and apoptotic activities in spite of the likely presence of oncogenic mutations in melanoma tumors.

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

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    Raquel Bonfá

    2011-04-01

    Full Text Available FUNDAMENTOS: A incidência do melanoma cutâneo e as taxas de mortalidade a ele associadas estão crescendo na maioria dos países do mundo. OBJETIVO: Descrever as características histopatológicas do melanoma cutâneo, segundo critérios do Grupo Brasileiro de Melanoma, e avaliar a precocidade diagnóstica em hospital de referência do sul do Brasil para o atendimento de melanoma. MÉTODOS: Estudo transversal com casos de melanoma cutâneo primário reconhecidos após biópsia excisional, processados no laboratório de Patologia do Complexo Hospitalar Santa Casa de Porto Alegre entre 1º/1/2000 e 15/1/2005. Outras variáveis analisadas: idade, sexo, topogra fia da lesão, subtipos histopatológicos, índice Breslow, fase de crescimento, índice de Clark, índice mitótico, infiltrado inflamatório linfocitário peritumoral e intratumoral, invasão angiolinfática e perineural, presença de úlcera e regressão, tipo de regressão, satelitose microscópica e margens cirúrgicas. RESULTADOS: Incluídos 328 casos, sendo 57% mulheres e 43% homens, com média de idade de 55,63 anos. A localização foi preferencialmente nos membros inferiores (29,26% e superiores (23,94% nas mulheres. Nos homens, predominou no dorso (35% e no tórax anterior/abdome (14,29% (pBACKGROUND: The incidence of melanoma cutaneous and the mortalities rates are rising in most countries worldwide. OBJECTIVE: to describe the histopathological characteristics of cutaneous melanoma, according to the criteria established by the Brazilian Group of Melanoma, and to evaluate early diagnosis in a cancer treatment referral center. METHODS: we performed a cross-sectional descriptive study of cases of primary cutaneous melanoma identified after excisional biopsy and processed at the pathology laboratory of Complexo Hospitalar Santa Casa between Jan 1st 2000 and Jan 15th 2005. The following variables were analyzed: age, gender, topography, histopathologic subtype, Breslow thickness

  14. Variant on Manifestation of Duodenal Metastasis 26 Years after Initial Diagnosis of Primary Cutaneous Melanoma

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    Kumiko Kitajima

    2010-03-01

    Full Text Available Malignant duodenal neoplasms are relatively rare, and the diagnosis is often delayed because of their vague and nonspecific symptoms. We report the case of a 79-year-old female who had a medical history of malignant melanoma of the cheek that had initially been diagnosed at 53 years of age. Work-up revealed severe stenosis of the duodenum caused by a large mass with ulceration at the tip of its mucosal surface. Tumor biopsy led to a histological diagnosis of extremely poorly differentiated carcinoma, but it was impossible to determine whether the lesion was a primary neoplasm or represented secondary involvement. Pancreatoduodenectomy was performed, and the surgical specimen showed a protuberant tumor in the nonampullary region of the second portion of the duodenum. Final diagnosis of metastatic duodenal melanoma was made by immunohistological examination. She is currently alive without recurrence 28 months after the surgical treatment.

  15. 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 m...

  16. Correlation of local and systemic expression of survivin with histopathological parameters of cutaneous melanoma

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    Jović Milena

    2016-01-01

    Full Text Available Background/Aim. Survivin is a multifunctional protein abundantly expressed in tumors of various types, including melanoma. There are still sparse data regarding relationship of melanoma cell survivin expression with accepted histopathological characteristics as well as serum concentration. The aim of this study was to investigate the association of local tumor survivin expression (primary tumor and metastatic lesions and serum concentration with clinical and histopathological parameters in melanoma patients. Methods. The level of survivin expression was determined immunocytochemically in tumor tissue and with ELISA test in the serum of 84 melanoma patients diagnosed from 2009 to 2013 at the Institute for Pathology and Forensic Medicine and Institute for Medical Research at Military Medical Academy, Belgrade, Serbia. Results. The intensity of survivin expression was significantly higher in the patients whose tumor had ulceration, higher mitotic index, higher Clark and Breslow stage, that made vascular invasion or spread through lymphatic vessels in primary tumor, and was significantly higher in the patients with metastatic disease. Survivin expression and the number of survivin positive cells in metastatic lesions were significantly associated with the duration of disease free interval (DFI. The patients with high expression score had almost double shorter DFI comparing to those with weak local survivin expression and a small number of survivin+cells (9 ± 7 vs 19 ± 13 months, respectively. The degree of tumor infiltrating lymphocytes presence in tumor tissue was significantly associated with serum survivin concentration, with lowest average level detected in samples of patients with the highest degree of infiltration. Serum survivin concentrations were highest in samples of melanoma patients with IA American Joint Commission on Cancer (AJCC clinical stage, pT1a histological stage, patients whose tumors were still in horizontal growth phase

  17. Localised cutaneous microvascular adaptation to exercise training in humans.

    Science.gov (United States)

    Atkinson, Ceri L; Carter, Howard H; Thijssen, Dick H J; Birk, Gurpreet K; Cable, N Timothy; Low, David A; Kerstens, Floortje; Meeuwis, Iris; Dawson, Ellen A; Green, Daniel J

    2018-02-07

    Exercise training induces adaptation in conduit and resistance arteries in humans, partly as a consequence of repeated elevation in blood flow and shear stress. The stimuli associated with intrinsic cutaneous microvascular adaptation to exercise training have been less comprehensively studied. We studied 14 subjects who completed 8-weeks cycle ergometer training, with partial cuff inflation on one forearm to unilaterally attenuate cutaneous blood flow responses during each exercise-training bout. Before and after training, bilateral forearm skin microvascular dilation was determined using cutaneous vascular conductance (CVC: skin flux/blood pressure) responses to gradual localised heater disk stimulation performed at rest (33, 40, 42 and 44 °C). Cycle exercise induced significant increases in forearm cutaneous flux and temperature, which were attenuated in the cuffed arm (2-way ANOVA interaction-effect; P < 0.01). We found that forearm CVC at 42 and 44 °C was significantly lower in the uncuffed arm following 8-weeks of cycle training (P < 0.01), whereas no changes were apparent in the contralateral cuffed arm (P = 0.77, interaction-effect P = 0.01). Lower limb exercise training in healthy young men leads to lower CVC-responses to a local heating stimulus, an adaptation mediated, at least partly, by a mechanism related to episodic increases in skin blood flow and/or skin temperature.

  18. BRAF mutations in cutaneous melanoma: no correlation with histological prognostic factors or overall survival Mutações BRAF em melanomas cutâneos: nenhuma correlação com fatores prognósticos e sobrevida global

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    Juliana Elizabeth Jung

    2010-12-01

    Full Text Available INTRODUCTION: Molecular biology techniques allow identification of molecular markers such as BRAF and c-Kit gene mutations in melanomas. Studies on genetic alterations in melanomas of South-American patients are sparse. OBJECTIVES: To identify the incidence of BRAF and c-Kit gene mutations in primary cutaneous melanomas in Brazilian patients and to evaluate pathogenetic and prognostic implications of these mutations correlating them with clinical and histopathological data. MATERIAL AND METHODS: Ninety-six surgical specimens of primary cutaneous melanoma and 15 corresponding metastasis were analyzed using TaqMan Real-Time polymerase chain reaction (PCR assays. RESULTS: In comparison with the medical literature, a relatively low frequency of BRAF mutation in primary (39% and metastatic (40% melanomas and complete absence of c-Kit gene mutations were demonstrated. BRAF mutations arose at an early stage during melanoma progression and were not involved in the transition of thin ( 1 mm melanomas. BRAF mutations are related to patients' younger age and to the pattern of sun exposure, although there was no correlation with any histological prognostic factor or overall survival. CONCLUSION: The identification of both BRAF and c-Kit mutation is not a suitable prognostic indicator in the Brazilian population. Moreover, the relatively low frequency of BRAF mutations brings into question if it actually plays a key role in melanoma pathogenesis.INTRODUÇÃO: Técnicas de biologia molecular permitem a identificação de marcadores moleculares como mutações dos genes BRAF e c-Kit em melanomas. Estudos de alterações genéticas em pacientes sul-americanos são escassos. OBJETIVOS: Identificar a incidência de mutações dos genes BRAF e c-Kit em melanomas cutâneos primários em uma série de pacientes brasileiros e avaliar as implicações patogenéticas e prognósticas dessas mutações, correlacionando-as com dados clínicos e histopatológicos. MATERIAL

  19. Cutaneous malignant melanoma and exposure to sunlamps or sunbeds: an EORTC multicenter case-control study in Belgium, France and Germany. EORTC Melanoma Cooperative Group.

    Science.gov (United States)

    Autier, P; Doré, J F; Lejeune, F; Koelmel, K F; Geffeler, O; Hille, P; Cesarini, J P; Lienard, D; Liabeuf, A; Joarlette, M

    1994-09-15

    The study objective was to assess whether exposure to sunlamps and sunbeds represents a risk factor for cutaneous malignant melanoma (CMM). A 1-to-1 unmatched case-control study was conducted among subjects 20 years old or more with naturally non-pigmented skin in Germany, France and Belgium. A total of 420 consecutive patients with CMM diagnosed from 1 January 1991 onward were derived from hospital registers; 447 controls with no history of skin cancer were chosen at random in the same municipality as the cases. Exposure to sunlamps or sunbeds starting before 1980 is associated with a crude estimated risk of CMM of 2.71 (95% CI: 1.06-7.78) for at least 10 hr of accumulated exposure. This risk is of 2.12 (95% CI: 0.84-5.37) after adjustment for age, sex, hair colour and average number of holiday weeks each year in sunny resorts. Subjects who experienced skin-burn due to sunlamps or sunbeds, and who had accumulated at least 10 hr of exposure, displayed a crude estimated CMM risk of 4.47 (95% CI: 1.45-13.7), which rose to 8.97 (95% CI: 2.10-38.6) for those who exposed their skin for tanning purposes. The risk associated with skin-burn is only marginally modified after multiple adjustments for host characteristics and recreational exposure to sunlight. Apparently, sunlamps and sunbeds share the increased risk of CMM, which seems to concentrate in subjects exhibiting hazardous behaviour towards ultraviolet radiation sources. However, although it is reasonable to believe that high doses of pure ultraviolet A radiation can be dangerous, this is not firmly established by this study. Most exposures to ultraviolet A tanning devices began after 1980; therefore, epidemiologic studies have difficulty in revealing any increase in risk of CMM starting after 1980 because of the latent period between exposure and occurrence of melanoma. Public health authorities should have a cautious approach towards the rapidly developing fashion of tanning under sunlamps or sunbeds.

  20. 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.

  1. Chimeric L2-Based Virus-Like Particle (VLP) Vaccines Targeting Cutaneous Human Papillomaviruses (HPV)

    Science.gov (United States)

    Huber, Bettina; Schellenbacher, Christina; Shafti-Keramat, Saeed; Jindra, Christoph; Christensen, Neil

    2017-01-01

    Common cutaneous human papillomavirus (HPV) types induce skin warts, whereas species beta HPV are implicated, together with UV-radiation, in the development of non-melanoma skin cancer (NMSC) in immunosuppressed patients. Licensed HPV vaccines contain virus-like particles (VLP) self-assembled from L1 major capsid proteins that provide type-restricted protection against mucosal HPV infections causing cervical and other ano-genital and oro-pharyngeal carcinomas and warts (condylomas), but do not target heterologous HPV. Experimental papillomavirus vaccines have been designed based on L2 minor capsid proteins that contain type-common neutralization epitopes, to broaden protection to heterologous mucosal and cutaneous HPV types. Repetitive display of the HPV16 L2 cross-neutralization epitope RG1 (amino acids (aa) 17–36) on the surface of HPV16 L1 VLP has greatly enhanced immunogenicity of the L2 peptide. To more directly target cutaneous HPV, L1 fusion proteins were designed that incorporate the RG1 homolog of beta HPV17, the beta HPV5 L2 peptide aa53-72, or the common cutaneous HPV4 RG1 homolog, inserted into DE surface loops of HPV1, 5, 16 or 18 L1 VLP scaffolds. Baculovirus expressed chimeric proteins self-assembled into VLP and VLP-raised NZW rabbit immune sera were evaluated by ELISA and L1- and L2-based pseudovirion (PsV) neutralizing assays, including 12 novel beta PsV types. Chimeric VLP displaying the HPV17 RG1 epitope, but not the HPV5L2 aa53-72 epitope, induced cross-neutralizing humoral immune responses to beta HPV. In vivo cross-protection was evaluated by passive serum transfer in a murine PsV challenge model. Immune sera to HPV16L1-17RG1 VLP (cross-) protected against beta HPV5/20/24/38/96/16 (but not type 76), while antisera to HPV5L1-17RG1 VLP cross-protected against HPV20/24/96 only, and sera to HPV1L1-4RG1 VLP cross-protected against HPV4 challenge. In conclusion, RG1-based VLP are promising next generation vaccine candidates to target cutaneous

  2. Chimeric L2-Based Virus-Like Particle (VLP Vaccines Targeting Cutaneous Human Papillomaviruses (HPV.

    Directory of Open Access Journals (Sweden)

    Bettina Huber

    Full Text Available Common cutaneous human papillomavirus (HPV types induce skin warts, whereas species beta HPV are implicated, together with UV-radiation, in the development of non-melanoma skin cancer (NMSC in immunosuppressed patients. Licensed HPV vaccines contain virus-like particles (VLP self-assembled from L1 major capsid proteins that provide type-restricted protection against mucosal HPV infections causing cervical and other ano-genital and oro-pharyngeal carcinomas and warts (condylomas, but do not target heterologous HPV. Experimental papillomavirus vaccines have been designed based on L2 minor capsid proteins that contain type-common neutralization epitopes, to broaden protection to heterologous mucosal and cutaneous HPV types. Repetitive display of the HPV16 L2 cross-neutralization epitope RG1 (amino acids (aa 17-36 on the surface of HPV16 L1 VLP has greatly enhanced immunogenicity of the L2 peptide. To more directly target cutaneous HPV, L1 fusion proteins were designed that incorporate the RG1 homolog of beta HPV17, the beta HPV5 L2 peptide aa53-72, or the common cutaneous HPV4 RG1 homolog, inserted into DE surface loops of HPV1, 5, 16 or 18 L1 VLP scaffolds. Baculovirus expressed chimeric proteins self-assembled into VLP and VLP-raised NZW rabbit immune sera were evaluated by ELISA and L1- and L2-based pseudovirion (PsV neutralizing assays, including 12 novel beta PsV types. Chimeric VLP displaying the HPV17 RG1 epitope, but not the HPV5L2 aa53-72 epitope, induced cross-neutralizing humoral immune responses to beta HPV. In vivo cross-protection was evaluated by passive serum transfer in a murine PsV challenge model. Immune sera to HPV16L1-17RG1 VLP (cross- protected against beta HPV5/20/24/38/96/16 (but not type 76, while antisera to HPV5L1-17RG1 VLP cross-protected against HPV20/24/96 only, and sera to HPV1L1-4RG1 VLP cross-protected against HPV4 challenge. In conclusion, RG1-based VLP are promising next generation vaccine candidates to target

  3. Incidence, Survival, and Mortality of Malignant Cutaneous Melanoma in Wisconsin, 1995-2011.

    Science.gov (United States)

    Peterson, Molly; Albertini, Mark R; Remington, Patrick

    2015-10-01

    To assess trends in malignant melanoma incidence, survival, and mortality in Wisconsin. Incidence data for Wisconsin were obtained from the Wisconsin Cancer Reporting System Bureau of Health Information using Wisconsin Interactive Statistics on Health, while incidence data for the United States were obtained from the Surveillance, Epidemiology, and End Results system (SEER). The mortality to incidence ratio [1 - (mortality/incidence)] was used as a proxy to estimate relative 5-year survival in Wisconsin, while observed 5-year survival rates for the United States were obtained from SEER. Mortality data for both Wisconsin and the United States were extracted using the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research. During the past decade, malignant melanoma incidence rates increased 57% in Wisconsin (from 12.1 to 19.0 cases per 100,000) versus a 33% increase (from 20.9 to 27.7 cases per 100,000) in the United States during the same time period. The greatest Wisconsin increase in incidence was among women ages 45-64 years and among men ages 65 years and older. Overall relative percent difference in 5-year survival in Wisconsin rose 10% (from 77% to 85%) and was unchanged (82%) for the United States. Wisconsin overall mortality rates were unchanged at 2.8 deaths per 100,000, compared to a 10% increase in the United States (from 3.1 to 3.4 deaths per 100,000). Wisconsin mortality rates improved for women ages 45-64 and for men ages 25-44. Despite improvements in malignant melanoma survival rates, increases in incidence represent a major public health challenge for physicians and policymakers.

  4. 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

    and the national Melanoma Quality Register. Geographic and socioeconomic differences in incidence per stage at diagnosis were mapped and correlated to excess mortality. Results Disease mapping based on 9743 cases in 99 municipalities and 20 metropolitan districts showed marked, regional disparities in stage......-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...

  5. Influence of having a home garden on personal UVR exposure behavior and risk of cutaneous malignant melanoma in Denmark.

    Science.gov (United States)

    Idorn, Luise Winkel; Thieden, Elisabeth; Philipsen, Peter Alshede; Wulf, Hans Christian

    2013-03-15

    There is a need for more knowledge concerning the association of higher socioeconomic status (SES) with cutaneous malignant melanoma (CMM). Having a home garden is associated with a higher SES. We aimed to study the influence of having a home garden on UVR exposure behavior and risk of CMM. Register study: We collected information from Danish national registers about gender, age, type of home and CMM among persons aged 16-75 in 2002-2006. A total of 5,118 CMM cases were identified. Risk of CMM of the trunk was increased by 46% (p personal electronic UVR dosimeters measuring time-stamped UVR doses continuously and filled in sun exposure diaries. While no difference was found in estimated yearly UVR dose between groups, participants with a home garden had more days exposing shoulders or upper body, and upper extremities outdoors than those without a garden (p = 0.026, age adjusted). People with a home garden are at increased risk of CMM of the trunk and extremities-body sites that seems to be exposed to a higher extent among people with home gardens. People with a higher SES are more likely to have a home garden. This may partly explain the well-known association of higher SES with CMM incidence. Copyright © 2012 UICC.

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

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    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

  7. Prospective Validation of Molecular Prognostic Markers in Cutaneous Melanoma: A Correlative Analysis of E1690.

    Science.gov (United States)

    Kashani-Sabet, Mohammed; Nosrati, Mehdi; Miller, James R; Sagebiel, Richard W; Leong, Stanley P L; Lesniak, Andrew; Tong, Schuyler; Lee, Sandra J; Kirkwood, John M

    2017-11-15

    Purpose: To validate the prognostic impact of combined expression levels of three markers (SPP1, RGS1, and NCOA3) in melanoma specimens from patients enrolled in the E1690 clinical trial of high-dose or low-dose IFNα-2b versus observation.Experimental Design: Tissue was available from 248 patients. Marker expression was determined by digital imaging of immunohistochemically stained slides. The prognostic impact of each marker was first assessed by recording its expression value relative to the median. A multimarker index was then developed to combine marker expression levels by counting for each patient the number of markers with high expression. The impact of the multimarker index on relapse-free survival (RFS) and overall survival (OS) was assessed using Kaplan-Meier analysis, and both univariate and multivariate Cox regression analyses.Results: By Kaplan-Meier analysis, high multimarker expression scores were significantly predictive of RFS (P melanoma in a prospectively collected cohort. Clin Cancer Res; 23(22); 6888-92. ©2017 AACR. ©2017 American Association for Cancer Research.

  8. Ultraviolet radiation A-induced precursors of cutaneous melanoma in Monodelphis domestica.

    Science.gov (United States)

    Ley, R D

    1997-09-01

    Two groups of 30 dorsally shaved opossums (Monodelphis domestica) were exposed three times per week for 81 weeks to 250 J/m2 of UV radiation from FS40 sunlamps (approximately 150 J/m2 of UV radiation B; UV-B), or to 2.5 x 10(4) J/m2 of UV radiation A (UV-A) from filtered F40BLB fluorescent lamps (black lights). Animals were monitored for the appearance of nonmelanoma skin tumors (NMSTs) and melanocytic hyperplasia (MH). After 81 weeks of exposures, the prevalence of NMSTs was 71% and 4% for animals exposed to UV-B and UV-A, respectively. The difference between the treatment groups was statistically significant (P 0.05). Thus, a dose of UV-A that was relatively ineffective in producing NMSTs, compared to UV-B, was as effective as UV-B in the induction of MH. If, as shown previously, MH is the precursor lesion for melanoma in this model, these results suggest that the action spectra for the induction of melanoma and NMSTs in the opossum are different.

  9. Wide versus narrow excision margins for high-risk, primary cutaneous melanomas: long-term follow-up of survival in a randomised trial.

    Science.gov (United States)

    Hayes, Andrew J; Maynard, Lauren; Coombes, Gillian; Newton-Bishop, Julia; Timmons, Michael; Cook, Martin; Theaker, Jeffrey; Bliss, Judith M; Thomas, J Meirion

    2016-02-01

    The necessary margin of excision for cutaneous melanomas greater than 2 mm in thickness is controversial. At a median follow-up of 5 years, findings from our previously published randomised trial of narrow (1 cm) versus wide (3 cm) excision margins in patients with thick cutaneous melanomas showed that narrow margins were associated with an increased frequency of locoregional relapse, but no significant difference in overall survival was apparent. We now report a long-term survival analysis of that trial. We did a randomised, open-label multicentre trial in 59 hospitals--57 in the UK, one in Poland, and one in South Africa. Patients with one primary localised cutaneous melanoma greater than 2 mm in Breslow thickness on the trunk or limbs (excluding palms or soles) were randomly assigned (1:1) centrally to receive surgery with either a 1 cm or 3 cm excision margin following an initial surgery. The randomisation lists were generated with random permuted blocks and stratified by centre and extent of initial surgery. The endpoints of this analysis were overall survival and melanoma-specific survival. Analyses were done in the intention-to-treat population. This trial was not registered because it predated mandatory trial registration. Between Dec 16, 1992, and May 22, 2001, we randomly assigned 900 patients to surgery with either a 1 cm excision margin (n=453) or a 3 cm excision margin (n=447). At a median follow-up of 8·8 years (106 months [IQR 76-135], 494 patients had died, with 359 of these deaths attributed to melanoma. 194 deaths were attributed to melanoma in the 1 cm group compared with 165 in the 3 cm group (unadjusted hazard ratio [HR] 1·24 [95% CI 1·01-1·53]; p=0·041). Although a higher number of deaths overall occurred in the 1 cm group compared with the 3 cm group (253 vs 241), the difference was not significant (unadjusted HR 1·14 [95% CI 0·96-1·36]; p=0·14). Surgical complications were reported in 35 (8%) patients in the 1 cm excision margin

  10. Improvement of Genetic Testing for Cutaneous Melanoma in Countries With Low to Moderate Incidence: The Rule of 2 vs the Rule of 3.

    Science.gov (United States)

    Delaunay, Juliette; Martin, Ludovic; Bressac-de Paillerets, Brigitte; Duru, Gerard; Ingster, Olivier; Thomas, Luc

    2017-11-01

    Genetic testing for melanoma-prone mutation in France, a country with low to moderate incidence of melanoma, is proposed in cases with 2 invasive cutaneous melanomas and/or related cancers in the same patient, or in first- or second-degree relatives (rule of 2). In preclinical studies, these rules led to disclosure of mutation(s) in more than 10% of these families, the threshold widely accepted to justify genetic testing for cancers. To reconsider these criteria in a general population testing of patients. This was a retrospective study, performed from 2004 to 2015 at Angers and Lyons University Hospitals, of a cohort of 1032 patients who underwent genetic testing. Frequency of mutation in high (CDKN2A, CDK4, and BAP1) and intermediate (MITF) susceptibility genes; statistical effect of histologic subtype, age, dysplastic nevi syndrome, and associated cancers on mutation rate; and evaluation of cases with anamnestic uncertainty. The mutation rate was 67 of 1032 patients (6.5%). Their mean (SD) age was 54.5 (14.2) years [range, 18-89 years], and 543 (52.6%) were men. It increased to 38 of 408 patients (9.3%) when applying a rule of 3 (those with ≥3 primary melanomas or genetically related cancers) (P = .68) and to 27 of 150 patients (18.0%) with a rule of 4 (4 primary melanomas or related cancer) (P mutated-families when applying the rule of 3 from 14 of 43 to 7 of 43. Anamnestic uncertainty, found in 88 families (8.5%), if excluded, would have led us to withdraw of only 21 cases (23.8%), and only 1 mutation would have been missed. We propose using the rule of 3 to recommend genetic testing in France and countries with low to moderate incidence of melanoma, except in families and patients with a first melanoma occurrence before age 40 years in whom the rule of 2 could be maintained.

  11. Detection of Melanoma Metastases in Resected Human Lymph Nodes by Noninvasive Multispectral Photoacoustic Imaging

    NARCIS (Netherlands)

    Langhout, Gerrit Cornelis; Grootendorst, Diederik; Nieweg, Omgo Edo; Wilhelmus, Michel; Wouters, Jacobus Maria; van der Hage, Jos Alexander; Jose, Jithin; van Boven, Hester; Steenbergen, Wiendelt; Manohar, Srirang; Ruers, Theo J.M.

    2014-01-01

    Objective. Sentinel node biopsy in patients with cutaneous melanoma improves staging, provides prognostic information, and leads to an increased survival in node-positive patients. However, frozen section analysis of the sentinel node is not reliable and definitive histopathology evaluation requires

  12. First Experiences of Photoacoustic Imaging for Detection of Melanoma Metastases in Resected Human Lymph Nodes

    NARCIS (Netherlands)

    Grootendorst, Diederik; Jose, J.; Wouters, M.W.; van Boven, H.H.; van der Hage, J.A.; ten Haken, Bernard; van Leeuwen, Ton; Steenbergen, Wiendelt; Manohar, Srirang; Ruers, Theo J.M.

    2012-01-01

    Background and Objective: Excision and histological assessment of the first draining node (sentinel lymph node) is a frequently used method to assess metastatic lymph node involvement related to cutaneous melanoma. Due to the time required for accurate histological assessment, nodal status is not

  13. 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

    if there is a difference in nodal recurrence and survival after radical, modified or selective neck dissection. METHODS: A total of 57 patients treated for regional meta-stases of head and neck melanoma were analysed retrospectively with respect to type of neck dissection, use of sentinel node biopsy, nodal recurrence...... deposits in sentinel nodes had a better survival than patients with clinically palpable nodes (five-year survival rate: 70% versus 36%, p = 0.008). CONCLUSION: The extent of neck dissection does not significantly influence the rate of recurrence or survival. This study indicates that there is a survival...... benefit for patients who undergo completion lymph node dissection following a positive sentinel node biopsy. FUNDING: not relevant. TRIAL REGISTRATION: not relevant....

  14. 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

    if there is a difference in nodal recurrence and survival after radical, modified or selective neck dissection. METHODS: A total of 57 patients treated for regional meta-stases of head and neck melanoma were analysed retrospectively with respect to type of neck dissection, use of sentinel node biopsy, nodal recurrence...... > 0.05). No significant difference in five-year survival was observed between the dissection types (56% for radical node dissection, 61% for modified radical node dissection and 48% for selective node dissection, p = 0.613). Multivariate and univariate analysis revealed that patients with metastatic...... deposits in sentinel nodes had a better survival than patients with clinically palpable nodes (five-year survival rate: 70% versus 36%, p = 0.008). CONCLUSION: The extent of neck dissection does not significantly influence the rate of recurrence or survival. This study indicates that there is a survival...

  15. Quality of Life Following Sentinel Node Biopsy for Primary Cutaneous Melanoma: Health Economic Implications.

    Science.gov (United States)

    Morton, Rachael L; Tran, Anh; Vessey, Johan Yusof; Rowbotham, Nick; Winstanley, Julie; Shannon, Kerwin; Spillane, Andrew J; Stretch, Jonathan; Thompson, John F; Saw, Robyn P-M

    2017-08-01

    Sentinel node biopsy (SNB) is commonly performed in contemporary melanoma management, however there is a paucity of long-term quality of life (QoL) estimates required for economic evaluation of this treatment. A single-center, prospective, cross-sectional study of adults with American Joint Committee on Cancer stage I/II/IIIA melanoma of the limbs, trunk, or neck who had undergone wide excision and SNB, but not complete regional node dissection, was undertaken. Limb volume was measured using perometry, with lymphedema defined as a ≥10% volume increase in the ipsilateral limb compared with the contralateral limb. The Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire measured QoL. Associations between patient and treatment characteristics were assessed using linear regression. Among 694 patients (median time from SNB of 37 months), 14 (2%) had objectively measured lymphedema (i.e. an increase in limb volume of ≥10%). Of 687 stage I/II patients with complete QoL data, the mean weighted QoL was 0.745 (standard deviation 0.04) on a 0-1 scale (i.e. death to full health). In multivariable analysis, weighted QoL was 0.0004 higher for each year of increasing age (p = 0.001); 0.011 lower for females (p = 0.001), 0.018 lower following post-SNB limb trauma (p = 0.002); 0.252 lower for patients who perceived a large increase in limb size (p = 0.015); and 0.027 lower with self-reported difficulty in walking, running, or climbing stairs (p = 0.043). Our data suggest that very few patients treated at our institution had lymphedema in the long-term following SNB, with weighted QoL strongly associated with perceived rather than actual changes in limb size.

  16. 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

    Directory of Open Access Journals (Sweden)

    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

  17. [Melanoma].

    Science.gov (United States)

    Saida, Toshiaki

    2006-10-01

    The definition of the TNM classification and staging system of malignant melanoma have been fundamentally revised. Moreover, several clinical guidelines for the management of this neoplasm were recently proposed. Advances in surgical procedures are excision of primary lesions with narrow margin and introduction of sentinel node biopsy, which contribute to maintain the good quality of life of patients. The significance of high-dose interferon-alpha as adjuvant therapy is still controversial. No effective chemotherapy or biotherapy has been established to date, however, interesting new findings were recently reported in the fields of immunotherapy and molecular targeting therapy.

  18. Akt Inhibitor MK2206 and Hydroxychloroquine in Treating Patients With Advanced Solid Tumors, Melanoma, Prostate or Kidney Cancer

    Science.gov (United States)

    2017-12-05

    Adult Solid Neoplasm; Hormone-Resistant Prostate Cancer; Recurrent Melanoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; 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; Stage IV Prostate Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7

  19. Melanoma cells treated with GGTI and IFN-gamma allow murine vaccination and enhance cytotoxic response against human melanoma cells.

    Directory of Open Access Journals (Sweden)

    Guillaume Sarrabayrouse

    Full Text Available BACKGROUND: Suboptimal activation of T lymphocytes by melanoma cells is often due to the defective expression of class I major histocompatibility antigens (MHC-I and costimulatory molecules. We have previously shown that geranylgeranyl transferase inhibition (done with GGTI-298 stimulates anti-melanoma immune response through MHC-I and costimulatory molecule expression in the B16F10 murine model [1]. METHODOLOGY/PRINCIPAL FINDINGS: In this study, it is shown that vaccination with mIFN-gand GGTI-298 pretreated B16F10 cells induces a protection against untreated tumor growth and pulmonary metastases implantation. Furthermore, using a human melanoma model (LB1319-MEL, we demonstrated that in vitro treatment with hIFN-gamma and GGTI-298 led to the up regulation of MHC-I and a costimulatory molecule CD86 and down regulation of an inhibitory molecule PD-1L. Co-culture experiments with peripheral blood mononuclear cells (PBMC revealed that modifications induced by hIFN-gamma and GGTI-298 on the selected melanoma cells, enables the stimulation of lymphocytes from HLA compatible healthy donors. Indeed, as compared with untreated melanoma cells, pretreatment with hIFN-gamma and GGTI-298 together rendered the melanoma cells more efficient at inducing the: i activation of CD8 T lymphocytes (CD8+/CD69+; ii proliferation of tumor-specific CD8 T cells (MelanA-MART1/TCR+; iii secretion of hIFN-gamma; and iv anti-melanoma specific cytotoxic cells. CONCLUSIONS/SIGNIFICANCE: These data indicate that pharmacological treatment of melanoma cell lines with IFN-gamma and GGTI-298 stimulates their immunogenicity and could be a novel approach to produce tumor cells suitable for vaccination and for stimulation of anti-melanoma effector cells.

  20. 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.

  1. Cutaneous furuncular myiasis: Human infestation by the botfly

    Science.gov (United States)

    Jacobs, Bryan; Brown, David L

    2006-01-01

    Dermatobia hominis, the botfly, is indigenous to Central and South America. Its usual host is a mammal, often a horse or cow. Cutaneous furuncular myiasis, human infestation by the botfly, has rarely been reported. Symptoms of infestation include a locally painful, firm furuncular lesion, often with a centrally located pore. Due to their infrequent occurrence, these lesions are often misdiagnosed as cellulitis, leishmaniasis, furunculosis, staphylococcal boil, insect bite or sebaceous cyst – conditions with similar presentations. The present case reiterates the need to think of ‘zebras’ when hearing ‘hoof beats’ that may have originated in a different land. PMID:19554228

  2. Validity of ultrasound-guided aspiration needle biopsy in the diagnosis of micrometastases in sentinel lymph nodes in patients with cutaneous melanoma

    Directory of Open Access Journals (Sweden)

    Šijan Goran

    2016-01-01

    Full Text Available Background/Aim. Cutaneous melanoma is one of the most aggressive solid cancers, that develops local, regional and distant metastases. The presence of metastases in lymph nodes is in correlation with Breslow tumor thickness. According to various researches, in melanoma with more than 4 mm Breslow thickness, lymph node micrometastases can be found in 60-70% of cases. Sentinel lymph nodes biopsy is a diagnostic procedure for lymph node micrometastasis detection, which is necessary for disease staging. In recent studies, ultrasound-guided fine needle aspiration with cytology (US FNAC of the sentinel lymph node was used as less invasive procedure, but is not accepted as the standard procedure. The goal of this work was to define sensitivity, specification and precision of the ultrasound-guided fine needle aspiration method in comparison with standard sentinel lymph node biopsy. Methods. After obtaining the Ethics Committee’s permission, from 2012 to 2014 a total of 60 patients with cutaneous melanoma were enrolled, and divided into three groups: group I with thin melanoma, group II with intermediate thickness melanoma and group III with thick melanoma. The presence of micrometastases in sentinel regional lymph nodes was analyzed by US FNAC. The results obtained were compared to sentinel lymph nodes biopsy (SLNB results. The golden standard for calculating the specific, sensitive and precise characteristics of the method of US FNAC of sentinel lymph nodes was histopathologic lymph node examination of sentinel lymph nodes acquired through biopsy. Results. Detection rate of US FNAC was 0% in the group I, 5% in the group II and 30% in the group III. SLNB detection rates were: 10% in the group I, 15% in the group II, and 45% in the group III. In melanoma thicker than 4 mm, 15% of the patients were false negative by US FNAC. The sensitivity of US FNAC for all the patients was 50%: in the group I, 0%; in the group II, 33.3%; and in the group III, 66

  3. Melanoma genetics.

    Science.gov (United States)

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

    2016-01-01

    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 heritable melanoma risk genes is an important component of disease occurrence. Susceptibility for some families is due to mutation in one of the known high penetrance melanoma predisposition genes: CDKN2A, CDK4, BAP1, POT1, ACD, TERF2IP and TERT. However, despite such mutations being implicated 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 in melanoma families at rates greater than expected by chance. The most extensively documented association is between CDKN2A germ line mutations and pancreatic cancer, and a cancer syndrome including cutaneous melanoma, uveal melanoma and mesothelioma has been proposed for BAP1 germ line mutations. Other medium to high penetrance melanoma predisposition genes have been associated with renal cell carcinoma (MITF, BAP1) and glioma (POT1). These associations between melanoma and other cancers hint at the possibility of common pathways for oncogenesis, and better knowledge of these pathways may improve understanding of the genetic basis underpinning familial melanoma. It is likely that 'melanoma' risk genes will impact on mutation screening and genetic counselling not only for melanoma but

  4. Correlation of histopathological patterns in cutaneous melanoma with BRAF mutations Correlação de padrões histopatológicos de melanomas cutâneos com mutações BRAF

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    Juliana Elizabeth Jung

    2010-12-01

    Full Text Available INTRODUCTION: Mutations on BRAF gene located on chromosome 7q are the most frequently found in cutaneous melanomas (60%-80%. The only study correlating histopathological patterns of cutaneous melanomas with the presence of BRAF mutations was undertaken by Viros et al. in 2008. The authors observed that morphological features of melanomas are associated with BRAF mutations. OBJECTIVES: To correlate histopathological patterns in cutaneous melanoma with the presence of BRAF mutations in order to corroborate the results of the study performed by Viros et al. METHODS: Paraffin embedded surgical specimens of 20 primary cutaneous melanomas with BRAF mutation and 20 specimens without BRAF mutation were evaluated independently by two dermatologists that carried out a blind experiment. The features analyzed were nesting, circumscription, presence of isolated melanocytes in the lesion, size and shape of neoplastic cells, and tumor cell pigmentation. RESULTS: "Nesting" was the most prevalent variable for the determination of melanomas with BRAF mutations according to both observers (r = 0.46; p = 0.04. CONCLUSION: As far as mutational status is concerned, it was not possible to confirm any predictive value for histopathological patterns such as circumscription, presence of isolated melanocytes in the lesion and cytological features. Difficulties in the interpretation of some histological criteria were demonstrated by the variation in the observers' conclusions. It is difficult to state if genetic alterations such as BRAF mutations may serve as biomarkers for melanoma classification.INTRODUÇÃO: Mutações do gene BRAF localizado no cromossomo 7q são as mais frequentemente encontradas em melanomas cutâneos (60%-80%. O único estudo que correlacionou padrões histopatológicos de melanomas cutâneos com a presença de mutações BRAF foi realizado por Viros et al., em 2008, que observaram que características morfológicas de melanomas estavam associadas a

  5. Epigenetic impacts of ascorbate on human metastatic melanoma cells

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    Sascha eVenturelli

    2014-08-01

    Full Text Available In recent years, increasing evidence has emerged demonstrating that high-dose ascorbate bears cytotoxic effects on cancer cells in vitro and in vivo, making ascorbate a pro-oxidative drug that catalyzes hydrogen peroxide production in tissues instead of acting as a radical scavenger. This anticancer effect of ascorbate is HIF-1α- and O2–dependent. However, whether the intracellular mechanisms governing this effect are modulated by epigenetic phenomena remains unknown. We treated human melanoma cells with physiological (200 µM or pharmacological (8 mM ascorbate for 1 h to record the impact on DNA methyltransferase (DNMT-activity, histone deacetylases (HDACs and microRNA expression after 12 h. The results were analyzed with the MIRUMIR online tool that estimates the power of microRNA to serve as potential biomarkers to predict survival of cancer patients.FACS cell cycle analyses showed that 8 mM ascorbate shifted BLM melanoma cells towards the sub-G1 fraction starting at 12 h after an initial primary G2/M arrest, indicative for secondary apoptosis induction. In pharmacological doses ascorbate inhibited the DNMT-activity in nuclear extracts of MeWo and BLM melanoma cells, but did not inhibit human HDAC enzymes of classes I, II and IV. The expression of 151 microRNAs was altered 12 h after ascorbate treatment of BLM cells in physiological or pharmacological doses. Pharmacological doses up-regulated 32 microRNAs (≥4-fold mainly involved in tumor suppression and drug resistance in our preliminary microRNA screening array. The most prominently up-regulated microRNAs correlated with a significantly increased overall survival of breast cancer- or nasopharyngeal carcinoma patients of the MIRUMIR database with high expression of the respective microRNA. Our results suggest a possible epigenetic signature of pharmacological doses of ascorbate in human melanoma cells and support further pre-clinical and possibly even clinical evaluation of ascorbate

  6. Irreversible electroporation of human primary uveal melanoma in enucleated eyes.

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    Yossi Mandel

    Full Text Available Uveal melanoma (UM is the most common primary intraocular tumor in adults and is characterized by high rates of metastatic disease. Although brachytherapy is the most common globe-sparing treatment option for small- and medium-sized tumors, the treatment is associated with severe adverse reactions and does not lead to increased survival rates as compared to enucleation. The use of irreversible electroporation (IRE for tumor ablation has potential advantages in the treatment of tumors in complex organs such as the eye. Following previous theoretical work, herein we evaluate the use of IRE for uveal tumor ablation in human ex vivo eye model. Enucleated eyes of patients with uveal melanoma were treated with short electric pulses (50-100 µs, 1000-2000 V/cm using a customized electrode design. Tumor bioimpedance was measured before and after treatment and was followed by histopathological evaluation. We found that IRE caused tumor ablation characterized by cell membrane disruption while sparing the non-cellular sclera. Membrane disruption and loss of cellular capacitance were also associated with significant reduction in total tumor impedance and loss of impedance frequency dependence. The effect was more pronounced near the pulsing electrodes and was dependent on time from treatment to fixation. Future studies should further evaluate the potential of IRE as an alternative method of uveal melanoma treatment.

  7. 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.

  8. Primary glandular melanoma of male breast with nodal metastasis

    OpenAIRE

    Jayabal Pandiaraja

    2016-01-01

    Malignant melanoma is a malignancy that develops from melanocytes. Breast is an uncommon site for malignant melanoma. Melanoma of the breast occurs in various situations such as primary melanoma of breast skin, metastatic melanoma of breast, in-transit metastasis to the breast, and primary glandular breast melanoma. Most of the melanoma breast either cutaneous melanoma or metastatic melanoma. Primary glandular melanoma of male breast with nodal involvement is rarely reported compared to prima...

  9. MC1R variants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians: a pooled-analysis from the M-SKIP project.

    Science.gov (United States)

    Pasquali, Elena; García-Borrón, José C; Fargnoli, Maria Concetta; Gandini, Sara; Maisonneuve, Patrick; Bagnardi, Vincenzo; Specchia, Claudia; Liu, Fan; Kayser, Manfred; Nijsten, Tamar; Nagore, Eduardo; Kumar, Rajiv; Hansson, Johan; Kanetsky, Peter A; Ghiorzo, Paola; Debniak, Tadeusz; Branicki, Wojciech; Gruis, Nelleke A; Han, Jiali; Dwyer, Terry; Blizzard, Leigh; Landi, Maria Teresa; Palmieri, Giuseppe; Ribas, Gloria; Stratigos, Alexander; Council, M Laurin; Autier, Philippe; Little, Julian; Newton-Bishop, Julia; Sera, Francesco; Raimondi, Sara

    2015-02-01

    The MC1R gene is a key regulator of skin pigmentation. We aimed to evaluate the association between MC1R variants and the risk of sporadic cutaneous melanoma (CM) within the M-SKIP project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. Data included 5,160 cases and 12,119 controls from 17 studies. We calculated a summary odds ratio (SOR) for the association of each of the nine most studied MC1R variants and of variants combined with CM by using random-effects models. Stratified analysis by phenotypic characteristics were also performed. Melanoma risk increased with presence of any of the main MC1R variants: the SOR for each variant ranged from 1.47 (95%CI: 1.17-1.84) for V60L to 2.74 (1.53-4.89) for D84E. Carriers of any MC1R variant had a 66% higher risk of developing melanoma compared with wild-type subjects (SOR; 95%CI: 1.66; 1.41-1.96) and the risk attributable to MC1R variants was 28%. When taking into account phenotypic characteristics, we found that MC1R-associated melanoma risk increased only for darker-pigmented Caucasians: SOR (95%CI) was 3.14 (2.06-4.80) for subjects with no freckles, no red hair and skin Type III/IV. Our study documents the important role of all the main MC1R variants in sporadic CM and suggests that they have a direct effect on melanoma risk, independently on the phenotypic characteristics of carriers. This is of particular importance for assessing preventive strategies, which may be directed to darker-pigmented Caucasians with MC1R variants as well as to lightly pigmented, fair-skinned subjects. © 2014 UICC.

  10. Clinical significance of BRAF V600E mutational status in capsular nevi of sentinel lymph nodes in patients with primary cutaneous melanoma.

    Science.gov (United States)

    Siroy, Alan E; Aung, Phyu P; Torres-Cabala, Carlos A; Tetzlaff, Michael T; Nagarajan, Priyadharsini; Milton, Denái R; Curry, Jonathan L; Ivan, Doina; Prieto, Victor G

    2017-01-01

    Capsular nevi (CN) are clusters of benign melanocytes situated in the capsule of lymph nodes and occur in up to 20% of lympadenectomy specimens. The molecular profile of CN in relation to prognostic parameters in patients with primary cutaneous melanoma (PCM) has not been previously investigated. We assessed BRAF V600E mutation by immunohistochemistry (IHC) in the CN of sentinel lymph nodes (SLN) in PCM patients and correlated the findings with demographic characteristics, PCM histopathologic and molecular features, and clinical outcome parameters. Seventy-eight cases of CN involving SLN of PCM patients were evaluated for BRAF V600E mutation by IHC. The results were correlated with patient demographics, PCM histopathologic and molecular features, and outcome measures. Thirty-six (46%) of 78 CN cases expressed BRAF V600E mutation by IHC. Nineteen (53%) of those BRAF-positive CN cases were from patients with at least American Joint Committee on Cancer stage II melanoma, whereas 62% of BRAF-negative CN cases (26/42) were from patients with stage I melanoma (P = .013). Twelve (33%) of the 36 BRAF-positive CN cases had metastatic melanoma involving lymph nodes, compared with 14% (6/42) of BRAF-negative CN cases (P = .061). CN mutation status was not associated with patient demographics, histopathologic or molecular features of the PCM, or survival outcomes. A high percentage of CN identified in the SLN of patients with PCM harbor BRAF V600E mutation. Positive mutation was associated with adverse clinicopathological parameters, specifically increased tumor stage and lymph node metastasis. These findings suggest that BRAF V600E mutation in CN of SLN may be useful as an adverse predictive biomarker in patients with melanoma. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. 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

  12. 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.

  13. Are all melanomas dangerous?

    DEFF Research Database (Denmark)

    Nørgaard, Carsten; Glud, Martin; Gniadecki, Robert

    2011-01-01

    The increased incidence of cutaneous malignant melanoma, together with only minor changes in mortality, has brought into question the existence of a melanoma epidemic. The discrepancy between incidence and mortality suggests that most newly diagnosed melanomas have indolent behaviour. This review...

  14. A cluster of cutaneous leishmaniasis associated with human smuggling.

    Science.gov (United States)

    Cannella, Anthony P; Nguyen, Bichchau M; Piggott, Caroline D; Lee, Robert A; Vinetz, Joseph M; Mehta, Sanjay R

    2011-06-01

    Cutaneous leishmaniasis (CL) is rarely seen in the United States, and the social and geographic context of the infection can be a key to its diagnosis and management. Four Somali and one Ethiopian, in U.S. Border Patrol custody, came to the United States by the same human trafficking route: Djibouti to Dubai to Moscow to Havana to Quito; and then by ground by Columbia/Panama to the United States-Mexico border where they were detained. Although traveling at different times, all five patients simultaneously presented to our institution with chronic ulcerative skin lesions at different sites and stages of evolution. Culture of biopsy specimens grew Leishmania panamensis. Soon thereafter, three individuals from East Africa traveling the identical route presented with L. panamensis CL to physicians in Tacoma, WA. We document here the association of a human trafficking route and new world CL. Clinicians and public health officials should be aware of this emerging infectious disease risk.

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

    Directory of Open Access Journals (Sweden)

    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. Membrane properties in small cutaneous nerve fibers in humans.

    Science.gov (United States)

    Hennings, Kristian; Frahm, Ken Steffen; Petrini, Laura; Andersen, Ole K; Arendt-Nielsen, Lars; Mørch, Carsten D

    2017-02-01

    Assessment of membrane properties is important for understanding the mechanisms of painful peripheral neuropathy, developing new diagnostic techniques, and screening/profiling of analgesics that target ion channels. Small cutaneous nerves were activated electrically by small diameter (0.2 mm) cathodes, and large nerves were activated by ordinary patch electrodes. This new perception threshold tracking method combines perception threshold assessment and stimulation paradigms from conventional threshold tracking. The strength-duration time-constant of large fibers (580 µs ± 160 µs) was lower than the time constant of small fibers (1060 µs ± 690 µs; P fibers showed less threshold reduction than large fibers (repeated-measures analysis of variance, Bonferroni, P = 0.006). This is a reliable method to investigate the membrane properties of small cutaneous nerve fibers in humans and may be used in clinical settings as a diagnostic or profiling tool. Muscle Nerve 55: 195-201, 2017. © 2016 Wiley Periodicals, Inc.

  17. MicroRNA 211 Functions as a Metabolic Switch in Human Melanoma Cells.

    Science.gov (United States)

    Mazar, Joseph; Qi, Feng; Lee, Bongyong; Marchica, John; Govindarajan, Subramaniam; Shelley, John; Li, Jian-Liang; Ray, Animesh; Perera, Ranjan J

    2016-01-19

    MicroRNA 211 (miR-211) negatively regulates genes that drive invasion of metastatic melanoma. Compared to normal human melanocytes, miR-211 expression is significantly reduced or absent in nonpigmented melanoma cells and lost during human melanoma progression. To investigate the molecular mechanism of its tumor suppressor function, miR-211 was ectopically expressed in nonpigmented melanoma cells. Ectopic expression of miR-211 reduced hypoxia-inducible factor 1α (HIF-1α) protein levels and decreased cell growth during hypoxia. HIF-1α protein loss was correlated with the downregulation of a miR-211 target gene, pyruvate dehydrogenase kinase 4 (PDK4). We present evidence that resumption of miR-211-mediated downregulation of PDK4 in melanoma cells causes inhibition of invasion by nonpigmented melanomas via HIF-1α protein destabilization. Thus, the tumor suppressor miR-211 acts as a metabolic switch, and its loss is expected to promote cancer hallmarks in human melanomas. Melanoma, one of the deadliest forms of skin cancer, kills nearly 10,000 people in the United States per year. We had previously shown that a small noncoding RNA, termed miR-211, suppresses invasion and the growth of aggressive melanoma cells. The results presented here support the hypothesis that miR-211 loss in melanoma cells causes abnormal regulation of energy metabolism, which in turn allows cancer cells to survive under low oxygen concentrations-a condition that generally kills normal cells. These findings highlight a novel mechanism of melanoma formation: miR-211 is a molecular switch that is turned off in melanoma cells, raising the hope that in the future we might be able to turn the switch back on, thus providing a better treatment option for melanoma. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  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. Micronuclei with kinetochores in human melanoma cells and rectal carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Weissenborn, U.; Streffer, C. (Essen Univ. (Gesamthochschule) (Germany, F.R.). Inst. fuer Medizinische Strahlenbiologie)

    1991-02-01

    Micronucleus frequencies were analysed in an X-irradiated human melanoma cell line and in untreated rectal carcinoma cells. As a special aspect of the micronucleus formation, micronuclei-containing kinetochores were analysed by the method of indirect immunofluorescence. The incidence of kinetochore-positive micronuclei was taken as a measure of chromosome loss. The authors have attempted to summarize the data by means of a numerical expression which takes into account the relation between lost chromosomes, visible as kinetochore-positive micronuclei, and the total sum of micronuclei. (author).

  20. 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

  1. Vesicular Stomatitis Virus Variants Selectively Infect and Kill Human Melanomas but Not Normal Melanocytes

    Science.gov (United States)

    Wollmann, Guido; Davis, John N.; Bosenberg, Marcus W.

    2013-01-01

    Metastatic malignant melanoma remains one of the most therapeutically challenging forms of cancer. Here we test replication-competent vesicular stomatitis viruses (VSV) on 19 primary human melanoma samples and compare these infections with those of normal human melanocyte control cells. Even at a low viral concentration, we found a strong susceptibility to viral oncolysis in over 70% of melanomas. In contrast, melanocytes displayed strong resistance to virus infection and showed complete protection by interferon. Several recombinant VSVs were compared, and all infected and killed most melanomas with differences in the time course with increasing rates of melanoma infection, as follows: VSV-CT9-M51 VSV-M51 VSV-G/GFP VSV-rp30. VSV-rp30 sequencing revealed 2 nonsynonymous mutations at codon positions P126 and L223, both of which appear to be required for the enhanced phenotype. VSV-rp30 showed effective targeting and infection of multiple subcutaneous and intracranial melanoma xenografts in SCID mice after tail vein virus application. Sequence analysis of mutations in the melanomas used revealed that BRAF but not NRAS gene mutation status was predictive for enhanced susceptibility to infection. In mouse melanoma models with specific induced gene mutations including mutations of the Braf, Pten, and Cdkn2a genes, viral infection correlated with the extent of malignant transformation. Similar to human melanocytes, mouse melanocytes resisted VSV-rp30 infection. This study confirms the general susceptibility of the majority of human melanoma types for VSV-mediated oncolysis. PMID:23552414

  2. Vesicular stomatitis virus variants selectively infect and kill human melanomas but not normal melanocytes.

    Science.gov (United States)

    Wollmann, Guido; Davis, John N; Bosenberg, Marcus W; van den Pol, Anthony N

    2013-06-01

    Metastatic malignant melanoma remains one of the most therapeutically challenging forms of cancer. Here we test replication-competent vesicular stomatitis viruses (VSV) on 19 primary human melanoma samples and compare these infections with those of normal human melanocyte control cells. Even at a low viral concentration, we found a strong susceptibility to viral oncolysis in over 70% of melanomas. In contrast, melanocytes displayed strong resistance to virus infection and showed complete protection by interferon. Several recombinant VSVs were compared, and all infected and killed most melanomas with differences in the time course with increasing rates of melanoma infection, as follows: VSV-CT9-M51 VSV-M51 VSV-G/GFP VSV-rp30. VSV-rp30 sequencing revealed 2 nonsynonymous mutations at codon positions P126 and L223, both of which appear to be required for the enhanced phenotype. VSV-rp30 showed effective targeting and infection of multiple subcutaneous and intracranial melanoma xenografts in SCID mice after tail vein virus application. Sequence analysis of mutations in the melanomas used revealed that BRAF but not NRAS gene mutation status was predictive for enhanced susceptibility to infection. In mouse melanoma models with specific induced gene mutations including mutations of the Braf, Pten, and Cdkn2a genes, viral infection correlated with the extent of malignant transformation. Similar to human melanocytes, mouse melanocytes resisted VSV-rp30 infection. This study confirms the general susceptibility of the majority of human melanoma types for VSV-mediated oncolysis.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  4. Fibroblasts from patients with hereditary cutaneous malignant melanoma are abnormally sensitive to the mutagenic effect of simulated sunlight and 4-nitroquinoline 1-oxide

    Energy Technology Data Exchange (ETDEWEB)

    Howell, J.N.; Greene, M.H.; Corner, R.C.; Maher, V.M.; McCormick, J.J.

    1984-02-01

    Because of a possible etiologic link between mutations and carcinogenesis, the authors compared fibroblasts derived from skin biopsies of several patients with hereditary cutaneous malignant melanoma and the dysplastic nevus syndrome for sensitivity to the mutagenic and/or cytotoxic effect of broad-spectrum simulated sunlight and of a UV mimetic carcinogen, 4-nitroquinoline 1-oxide (4NQO). The genetic marker was resistant to 6-thioguanine; loss of colony-forming ability was the assay for cytotoxicity. All five strains tested were more sensitive than normal to the killing effect of 4NQO (slopes of survival curves were 2- to 3-fold steeper), but only one strain was hypersensitive to killing by Sun Lamp radiation. Two strains were tested for mutagenicity. The response of each to the mutagenic action of these agents corresponded to its response to cell killing. Both strains were hypermutable after exposure to 4NQO, but only one showed a higher than normal frequency of mutants induced by simulated sunlight. The finding that nonmalignant fibroblasts from patients with a hereditary variant of malignant fibroblasts from patients with a hereditary variant of malignant melanoma are abnormally susceptible to carcinogen-induced mutations suggests that hypersensitivity to mutagens contributes to risk of melanoma in patients. It also supports the somatic cell mutation hypothesis for the origin of cancer. 46 references, 3 figures.

  5. Algunos factores pronósticos de interés en el melanoma maligno cutáneo Some interesting prognostic factors related to cutaneous malignant melanoma

    Directory of Open Access Journals (Sweden)

    AlejandroYuri Joan Figueroa

    2010-03-01

    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.

  6. Human Single-Chain Fv Immunoconjugates Targeted to a Melanoma-Associated Chondroitin Sulfate Proteoglycan Mediate Specific Lysis of Human Melanoma Cells by Natural Killer Cells and Complement

    Science.gov (United States)

    Wang, Baiyang; Chen, Yi-Bin; Ayalon, Oran; Bender, Jeffrey; Garen, Alan

    1999-02-01

    Two antimelanoma immunoconjugates containing a human single-chain Fv (scFv) targeting domain conjugated to the Fc effector domain of human IgG1 were synthesized as secreted two-chain molecules in Chinese hamster ovary and Drosophila S2 cells, and purified by affinity chromatography on protein A. The scFv targeting domains originally were isolated as melanoma-specific clones from a scFv fusion-phage library, derived from the antibody repertoire of a vaccinated melanoma patient. The purified immunoconjugates showed similar binding specificity as did the fusion-phage clones. Binding occurred to human melanoma cells but not to human melanocytes or to several other types of normal cells and tumor cells. A 250-kDa melanoma protein was immunoprecipitated by the immunoconjugates and analyzed by mass spectrometry, using two independent procedures. A screen of protein sequence databases showed an exact match of several peptide masses between the immunoprecipitated protein and the core protein of a chondroitin sulfate proteoglycan, which is expressed on the surface of most human melanoma cells. The Fc effector domain of the immunoconjugates binds natural killer (NK) cells and also the C1q protein that initiates the complement cascade; both NK cells and complement can activate powerful cytolytic responses against the targeted tumor cells. An in vitro cytolysis assay was used to test for an immunoconjugate-dependent specific cytolytic response against cultured human melanoma cells by NK cells and complement. The melanoma cells, but not the human fibroblast cells used as the control, were efficiently lysed by both NK cells and complement in the presence of the immunoconjugates. The in vitro results suggest that the immunoconjugates also could activate a specific cytolytic immune response against melanoma tumors in vivo.

  7. Changes in expression of putative antigens encoded by pigment genes in mouse melanomas at different stages of malignant progression.

    OpenAIRE

    Orlow, S J; Hearing, V. J.; Sakai, C.; Urabe, K; Zhou, B K; Silvers, W. K.; Mintz, B

    1995-01-01

    Cutaneous melanomas of Tyr-SV40E transgenic mice (mice whose transgene consists of the tyrosinase promoter fused to the coding regions of simian virus 40 early genes) strikingly resemble human melanomas in their development and progression. Unlike human melanomas, the mouse tumors all arise in genetically identical individuals, thereby better enabling expression of specific genes to be characterized in relation to advancing malignancy. The products of pigment genes are of particular interest ...

  8. Are all melanomas dangerous?

    DEFF Research Database (Denmark)

    Nørgaard, Carsten; Glud, Martin; Gniadecki, Robert

    2011-01-01

    The increased incidence of cutaneous malignant melanoma, together with only minor changes in mortality, has brought into question the existence of a melanoma epidemic. The discrepancy between incidence and mortality suggests that most newly diagnosed melanomas have indolent behaviour. This review....... These findings indicate the existence of a certain degree of overdiagnosis of melanoma. They also indicate the existence of two different types of epidemic, for younger and older subgroups....

  9. One Step Surgery for Cutaneous Melanoma: “We Cannot Solve Our Problems with the Same Thinking We Used When We Created Them?”

    Directory of Open Access Journals (Sweden)

    Georgi Tchernev

    2017-10-01

    Full Text Available One step melanoma surgery is, in fact, an innovative combined method for diagnosis and treatment of cutaneous melanoma (at the same time. The methodology allows an accurate assessment of the actual status of the affected patients by 1 clinical status, dermatoscopy, high-frequent ultrasonography (HFUS of the pigmented lesion (eventually in combination with normal lymph nodes ultrasonography, followed by a single surgical intervention. Within this intervention, the primary tumour is removed with the appropriate surgical field, with or without parallel detection and draining lymph node biopsy (depending on the established tumour thickness. Removal of the lymph node may, in turn, be associated with or without locoregional lymphadenectomy, which is determined by its macroscopic appearance, established intraoperatively or after the histopathological evaluation. The methodology is sparing, innovative, easy to apply, tested in its functionality and logically justified. For an unknown reason, this methodology is not applicable in melanoma treatment’s guidelines in Europe and America. In Bulgaria and France, however, there are centres and hospitals that apply the technique mentioned above with enormous results, in particular in Bulgaria, the methodology is getting more and more improved to the current moment. Based on the above, as well as on the scant experience, we may share the opinion that the current melanoma treatment’s guidelines need major corrections in their recommendations, which are not optimal for patients due to the following facts: (1 the adverse effects on patients as a result of the necessity of at least 2 surgical interventions; (2 the frequent occurrence of changes in the lymph flow after the primary excision; (3 the frequent non-obtaining of the suggested in the guidelines terms for re-excisions with or without sentinel lymph node removal; and (4 the creation of additional financial difficulties for the patients in the framework of

  10. Excitation-emission matrices measurements of human cutaneous lesions: tool for fluorescence origin

    Science.gov (United States)

    Zhelyazkova, A.; Borisova, E.; Angelova, L.; Pavlova, E.; Keremedchiev, M.

    2013-11-01

    The light induced fluorescence (LIF) technique has the potential of providing real-time diagnosis of malignant and premalignant skin tissue; however, human skin is a multilayered and inhomogeneous organ with different optical properties that complicate the analysis of cutaneous fluorescence spectra. In spite of the difficulties related to the detection and analysis of fluorescent data from skin lesions, this technique is among the most widely applied techniques in laboratorial and pre-clinical investigations for early skin neoplasia diagnosis. The important point is to evaluate all sources of intrinsic fluorescence and find any significant alterations distinguishing the normal skin from a cancerous state of the tissue; this would make the autofluorescence signal obtained useful for the development of a non-invasive diagnostic tool for the dermatological practice. Our investigations presented here were based on ex vivo point-by-point measurements of excitation-emission matrices (EEM) from excised tumor lesions and the surrounding skin taken during the daily clinical practice of Queen Jiovanna- ISUL University Hospital, Sofia, the local Ethical Committee's approval having already been obtained. The fluorescence emission was measured between 300 nm and 800 nm using excitation in the 280-440 nm spectral range. In the process of excitation-emission matrices (EEM) measurements we could establish the origin of the autofluorescence and the compounds related by assigning the excitation and emission maxima obtained during the experiments. The EEM were compared for normal human skin, basal cell carcinoma, squamous cell carcinoma, benign nevi and malignant melanoma lesions to obtain information for the most common skin malignancies and their precursors. The main spectral features and the applicability of the technique of autofluorescent spectroscopy of human skin in general as an initial diagnostic tool are discussed as well.

  11. Lymphatic vessels regulate immune microenvironments in human and murine melanoma.

    Science.gov (United States)

    Lund, Amanda W; Wagner, Marek; Fankhauser, Manuel; Steinskog, Eli S; Broggi, Maria A; Spranger, Stefani; Gajewski, Thomas F; Alitalo, Kari; Eikesdal, Hans P; Wiig, Helge; Swartz, Melody A

    2016-09-01

    Lymphatic remodeling in tumor microenvironments correlates with progression and metastasis, and local lymphatic vessels play complex and poorly understood roles in tumor immunity. Tumor lymphangiogenesis is associated with increased immune suppression, yet lymphatic vessels are required for fluid drainage and immune cell trafficking to lymph nodes, where adaptive immune responses are mounted. Here, we examined the contribution of lymphatic drainage to tumor inflammation and immunity using a mouse model that lacks dermal lymphatic vessels (K14-VEGFR3-Ig mice). Melanomas implanted in these mice grew robustly, but exhibited drastically reduced cytokine expression and leukocyte infiltration compared with those implanted in control animals. In the absence of local immune suppression, transferred cytotoxic T cells more effectively controlled tumors in K14-VEGFR3-Ig mice than in control mice. Furthermore, gene expression analysis of human melanoma samples revealed that patient immune parameters are markedly stratified by levels of lymphatic markers. This work suggests that the establishment of tumor-associated inflammation and immunity critically depends on lymphatic vessel remodeling and drainage. Moreover, these results have implications for immunotherapies, the efficacies of which are regulated by the tumor immune microenvironment.

  12. 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.

  13. Organotypic in vitro models of human cutaneous squamous cell carcinoma

    NARCIS (Netherlands)

    Commandeur, Suzan

    2013-01-01

    Skin cancer is the most common type of cancer in fair-skinned populations. Cutaneous squamous cell carcinoma (SCC) comprises about 15% of all skin cancer diagnoses. Treatment associated with the high and rising prevalence of cutaneous SCC puts an increasingly high financial burden on society,

  14. Human melanoma immunotherapy using tumor antigen-specific T cells generated in humanized mice.

    Science.gov (United States)

    Hu, Zheng; Xia, Jinxing; Fan, Wei; Wargo, Jennifer; Yang, Yong-Guang

    2016-02-09

    A major factor hindering the exploration of adoptive immunotherapy in preclinical settings is the limited availability of tumor-reactive human T cells. Here we developed a humanized mouse model that permits large-scale production of human T cells expressing the engineered melanoma antigen MART-1-specific TCR. Humanized mice, made by transplantation of human fetal thymic tissue and CD34+ cells virally-transduced with HLA class I-restricted melanoma antigen (MART-1)-specific TCR gene, showed efficient development of MART-1-TCR+ human T cells with predominantly CD8+ cells. Importantly, MART-1-TCR+CD8+ T cells developing in these mice were capable of mounting antigen-specific responses in vivo, as evidenced by their proliferation, phenotypic conversion and IFN-γ production following MART-1 peptide immunization. Moreover, these MART-1-TCR+CD8+ T cells mediated efficient killing of melanoma cells in an HLA/antigen-dependent manner. Adoptive transfer of in vitro expanded MART-1-TCR+CD8+ T cells induced potent antitumor responses that were further enhanced by IL-15 treatment in melanoma-bearing recipients. Finally, a short incubation of MART-1-specific T cells with rapamycin acted synergistically with IL-15, leading to significantly improved tumor-free survival in recipients with metastatic melanoma. These data demonstrate the practicality of using humanized mice to produce potentially unlimited source of tumor-specific human T cells for experimental and preclinical exploration of cancer immunotherapy. This study also suggests that pretreatment of tumor-reactive T cells with rapamycin in combination with IL-15 administration may be a novel strategy to improve the efficacy of adoptive T cell therapy.

  15. Pathways from senescence to melanoma: focus on MITF sumoylation.

    Science.gov (United States)

    Leclerc, J; Ballotti, R; Bertolotto, C

    2017-11-30

    Cutaneous melanoma is a deadly skin cancer that originates from melanocytes. The development of cutaneous melanoma involves a complex interaction between environmental factors, mainly ultraviolet radiation from sunlight, and genetic alterations. Melanoma can also occur from a pre-existing nevus, a benign lesion formed from melanocytes harboring oncogenic mutations that trigger proliferative arrest and senescence entry. Senescence is a potent barrier against tumor progression. As such, the acquisition of mutations that suppress senescence and promote cell division is mandatory for cancer development. This topic appears central to melanoma development because, in humans, several somatic and germline mutations are related to the control of cellular senescence and proliferative activity. Consequently, primary melanoma can be viewed as a paradigm of senescence evasion. In support of this notion, a sumoylation-defective germline mutation in microphthalmia-associated transcription factor (MITF), a master regulator of melanocyte homeostasis, is associated with the development of melanoma. Interestingly, this MITF variant has also been recently reported to negatively impact the program of senescence. This article reviews the genetic alterations that have been shown to be involved in melanoma and that alter the process of senescence to favor melanoma development. Then, the transcription factor MITF and its sumoylation-defective mutant are described. How sumoylation misregulation can change MITF activity and impact the process of senescence is discussed. Finally, the contribution of such information to the development of anti-malignant melanoma strategies is evaluated.

  16. Regulated Expression of Vascular Cell Adhesion Molecule-1 in Human Malignant Melanoma

    Science.gov (United States)

    Jonjic, Nives; Martìn-Padura, Inés; Pollicino, Teresa; Bernasconi, Sergio; Jílek, Petr; Bigotti, Aldo; Mortarini, Roberta; Anichini, Andrea; Parmiani, Giorgio; Colotta, Francesco; Dejana, Elisabetta; Mantovani, Alberto; Natali, Pier Giorgio

    1992-01-01

    Expression of the endothelial adhesion molecule VCAM-1 was studied in human malignant melanoma lines by flow cytometry. Clones 2/4 and 2/14(derived from the same lesion) had appreciable levels of VCAM-1 expression, whereas clone 2/21 and thelines A2058, Mel24, and A375 were negative. Clone 2/14 was selected for further analysis. Exposure to tumor necrosis factor (TNF) markedly augmented VCAM-1 on melanoma cells. Surface VCAM-1 was associated with expression of specific transcripts that were augmented by TNF. Analysis by reverse transcriptase and polymerase chain reaction using appropriate primers revealed that TNF-stimulated melanoma cells expressed both 7 and 6 immunoglobulin domain transcripts with predominance of the longer species. Tumor necrosis factor-stimulated melanoma cells bound more VLA-4-expressing cells (melanoma and monocytes) than resting tumor cells and anti-VCAM-1 monoclonal antibodies significantly inhibited binding, thus suggesting that surface VCAM-1 on melanoma is functional. Analysis of melanoma tissue sections demonstrated that VCAM-1 is not a marker of transformation of melanocytes because it can be detected in benign nevi. Although, unlike ICAM-1, VCAM-1 is not correlated with tumor progression, its expression in a fraction of primary melanomas indicates that it may play a role in regulating host immune response and homotypic interactions in some malignant melanomas ImagesFigure 2Figure 3Figure 5 PMID:1281617

  17. MiR-767 promoted cell proliferation in human melanoma by suppressing CYLD expression.

    Science.gov (United States)

    Zhang, Kejin; Guo, Ling

    2018-01-30

    MicroRNAs (miRNAs) have emerged as critical regulators for cancer development and progression of human melanoma. However, the potential molecular mechanism of miR-767 in human melanoma has not been intensively investigated. In this present study, we confirmed that miR-767 was frequently up-regulated in human melanoma tissues and cell lines. Ectopic expression of miR-767 promoted cell proliferation in human melanoma cell lines A375 and WM35, whereas miR-767-in reversed the function. Bioinformatics analysis revealed that cylindromatosis (CYLD) was hypothesized to be a possible target gene of miR-767, and this was confirmed by luciferase activity assay. Knockdown of CYLD counteracted the proliferation arrest by miR-767-in in melanoma cells A375 and WM35. In conclusion, our study indicated that miR-767 acted as a role of tumor promoter by targeting CYLD in human melanoma, and might serve as a prognostic or therapeutic target for human melanoma. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. 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.

  19. 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...... and 174 matched controls and in 168 CMM patients and 176 matched controls. Measurements were performed at the forehead, the upper chest, the upper back, the lateral and medial aspects of the upper arm, and the buttocks. Self-estimation of sun exposure in childhood, in youth and in adulthood was performed...... 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...

  20. JARID1B expression in human melanoma and benign melanocytic skin lesions.

    Science.gov (United States)

    Kuźbicki, Lukasz; Lange, Dariusz; Strączyńska-Niemiec, Anita; Chwirot, Barbara W

    2013-02-01

    It has been suggested that dynamically regulated expression of the JARID1B protein is required for the continuous growth of tumors and at the same time downregulated in melanoma. The majority of the data on a role of JARID1B in maintaining tumor growth has come from in-vitro and xenografting experiments, with only one immunohistochemical study involving human tissues. We compared JARID1B expression levels in human melanomas and benign nevi and analyzed patterns of spatial distributions of positive cells among different skin layers of the lesions. The expression of JARID1B was evaluated by immunohistochemistry in formalin-fixed paraffin-embedded samples of 30 nevi, 27 primary melanomas, four lymph node metastases, and one local recurrence of melanoma. Staining for JARID1B protein was stronger in melanomas compared with nevi. We also found a significant difference in the spatial distribution of positive cells in individual skin layers of nevi and melanomas. Staining of melanocytes located in granular and spinous layers of nevi was observed very rarely, whereas for melanomas, the mean percentage fractions of positive cells present in these layers exceeded the maximum values found for nevi. The spatial patterns and expression levels of JARID1B did not change significantly with melanoma progression and were similar for primary, metastatic, and recurrent melanomas. Contrary to earlier reports, this study shows enhanced expression of JARID1B by melanoma cells and indicates that such an enhancement may be an early event in the disease progression, is not correlated with melanoma invasiveness, and therefore may not be a suitable candidate as a prognostic marker.

  1. Serum anti-BPAG1 auto-antibody is a novel marker for human melanoma.

    Directory of Open Access Journals (Sweden)

    Takashi Shimbo

    2010-05-01

    Full Text Available Malignant melanoma is one of the most aggressive types of tumor. Because malignant melanoma is difficult to treat once it has metastasized, early detection and treatment are essential. The search for reliable biomarkers of early-stage melanoma, therefore, has received much attention. By using a novel method of screening tumor antigens and their auto-antibodies, we identified bullous pemphigoid antigen 1 (BPAG1 as a melanoma antigen recognized by its auto-antibody. BPAG1 is an auto-antigen in the skin disease bullous pemphigoid (BP and anti-BPAG1 auto-antibodies are detectable in sera from BP patients and are used for BP diagnosis. However, BPAG1 has been viewed as predominantly a keratinocyte-associated protein and a relationship between BPAG1 expression and melanoma has not been previously reported. In the present study, we show that bpag1 is expressed in the mouse F10 melanoma cell line in vitro and F10 melanoma tumors in vivo and that BPAG1 is expressed in human melanoma cell lines (A375 and G361 and normal human melanocytes. Moreover, the levels of anti-BPAG1 auto-antibodies in the sera of melanoma patients were significantly higher than in the sera of healthy volunteers (p<0.01. Furthermore, anti-BPAG1 auto-antibodies were detected in melanoma patients at both early and advanced stages of disease. Here, we report anti-BPAG1 auto-antibodies as a promising marker for the diagnosis of melanoma, and we discuss the significance of the detection of such auto-antibodies in cancer biology and patients.

  2. Bronzeamento e risco de melanoma cutâneo: revisão da literatura Suntanning and risk of cutaneous melanoma: a literature review

    Directory of Open Access Journals (Sweden)

    Sonia R P de Souza

    2004-08-01

    Full Text Available Estudos epidemiológicos sugerem a relação entre comportamentos relacionados ao bronzeamento e risco elevado de melanoma. Nesse sentido, realizou-se revisão sobre essa temática que abrangeu o período correspondente aos anos de 1977 a 1998. Foram pesquisadas as bases de dados Medline e Embase (Excerpta Medica. A análise mostrou que entre os jovens, apesar do conhecimento sobre os riscos da exposição excessiva à radiação ultravioleta e sobre as práticas visando à proteção da pele, prevalece o hábito de expor-se intencionalmente ao sol. Esse hábito é alimentado por crenças e atitudes em relação ao bronzeado e estimulado por influência do grupo e de pessoas consideradas "referências". As práticas mais freqüentemente adotadas para bronzear a pele apresentam risco elevado para o desenvolvimento de melanoma. Conclui-se que a forma mais eficaz de prevenir o melanoma é divulgar nos meios de comunicação que a pele bronzeada não é saudável, pois foi danificada pela radiação ultravioleta solar; e iniciar campanhas com ações efetivas para mudar comportamentos, naquilo que os motiva e os alimenta.Epidemiological studies suggest a relationship between suntanning habits and high risk of melanoma. A literature review was carried out for the period between 1977 and 1998 using Medline and Embase (Excerpta Medica databases. The analysis showed that intentional sun exposure is highly prevalent among youths, despite their awareness of the risks involved in excessive exposure to ultraviolet radiation and their knowledge on skin protection measures. Intentional exposure is a habit fostered by certain beliefs and attitudes towards suntanning and stimulated by peer pressure and aesthetic referents.The most common tanning practices involve a high risk of developing melanoma. It was concluded that the most effective means to prevent melanoma is mass media dissemination of the concept that having a tanned skin is not healthy - since it

  3. Variations in supportive care needs of patients after diagnosis of localised cutaneous melanoma: a 2-year follow-up study.

    Science.gov (United States)

    Beesley, Vanessa L; Smithers, B Mark; O'Rourke, Peter; Janda, Monika; Khosrotehrani, Kiarash; Green, Adèle C

    2017-01-01

    We aimed to describe variations in unmet supportive care needs of patients diagnosed with localised melanoma at high risk of recurrence and factors associated with initial and persisting moderate-to-high needs. We ascertained 386 patients diagnosed with clinical stage IB-II melanoma and administered surveys every 6 months for 2 years. The proportion experiencing at least one moderate-to-high need was assessed among salient subgroups: 306 patients with no previous melanoma and 80 with previous melanoma at enrolment, 30 who experienced disease recurrence during follow-up and 31 who developed another primary. Baseline factors associated with (a) needs at enrolment and (b) persistent needs over 2 years (or as long as disease-free) were identified by logistic regression analyses. The proportion of patients with needs substantially declined over the first 6 months (if no previous melanoma, from 48 to 22 %, p melanoma, 35 to 17 %, p = 0.007), and in those remaining disease-free, needs declined further by 24 months (to 14 and 6 % respectively). By contrast, 50 % of those experiencing recurrence, and 39 % of those who developed another primary, reported needs. Stressful life events and anxiety were associated with needs at enrolment. At least one need, mainly fear of recurrence, persisted in 22 % of disease-free participants. Persistent needs were predicted by age, depression, anxiety and other stressful life events. Melanoma patients' needs peak when first diagnosed and if disease recurs. Younger people or those experiencing additional stressful events, anxiety or depression are more likely to experience persistent needs and may benefit from tailored support.

  4. Sentinel Lymph Node Biopsy in Cutaneous Melanoma: Standard and New Technical Procedures and Clinical Advances. A Systematic Review of the Literature.

    Science.gov (United States)

    Tardelli, Elisa; Mazzarri, Sara; Rubello, Domenico; Gennaro, Marta; Fantechi, Lorenzo; Duce, Valerio; Romanini, Antonella; Chondrogiannis, Sotirios; Volterrani, Duccio; Colletti, Patrick M; Manca, Gianpiero

    2016-12-01

    Melanoma is an important public health problem, and its incidence is increasing worldwide. The disease status of regional lymph nodes is the most important prognostic factor in early-stage melanoma patients. Sentinel lymph node biopsy (SLNB) was introduced in the early 1990s as a less invasive procedure than complete lymph node dissection to allow histopathologic evaluation of the "sentinel lymph node" (SLN), which is the first node along the lymphatic pathway from a primary tumor. Sentinel lymph node biopsy has minimal complication risks compared with standard complete lymph node dissection. Currently, SLNB is the accepted method for staging patients with clinically node-negative cutaneous melanoma and provides the most powerful prognostic information by evaluating the nodal basin status. The current practice of SLNB consists of the injection of Tc-labeled radiopharmaceutical, preoperative lymphoscintigraphy with the possibility of using the SPECT/CT hybrid imaging, and intraoperative SLN localization using a handheld gamma probe with or without the use of blue dye. Recently, the SLN localization and detection have been enhanced with the use of new tracers and new intraoperative devices, which have demonstrated to be particularly useful in melanomas of the head and neck region and in area of complex anatomy. Despite these important advances in the technology and the increasing experience in SLN mapping, major research centers have reported a false-negative rate higher than 15%. This relatively high false-negative rate, greater than those reported in the initial validation studies, points out the importance for the nuclear medicine community to continuously improve their knowledge on the biological behavior of melanoma and to improve the technical aspects that may allow more precise staging. For the SLNB procedure to be accurate, it is of critical importance that all "true" SLNs are identified and removed for examination. The aim of this article is to provide

  5. 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

  6. Dissection of T-cell antigen specificity in human melanoma

    DEFF Research Database (Denmark)

    Andersen, Rikke Sick; Albæk Thrue, Charlotte; Junker, Niels

    2012-01-01

    Tumor-infiltrating lymphocytes (TIL) isolated from melanoma patients and expanded in vitro by interleukin (IL)-2 treatment can elicit therapeutic response after adoptive transfer, but the antigen specificities of the T cells transferred have not been determined. By compiling all known melanoma......-associated antigens and applying a novel technology for high-throughput analysis of T-cell responses, we dissected the composition of melanoma-restricted T-cell responses in 63 TIL cultures. T-cell reactivity screens against 175 melanoma-associated epitopes detected 90 responses against 18 different epitopes...

  7. Case report: cutaneous myiasis caused by Dermatobia hominis, the human botfly.

    Science.gov (United States)

    Garvin, Kanishka W; Singh, Virtaj

    2007-05-01

    Cutaneous myiasis caused by Dermatobia hominis, the human botfly, involves the infestation of human tissue with fly larvae, and is common in Central and South America. We report a case of a 57-year-old man with cutaneous myiasis imported into the US from Belize. The epidemiology, biological life cycle, clinical presentation, and various methods of larval extraction, including incision and drainage, are discussed.

  8. Near-infrared autofluorescence imaging of cutaneous melanins and human skin in vivo

    Science.gov (United States)

    Han, Xiao; Lui, Harvey; McLean, David I.; Zeng, Haishan

    2009-03-01

    In recent years, near-infrared (NIR) autofluorescence imaging has been explored as a novel technique for tissue evaluation and diagnosis. We present an NIR fluorescence imaging system optimized for the dermatologic clinical setting, with particular utility for the direct characterization of cutaneous melanins in vivo. A 785-nm diode laser is coupled into a ring light guide to uniformly illuminate the skin. A bandpass filter is used to purify the laser light for fluorescence excitation, while a long-pass filter is used to block the main laser wavelength but pass the spontaneous components for NIR reflectance imaging. A computer-controlled filter holder is used to switch these two filters to select between reflectance and fluorescence imaging modes. Both the reflectance and fluorescence photons are collected by an NIR-sensitive charge-coupled device (CCD) camera to form the respective images. Preliminary results show that cutaneous melanin in pigmented skin disorders emits higher NIR autofluorescence than surrounding normal tissue. This confirmed our previous findings from NIR fluorescence spectroscopy study of cutaneous melanins and provides a new approach to directly image the distributions of cutaneous melanins in the skin. In-vivo NIR autofluorescence images may be useful for clinical evaluation and diagnosis of pigmented skin lesions, including melanoma.

  9. The cutaneous rabbit illusion affects human primary sensory cortex somatotopically.

    Directory of Open Access Journals (Sweden)

    Felix Blankenburg

    2006-03-01

    Full Text Available We used functional magnetic resonance imaging (fMRI to study neural correlates of a robust somatosensory illusion that can dissociate tactile perception from physical stimulation. Repeated rapid stimulation at the wrist, then near the elbow, can create the illusion of touches at intervening locations along the arm, as if a rabbit hopped along it. We examined brain activity in humans using fMRI, with improved spatial resolution, during this version of the classic cutaneous rabbit illusion. As compared with control stimulation at the same skin sites (but in a different order that did not induce the illusion, illusory sequences activated contralateral primary somatosensory cortex, at a somatotopic location corresponding to the filled-in illusory perception on the forearm. Moreover, the amplitude of this somatosensory activation was comparable to that for veridical stimulation including the intervening position on the arm. The illusion additionally activated areas of premotor and prefrontal cortex. These results provide direct evidence that illusory somatosensory percepts can affect primary somatosensory cortex in a manner that corresponds somatotopically to the illusory percept.

  10. IQGAP1 is an oncogenic target in canine melanoma.

    Directory of Open Access Journals (Sweden)

    Becky H Lee

    Full Text Available Canine oral mucosal melanoma is an aggressive malignant neoplasm and is characterized by local infiltration and a high metastatic potential. The disease progression is similar to that of human oral melanomas. Whereas human cutaneous melanoma is primarily driven by activating mutations in Braf (60% or Nras (20%, human mucosal melanoma harbors these mutations much less frequently. This makes therapeutic targeting and research modeling of the oral form potentially different from that of the cutaneous form in humans. Similarly, research has found only rare Nras mutations and no activating Braf mutations in canine oral melanomas, but they are still reliant on MAPK signaling. IQGAP1 is a signaling scaffold that regulates oncogenic ERK1/2 MAPK signaling in human Ras- and Raf- driven cancers, including melanomas. To investigate whether IQGAP1 is a potential target in canine melanoma, we examined the expression and localization of IQGAP1 in primary canine melanomas and canine oral melanoma cell lines obtained from the University of California-Davis. Using CRISPR/Cas9 knockout of IQGAP1, we examined effects on downstream ERK1/2 pathway activity and assayed proliferation of cell lines when treated with a peptide that blocks the interaction between IQGAP1 and ERK1/2. We observed that canine IQGAP1 is expressed and localizes to a similar extent in both human and canine melanoma by qPCR, Western blot, and immunofluorescence. Deletion of IQGAP1 reduces MAPK pathway activation in cell lines, similar to effects seen in human BrafV600E cell lines. Additionally, we demonstrated reduced proliferation when these cells are treated with a blocking peptide in vitro.

  11. Constitutive Aberrant Endogenous Interleukin-1 Facilitates Inflammation and Growth in Human Melanoma

    Science.gov (United States)

    Qin, Yong; Ekmekcioglu, Suhendan; Liu, Ping; Duncan, Lyn M.; Lizée, Gregory; Poindexter, Nancy; Grimm, Elizabeth A.

    2011-01-01

    Interleukin-1-mediated inflammation is proposed to contribute to the development and progression of some cancers. IL-1 family member proteins are known to be expressed constitutively in many melanoma tumor cells, and we hypothesize that these support molecular pathways of inflammation and facilitate tumor growth. To investigate the expression of IL-1α and IL-1β in melanoma patients, and their association with disease progression, immunohistochemical staining was performed on tissues from 170 patients including benign nevi, primary melanomas, and metastatic melanomas. IL-1β levels were low (or zero) in benign nevi, and higher in primary and metastatic melanomas (Pmelanomas, with levels significantly higher in primary tumors (Pmelanoma samples were positive for IL-1α. In vitro studies with 7 human melanoma cell lines showed that 5 cell lines expressed IL-1α and IL-1β proteins and mRNA. We identified for the first time several important downstream signaling pathways affected by endogenous IL-1, including reactive oxygen and nitrogen species, COX-2, and phosphorylated IκB and SAPK/JNK; all of which were decreased by siRNA to IL-1s. Downregulation of IL-1α, IL-1β, or MyD88 substantially increased p21 and p53 levels. Treatment with IL-1 receptor type I neutralizing antibody or IL-1-pathway-specific siRNAs led to growth arrest in IL-1-positive melanoma cells. Furthermore, blocking the IL-1 pathway increased autophagy in IL-1-positive melanoma cells. These results indicate that the endogenous IL-1 system is functional in most human melanoma, and interrupting its signaling inhibits the growth of IL-1-positive melanoma cells. PMID:21954434

  12. Human melanoma metastasis in NSG mice correlates with clinical outcome in patients

    Science.gov (United States)

    Quintana, Elsa; Piskounova, Elena; Shackleton, Mark; Weinberg, Daniel; Eskiocak, Ugur; Fullen, Douglas R.; Johnson, Timothy M.; Morrison, Sean J.

    2015-01-01

    Studies of human cancer metastasis have been limited by a lack of experimental assays in which cancer cells from patients metastasize in vivo in a way that correlates with clinical outcome. This makes it impossible to study intrinsic differences in the metastatic properties of cancers from different patients. We recently developed an assay in which human melanomas readily engraft in NOD/SCID IL2Rγnull (NSG) mice (1, 2). Here we show that melanomas from 25 patients exhibited reproducible differences in the rate of spontaneous metastasis after transplantation into NSG mice and that these differences correlated with clinical outcome in the patients. Stage IIIB/C melanomas that formed distant metastases within 22 months in patients also formed tumors that metastasized widely in NSG mice, while stage IIIB/C melanomas that did not form distant metastases within 22–50 months in patients metastasized more slowly in NSG mice. These differences in the efficiency of metastasis correlated with the frequency of circulating melanoma cells in the blood of NSG mice, suggesting that the rate of entry into the blood is one factor that limits the rate of metastasis. NSG mice can therefore be used to study the metastasis of human melanomas in vivo, revealing intrinsic differences among stage III melanomas in their ability to circulate/survive in the blood and metastasize. PMID:23136044

  13. Quantitative Imaging In Vivo of Functioning Lymphatic Vessels Around Human Melanoma and Benign Nevi.

    Science.gov (United States)

    Akhras, Victoria; Ramakrishnan, Rathi; Stanton, Anthony W B; Levick, John R; Cook, Martin G; Chong, Heung; Mortimer, Peter S

    2015-08-01

    The density of functioning human lymphatics in vivo and of immunohistochemically defined lymphatics was quantified around melanomas, benign nevi, and matched normal skin, to assess the current lymphangiogenesis paradigm. We investigated whether histological and functioning density increased around melanomas compared with benign nevi or matched skin; whether functioning and histological density increased similarly; and whether larger increases occurred around metastatic melanomas. Functioning density was quantified in vivo as the total amount of human dermal microlymphatics taking up fluorescent marker injected at the lesion margin. After tissue excision, perilesion histological density was quantified using podoplanin marker D2-40. Histological density was raised similarly around metastasising and non-metastasising melanomas compared with normal skin (+71%, p benign nevi (+17%, p = 0.03, n = 20). In contrast, functioning lymphatic density was substantially reduced around the margins of melanomas (both metastasising and non-metastasising) compared with benign nevi (by 65%, p = 0.02) or normal skin (by 53%, p = 0.0014). Raised perilesion histological lymphatic density is not unique to melanoma but occurs also around benign nevi. The findings indicated that the number of functioning lateral lymphatics around human melanomas in vivo but not benign nevi is reduced, despite histologically increased numbers of lymphatics. © 2015 John Wiley & Sons Ltd.

  14. Fully Regressive Melanoma: A Case Without Metastasis.

    Science.gov (United States)

    Ehrsam, Eric; Kallini, Joseph R; Lebas, Damien; Khachemoune, Amor; Modiano, Philippe; Cotten, Hervé

    2016-08-01

    Fully regressive melanoma is a phenomenon in which the primary cutaneous melanoma becomes completely replaced by fibrotic components as a result of host immune response. Although 10 to 35 percent of cases of cutaneous melanomas may partially regress, fully regressive melanoma is very rare; only 47 cases have been reported in the literature to date. AH of the cases of fully regressive melanoma reported in the literature were diagnosed in conjunction with metastasis on a patient. The authors describe a case of fully regressive melanoma without any metastases at the time of its diagnosis. Characteristic findings on dermoscopy, as well as the absence of melanoma on final biopsy, confirmed the diagnosis.

  15. Cutaneous Manifestations of Human Immunodeficiency Virus Infection in Taiwan

    Directory of Open Access Journals (Sweden)

    Tien-Yi Tzung

    2004-05-01

    Full Text Available Cutaneous manifestations are common and often the presenting feature of human immunodeficiency virus (HIV infection, but a comprehensive study of HIV-associated skin lesions is not available in Taiwan. We reviewed all skin lesions in all HIV patients diagnosed in our department between 1990 and 1998 to document the spectrum of skin manifestations, the frequency of each disorder, and their relationship with CD4 counts. A total of 64 HIV patients were studied, including 38 with acquired immunodeficiency syndrome (AIDS (CD4 < 200 × 106 cells/L and 26 who had not developed AIDS (non-AIDS. There were 142 episodes of skin conditions representing 25 different skin diseases, including oral candidiasis (15% in non-AIDS vs 71% in AIDS patients, drug eruptions, herpes simplex, seborrheic dermatitis, dermatophytosis, herpes zoster, secondary syphilis, condyloma acuminatum, Kaposi's sarcoma (16% among AIDS patients, hairy leukoplakia, and molluscum contagiosum (13% among AIDS patients, in decreasing order. Several unusual cases are briefly described, including verrucous herpes infection, condyloma-like molluscum contagiosum, and AIDS-associated pigmented erythroderma. In our study, 70% of all HIV patients had skin diseases, with an average of 2.2 conditions per patient (3.2 in AIDS patients vs 0.7 in non-AIDS patients; p < 0.001. A broad spectrum of HIV-associated skin diseases was observed in our series. The frequency of HIV-associated skin disease was 92% in AIDS patients and 39% in non-AIDS patients; 78% of skin lesions in AIDS patients were diagnosed when CD4 counts were below 100 × 106 cells/L.

  16. Interleukin-32α induces migration of human melanoma cells through downregulation of E-cadherin.

    Science.gov (United States)

    Lee, Joohyun; Kim, Kyung Eun; Cheon, Soyoung; Song, Ju Han; Houh, Younkyung; Kim, Tae Sung; Gil, Minchan; Lee, Kyung Jin; Kim, Seonghan; Kim, Daejin; Hur, Dae Young; Yang, Yoolhee; Bang, Sa Ik; Park, Hyun Jeong; Cho, Daeho

    2016-10-04

    Interleukin (IL)-32α, the shortest isoform of proinflammatory cytokine IL-32, is associated with various inflammatory diseases and cancers. However, its involvement in human melanoma is not understood. To determine the effect of IL-32α in melanoma, IL-32α levels were examined in human melanoma cell lines that exhibit different migratory abilities. IL-32α levels were higher in human melanoma cell lines with more migratory ability. An IL-32α-overexpressing G361 human melanoma cell line was generated to investigate the effect of IL-32α on melanoma migration. IL-32α-overexpressing G361 cells (G361-IL-32α) exhibit an increased migratory ability compared to vector control cells (G361-vector). To identify factors involved in IL-32α-induced migration, we compared expression of E-cadherin in G361-vector and G361-IL-32α cells. We observed decreased levels of E-cadherin in G361-IL-32α cells, resulting in F-actin polymerization. To further investigate signaling pathways related to IL-32α-induced migration, we treated G361-vector and G361-IL-32α cells with PD98059, a selective MEK inhibitor. Inhibition of Erk1/2 by PD98059 restored E-cadherin expression and decreased IL-32α-induced migration. In addition, cell invasiveness of G361-IL-32α cells was tested using an in vivo lung metastasis model. As results, lung metastasis was significantly increased by IL-32α overexpression. Taken together, these data indicate that IL-32α induced human melanoma migration via Erk1/2 activation, which repressed E-cadherin expression. Our findings suggest that IL-32α is a novel regulator of migration in melanoma.

  17. Melanoma with gastric metastases

    Directory of Open Access Journals (Sweden)

    Katherine Wong

    2016-09-01

    Full Text Available An 81-year-old woman with a history of malignant melanoma who presented with dyspnea and fatigue was found to have metastases to the stomach detected on endoscopy. Primary cutaneous malignant melanoma with gastric metastases is a rare occurrence, and it is often not detected until autopsy because of its non-specific manifestations.

  18. Seroprevalence of cutaneous human papillomaviruses (HPVs) among men in the multinational HPV Infection in Men study

    Science.gov (United States)

    Rahman, Shams; Pierce Campbell, Christine M.; Waterboer, Tim; Rollison, Dana E.; Ingles, Donna J.; Torres, B. Nelson; Michel, Angelika; Sudenga, Staci L.; Pawlita, Michael; Villa, Luisa L.; Lazcano Ponce, Eduardo; Borenstein, Amy R.; Wang, Wei

    2016-01-01

    Data on cutaneous human papillomavirus (HPV) seroprevalence are primarily derived from skin cancer case–control studies. Few studies have reported the seroprevalence of cutaneous HPV among healthy men. This study investigated the seroprevalence of cutaneous HPV types and associated risk factors among men residing in Brazil, Mexico and the USA. Six hundred men were randomly selected from the HPV Infection in Men study. Archived serum specimens were tested for antibodies against 14 cutaneous HPV genotypes, β-HPV types (5/8/12/14/17/22/23/24/38/48), α-HPV 27, γ-HPV 4, µ-HPV1 and ν-HPV 41 using a glutathione S-transferase L1-based multiplex serology assay. Risk factor data were collected by a questionnaire. Binomial proportions were used to estimate seroprevalence, and logistic regression to examine factors associated with seropositivity. Overall, 65.4 % of men were seropositive to ≥1 of the 14 cutaneous HPV types, and 39.0 % were positive for ≥1 β-HPV types. Seroprevalence was 8.9, 30.9, 28.6 and 9.4 % for α-HPV 27, γ-HPV 4, µ-HPV 1 and ν-HPV 41, respectively. In multivariate analyses, seropositivity for any cutaneous HPV type was associated with higher education [adjusted odds ratio (AOR) 1.75; 95 % confidence interval (CI) 1.08–2.83], and seropositivity of any β-HPV type was significantly associated with increasing age (AOR 1.72; 95 % CI 1.12–2.63, for men aged 31–44 years vs men aged 18–30 years). Other factors associated with various type-specific cutaneous HPV seropositivity included country, circumcision and lifetime number of male sexual partners. These data indicate that exposure to cutaneous HPV is common. Future studies are needed to assess the role of cutaneous HPV in diseases. PMID:27902363

  19. Seroprevalence of cutaneous human papillomaviruses (HPVs) among men in the multinational HPV Infection in Men study.

    Science.gov (United States)

    Rahman, Shams; Pierce Campbell, Christine M; Waterboer, Tim; Rollison, Dana E; Ingles, Donna J; Torres, B Nelson; Michel, Angelika; Sudenga, Staci L; Pawlita, Michael; Villa, Luisa L; Lazcano Ponce, Eduardo; Borenstein, Amy R; Wang, Wei; Giuliano, Anna R

    2016-12-01

    Data on cutaneous human papillomavirus (HPV) seroprevalence are primarily derived from skin cancer case-control studies. Few studies have reported the seroprevalence of cutaneous HPV among healthy men. This study investigated the seroprevalence of cutaneous HPV types and associated risk factors among men residing in Brazil, Mexico and the USA. Six hundred men were randomly selected from the HPV Infection in Men study. Archived serum specimens were tested for antibodies against 14 cutaneous HPV genotypes, β-HPV types (5/8/12/14/17/22/23/24/38/48), α-HPV 27, γ-HPV 4, µ-HPV1 and ν-HPV 41 using a glutathione S-transferase L1-based multiplex serology assay. Risk factor data were collected by a questionnaire. Binomial proportions were used to estimate seroprevalence, and logistic regression to examine factors associated with seropositivity. Overall, 65.4 % of men were seropositive to ≥1 of the 14 cutaneous HPV types, and 39.0 % were positive for ≥1 β-HPV types. Seroprevalence was 8.9, 30.9, 28.6 and 9.4 % for α-HPV 27, γ-HPV 4, µ-HPV 1 and ν-HPV 41, respectively. In multivariate analyses, seropositivity for any cutaneous HPV type was associated with higher education [adjusted odds ratio (AOR) 1.75; 95 % confidence interval (CI) 1.08-2.83], and seropositivity of any β-HPV type was significantly associated with increasing age (AOR 1.72; 95 % CI 1.12-2.63, for men aged 31-44 years vs men aged 18-30 years). Other factors associated with various type-specific cutaneous HPV seropositivity included country, circumcision and lifetime number of male sexual partners. These data indicate that exposure to cutaneous HPV is common. Future studies are needed to assess the role of cutaneous HPV in diseases.

  20. Anoxia-Induced Up-Regulation of Interleukin-8 in Human Malignant Melanoma

    Science.gov (United States)

    Kunz, Manfred; Hartmann, Anke; Flory, Egbert; Toksoy, Atiye; Koczan, Dirk; Thiesen, Hans-Jürgen; Mukaida, Nafoumi; Neumann, Manfred; Rapp, Ulf Rüdiger; Bröcker, Eva-Bettina; Gillitzer, Reinhard

    1999-01-01

    Besides its proinflammatory properties, interleukin-8 (IL-8) has been suggested as an important promoter for melanoma growth. To study the role of IL-8 in melanoma biology, we determined the in vivo expression of IL-8 mRNA by in situ hybridization in primary melanoma lesions and metastases. High levels of melanoma cell-associated IL-8-specific transcripts were exclusively detected in close vicinity of necrotic/hypoxic areas of melanoma metastases, whereas both in primary melanomas and in non-necrotic metastases IL-8 expression was low or absent. To analyze further the up-regulation of IL-8 mRNA expression in necrotic/hypoxic tumor areas, human melanoma cell lines of different aggressiveness exposed to severe hypoxic stress (anoxia) were used as an in vitro model. Anoxia induced IL-8 mRNA and protein expression in the highly aggressive/metastatic cell lines MV3 and BLM but not in the low aggressive cell lines IF6 and 530. As shown by IL-8 promoter-dependent reporter gene analysis and mRNA stability assays, elevated mRNA levels in melanoma cells were due to both enhanced transcriptional activation and enhanced IL-8 mRNA stability. Interestingly, transcriptional activation was abolished by mutations in the AP-1 and the NF-κB-like binding motifs, indicating that both sites are critical for IL-8 induction. Concomitantly, anoxia induced an enhanced binding activity of AP-1 and NF-κB transcription factors only in the highly aggressive cells. From our in vitro and in vivo data we suggest that anoxia-induced regulation of IL-8 might be a characteristic feature of aggressive tumor cells, thus indicating that IL-8 might play a critical role for tumor progression in human malignant melanoma. PMID:10487833

  1. 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

  2. The sentinel node in cutaneous melanoma: spanish experience; Ganglion sentinelle chez les porteurs de melanome malin. Technique et experience espagnole

    Energy Technology Data Exchange (ETDEWEB)

    Vidal Sicart, S. [Hospital Clinic, Servicio de Medicina Nuclear, Barcelona (Spain)

    2000-10-01

    The sentinel lymph node biopsy performed with previous lymphatic drainage scintigraphic study and a gamma detection probe is a technique that has been gained a remarkable growth worldwide during last years. Its inclusion in clinical guidelines of malignant melanoma in order to avoid unnecessary lymphaden-ectomies is a fact. In this issue a brief description of indications, technical aspects and cumulative experience in Spanish Nuclear Medicine departments is discussed. (author)

  3. Plasmonic enhanced fs-laser optoporation of human melanoma cells

    Science.gov (United States)

    Baumgart, J.; Humbert, L.; St.-Louis Lalonde, B.; Lebrun, J.-J.; Meunier, M.

    2011-03-01

    In this paper, we present the results of in vitro gene transfer by plasmonic enhanced optoporation of human melanoma cells. The fs-laser based optoporation is a gentle and efficient method for transfection. An optimum perforation rate with efficient dye or DNA uptake and high viability of the cells (~90%) was found for different types of nanostructures, spherical and rod shaped. The technique offers a very high selectivity and the low damage induced to the cell leads to a high transfection efficiency. The cell selectivity of this technique on the one hand is realized by using bioconjugated nanostructures, that couple selectively to a special cell type, and on the other hand, the spatial selectivity is due to the fact that only irradiated cells are perforated. In many biological applications a virus free and efficient transfection method is needed, especially in terms of its use in vivo. In cancer cells, the aggressiveness of the cells is shown in the migration and invasion velocity. The laser based and nanostructure enhanced transfection of cells offers the possibility to directly compare the treated and untreated cells. The treatment for migration and invasion assays can be performed by laser-scraping and laser transfection, resulting in a fully non-contact and therefore sterile method where the shape and the size of the scrape is well defined and reproducible. The laser based scrape test therefore offers less uncertainty due to scrape variations, high transfection efficiency, as well as direct comparison of treated and control cells in the same dish.

  4. A functional screen identifies specific microRNAs capable of inhibiting human melanoma cell viability.

    Directory of Open Access Journals (Sweden)

    Jos B Poell

    Full Text Available Malignant melanoma is an aggressive form of skin cancer with poor prognosis. Despite improvements in awareness and prevention of this disease, its incidence is rapidly increasing. MicroRNAs (miRNAs are a class of small RNA molecules that regulate cellular processes by repressing messenger RNAs (mRNAs with partially complementary target sites. Several miRNAs have already been shown to attenuate cancer phenotypes, by limiting proliferation, invasiveness, tumor angiogenesis, and stemness. Here, we employed a genome-scale lentiviral human miRNA expression library to systematically survey which miRNAs are able to decrease A375 melanoma cell viability. We highlight the strongest inhibitors of melanoma cell proliferation, including the miR-15/16, miR-141/200a and miR-96/182 families of miRNAs and miR-203. Ectopic expression of these miRNAs resulted in long-term inhibition of melanoma cell expansion, both in vitro and in vivo. We show specifically miR-16, miR-497, miR-96 and miR-182 are efficient effectors when introduced as synthetic miRNAs in several melanoma cell lines. Our study provides a comprehensive interrogation of miRNAs that interfere with melanoma cell proliferation and viability, and offers a selection of miRNAs that are especially promising candidates for application in melanoma therapy.

  5. Further evidence for a locus for cutaneous malignant melanoma-dysplastic nevus (CMM/DN) on chromosome Ip, and evidence for genetic heterogeneity

    Energy Technology Data Exchange (ETDEWEB)

    Goldstein, A.M.; Fraser, M.C.; McBride, O.W.; Tucker, M.A. (National Cancer Inst., Bethesda, MD (United States)); Dracopoli, N.C.; Ho, E.C. (Massachusetts Inst. of Technology, Cambridge (United States)); Kearns, K.S.; Bale, S.J. (National Inst. of Arthritis, Bethesda, MD (United States)); Clark, W.H. Jr. (Univ. of Pennsylvania School of Medicine, Philadelphia (United States))

    1993-03-01

    Assignment of a susceptibility locus for cutaneous malignant melanoma-dysplastic nevus (CMM/DN) to chromosome 1p remains controversial. The authors examined the relationship between CMM/DN and markers D1S47, PND, and D1S160 on seven new families (set B) plus updated versions of six previously reported families (set A). Three linkage analyses were performed: (1) CMM alone - all individuals without confirmed melanoma or borderline lesions were considered unaffected (model I); (2) CMM/DN with variable age at onset and sporadics (model II); and (3) CMM/DN using the model of Bale et al. (model III). For CMM alone and D1S47, Z[sub max] = 3.12 at [theta] = .10. For D1S160 and CMM alone, Z[sub max] = 1.76 at [theta] = .10. PND showed no evidence for linkage to CMM alone. Models II and III showed strong evidence for linkage to D1S47, D1S160, and PND in the set A pedigrees but not in the set B families. The authors tested for homogeneity of CMM/DN (model II) by splitting families into two groups on the basis of (1) the proportion of CMM/DN cases and (2) the occurrence of immune-related tumors. In group 1 there was significant evidence of heterogeneity with both D1S47 and D1S160, and in group 2 there was significant evidence of heterogeneity with D1S160. Thus, diagnostic, clinical, and genetic heterogeneity are the likely reasons that previous studies have failed to confirm linkage of CMM/DN to chromosome 1p. The results showed significant evidence for a CMM locus linked to D1S47, as well as significant evidence for heterogeneity with only a subset of the families appearing linked to chromosome 1p. 38 refs., 1 fig., 5 tabs.

  6. Country of origin, age at migration and risk of cutaneous melanoma: a migrant cohort study of 1,100,000 Israeli men.

    Science.gov (United States)

    Levine, Hagai; Afek, Arnon; Shamiss, Ari; Derazne, Estela; Tzur, Dorit; Astman, Nadav; Keinan-Boker, Lital; Mimouni, Daniel; Kark, Jeremy D

    2013-07-15

    Cutaneous melanoma (CM) is a common cancer with increasing incidence in many parts of the world where light-skinned populations live. We conducted a large-scale nationally representative migrant cohort study to assess country of origin and age at migration as predictors of CM, controlling for possible confounders. Data on 1,086,569 Israeli Jewish males, who underwent a general health examination before compulsory military service at ages 16-19 between the years 1967-2005, were linked to Israel National Cancer Registry to obtain incident CM up to 2006. Cox proportional hazards was used to model time to event. Overall, 1562 incident cases were detected during 19.3 million person-years of follow-up. Origin was a strong independent predictor of CM. Incidence was higher for European (hazard ratio [HR] = 4.08, 95% confidence interval [CI]: 3.55-4.67) and Israeli origin (HR = 2.92, 95% CI: 2.25-3.79) compared to N. African/Asian origin, adjusted for year of birth, years of education, residential socio-economic position, rural residence and body surface area (or height). Among those of European origin, the adjusted risk was significantly lower for those who immigrated after the age of 10 years (HR = 0.58, 95% CI: 0.45-0.73) but not for younger ages (HR = 1.02, 95% CI 0.84-1.23) compared to Israeli born. The high rates of CM among men of European origin and the almost twofold lower risk among those immigrating after age 10 provide solid support for the deleterious role of childhood sun exposure as a risk factor for melanoma. These findings will serve in directing public health and research efforts. Copyright © 2013 UICC.

  7. Stage-specific survival and recurrence in patients with cutaneous malignant melanoma in Europe – a systematic review of the literature

    Directory of Open Access Journals (Sweden)

    Svedman FC

    2016-05-01

    Full Text Available Fernanda Costa Svedman,1 Demetris Pillas,2 Aliki Taylor,2 Moninder Kaur,2 Ragnar Linder,3 Johan Hansson1 1Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden; 2Centre for Observational Research, Amgen Ltd, Uxbridge, UK; 3IMS Health Sweden, Stockholm, Sweden Background: Given the increasing incidence in cutaneous malignant melanoma (CMM and the recent changes in the treatment landscape, it is important to understand stage-specific overall and recurrence-free survival patterns in Europe. Despite publications such as EUROCARE-5, there is limited information on stage-specific survival for CMM in Europe. Method: We carried out a systematic literature review to provide an up-to-date summary of stage-specific survival and recurrence-free survival patterns in patients with CMM in Europe. Studies were included if they were published in Medline during the past 12 years and included information on stage-specific survival and/or recurrence in CMM. Results: Of the 8,749 studies identified, 26 studies were included, representing nine countries. Collectively, the studies covered a population of 152,422 patients and included data from 1978 to 2011. Randomized clinical trials and single-center observational studies comprised the most common study designs, including five large registry-based studies. Stage-specific information for survival and recurrence varied: 5-year overall survival: 95%–100% (stage I, 65%–92.8% (stage II, 41%–71% (stage III, and 9%–28% (stage IV; 5-year relapse-free survival was reported less frequently: 56% (stage II, and 28%–44% (stage III. Studies reporting survival by sentinel node (SN status reported 5-year overall survival as 80%–95% for negative SN (stage I/II and 35%–75% for positive SN (stage III status; recurrence-free survival at 5 years: 76%–90% for negative and 35%–58% for positive SN status. Some studies included comparisons of survival by key patient

  8. Integrative genome comparison of primary and metastatic melanomas.

    Directory of Open Access Journals (Sweden)

    Omar Kabbarah

    2010-05-01

    Full Text Available A cardinal feature of malignant melanoma is its metastatic propensity. An incomplete view of the genetic events driving metastatic progression has been a major barrier to rational development of effective therapeutics and prognostic diagnostics for melanoma patients. In this study, we conducted global genomic characterization of primary and metastatic melanomas to examine the genomic landscape associated with metastatic progression. In addition to uncovering three genomic subclasses of metastastic melanomas, we delineated 39 focal and recurrent regions of amplification and deletions, many of which encompassed resident genes that have not been implicated in cancer or metastasis. To identify progression-associated metastasis gene candidates, we applied a statistical approach, Integrative Genome Comparison (IGC, to define 32 genomic regions of interest that were significantly altered in metastatic relative to primary melanomas, encompassing 30 resident genes with statistically significant expression deregulation. Functional assays on a subset of these candidates, including MET, ASPM, AKAP9, IMP3, PRKCA, RPA3, and SCAP2, validated their pro-invasion activities in human melanoma cells. Validity of the IGC approach was further reinforced by tissue microarray analysis of Survivin showing significant increased protein expression in thick versus thin primary cutaneous melanomas, and a progression correlation with lymph node metastases. Together, these functional validation results and correlative analysis of human tissues support the thesis that integrated genomic and pathological analyses of staged melanomas provide a productive entry point for discovery of melanoma metastases genes.

  9. Formaldehyde solutions in simulated sweat increase human melanoma but not normal human keratinocyte cells proliferation.

    Science.gov (United States)

    Rizzi, M; Cravello, B; Tonello, S; Renò, F

    2016-12-01

    Our skin is in close contact with clothes most of the time thus risking potentially noxious chemicals contact. One of the potentially harmful manufacturing by-products that can be released by textiles when sweating is formaldehyde, used as an anti-crease treatment. As it is known to be carcinogenic to humans and a potent skin sensitizer, the aim of this study was to investigate its effects on both normal human keratinocytes (HaCaT cells) and on a highly invasive malignant melanoma cell line (SK-MEL-28) in order to contribute to the definition of safety cut-off to be applied to the production processes. Formaldehyde concentrations below the commonly accepted limits (10-50μM) were obtained by diluting formaldehyde in simulated sweat (UNI EN ISO 105-E04). The effects on cell proliferation were evaluated by cell counting, while ERK pathway activation was evaluated by western blot. Low concentrations of formaldehyde (10μM) in both acidic and alkaline simulated sweat were able to increase malignant melanoma cell proliferation, while not affecting normal keratinocytes. Melanoma proliferation increase was greater in acidic (pH=5.5) than in alkaline (pH=8) conditions. Moreover, formaldehyde stimulation was able to induce ERK pathway activation. The data obtained suggest the need for an even increasing attention to the potentially harmful effects of textile manufacturing by-products. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Human malignant melanoma-derived progestagen-associated endometrial protein immunosuppresses T lymphocytes in vitro.

    Directory of Open Access Journals (Sweden)

    Suping Ren

    Full Text Available Progestagen-associated endometrial protein (PAEP is a glycoprotein of the lipocalin family that acts as a negative regulator of T cell receptor-mediated activation. However, the function of tumor-derived PAEP on the human immune system in the tumor microenvironment is unknown. PAEP is highly expressed in intermediate and thick primary melanomas (Breslow's 2.5mm or greater and metastatic melanomas, correlating with its expression in daughter cell lines established in vitro. The current study investigates the role of melanoma cell-secreted PAEP protein in regulating T cell function. Upon the enrichment of CD3+, CD4+ and CD8+ T cells from human peripheral blood mononuclear cells, each subset was then mixed with either melanoma-derived PAEP protein or PAEP-poor supernatant of gene-silenced tumor cells. IL-2 and IFN-γ secretion of CD4+ T cells significantly decreased with the addition of PAEP-rich supernatant. And the addition of PAEP-positive cell supernatant to activated lymphocytes significantly inhibited lymphocyte proliferation and cytotoxic T cell activity, while increasing lymphocyte apoptosis. Our result suggests that melanoma cell-secreted PAEP protein immunosuppresses the activation, proliferation and cytotoxicity of T lymphocytes, which might partially explain the mechanism of immune tolerance induced by melanoma cells within the tumor microenvironment.

  11. Dissection of T-cell antigen specificity in human melanoma.

    Science.gov (United States)

    Andersen, Rikke Sick; Thrue, Charlotte Albæk; Junker, Niels; Lyngaa, Rikke; Donia, Marco; Ellebæk, Eva; Svane, Inge Marie; Schumacher, Ton N; Thor Straten, Per; Hadrup, Sine Reker

    2012-04-01

    Tumor-infiltrating lymphocytes (TIL) isolated from melanoma patients and expanded in vitro by interleukin (IL)-2 treatment can elicit therapeutic response after adoptive transfer, but the antigen specificities of the T cells transferred have not been determined. By compiling all known melanoma-associated antigens and applying a novel technology for high-throughput analysis of T-cell responses, we dissected the composition of melanoma-restricted T-cell responses in 63 TIL cultures. T-cell reactivity screens against 175 melanoma-associated epitopes detected 90 responses against 18 different epitopes predominantly from differentiation and cancer-testis antigens. Notably, the majority of these responses were of low frequency and tumor-specific T-cell frequencies decreased during rapid expansion. A further notable observation was a large variation in the T-cell specificities detected in cultures established from different fragments of resected melanoma lesions. In summary, our findings provide an initial definition of T-cell populations contributing to tumor recognition in TILs although the specificity of many tumor-reactive TILs remains undefined.

  12. Pigmentary traits, modalities of sun reaction, history of sunburns, and melanocytic nevi as risk factors for cutaneous malignant melanoma in the Italian population: results of a collaborative case-control study.

    Science.gov (United States)

    Naldi, L; Lorenzo Imberti, G; Parazzini, F; Gallus, S; La Vecchia, C

    2000-06-15

    To the authors' knowledge, limited data are available from Mediterranean populations concerning risk factors for malignant melanoma. A few Italian case-control studies have produced conflicting results regarding the association between malignant melanoma and pigmentary traits, sunburns, and melanocytic nevi. A case-control study was conducted within the framework of the Italian Group for Epidemiologic Research in Dermatology (GISED). Twenty-seven centers in the north and south of Italy participated. A total of 542 cases and 538 controls were entered onto the study. A standardized questionnaire was administered to cases and controls. Cases and controls also were examined by trained dermatologists who were required to count the number of melanocytic nevi (those measuring > or = 2 mm and > 6 mm in greatest dimension, separately) and to make judgments regarding pigmentary traits. In the multivariate analysis, eye and skin color, propensity to sunburn, history of sunburns before age 15 years, and solar lentigines all were associated with malignant melanoma. In addition, the risk of melanoma increased with the number of melanocytic nevi > or = 2 mm. Nevi > 6 mm in greatest dimension had effects on risk that appeared to be independent from the effects of smaller nevi (2-6 mm). The results of the current study largely are similar to those obtained in northern European countries, the U.S., and Australia and provide further evidence of the importance of selected pigmentary traits, sun exposure, and the number of melanocytic nevi in the risk of cutaneous malignant melanoma. Copyright 2000 American Cancer Society.

  13. Inherited variants in the MC1R gene and survival from cutaneous melanoma: a BioGenoMEL study

    Science.gov (United States)

    Davies, John R; Randerson-Moor, Juliette; Kukalizch, Kairen; Harland, Mark; Kumar, Rajiv; Madhusudan, Srinivasan; Nagore, Eduardo; Hansson, Johan; Höiom, Veronica; Ghiorzo, Paola; Gruis, Nelleke A; Kanetsky, Peter A; Wendt, Judith; Pjanova, Dace; Puig, Susana; Saiag, Philippe; Schadendorf, Dirk; Soufir, Nadem; Okamoto, Ichiro; Affleck, Paul; García-Casado, Zaida; Ogbah, Zighereda; Ozola, Aija; Queirolo, Paola; Sucker, Antje; Barrett, Jennifer H; van Doorn, Remco; Bishop, D Timothy; Newton-Bishop, Julia

    2012-01-01

    Summary Inherited MC1R variants modulate MITF transcription factor signaling, which in turn affects tumor cell proliferation, apoptosis, and DNA repair. The aim of this BioGenoMEL collaborative study in 10 melanoma cohorts was to test the hypothesis that inherited variants thereby moderate survival expectation. A survival analysis in the largest cohort (Leeds) was carried out adjusting for factors known to impact on survival. The results were then compared with data from nine smaller cohorts. The absence of any consensus MC1R alleles was associated with a significantly lower risk of death in the Leeds set (HR, 0.64; 95% CI, 0.46–0.89) and overall in the 10 data sets (HR, 0.78; 95% CI, 0.65–0.94) with some support from the nine smaller data sets considered together (HR, 0.83; 95% CI, 0.67–1.04). The data are suggestive of a survival benefit for inherited MC1R variants in melanoma patients. PMID:22325793

  14. Expression of glycoprotein non-metastatic melanoma protein B in cutaneous malignant and benign lesions: a tissue microarray study.

    Science.gov (United States)

    Zhao, Yan; Qiao, Zheng-guo; Shan, Shi-jun; Sun, Qing-miao; Zhang, Jian-zhong

    2012-09-01

    Glycoprotein non-metastatic melanoma protein B (GPNMB) plays an important role in the pathogenesis of inflammatory and malignant diseases. We investigated the expression of GPNMB in benign and malignant skin diseases. Tissue microarray was performed in the skin tissues of 102 cases including malignant melanoma (MM), squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and benign dermatosis. The expression of GPNMB in the tissues was detected by immunohistochemistry. Twenty cases of normal skin and adjacent neoplastic normal skin tissues were selected as controls. GPNMB was positively stained in skin malignancies (38/50, 76%), which was significantly higher than that in the control and the benign skin tissues (P = 0.001 and < 0.001 respectively). GPNMB was positively stained in MM (13/15, 87%) and SCC (16/20, 80%) (P < 0.001). Significant higher expression of GPNMB was observed in patients aged ≥ 65 years than those less than 65 years (n = 11 and n = 9 respectively, P = 0.027). No significant difference of the expression rates was observed between normal control and BCC; however, stronger intensity was detected in the latter. Negative or weak expression was observed in the controls. Over-expression of GPNMB correlated strongly and might play an important role in the pathogenesis of MM and SCC.

  15. PRMT1 regulates tumor growth and metastasis of human melanoma via targeting ALCAM.

    Science.gov (United States)

    Li, Lei; Zhang, Zhengwen; Ma, Tengxiao; Huo, Ran

    2016-07-01

    Overexpression of protein arginine methyltransferases (PRMTs) is associated with various types of cancer. The present study aimed to determine the expression level of PRMT1 in human melanoma and investigate its biological function. The clinical significance of PRMT1 was determined by screening the Oncomine database, and the increased expression of PRMT in melanoma was confirmed by western blot analysis. Furthermore, the current study demonstrated that PRMT1 was overexpressed in melanoma cell lines compared with human immortalized keratinocytes and PIG1 immortalized human melanocytes. Silencing PRMT1 in A375 and Hs294T cells significantly suppressed tumor growth and metastatic ability of the melanoma cell line compared with the negative control. These changes were in accordance with the upregulation of the cadherin 1 level and downregulation of several metastatic‑associated genes determined by a quantitative polymerase chain reaction array. Liquid chromatography‑mass spectrometry demonstrated that activated leukocyte cell adhesion molecule (ALCAM) may be a direct target of PRMT1, and the interaction was confirmed by co‑immunoprecipitation. Compared with negative controls, the protein level of ALCAM was decreased following the silencing of PRMT1, and re‑expression of ALCAM in A375/shPRMT1 or Hs294T/shPRMT1 cells using an expression vector restored the colony formation and metastatic ability of the cells. In conclusion, the current results indicated that PRMT1 is overexpressed in human melanoma, and may regulate tumor growth and metastasis via targeting ALCAM.

  16. Differential BMI1, TWIST1, SNAI2 mRNA expression pattern correlation with malignancy type in a spectrum of common cutaneous malignancies: basal cell carcinoma, squamous cell carcinoma, and melanoma.

    Science.gov (United States)

    Vand-Rajabpour, F; Sadeghipour, N; Saee-Rad, S; Fathi, H; Noormohammadpour, P; Yaseri, M; Hesari, K K; Bagherpour, Z; Tabrizi, M

    2017-04-01

    Melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) can be used as a unique model to identify molecular mechanisms to distinguish rarely metastatic (BCC), often metastatic (SCC) and most metastatic (melanoma) cancer. It is known that epithelial-mesenchymal transition and stemness transcription factors (TWIST1, SNAI2/SLUG, and BMI1) play an important role in metastasis and their dysregulation has been demonstrated in metastatic cancers. We hypothesized that this spectrum of cutaneous cancers (BCC, SCC, and melanoma) would be a unique cancer model system to elucidate steps toward cancer invasion and metastasis. We evaluated the mRNA expression level of BMI1, TWIST1, and SNAI2/SLUG and studied clinicopathological features in 170 skin cancers along with normal tissue samples. We demonstrate downregulation of BMI1 mRNA expression in BCC samples compared with controls (p = 0.0001), SCC (p = 0.001), and melanoma (p = 0.0001) samples. Downregulation of TWIST1 mRNA expression is seen in only BCC samples compared with controls (p = 0.031). High SNAI2 mRNA expression is represented in melanoma samples compared with controls (p = 0.022) and SCC samples (p = 0.031). High mRNA expression of TWIST1 is seen in patients with positive history of cancers. Extremely low mRNA expression of BMI1 is detected in patients with positive history of cancers other than skin cancer. These findings provide support for the hypothesis that the spectrum of cutaneous cancers could be better understood as a series of gene dosage-dependent entities with distinct molecular events. Oncogene-induced senescence, mechanism of which is still unclear, could be one explanation for these results.

  17. 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

  18. Melanoma: Clinical Presentations.

    Science.gov (United States)

    Kibbi, Nour; Kluger, Harriet; Choi, Jennifer Nam

    2016-01-01

    The malignant cell in melanoma is the melanocyte. Because melanocytes are located in the basal layer of the epidermis, melanoma is most commonly seen on the skin. However, melanoma can also arise on mucosal surfaces such as the oral cavity, the upper gastrointestinal mucosa, the genital mucosa, as well as the uveal tract of the eye and leptomeninges. Melanomas tend to be pigmented but can also present as pink or red lesions. They can mimic benign or other malignant skin lesions. This chapter presents the spectrum of typical and less typical presentations of melanoma, as well as patterns of spread. It is divided into (1) cutaneous lesions; (2) patterns of regional spread, (3) non-cutaneous lesions; and (4) distant metastases.

  19. Temporary shielding of hot spots in the drainage areas of cutaneous melanoma improves accuracy of lymphoscintigraphic sentinel lymph node diagnostics

    Energy Technology Data Exchange (ETDEWEB)

    Maza, S.; Valencia, R.; Geworski, L.; Zander, A.; Munz, D.L. [Clinic for Nuclear Medicine, University Hospital Charite, Humboldt University of Berlin, Schumannstrasse 20-21, 10117 Berlin (Germany); Draeger, E.; Winter, H.; Sterry, W. [Clinic for Dermatology, Venereology and Allergology, University Hospital Charite, Humboldt University of Berlin, Berlin (Germany)

    2002-10-01

    Detection of the ''true'' sentinel lymph nodes, permitting correct staging of regional lymph nodes, is essential for management and prognostic assessment in malignant melanoma. In this study, it was prospectively evaluated whether simple temporary shielding of hot spots in lymphatic drainage areas could improve the accuracy of sentinel lymph node diagnostics. In 100 consecutive malignant melanoma patients (45 women, 55 men; age 11-91 years), dynamic and static lymphoscintigraphy in various views was performed after strict intracutaneous application of technetium-99m nanocolloid (40-150 MBq; 0.05 ml/deposit) around the tumour (31 patients) or the biopsy scar (69 patients, safety distance 1 cm). The images were acquired with and without temporary lead shielding of the most prominent hot spots in the drainage area. In 33/100 patients, one or two additional sentinel lymph nodes that showed less tracer accumulation or were smaller (<1.5 cm) were detected after shielding. Four of these patients had metastases in the sentinel lymph nodes; the non-sentinel lymph nodes were tumour negative. In 3/100 patients, hot spots in the drainage area proved to be lymph vessels, lymph vessel intersections or lymph vessel ectasias after temporary shielding; hence, a node interpreted as a non-sentinel lymph node at first glance proved to be the real sentinel lymph node. In two of these patients, lymph node metastasis was histologically confirmed; the non-sentinel lymph nodes were tumour free. In 7/100 patients the exact course of lymph vessels could be mapped after shielding. In one of these patients, two additional sentinel lymph nodes (with metastasis) were detected. Overall, in 43/100 patients the temporary shielding yielded additional information, with sentinel lymph node metastases in 7%. In conclusion, when used in combination with dynamic acquisition in various views, temporary shielding of prominent hot spots in the drainage area of a malignant melanoma of the

  20. Critérios histopatológicos para diagnóstico de melanoma maligno cutâneo: análise comparativa de sua freqüência em lesões benignas e melanomas de pequena espessura (< 2 mm Histopathological criteria for cutaneous malignant melanoma: comparative analysis between benign and thin malignant lesions (< 2 mm

    Directory of Open Access Journals (Sweden)

    Luiz Alberto Veronese

    2007-10-01

    Full Text Available INTRODUÇÃO: A histopatologia convencional continua sendo o padrão-ouro no diagnóstico dos melanomas cutâneos, apesar do progresso da imuno-histoquímica e da biologia molecular. Os critérios microscópicos existentes para esse diagnóstico são numerosos, porém nenhum deles é específico para se afirmar que uma determinada lesão é maligna quando ele está presente, ou é benigna na sua ausência. Alguns critérios têm uma relevância maior para o diagnóstico em relação a outros. OBJETIVO: Este estudo propõe uma análise daqueles critérios considerados mais importantes, comparando sua presença em lesões melanocíticas benignas e melanomas. MATERIAL E MÉTODOS: Foram estudadas 33 lesões melanocíticas benignas (nevo de Spitz: 13; nevo de Reed: 6; nevo displásico: 6; nevo congênito: 3; nevo adquirido: 3; nevo combinado: 1; nevo recorrente: 1, bem como 101 casos de melanomas extensivo/superficiais: 25 intra-epidérmicos e 76 invasivos de pequena espessura (INTRODUCTION: Conventional histopathology has been considered as the gold standard in the diagnosis of cutaneous malignant melanoma, despite the progress of molecular biology and immunohistochemistry. There are many microscopic criteria for diagnosis of melanoma, however there is not a single one that can be useful to define malignancy. AIM: Our purpose is to analyse the criteria considered more important to the diagnosis of melanoma, comparing their presence in benign melanocytic lesions and melanomas. MATERIAL AND METHODS: We studied 33 benign melanocytic lesions (Spitz nevi, 13; Reed nevi, 6; dysplastic nevi, 6; congenital nevi, 3; acquired nevi, 3; combined nevus, 1; recurrent nevus, 1 and 101 extensive/superficial melanomas (25 in situ and 76 invasive up to 2 mm thickness. RESULTS: Some criteria showed high frequency in benign lesions, showing low-specificity, while others had low-positivity in the benign and high-frequency in malignant lesions, consequently high

  1. In vitro efficiency and mechanistic role of indocyanine green as photodynamic therapy agent for human melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Mamoon, A.M.; Miller, L.; Gamal-Eldeen, A. M.; Ruppel, M. E.; Smith, R. J.; Tsang, T.; Miller, L. M.

    2009-05-02

    Photodynamic therapy (PDT) is a promising treatment for superficial cancer. However, poor therapeutic results have been reported for melanoma, due to the high melanin content. Indocyanine green (ICG) has near infrared absorption (700-800 nm) and melanins do not absorb strongly in this area. This study explores the efficiency of ICG as a PDT agent for human melanoma, and its mechanistic role in the cell death pathway. Human skin melanoma cells (Sk-Mel-28) were incubated with ICG and exposed to a low power Ti:Sapphire laser. Synchrotron-assisted Fourier transform infrared microspectroscopy and hierarchical cluster analysis were used to assess the cell damage and changes in lipid, protein, and nucleic acids. The cell death pathway was determined by analysis of cell viability and apoptosis and necrosis markers. In the cell death pathway, {sup 1}O{sub 2} generation evoked rapid multiple consequences that trigger apoptosis after laser exposure for only 15min including the release of cytochrome c, the activation of total caspases, caspase-3, and caspase-9, the inhibition of NF-{Kappa}B P65, and the enhancement of DNA fragmentation, and histone acetylation. ICG/PDT can efficiently and rapidly induce apoptosis in human melanoma cells and it can be considered as a new therapeutic approach for topical treatment of melanoma.

  2. Cutaneous human papillomavirus types detected on the surface of male external genital lesions: A case series within the HPV Infection in Men Study

    Science.gov (United States)

    Pierce Campbell, Christine M.; Messina, Jane L.; Stoler, Mark H.; Jukic, Drazen M.; Tommasino, Massimo; Gheit, Tarik; Rollison, Dana E.; Sichero, Laura; Sirak, Bradley A.; Ingles, Donna J.; Abrahamsen, Martha; Lu, Beibei; Villa, Luisa L.; Lazcano-Ponce, Eduardo; Giuliano, Anna R.

    2013-01-01

    Background Cutaneous human papillomaviruses (HPVs) may be associated with cutaneous epithelial lesions and non-melanoma skin cancers. No study has systematically evaluated the presence of genus beta [β]-HPV in male genital skin or external genital lesions (EGLs). Objectives To examine cutaneous β-HPV types detected on the surface of EGLs in men and describe their presence prior to EGL development. Study design A retrospective case series was conducted among 69 men with pathologically confirmed EGLs (n=72) who participated in the HPV Infection in Men Study. Archived exfoliated cells collected from the surface of each EGL and normal genital skin specimens 6–12 months preceding EGL development were tested for β-HPV DNA using a type-specific multiplex genotyping assay. Results β-HPV DNA was detected on 61.1% of all EGLs, with types 38 (16.7%), 5 (15.3%), and 12 (12.5%) most commonly identified. HPV prevalence differed across pathological diagnoses, with the largest number of β-HPV types detected on condylomas. Most β-HPV types were detected on normal genital skin prior to EGL development, though the prevalence was lower on EGLs compared to preceding normal genital skin. Conclusions EGLs and the normal genital skin of men harbor a large number of β-HPV types; however, it appears that β-HPVs are unrelated to EGL development in men. Despite evidence to support a causal role in skin carcinogenesis at UVR-exposed sites, cutaneous HPV appears unlikely to cause disease at the UVR-unexposed genitals. PMID:24210970

  3. Oral amelanotic melanoma.

    Science.gov (United States)

    Adisa, A O; Olawole, W O; Sigbeku, O F

    2012-06-01

    Malignant melanomas of the mucosal regions of the head and neck are extremely rare neoplasms accounting for less than 1% of all melanomas. Approximately half of all head and neck melanomas occur in the oral cavity. Less than 2% of all melanomas lack pigmentation, in the oral mucosa however, up to 75% of cases are amelanotic. No etiologic factors or risk factors have been recognized for oral melanomas. Some authors have suggested that oral habits and selfmedication may be of etiological significance. Oral melanoma is rare but it is relatively frequent in countries like Japan, Uganda, and India. It is rarely identified under the age of 20 years. In Australia where cutaneous melanomas are relatively common primary melanoma of the oral mucosa is rare. The surface architecture of oral melanomas ranges from macular to ulcerated and nodular. The lesion is said to be asymptomatic in the early stages but may become ulcerated and painful in advanced lesions. The diagnosis of amelanotic melanoma is more difficult than that of pigmented lesions. The neoplasm consists of spindle-shaped cells with many mitotic figures and no cytoplasmic melanin pigmentation. Immunohistochemistry using S-100, HMB-45, Melan-A and MART-1 will help in establishing the correct diagnosis. Radical surgery with ample margins and adjuvant chemotherapy are appropriate management protocol for malignant melanoma. Oral melanoma is associated with poor prognosis but its amelanotic variant has even worse prognosis because it exhibits a more aggressive biology and because of difficulty in diagnosis which leads to delayed treatment.

  4. Cutaneous silent period in human FDI motor units.

    Science.gov (United States)

    Kahya, Mehmet C; Yavuz, S Utku; Türker, Kemal S

    2010-09-01

    In this study, we aimed to use both the probability-based and the frequency-based analyses methods simultaneously to examine cutaneous silent period (CSP) induced by strong electrical currents. Subjects were asked to contract their first dorsal interosseus muscles so that one motor unit monitored via intramuscular wire electrodes discharged at a rate of approximately 8 Hz. Strong electrical stimuli were delivered to the back of the hand that created a subjective discomfort level of between 4 and 7 [0-10 visual analogue scale] and induced cutaneous silent period in all units. It was found that the duration of the CSP was significantly longer when the same data were analysed using frequency-based analysis method compared with the probability-based methods. Frequency-based analysis indicated that the strong electrical stimuli induce longer lasting inhibitory currents than what was indicated using the probability-based analyses such as surface electromyogram and peristimulus time histogram. Usage of frequency-based analysis for bringing out the synaptic activity underlying CSP seems essential as its characteristics have been subject to a large number of studies in experimental and clinical settings.

  5. The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors.

    Science.gov (United States)

    Zingg, Daniel; Debbache, Julien; Schaefer, Simon M; Tuncer, Eylul; Frommel, Sandra C; Cheng, Phil; Arenas-Ramirez, Natalia; Haeusel, Jessica; Zhang, Yudong; Bonalli, Mario; McCabe, Michael T; Creasy, Caretha L; Levesque, Mitchell P; Boyman, Onur; Santoro, Raffaella; Shakhova, Olga; Dummer, Reinhard; Sommer, Lukas

    2015-01-22

    Increased activity of the epigenetic modifier EZH2 has been associated with different cancers. However, evidence for a functional role of EZH2 in tumorigenesis in vivo remains poor, in particular in metastasizing solid cancers. Here we reveal central roles of EZH2 in promoting growth and metastasis of cutaneous melanoma. In a melanoma mouse model, conditional Ezh2 ablation as much as treatment with the preclinical EZH2 inhibitor GSK503 stabilizes the disease through inhibition of growth and virtually abolishes metastases formation without affecting normal melanocyte biology. Comparably, in human melanoma cells, EZH2 inactivation impairs proliferation and invasiveness, accompanied by re-expression of tumour suppressors connected to increased patient survival. These EZH2 target genes suppress either melanoma growth or metastasis in vivo, revealing the dual function of EZH2 in promoting tumour progression. Thus, EZH2-mediated epigenetic repression is highly relevant especially during advanced melanoma progression, which makes EZH2 a promising target for novel melanoma therapies.

  6. Avaliação do perfil epidemiológico e da mortalidade dos pacientes com diagnóstico de melanoma cutâneo primário no município de Florianópolis - SC, Brasil Evaluation of the epidemiological profile and the mortality rate of the patients with primary cutaneous melanoma in Florianopolis - SC, Brazil

    Directory of Open Access Journals (Sweden)

    Rúbia Battisti

    2009-08-01

    Full Text Available FUNDAMENTOS: O melanoma é o câncer cutâneo com maior letalidade. Santa Catarina é o estado brasileiro com maior número de casos desse tumor. OBJETIVOS: Estimar a taxa de mortalidade por melanoma no quinto ano de doença. MÉTODOS: A amostra compreendeu 81 laudos de melanoma primário cutâneo, em 75 pacientes, emitidos em Florianópolis - SC em 2002 e 2003. O protocolo de pesquisa incluiu idade, sexo, cor do paciente e localização anatômica, tipo histológico, grau de invasão, índice de Breslow, infiltrado inflamatório, ulceração, regressão, invasão angiolinfática e estadiamento do tumor. Foi feito contato telefônico com os pacientes para verificar seu status (vivo, morto por melanoma ou morto por outra causa. Para análise estatística, utilizou-se o teste exato de Fisher e a curva de sobrevida de Kaplan-Meier. RESULTADOS: O perfil dos pacientes foi: feminino, branco, 51,3 anos, melanoma invasivo em tronco ou membros, tipo extensivo superficial, Breslow 2,63 mm. A taxa de mortalidade por melanoma cutâneo foi de 7,0%, maior entre homens (11,1%, com Breslow superior a 4,0 mm (66,0%, com ulceração (33,3% e em estádio IV (80,0%. A sobrevida média foi de 56,7 meses. Conclusões: A taxa de mortalidade por melanoma primário cutâneo foi de 7,0%, e a ulceração e o estadiamento final foram os fatores com significância estatística sobre o resultado.BACKGROUND: Melanoma is the cutaneous cancer which has the greatest lethality. Santa Catarina is the Brazilian State that contributes the most to increase this rate. OBJECTIVES: To estimate the mortality rate of melanoma in the fifth year of illness. METHODS: The sample comprises 81 reports of primary cutaneous melanoma, in 75 patients, diagnosed in lorianopolis - SC in 2002 and 2003. The protocol of research includes age, sex, patient's color, anatomical location, histological type, degree of invasion, Breslow index, inflammatory reaction, ulceration, regression, angiolymphatic

  7. Ophiobolin A Induces Autophagy and Activates the Mitochondrial Pathway of Apoptosis in Human Melanoma Cells.

    Directory of Open Access Journals (Sweden)

    Carlo Rodolfo

    Full Text Available Ophiobolin A, a fungal toxin from Bipolaris species known to affect different cellular processes in plants, has recently been shown to have anti-cancer activity in mammalian cells. In the present study, we investigated the anti-proliferative effect of Ophiobolin A on human melanoma A375 and CHL-1 cell lines. This cellular model was chosen because of the incidence of melanoma malignant tumor on human population and its resistance to chemical treatments. Ophyobolin A strongly reduced cell viability of melanoma cells by affecting mitochondrial functionality. The toxin induced depolarization of mitochondrial membrane potential, reactive oxygen species production and mitochondrial network fragmentation, leading to autophagy induction and ultimately resulting in cell death by activation of the mitochondrial pathway of apoptosis. Finally, a comparative proteomic investigation on A375 cells allowed to identify several Ophiobolin A down-regulated proteins, which are involved in fundamental processes for cell homeostasis and viability.

  8. Initial results of imaging melanoma metastasis in resected human lymph nodes using photoacoustic computed tomography

    Science.gov (United States)

    Jose, Jithin; Grootendorst, Diederik J.; Vijn, Thomas W.; Wouters, Michel W.; van Boven, Hester; van Leeuwen, Ton G.; Steenbergen, Wiendelt; Ruers, Theo J. M.; Manohar, Srirang

    2011-09-01

    The pathological status of the sentinel lymph node is important for accurate melanoma staging, ascertaining prognosis and planning treatment. The standard procedure involves biopsy of the node and histopathological assessment of its status. Drawbacks of this examination include a finite sampling of the node with the likelihood of missing metastases, and a significant time-lag before histopathological results are available to the surgeon. We studied the applicability of photoacoustic computed tomographic imaging as an intraoperative modality for examining the status of resected human sentinel lymph nodes. We first applied the technique to image ex vivo pig lymph nodes carrying metastases-simulating melanoma cells using multiple wavelengths. The experience gained was applied to image a suspect human lymph node. We validated the photoacoustic imaging results by comparing a reconstructed slice with a histopathological section through the node. Our results suggest that photoacoustics has the potential to develop into an intraoperative imaging method to detect melanoma metastases in sentinel lymph nodes.

  9. Melanoma: Molecular Pathogenesis and Therapeutic Management

    OpenAIRE

    Liu, Yuxin; Sheikh, M Saeed

    2014-01-01

    Malignant melanoma remains one of the fastest growing cancers worldwide. Although the primary cutaneous melanoma can be managed by surgery, the advanced metastatic melanoma cannot be managed by surgery alone and thus, requires better therapeutic approaches. In view of high mortality rates due to metastatic melanoma, better understanding of the molecular pathogenesis of malignant melanoma is urgently needed. Such information is expected to prove very valuable in early detection of potential me...

  10. Histopathology of cutaneous and mucosal lesions in human paracoccidioidomycosis

    Directory of Open Access Journals (Sweden)

    Fabio Uribe

    1987-04-01

    Full Text Available Biopsies from cutaneous and mucosal lesions from 40 patients with active paracoccidioidomycosis, were studied histopathologically. All cases exhibited chronic granulomatous inflammation and 38 also presented suppuration; this picture corresponded to the mixed mycotic granuloma (MMG. Pseudoepitheliomatous hyperplasia and the transepidermic (or epithelial elimination of the parasite, were observed in all cases. In paracoccidioidomycosis elimination takes place through formation of progressive edema, accompained by exocytosis. The edema gives rise to spongiosis, microvesicles and microabscesses which not only contain the fungus but also, various cellular elements. Cells in charge of the phagocytic process were essentialy Langhans giant cells; PMN's, epithelioid and foreign body giant cells were poor phagocytes. An additional finding was the presence of fibrosis in most biopsies.

  11. Volumetric cutaneous microangiography of human skinin vivoby VCSEL swept-source optical coherence tomography.

    Science.gov (United States)

    Choi, Woo June; Wang, Ruikang K

    Three-dimensional (3D) assessment of cutaneous microcirculation in human skin is essential in the identification of disease states in skin or other organs. Few 3D imaging techniques have revealed the skin micro-vasculatures non-invasively and with sufficient imaging depth. Here, we demonstrate volumetric cutaneous microangiography of the human skin in vivo that utilizes a 1.3 µm high-speed swept-source optical coherence tomography (SS-OCT). The swept source is based on a MEMS tunable vertical cavity surface emission laser (VCSEL) that is advantageous in terms of long coherence length over 50 mm and 100 nm spectral bandwidth that enables the visualization of microstructures within a few mm from the skin surface. We show that skin microvasculature can be delineated in 3D SS-OCT images using ultrahigh-sensitive optical microangiography (UHS-OMAG) with a correlation mapping mask, providing a contrast enhanced blood perfusion map with capillary flow sensitivity. 3D microangiograms of a healthy human finger are shown with distinct cutaneous vessel architectures from different dermal layers and even within hypodermis. These findings suggest that the OCT microangiography could be a beneficial biomedical assay to assess cutaneous vascular functions in clinic.

  12. Human Melanoma-Derived Extracellular Vesicles Regulate Dendritic Cell Maturation

    OpenAIRE

    Maus, Rachel L. G.; Jakub, James W.; Nevala, Wendy K.; Trace A. Christensen; Noble-Orcutt, Klara; Sachs, Zohar; Hieken, Tina J.; Markovic, Svetomir N.

    2017-01-01

    Evolution of melanoma from a primary tumor to widespread metastasis is crucially dependent on lymphatic spread. The mechanisms regulating the initial step in metastatic dissemination via regional lymph nodes remain largely unknown; however, evidence supporting the establishment of a pre-metastatic niche is evolving. We have previously described a dysfunctional immune profile including reduced expression of dendritic cell (DC) maturation markers in the first node draining from the primary tumo...

  13. Substantial expression of luteinizing hormone-releasing hormone (LHRH) receptor type I in human uveal melanoma

    Science.gov (United States)

    Schally, Andrew V.; Block, Norman L; Dezso, Balazs; Olah, Gabor; Rozsa, Bernadett; Fodor, Klara; Buglyo, Armin; Gardi, Janos; Berta, Andras; Halmos, Gabor

    2013-01-01

    Uveal melanoma is the most common primary intraocular malignancy in adults, with a very high mortality rate due to frequent liver metastases. Consequently, the therapy of uveal melanoma remains a major clinical challenge and new treatment approaches are needed. For improving diagnosis and designing a rational and effective therapy, it is essential to elucidate molecular characteristics of this malignancy. The aim of this study therefore was to evaluate as a potential therapeutic target the expression of luteinizing hormone-releasing hormone (LHRH) receptor in human uveal melanoma. The expression of LHRH ligand and LHRH receptor transcript forms was studied in 39 human uveal melanoma specimens by RT-PCR using gene specific primers. The binding charachteristics of receptors for LHRH on 10 samples were determined by ligand competition assays. The presence of LHRH receptor protein was further evaluated by immunohistochemistry. The expression of mRNA for type I LHRH receptor was detected in 18 of 39 (46%) of tissue specimens. mRNA for LHRH-I ligand could be detected in 27 of 39 (69%) of the samples. Seven of 10 samples investigated showed high affinity LHRH-I receptors. The specific presence of full length LHRH receptor protein was further confirmed by immunohistochemistry. A high percentage of uveal melanomas express mRNA and protein for type-I LHRH receptors. Our results support the merit of further investigation of LHRH receptors in human ophthalmological tumors. Since diverse analogs of LHRH are in clinical trials or are already used for the treatment of various cancers, these analogs could be considered for the LHRH receptor-based treatment of uveal melanoma. PMID:24077773

  14. NRAS-mutant melanoma: current challenges and future prospect

    Directory of Open Access Journals (Sweden)

    Muñoz-Couselo E

    2017-08-01

    Full Text Available Eva Muñoz-Couselo,1,2 Ester Zamora Adelantado,1,2 Carolina Ortiz,1,2 Jesús Soberino García,3 José Perez-Garcia31Medical Oncology Department, Vall d’Hebron Hospital, Barcelona, Spain; 2Vall d’Hebron Institute of Oncology (VHIO, Barcelona, Spain; 3Baselga Institute of Oncology, Hospital Quirón, Barcelona, SpainAbstract: Melanoma is one of the most common cutaneous cancers worldwide. Activating mutations in RAS oncogenes are found in a third of all human cancers and NRAS mutations are found in 15%–20% of melanomas. The NRAS-mutant subset of melanoma is more aggressive and associated with poorer outcomes, compared to non-NRAS-mutant melanoma. Although immune checkpoint inhibitors and targeted therapies for BRAF-mutant melanoma are transforming the treatment of metastatic melanoma, the ideal treatment for NRAS-mutant melanoma remains unknown. Despite promising preclinical data, current therapies for NRAS-mutant melanoma remain limited, showing a modest increase in progression-free survival but without any benefit in overall survival. Combining MEK inhibitors with agents inhibiting cell cycling and the PI3K–AKT pathway appears to provide additional benefit; in particular, a strategy of MEK inhibition and CDK4/6 inhibition is likely to be a viable treatment option in the future. Patients whose tumors had NRAS mutations had better response to immunotherapy and better outcomes than patients whose tumors had other genetic subtypes, suggesting that immune therapies – especially immune checkpoint inhibitors – may be particularly effective as treatment options for NRAS-mutant melanoma. Improved understanding of NRAS-mutant melanoma will be essential to develop new treatment strategies for this subset of patients with melanoma.Keywords: metastatic melanoma, NRAS mutation, MEK inhibitor, immunotherapy, trametinib, binimetinib

  15. 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.

  16. Sun exposure before and after a diagnosis of cutaneous malignant melanoma: estimated by developments in serum vitamin D, skin pigmentation and interviews.

    Science.gov (United States)

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

    2011-07-01

    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. To assess changes in UVR exposure in patients with CMM using objective surrogate parameters in a descriptive study. Ten patients recently diagnosed with CMM during the 5 months (autumn and winter) preceding study start in February 2009; 21 patients diagnosed from 12 months to 6 years before study start; and 15 controls, who matched the recently diagnosed patients on age, sex, residential area, constitutive skin type and occupation completed the investigations. UVR exposure before and after diagnosis of CMM was assessed using measures of serum 25-hydro vitamin D [25(OH)D], skin pigmentation and by interviews. Winter 25(OH)D was used as a surrogate parameter of UVR exposure the previous summer - the summer before CMM diagnosis in recently diagnosed patients. Winter 25(OH)D was significantly higher among recently diagnosed patients compared with controls (P = 0·02, R² = 0·60) and patients diagnosed up to 6 years earlier (P = 0·01). The increase in 25(OH)D during the summer after diagnosis was significantly lower for recently diagnosed patients than for controls (P = 0·005, R² = 0·51) and patients diagnosed up to 6 years earlier (P = 0·008). No difference was found in summer 25(OH)D between the groups. Our findings suggest that patients with CMM had a higher UVR exposure the summer before diagnosis than did controls and patients diagnosed up to 6 years earlier, and that after diagnosis UVR exposure fell to the level of controls in patients with CMM. © 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.

  17. Diagnostic Accuracy and Impact of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Preoperative Staging of Cutaneous Malignant Melanoma: Results of a Prospective Study in Indian Population

    Science.gov (United States)

    Chandra, Piyush; Purandare, Nilendu; Shah, Sneha; Agrawal, Archi; Puri, Ajay; Gulia, Ashish; Rangarajan, Venkatesh

    2017-01-01

    The aim of the study was to evaluate the diagnostic accuracy of positron emission tomography/computed tomography (PET/CT) in staging patients with primary cutaneous malignant melanoma (CMM). We further compared the performance of PET/CT with conventional imaging (CI) (CT and ultrasonography [USG]) and assessed the impact of PET/CT on disease management. This was a single institution, prospective, double-blinded study, recruiting a total of 70 treatment naïve patients. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of PET/CT for N staging were 86%, 96%, 80%, and 97%, respectively. The sensitivity, specificity, NPV, and PPV of PET/CT for M staging were 87%, 100%, 93%, and 100%, respectively. The diagnostic accuracy of the PET/CT was superior to CI for N staging (90% vs. 84% for CT and 80% for USG) and M staging (95% vs. 90% for CT). No statistically significant difference was noted between PET/CT and CI for N staging (PET/CT vs. CT, P = 0.125; PET/CT vs. USG, P-0.063) or M staging (PET/CT vs. CT, P = 0.125). PET/CT upstaged 23% of patients with clinically localized disease and 58% of patients with clinically palpable regional nodes. To conclude, fluorodeoxyglucose PET/CT is a highly sensitive and specific imaging modality for preoperative staging of primary CMMs. PET/CT impacts disease management in significant number of patients and should be especially recommended in all patients with clinically palpable regional nodes. PMID:29033677

  18. Cutaneous malignancies of the perineum.

    Science.gov (United States)

    Carr, David; Pootrakul, Llana; Harmon, Jenna; Trotter, Shannon

    2015-03-01

    This review discusses multiple cutaneous malignancies that can present on the perineum. Although all of these neoplasms are uncommon, a focus will be on the more common neoplasms including extramammary Paget disease, basal cell carcinoma, squamous cell carcinoma, and melanoma. Other more rare entities discussed are superficial leiomyosarcoma, giant solitary trichoepithelioma, and cutaneous endometriosis.

  19. Proliferation kinetics of a human malignant melanoma serially grown in nude mice

    DEFF Research Database (Denmark)

    Spang-Thomsen, M; Vindeløv, L L

    1984-01-01

    The technique of labelled mitoses and flow cytometric DNA analysis were used to determine the proliferation kinetics of a human malignant melanoma grown in nude mice. The effect of tumour volume and of long-term serial transplantation on the kinetic parameters was investigated. The results showed...... that the cell loss factor, which was the dominant factor in the growth of this melanoma, increased from 52 to 69% with increasing tumour size, whereas the calculated growth fraction showed no systematic changes. The cell generation time increased from 34 to 44 hr with tumour size, mainly due to a prolongation...

  20. [Establishment of nude mice liver metastatic model of human primary malignant melanoma of the small intestine].

    Science.gov (United States)

    Tuo, Shuai; Zhang, Ning; Liu, Qiu-Zhen

    2008-07-01

    To provide ideal animal models for exploring pathogenesis and experimental therapy of primary malignant melanoma of the small intestine. The histologically intact primary and liver metastatic fragments derived from surgical specimens of one patient with metastatic malignant melanoma of the small intestine were orthotopically implanted in the small intestinal mucous layer of nude mice. The take rate, invasion and liver metastasis were observed. Morphology (light microscopy, electron microscopy), immunophenotype analysis, flow cytometry and karyotype analysis were applied for the original human tumors and the transplanted tumors. The primary and liver metastatic fragments of malignant melanoma of the small intestine were successfully implanted in nude mice. After continuous passages in nude mice,an orthotopic model of human primary malignant melanoma of the small intestine(from the primary focus)in nude mice (termed HSIM-0501) and a liver metastatic model of human primary malignant melanoma of the small intestine (from the liver metastatic focus) in nude mice (termed HSIM-0502) were established. Histological examination of transplanted tumors revealed high-grade melanoma. S-100 protein and HMB45 were positive. Massive melanin granules and melanin complex were seen in cytoplasm of tumor cells.Chromosomal modal number was between 55 and 59. DNA index (DI) was 1.49-1.61, representing heteroploid. HSIM-0501 and HSIM-0502 were maintained for 25 and 27 passages in nude mice respectively. Three hundred and seventeen nude mice were used for transplantation. Both the take rate after transplantation and resuscitation rate of liquid nitrogen cryopreservation were 100%. HSIM-0501 exhibited 46.2% liver metastasis and 36.7% lymph node metastases. In HSIM-0502, both liver and lymph node metastases were 100%.The transplanted tumors autonomically and invasively grew in the small intestines of nude mice and hematogenous metastasis, lymph node metastasis and celiac planting metastasis

  1. c-myc down-regulates class I HLA expression in human melanomas

    NARCIS (Netherlands)

    Versteeg, R.; NOORDERMEER, I. A.; Krüse-Wolters, M.; Ruiter, D. J.; Schrier, P. I.

    1988-01-01

    Expression of class I HLA antigen has been shown to be reduced in a number of human tumours. Here we show that in a panel of 11 melanoma cell lines with variable class I HLA expression an inverse correlation exists between the mRNA levels of c-myc and class I HLA. This suggests that high expression

  2. Laminin-dependent and laminin-independent adhesion of human melanoma cells to sulfatides

    DEFF Research Database (Denmark)

    Roberts, D D; Wewer, U M; Liotta, L A

    1988-01-01

    Sulfatides (galactosylceramide-I3-sulfate) but not neutral glycolipids or gangliosides adsorbed on plastic promote adhesion of the human melanoma cell line G361. Direct adhesion of G361 cells requires densities of sulfatide greater than 1 pmol/mm2. In the presence of laminin, however, specific...... adhesion of G361 cells to sulfatide or seminolipid (galactosylalkylacyl-glycerol-I3-sulfate) but not to other lipids is strongly stimulated and requires only 25 fmol/mm2 of adsorbed lipid. The effects of laminin and sulfatide on adhesion are synergistic, suggesting that laminin is mediating adhesion...... by cross-linking receptors on the melanoma cell surface to sulfatide adsorbed on the plastic. Although thrombospondin binds to sulfatides and G361 cells, it does not enhance, but rather inhibits direct and laminin-dependent G361 cell adhesion to sulfatide. In contrast, C32 melanoma cells also adhere...

  3. Familial melanoma and multiple primary melanoma.

    Science.gov (United States)

    DE Simone, Paola; Valiante, Michele; Silipo, Vitaliano

    2017-06-01

    Cutaneous melanoma (CM) has the highest mortality rates among the most common skin cancers, and its incidence is rising worldwide, thus representing a significant health care burden. CM is considered the most lethal skin cancer if not detected and treated during its early stages. Susceptibility to CM is also associated with an increased presence of atypical nevi and the occurrence of multiple primary melanoma. Personal history of CM increases the risk of developing a second melanoma by 5-8%. A family history of melanoma has also been strongly associated with an increased risk of melanoma. Approximately 5-10% of melanoma cases occur in a familial context. The main genes involved are CDKN2A, CDK4 and MC1R. The recent technological advances have allowed the identification of new genes involved in melanoma susceptibility: breast cancer 1 (BRCA1), BRCA1-associated protein 1 (BAP1), and telomerase reverse transcriptase (TERT).Tests on these genes allow to identify a larger number of high-risk individuals with a potential of developing familial melanoma and primary multiple melanomas. These patients also have a high risk of developing internal organ malignancies, especially pancreatic cancer. It is essential that these individuals receive adequate management along with frequent dermatological examinations, dermoscopic evaluation, genetic counselling and instrumental examinations aimed at the early identification of other tumors associated with CM.

  4. Effect of Genistein on vasculogenic mimicry formation by human uveal melanoma cells

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    Gu Haijuan

    2009-09-01

    Full Text Available Abstract Background Vasculogenic mimicry (VM was increasingly recognized as a form of aggressive melanoma acquiring blood supply. Genistein had attracted much attention as a potential anticancer agent. Therefore, we examined the effect of Genistein on VM in human uveal melanoma cells. Methods VM structure was detected by periodic acid-Schiff (PAS staining for uveal melanoma C918 cells cultured on the three-dimensional type I collagen gels after exposed to Genistein. We used reverse transcription polymerase chain reaction (RT-PCR and Western Blot analysis to examine the effect of Genistein on vascular endothelial cadherin (VE-cadherin mRNA and protein expression. The nude mice models of human uveal melanoma C918 cells were established to assess the number of VM using immunohistochemical and PAS double-staining. Results Genistein inhibited the survival of C918 cells in vitro. The ectopic model study showed that VM in tumor tissue sections were significantly reduced by Genistein in vivo. In vitro, the VM structure was found in control, 25 and 50 μM Genistein-treatment groups but not in 100 and 200 μM. RT-PCR and Western Blot showed that 100 and 200 μM concentration of Genistein could significantly decrease VE-cadherin mRNA and protein expression of C918 cells compared with control (P 0.05. Conclusion Genistein inhibits VM formation of uveal melanoma cells in vivo and in vitro. One possible underlying molecular mechanism by which Genistein could inhibit VM formation of uveal melanoma is related to down-regulation of VE-cadherin.

  5. Selective cytotoxic effect of 1-O-undecylglycerol in human melanoma cells

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    Marian Hernández-Colina

    2016-04-01

    Full Text Available Context: 1-O-alkylglycerols are ether-linked glycerols derived from shark liver oil and found in small amounts in human milk. Previous studies showed antineoplastic activity for this family of compounds, structurally related to alkylphospholipids, but the activity of linear chain synthetic alkylglycerols in cancer cell lines is less documented. Melanoma is a high incidence cancer, highly resistant to potential treatments. Finding new anti-cancer compounds to improve melanoma prognosis is a relevant research issue. Aims: To study the cytotoxic effect of 1-O-undecylglycerol in primary cultured normal fibroblasts and A375 human melanoma cell line. Methods: Cells were treated with different concentrations of 1-O-undecylglycerol and viability assessed by MTT assay. Morphological changes were visualized by DAPI and acridine orange-ethidium bromide staining. Mitochondrial membrane potential was evaluated, and gene expression of P53 and BcL-2 was semi-quantified. Results: 1-O-undecylglycerol decreased viability of A375 cells and exerted very low cytotoxicity on primary cultured normal fibroblasts. Necrosis appeared in A375 cells but not in fibroblasts, and no apoptotic changes were visualized in DAPI staining experiments. After 24 h fibroblasts and melanoma cells developed mitochondrial potential changes similar to valinomycin. The gene expression of P53 and BcL-2 decreased in treated cells. Conclusions: 1-O-undecylglycerol exhibited selective cytotoxic activity in A375 melanoma cells when compared with primary cultured fibroblast. Its toxicity is mediated by necrosis that may be related with mitochondrial events and decrease in P53 and BcL-2 expression. The results suggest that UDG could be a useful strategy to combine with other chemotherapeutic agents in melanoma treatment.

  6. Intralesional isotype profiles in human localized cutaneous leishmaniasis lesions

    Science.gov (United States)

    Aragort De Rossell, Raiza; Calcagno, Marina; Rossell, Osmán; Maizo De Segnini, Zulay; Rodríguez, Ana María

    2001-01-01

    This immunocytochemical study evaluates the presence of IgG1–4, IgA and IgE immunoglobulins in active lesions of 25 localized cutaneous leishmaniasis patients from three bioclimatic areas (Awa, Afa and Bsha) in Mérida State, Venezuela. All immunoglobulin isotypes except IgE were detected, with variable intensity, in one or more of the epidermal or dermal components of skin lesions. IgG1 and IgG2 were detected significantly more frequently than IgG3, IgG4 and IgA. The ranking of the isotypes according to frequency of detection was the same in all areas: IgG1 = IgG2 > IgG3 = IgG4 = IgA, but considered as whole, all isotypes were detected significantly more frequently in patients from the Awa area than in those from the Bsha area. The predominant expression of isotypes IgG1 and IgG2 suggests a preferential Th1 like immune response. Anti-Leishmania immunoserum stained only parasites and their debris, suggesting that most of the immunostaining was nonspecific. PMID:11454104

  7. The metastatic microenvironment: Claudin-1 suppresses the malignant phenotype of melanoma brain metastasis.

    Science.gov (United States)

    Izraely, Sivan; Sagi-Assif, Orit; Klein, Anat; Meshel, Tsipi; Ben-Menachem, Shlomit; Zaritsky, Assaf; Ehrlich, Marcelo; Prieto, Victor G; Bar-Eli, Menashe; Pirker, Christine; Berger, Walter; Nahmias, Clara; Couraud, Pierre-Olivier; Hoon, Dave S B; Witz, Isaac P

    2015-03-15

    Brain metastases occur frequently in melanoma patients with advanced disease whereby the prognosis is dismal. The underlying mechanisms of melanoma brain metastasis development are not well understood. Identification of molecular determinants regulating melanoma brain metastasis would advance the development of prevention and therapy strategies for this disease. Gene expression profiles of cutaneous and brain-metastasizing melanoma variants from three xenograft tumor models established in our laboratory revealed that expression of tight junction component CLDN1 was lower in the brain-metastasizing variants than in cutaneous variants from the same melanoma. The objective of our study was to determine the significance of CLDN1 downregulation/loss in metastatic melanoma and its role in melanoma brain metastasis. An immunohistochemical analysis of human cells of the melanocyte lineage indicated a significant CLDN1 downregulation in metastatic melanomas. Transduction of melanoma brain metastatic cells expressing low levels of CLDN1 with a CLDN1 retrovirus suppressed their metastatic phenotype. CLDN1-overexpressing melanoma cells expressed a lower ability to migrate and adhere to extracellular matrix, reduced tumor aggressiveness in nude mice and, most importantly, eliminated the formation of micrometastases in the brain. In sharp contrast, the ability of the CLDN1-overexpressing cells to form lung micrometastases was not impaired. CLDN1-mediated interactions between these cells and brain endothelial cells constitute the mechanism underlying these results. Taken together, we demonstrated that downregulation or loss of CLDN1 supports the formation of melanoma brain metastasis, and that CLDN1 expression could be a useful prognostic predictor for melanoma patients with a high risk of brain metastasis. © 2014 UICC.

  8. 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.

  9. Theranostic Properties of a Survivin-Directed Molecular Beacon in Human Melanoma Cells

    Science.gov (United States)

    Carpi, Sara; Fogli, Stefano; Giannetti, Ambra; Adinolfi, Barbara; Tombelli, Sara; Da Pozzo, Eleonora; Vanni, Alessia; Martinotti, Enrica; Martini, Claudia; Breschi, Maria Cristina; Pellegrino, Mario

    2014-01-01

    Survivin is an inhibitor of apoptosis overexpressed in different types of tumors and undetectable in most terminally differentiated normal tissues. In the current study, we sought to evaluate the in vitro theranostic properties of a molecular beacon-oligodeoxynucleotide (MB) that targets survivin mRNA. We used laser scanning confocal microscopy to study MB delivery in living cells and real-time PCR and western blot to assess selective survivin-targeting in human malignant melanoma cells. We further assess the pro-apoptotic effect of MB by measuring internucleosomal DNA fragmentation, dissipation of mitochondrial membrane potential (MMP) and changes in nuclear morphology. Transfection of MB into A375 and 501 Mel cells generated high signal intensity from the cytoplasm, while no signal was detected in the extracellular environment and in survivin-negative cells (i.e., human melanocytes and monocytes). MB time dependently decreased survivin mRNA and protein expression in melanoma cells with the maximum effect reached at 72 h. Treatment of melanoma cells with MB induced apoptosis by significant changes in MMP, accumulation of histone-complexed DNA fragments in the cytoplasm and nuclear condensation. MB also enhanced the pro-apoptotic effect of standard chemotherapeutic drugs tested at clinically relevant concentrations. The MB tested in the current study conjugates the ability of imaging with the pharmacological silencing activity against survivin mRNA in human melanoma cells and may represent an innovative approach for cancer diagnosis and treatment. PMID:25501971

  10. Theranostic properties of a survivin-directed molecular beacon in human melanoma cells.

    Directory of Open Access Journals (Sweden)

    Sara Carpi

    Full Text Available Survivin is an inhibitor of apoptosis overexpressed in different types of tumors and undetectable in most terminally differentiated normal tissues. In the current study, we sought to evaluate the in vitro theranostic properties of a molecular beacon-oligodeoxynucleotide (MB that targets survivin mRNA. We used laser scanning confocal microscopy to study MB delivery in living cells and real-time PCR and western blot to assess selective survivin-targeting in human malignant melanoma cells. We further assess the pro-apoptotic effect of MB by measuring internucleosomal DNA fragmentation, dissipation of mitochondrial membrane potential (MMP and changes in nuclear morphology. Transfection of MB into A375 and 501 Mel cells generated high signal intensity from the cytoplasm, while no signal was detected in the extracellular environment and in survivin-negative cells (i.e., human melanocytes and monocytes. MB time dependently decreased survivin mRNA and protein expression in melanoma cells with the maximum effect reached at 72 h. Treatment of melanoma cells with MB induced apoptosis by significant changes in MMP, accumulation of histone-complexed DNA fragments in the cytoplasm and nuclear condensation. MB also enhanced the pro-apoptotic effect of standard chemotherapeutic drugs tested at clinically relevant concentrations. The MB tested in the current study conjugates the ability of imaging with the pharmacological silencing activity against survivin mRNA in human melanoma cells and may represent an innovative approach for cancer diagnosis and treatment.

  11. Neoantigen landscape dynamics during human melanoma-T cell interactions

    DEFF Research Database (Denmark)

    Verdegaal, Els M. E.; De Miranda, Noel F. C. C.; Visser, Marten

    2016-01-01

    is constant over time is unclear. Here we analyse the stability of neoantigen-specific T-cell responses and the antigens they recognize in two patients with stage IV melanoma treated by adoptive T-cell transfer. The T-cell-recognized neoantigens can be selectively lost from the tumour cell population, either...... by overall reduced expression of the genes or loss of the mutant alleles. Notably, loss of expression of T-cell-recognized neoantigens was accompanied by development of neoantigen-specific T-cell reactivity in tumour-infiltrating lymphocytes. These data demonstrate the dynamic interactions between cancer...

  12. 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

  13. Expression and functions of galectin-7 in human and murine melanomas.

    Directory of Open Access Journals (Sweden)

    Katherine Biron-Pain

    Full Text Available The identification of galectin-7 as a p53-induced gene and its ability to induce apoptosis in many cell types support the hypothesis that galectin-7 has strong antitumor activity. This has been well documented in colon cancer. However, in some cases, such as breast cancer and lymphoma, its high expression level correlates with aggressive subtypes of cancer, suggesting that galectin-7 may have a dual role in cancer progression. In fact, in breast cancer, overexpression of galectin-7 alone is sufficient to promote metastasis to the bone and lung. In the present work, we investigated the expression and function of galectin-7 in melanoma. An analysis of datasets obtained from whole-genome profiling of human melanoma tissues revealed that galectin-7 mRNA was detected in more than 90% of biopsies of patients with nevi while its expression was more rarely found in biopsies collected from patients with malignant melanoma. This frequency, however, was likely due to the presence of normal epidermis tissues in biopsies, as shown our studies at the protein level by immunohistochemical analysis. Using the experimental melanoma B16F1 cell line, we found that melanoma cells can express galectin-7 at the primary tumor site and in lung metastasis. Moreover, we found that overexpression of galectin-7 increased the resistance of melanoma cells to apoptosis while inducing de novo egr-1 expression. Overexpression of galectin-7, however, was insufficient to modulate the growth of tumors induced by the subcutaneous injection of B16F1 cells. It also failed to modulate the dissemination of B16F1 cells to the lung.

  14. The Inhibitory Activity of Luzonicosides from the Starfish Echinaster luzonicus against Human Melanoma Cells

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    Olesya S. Malyarenko

    2017-07-01

    Full Text Available Malignant melanoma is the most dangerous form of skin cancer, with a rapidly increasing incidence rate. Despite recent advances in melanoma research following the approval of several novel targeted and immuno-therapies, the majority of oncological patients will ultimately perish from the disease. Thus, new effective drugs are still required. Starfish steroid glycosides possess different biological activities, including antitumor activity. The current study focused on the determination of the in vitro inhibitory activity and the mechanism of action of cyclic steroid glycosides isolated from the starfish Echinaster luzonicus—luzonicoside A (LuzA and luzonicoside D (LuzD—in human melanoma RPMI-7951 and SK-Mel-28 cell lines. LuzA inhibited proliferation, the formation of colonies, and the migration of SK-Mel-28 cells significantly more than LuzD. Anti-cancer activity has been ascribed to cell cycle regulation and apoptosis induction. The molecular mechanism of action appears to be related to the regulation of the activity of cleaved caspase-3 and poly(ADP-ribose polymerase (PARP, along with Survivin, Bcl-2, p21 and cyclin D1 level. Overall, our findings support a potential anti-cancer efficacy of luzonicosides A and D on human melanoma cells.

  15. Melanoma in the elderly.

    Science.gov (United States)

    Manganoni, Ausilia M; Pizzatti, Laura; Pavoni, Laura; Consoli, Francesca; Damiani, Enrico; Manca, Giorgio; Gualdi, Giulio; Calzavara-Pinton, Piergiacomo

    2017-06-01

    Among older patients, melanoma in general presents biological features related to a more aggressive biology, such as more locally advanced tumor. Management of melanoma in elderly may be difficult, mainly due to comorbidities. We report the experience of the Melanoma Unit of ASST Spedali Civili in Brescia, Italy. Study subjects were drawn from 3444 patients with histological confirmed melanoma. Data were extracted from electronic database of the Melanoma Unit of ASST Spedali Civili in Brescia, Italy. Patients who received diagnosis of cutaneous melanoma at age of 65 years or older were retrospectively evaluated. For each diagnosed melanoma, histological characteristics, treatment, and outcomes were evaluated. Of the 805 patients described in this study, 444 were males and 361 females. Statistically significant differences were found between patients aged 65-80 years and those aged >80 years considering melanoma prognostic factors, such as Breslow thickness, number of mitoses/mm2 and ulceration. Older age is recognized as an independent poor prognostic factor in melanoma patients, and melanoma in older patients have a distinct natural history. It was found that management of cancer in old person represents a major challenge to medical practice. We believe that the choice of therapy should be individualized and based upon the individual's overall health and that, particularly in these cases, management often requires interdisciplinary cooperation between dermatologist, surgical specialist, oncologist and geriatrician.

  16. Antigen expression of metastasizing and non-metastasizing human melanoma cells xenografted into nude mice.

    Science.gov (United States)

    Van Muijen, G N; Cornelissen, L M; Jansen, C F; Figdor, C G; Johnson, J P; Bröcker, E B; Ruiter, D J

    1991-01-01

    In order to study differences in antigen expression related to the different stages of the process of metastasis of human melanoma cell lines, we determined the expression pattern of a series of well-characterized genes in a set of human melanoma cell lines with different metastatic behavior in nude mice. This set included non-metastatic (IF6, 530), sporadically metastatic (M14, Mel 57), and frequently metastatic (BLM, MV3) cell lines after subcutaneous inoculation. To study the phenotype of these cell lines both the cultured cells and representative samples of local tumors at the inoculation site and their metastases in the lungs were immunostained with a panel of monoclonal antibodies directed against melanocytic differentiation or progression antigens. Although most cell lines (IF6, 530, M14 and Mel 57) showed HLA-DR expression in vitro, these antigens were lacking in all xenografted lesions studied with exception of the 530 cell line. 530 Xenografts, however, showed a dramatic down-regulation of HLA-DR compared with the cell line in vitro. The same phenomenon was seen with respect to ICAM-1 expression. The expression of all other antigens studied in xenografts, both in subcutaneous tumors and in lung lesions, was in general comparable to that in the melanoma cell lines in vitro, with exception of the 530 cell line. In all melanoma cell lines except 530 the degree of intra- and interlesional heterogeneity regarding the expression of all antigens studied was limited. Remarkably, comparison of the immunophenotype of the frequently metastasizing (BLM, MV3) and the sporadically (M14, Mel 57) or non-metastasizing (IF6, 530) cell lines showed that the two frequently metastasizing cell lines had marked expression of the progression antigens VLA-2 and epidermal growth factor receptor, and lack of expression of the differentiation antigen NKI-beteb. These findings warrant further studies on the role of these antigens in the process of metastasis of human melanoma cells

  17. Antibody directed against human YKL-40 increases tumor volume in a human melanoma xenograft model in scid mice

    DEFF Research Database (Denmark)

    Salamon, Johannes; Hoffmann, Tatjana; Elies, Eva

    2014-01-01

    Induced overexpression of the secretory protein YKL-40 promotes tumor growth in xenograft experiments. We investigated if targeting YKL-40 with a monoclonal antibody could inhibit tumor growth. YKL-40 expressing human melanoma cells (LOX) were injected subcutenously in Balb/c scid mice. Animals...

  18. Human metastatic melanoma cell lines express high levels of growth hormone receptor and respond to GH treatment

    DEFF Research Database (Denmark)

    Sustarsic, Elahu G; Junnila, Riia K; Kopchick, John J.

    2013-01-01

    Cancer Institute's NCI60 panel includes 60 cancer cell lines from nine types of human cancer: breast, CNS, colon, leukemia, melanoma, non-small cell lung, ovarian, prostate and renal. We utilized this panel to quantify expression of GHR, GH, prolactin receptor (PRLR) and prolactin (PRL) mRNA with real......Accumulating evidence implicates the growth hormone receptor (GHR) in carcinogenesis. While multiple studies show evidence for expression of growth hormone (GH) and GHR mRNA in human cancer tissue, there is a lack of quantification and only a few cancer types have been investigated. The National......-time RT qPCR. Both GHR and PRLR show a broad range of expression within and among most cancer types. Strikingly, GHR expression is nearly 50-fold higher in melanoma than in the panel as a whole. Analysis of human metastatic melanoma biopsies confirmed GHR gene expression in melanoma tissue. In these human...

  19. HER2 as a promising target for cytotoxicity T cells in human melanoma therapy.

    Directory of Open Access Journals (Sweden)

    Juan Ma

    Full Text Available Anti-HER2/neu antibody therapy has been reported to mediate tumor regression of HER2/ neu(+ tumors. Here we demonstrated the expression of HER2 in a wide range of human melanoma cells including a primary culture and seven cell lines, and we further investigated whether HER2 could be served as a target for T cell mediated immunotherapy of human melanoma. Specific cytolytic activity of activated T cells (ATC armed with anti-CD3 x anti-HER2 bispecific antibody (HER2Bi-Ab against Malme-3M-luc cells was evaluated by bioluminescent signal generated by luciferase reporter which did not alter HER2 expression or proliferation ability of Malme-3M cells. Contrast with unarmed ATC, increased cytotoxic activity of HER2Bi-armed ATC against Malme-3M-luc cells was observed at effector/target (E/T ratios of 1:1, 5:1, and 20:1. Moreover, HER2Bi-armed ATC expressed higher level of activation marker CD69 and secreted significantly higher level of IFN-γ than unarmed ATC counterpart at the E/T ratio of 20:1. In addition, compared with anti-HER2 mAb (Herceptin® or unarmed ATC, HER2Bi-armed ATC showed remarkable suppression effect on Malme-3M-luc tumor cells. Furthermore, in melanoma tumor cell xenograft mice, infusion of HER2Bi-armed ATC successfully inhibited the growth of melanoma tumors. The anti-tumor effect of HER2Bi-armed ATC may provide a promising immunotherapy for melanoma in the future.

  20. Upregulation of Mitf by Phenolic Compounds-Rich Cymbopogon schoenanthus Treatment Promotes Melanogenesis in B16 Melanoma Cells and Human Epidermal Melanocytes

    Directory of Open Access Journals (Sweden)

    Myra O. Villareal

    2017-01-01

    Full Text Available Melanin provides inherent protection against skin cancer by absorbing broad-spectrum radiant energy of UV radiation. Cutaneous malignant melanoma incidence has recently been observed to increase and the frequency is closely associated with the skin color, highlighting the importance of skin pigmentation. Here, we showed how melanin biosynthesis is enhanced by treatment with phenolic compounds-rich Cymbopogon schoenanthus (CYM in B16 murine melanoma cells and human epidermal melanocytes (HEM. CYM increased the melanin content of the cells by upregulating the expression of tyrosinase (TYR, tyrosinase-related protein 1 (TRP1, and dopachrome tautomerase (DCT at the protein and mRNA levels, comparable to the effect of α-melanocyte-stimulating hormone (MSH, in both B16 cells and HEM. Moreover, global gene expression analysis showed that at least 44 pigmentation-associated genes were modulated, including the microphthalmia-associated transcription factor (Mitf and its transcriptional regulators (Sox10, Pax3, and Lef1. Upregulation of copper transport-associated gene Atp7b indicates that CYM also promotes tyrosinase activity. CYM upregulated Mitf and possibly activates tyrosinase enzyme, providing evidence for its possible use to promote melanogenesis and as a therapeutic agent against hypopigmentation disorders.

  1. Interim analysis of survival in a prospective, multi-center registry cohort of cutaneous melanoma tested with a prognostic 31-gene expression profile test

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    Eddy C. Hsueh

    2017-08-01

    Full Text Available Abstract Background A 31-gene expression profile (GEP test that provides risk classification of cutaneous melanoma (CM patients has been validated in several retrospective studies. The objective of the reported study was a prospective evaluation of the GEP performance in patients enrolled in two clinical registries. Methods Three-hundred twenty two CM patients enrolled in the EXPAND (NCT02355587 and INTEGRATE (NCT02355574 registries met the criteria of age ≥ 16 years, successful GEP result and ≥1 follow-up visit for inclusion in this interim analysis. Primary endpoints were recurrence-free (RFS, distant metastasis-free (DMFS, and overall survival (OS. Results Median follow-up was 1.5 years for event-free patients. Median age for subjects was 58 years (range 18–87 and median Breslow thickness was 1.2 mm (range 0.2–12.0. Eighty-eight percent (282/322 of cases had stage I/II disease and 74% (237/322 had a SLN biopsy. Seventy-seven percent (248/322 had class 1 molecular profiles. 1.5-year RFS, DMFS, and OS rates were 97 vs. 77%, 99 vs. 89%, and 99 vs. 92% for class 1 vs. class 2, respectively (p < 0.0001 for each. Multivariate Cox regression showed Breslow thickness, mitotic rate, and GEP class to significantly predict recurrence (p < 0.01, while tumor thickness was the only significant predictor of distant metastasis and overall survival in this interim analysis. Conclusions Interim analysis of patient outcomes from a combined prospective cohort supports the 31-gene GEP’s ability to stratify early-stage CM patients into two groups with significantly different metastatic risk. RFS outcomes in this real-world cohort are consistent with previously published analyses with retrospective specimens. GEP testing complements current clinicopathologic features and increases identification of high-risk patients. Trial registration ClinicalTrials.gov, NCT02355574  and NCT02355587  

  2. Monitoring the Systemic Human Memory B Cell Compartment of Melanoma Patients for Anti-Tumor IgG Antibodies

    Science.gov (United States)

    Gilbert, Amy E.; Karagiannis, Panagiotis; Dodev, Tihomir; Koers, Alexander; Lacy, Katie; Josephs, Debra H.; Takhar, Pooja; Geh, Jenny L. C.; Healy, Ciaran; Harries, Mark; Acland, Katharine M.; Rudman, Sarah M.; Beavil, Rebecca L.; Blower, Philip J.; Beavil, Andrew J.; Gould, Hannah J.; Spicer, James; Nestle, Frank O.; Karagiannis, Sophia N.

    2011-01-01

    Melanoma, a potentially lethal skin cancer, is widely thought to be immunogenic in nature. While there has been much focus on T cell-mediated immune responses, limited knowledge exists on the role of mature B cells. We describe an approach, including a cell-based ELISA, to evaluate mature IgG antibody responses to melanoma from human peripheral blood B cells. We observed a significant increase in antibody responses from melanoma patients (n = 10) to primary and metastatic melanoma cells compared to healthy volunteers (n = 10) (Pcell cultures (n = 1,800) compared to 2% of cultures from healthy controls (n = 600) produced antibodies that recognized melanoma cells. Lastly, a patient-derived melanoma-specific monoclonal antibody was selected for further study. This antibody effectively killed melanoma cells in vitro via antibody-mediated cellular cytotoxicity. These data demonstrate the presence of a mature systemic B cell response in melanoma patients, which is reduced with disease progression, adding to previous reports of tumor-reactive antibodies in patient sera, and suggesting the merit of future work to elucidate the clinical relevance of activating humoral immune responses to cancer. PMID:21559411

  3. Volumetric cutaneous microangiography of human skin in vivo by VCSEL swept-source optical coherence tomography

    Energy Technology Data Exchange (ETDEWEB)

    Woo June Choi; Wang, R K [University of Washington, Department of Bioengineering, Seattle, Washington 98195 (United States)

    2014-08-31

    We demonstrate volumetric cutaneous microangiography of the human skin in vivo that utilises 1.3-μm high-speed sweptsource optical coherence tomography (SS-OCT). The swept source is based on a micro-electro-mechanical (MEMS)-tunable vertical cavity surface emission laser (VCSEL) that is advantageous in terms of long coherence length over 50 mm and 100 nm spectral bandwidth, which enables the visualisation of microstructures within a few mm from the skin surface. We show that the skin microvasculature can be delineated in 3D SS-OCT images using ultrahigh-sensitive optical microangiography (UHS-OMAG) with a correlation mapping mask, providing a contrast enhanced blood perfusion map with capillary flow sensitivity. 3D microangiograms of a healthy human finger are shown with distinct cutaneous vessel architectures from different dermal layers and even within hypodermis. These findings suggest that the OCT microangiography could be a beneficial biomedical assay to assess cutaneous vascular functions in clinic. (laser biophotonics)

  4. Cutaneous verruca with genital human papillomavirus in a 2-year-old girl.

    Science.gov (United States)

    Payne, D A; Sanchez, R; Tyring, S K

    1997-06-01

    Human papillomavirus (HPV) is the etiologic agent of warts and condyloma acuminatum (CDA). Condyloma acuminatium is believed to result from sexual transmission of HPV types 6 and 11 in adults. In contrast, nonsexual transmission of CDA occurs frequently between children and caregivers. Nonsexual-CDA are present almost exclusively in the mucosal epithelium in children. The authors analyzed a rapidly growing cutaneous wart on the thigh of a two-year-old girl for the presence of oncogenic and nononcogenic HPV types by in situ hybridization. This cutaneous wart was found to have the HPV types commonly found in CDA, namely types 6 and/or 11. This is an unusual finding and suggests that verruca vulgaris may result from papillomavirsuses other than HPV 2 in children.

  5. Molecular mechanism implicated in Pemetrexed-induced apoptosis in human melanoma cells

    Directory of Open Access Journals (Sweden)

    Buqué Aitziber

    2012-04-01

    Full Text Available Abstract Background Metastatic melanoma is a lethal skin cancer and its incidence is rising every year. It represents a challenge for oncologist, as the current treatment options are non-curative in the majority of cases; therefore, the effort to find and/or develop novel compounds is mandatory. Pemetrexed (Alimta®, MTA is a multitarget antifolate that inhibits folate-dependent enzymes: thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyltransferase, required for de novo synthesis of nucleotides for DNA replication. It is currently used in the treatment of mesothelioma and non-small cell lung cancer (NSCLC, and has shown clinical activity in other tumors such as breast, colorectal, bladder, cervical, gastric and pancreatic cancer. However, its effect in human melanoma has not been studied yet. Results In the current work we studied the effect of MTA on four human melanoma cell lines A375, Hs294T, HT144 and MeWo and in two NSCLC cell lines H1299 and Calu-3. We have found that MTA induces DNA damage, S-phase cell cycle arrest, and caspase- dependent and –independent apoptosis. We show that an increment of the intracellular reactive oxygen species (ROS and p53 is required for MTA-induced cytotoxicity by utilizing N-Acetyl-L-Cysteine (NAC to blockage of ROS and p53-defective H1299 NSCLC cell line. Pretreatment of melanoma cells with NAC significantly decreased the DNA damage, p53 up-regulation and cytotoxic effect of MTA. MTA was able to induce p53 expression leading to up-regulation of p53-dependent genes Mcl-1 and PIDD, followed by a postranscriptional regulation of Mcl-1 improving apoptosis. Conclusions We found that MTA induced DNA damage and mitochondrial-mediated apoptosis in human melanoma cells in vitro and that the associated apoptosis was both caspase-dependent and –independent and p53-mediated. Our data suggest that MTA may be of therapeutic relevance for the future treatment of human malignant melanoma.

  6. Expression of tissue-type transglutaminase correlates positively with metastatic properties of human melanoma cell lines.

    Science.gov (United States)

    van Groningen, J J; Klink, S L; Bloemers, H P; Swart, G W

    1995-01-27

    In this study the relationship between tissue-type transglutaminase (TGase2) activity and the propensity to metastasize was investigated in human melanoma cell lines with different metastatic behavior. TGase2 catalyzes an acyl-transfer reaction between peptide-bound glutamine residues and primary amines, including the epsilon-amino group of lysine residues. Northern-blot analysis demonstrated that TGase2 RNA-expression (3.7 kb) was elevated in highly metastatic cell lines (MV3 and BLM) as compared to weakly metastatic ones (IF6 and 530). Immunoprecipitation and enzyme assays of TGase2 showed that the differential expression at the mRNA level was also reflected at the protein level. These findings reveal a positive relation between the expression of TGase2 and the metastatic properties of the human melanoma cell lines.

  7. Efficacy of RG1-VLP vaccination against infections with genital and cutaneous human papillomaviruses.

    Science.gov (United States)

    Schellenbacher, Christina; Kwak, Kihyuck; Fink, Dieter; Shafti-Keramat, Saeed; Huber, Bettina; Jindra, Christoph; Faust, Helena; Dillner, Joakim; Roden, Richard B S; Kirnbauer, Reinhard

    2013-12-01

    Licensed human papillomavirus (HPV) vaccines, based on virus-like particles (VLPs) self-assembled from major capsid protein L1, afford type-restricted protection against HPV types 16/18/6/11 (or 16/18 for the bivalent vaccine), which cause 70% of cervical cancers (CxCas) and 90% of genital warts. However, they do not protect against less prevalent high-risk (HR) types causing 30% of CxCa, or cutaneous HPV. In contrast, vaccination with the minor capsid protein L2 induces low-level immunity to type-common epitopes. Chimeric RG1-VLP presenting HPV16 L2 amino acids 17-36 (RG1 epitope) within the DE-surface loop of HPV16 L1 induced cross-neutralizing antisera. We hypothesized that RG1-VLP vaccination protects against a large spectrum of mucosal and cutaneous HPV infections in vivo. Immunization with RG1-VLP adjuvanted with human-applicable alum-MPL (aluminum hydroxide plus 3-O-desacyl-4'-monophosphoryl lipid A) induced robust L2 antibodies (ELISA titers 2,500-12,500), which (cross-)neutralized mucosal HR HPV16/18/45/37/33/52/58/35/39/51/59/68/73/26/69/34/70, low-risk HPV6/11/32/40, and cutaneous HPV2/27/3/76 (titers 25-1,000) using native virion- or pseudovirion (PsV)-based assays, and a vigorous cytotoxic T lymphocyte response by enzyme-linked immunospot. In vivo, mice were efficiently protected against experimental vaginal challenge with mucosal HR PsV types HPV16/18/45/31/33/52/58/35/39/51/59/68/56/73/26/53/66/34 and low-risk HPV6/43/44. Enduring protection was demonstrated 1 year after vaccination. RG1-VLP is a promising next-generation vaccine with broad efficacy against all relevant mucosal and also cutaneous HPV types.

  8. Genetically engineered mesenchymal stromal cells producing TNFα have tumour suppressing effect on human melanoma xenograft.

    Science.gov (United States)

    Tyciakova, Silvia; Matuskova, Miroslava; Bohovic, Roman; Polakova, Katarina; Toro, Lenka; Skolekova, Svetlana; Kucerova, Lucia

    2015-01-01

    Mesenchymal stromal cells (MSC) are a promising tool for targeted cancer therapy due to their tumour-homing ability. Intrinsic resistance enables the MSC to longer tolerate therapeutic factors, such as prodrug converting enzymes, cytokines and pro-apoptotic proteins. Tumour necrosis factor alpha (TNFα) is known to be cytotoxic to a variety of cancer cells and exert a tumour-destructive capacity. MSC were retrovirally transduced to stable express an exogenous gene encoding the desired therapeutic agent hTNFα. The effect of a TNFα-producing adipose tissue-derived MSC (AT-MSC/hTNFα) was tested on the tumour cell lines of different origins: melanoma (A375), breast carcinoma (SKBR3, MDA-MB-231), colon carcinoma (HT29), ovarian carcinoma (SKOV3) and glioblastoma (U87-MG) cells. The tumour suppressing effect of AT-MSC/hTNFα on A375 melanoma xenografts was monitored in an immunodeficient mouse model in vivo. Engineered AT-MSC are able to constitutively secrete human TNFα protein, induce apoptosis of tumour cell lines via caspase 3/7 activation and inhibit the tumour cell proliferation in vitro. Melanoma A375 and breast carcinoma SKBR3 cells were the most sensitive, and their proliferation in vitro was reduced by conditioned media produced by AT-MSC/hTNFα to 60% and 40%, respectively. The previously reported tumour supportive effect of AT-MSC on subcutaneous A375 melanoma xenograft growth was neutralised and suppressed by engineered AT-MSC stably producing hTNFα. When AT-MSC/hTNFα were coinjected with A375 melanoma cells, the tumour mass inhibition was up to 97.5%. The results of the present study demonstrate that tumour cells respond to hTNFα-based treatment mediated by genetically engineered AT-MSC/hTNFα both in vitro and in vivo. Copyright © 2015 John Wiley & Sons, Ltd.

  9. Phosphorylation of ectopically expressed L-plastin enhances invasiveness of human melanoma cells.

    Science.gov (United States)

    Klemke, Martin; Rafael, Maria T; Wabnitz, Guido H; Weschenfelder, Tatjana; Konstandin, Mathias H; Garbi, Natalio; Autschbach, Frank; Hartschuh, Wolfgang; Samstag, Yvonne

    2007-06-15

    The leukocyte specific actin-binding protein L-plastin is aberrantly expressed in several nonhematopoetic malignant tumors. However, little is known about the functional consequences of L-plastin expression. Here, we investigated the function of L-plastin in human malignant melanoma cells. Knock-down of endogenous L-plastin by siRNA treatment reduced migration of the melanoma cell line IF6. However, in melanoma patients, no correlation existed between L-plastin expression and tumor stages. This implied that additional factors such as phosphorylation of L-plastin may influence its function in tumor cells. To investigate this further, EGFP-tagged wild-type L-plastin (wt-LPL-EGFP) and a mutated, nonphosphorylatable L-plastin protein (5A7A-LPL-EGFP), were expressed in the L-plastin negative melanoma cell line MV3. Biochemical analysis revealed that wt-LPL-EGFP is phosphorylated in MV3 cells while 5A7A-LPL-EGFP is not. Although both wt-LPL-EGFP and 5A7A-LPL-EGFP were targeted to, and promote the formation of, vinculin-containing adhesion sites, static adhesion to either Matrigel or isolated extracellular matrix molecules was neither influenced by expression of wt-LPL-EGFP nor by expression of 5A7A-LPL-EGFP when compared with EGFP expressing control cells. In contrast, haptotactic, but not chemotactic, migration of melanoma cells towards either Matrigel or isolated extracellular matrix molecules was similarly enhanced, if either 5A7A-LPL-EGFP or wt-LPL-EGFP were expressed in MV3 cells. Interestingly, only cells expressing the phosphorylatable wt-LPL-EGFP protein showed enhanced invasion into Matrigel. In line with these findings the in vivo metastatic capacity of mouse B16 melanoma cells correlates with expression and phosphorylation of L-plastin. These data show that an increase in melanoma cell invasiveness requires not only expression but also phosphorylation of L-plastin.

  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. A Novel Nanoprobe for Multimodal Imaging Is Effectively Incorporated into Human Melanoma Metastatic Cell Lines

    OpenAIRE

    Synnøve Nymark Aasen; Aneta Pospisilova; Tilo Wolf Eichler; Jiri Panek; Martin Hruby; Petr Stepanek; Endy Spriet; Daniel Jirak; Kai Ove Skaftnesmo; Frits Thorsen

    2015-01-01

    To facilitate efficient drug delivery to tumor tissue, several nanomaterials have been designed, with combined diagnostic and therapeutic properties. In this work, we carried out fundamental in vitro and in vivo experiments to assess the labeling efficacy of our novel theranostic nanoprobe, consisting of glycogen conjugated with a red fluorescent probe and gadolinium. Microscopy and resazurin viability assays were used to study cell labeling and cell viability in human metastatic melanoma cel...

  12. Expression of melanin-related genes in cultured adult human retinal pigment epithelium and uveal melanoma cells.

    Science.gov (United States)

    Lu, Fan; Yan, Dongsheng; Zhou, Xiangtian; Hu, Dan-Ning; Qu, Jia

    2007-11-03

    Controversy exists over melanogenesis of adult human RPE cells in vitro. This study investigated melanin content and production and expression of tyrosinase (TYR), tyrosinase-related-protein-1 (TRP1), tyrosinase-related-protein-2 (TRP2), and P gene in cultured human RPE cells and uveal melanoma cells. RPE cells were isolated and cultured from three adult donor eyes. A continuous human uveal melanoma cell line was established from primary choroidal melanoma. Melanin content and production were measured, and the expression of TYR, TRP1, TRP2, and P gene at the mRNA and protein levels were detected by RT-PCR and western blot, respectively. Melanin content per cell of cultured RPE decreased rapidly and in proportion to cell division. No melanin production could be demonstrated in any passages. In cultured RPE cells, mRNA expression of TYR, TRP1, TRP2, and P-gene and protein expression of TYR, TRP1, and TRP2 could not be detected. In uveal melanoma cells, melanin content per cell remained stable, and melanin production could be detected in each passage. Expression of mRNA of TYR, TRP1, TRP2, and P-gene and protein of TYR, TRP1, and TRP2 could be detected in melanoma cells. Human RPE cells under standard culture circumstances do not produce melanin and do not express the four key genes required in melanin biosynthesis pathway. In contrast, human uveal melanoma cells produce melanin and express all of these melanogenic genes in vitro.

  13. Restoration of E-cadherin sensitizes human melanoma cells for apoptosis.

    Science.gov (United States)

    Kippenberger, Stefan; Loitsch, Stefan; Thaçi, Diamant; Müller, Jutta; Guschel, Maike; Kaufmann, Roland; Bernd, August

    2006-10-01

    Cell-cell adhesion is considered to be important in the development and maintenance of organ tissue. The spatial association between melanocytes and keratinocytes within human epidermis is achieved by homophilic interaction of E-cadherin molecules located on adjacent cells. In contrast, downregulation of E-cadherin expression in melanoma cells is considered as a key event in metastasis. Besides the adhesive properties, E-cadherin serves as a signal receptor linking to the cadherin-catenin signaling complex. As cadherins act as negative regulators of beta-catenin, a contribution to tumor formation seems likely. In the present study, it was tested whether ectopic expression of E-cadherin triggers apoptosis in human melanoma cell lines (G-361, JPC-298, SK-Mel-13). It was found that restoration of E-cadherin caused sensitization against drug-induced apoptosis. Particularly, the release of mitochondrial cytochrome c was increased in response to staurosporine. Moreover, activation of caspase-3 and caspase-8 was elevated. Similarly, DNA fragmentation, serving as a marker for advanced apoptosis, was amplified in cells transduced with E-cadherin. Interestingly, transduction with an E-cadherin construct lacking the extracellular domain showed no modified apoptosis. In conclusion, our findings suggest therapeutic strategies that enable expression of E-cadherin in order to sensitize human melanoma cells towards apoptosis.

  14. Vemurafenib for the treatment of melanoma.

    LENUS (Irish Health Repository)

    Jordan, Emmet John

    2012-12-01

    Metastatic melanoma is an aggressive disease resistant to chemotherapy. Recent clinical trials have reported improved survival for two novel agents; ipilimumab, a humanized, IgG1 monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and vemurafenib , a BRAF (v-raf murine sarcoma viral oncogene homolog B1) inhibitor targeting an activating mutation in the serine-threonine-protein kinase BRAF gene. AREAS COVERED: The authors reviewed preclinical and clinical data examining the safety of vemurafenib in melanoma. MEDLINE and EMBASE were searched using the medical subject heading \\'vemurafenib\\' and the following text terms: melanoma, BRAF inhibition, vemurafenib. This review provides the reader with an overview of current data examining the efficacy and safety of vemurafenib in metastatic melanoma. EXPERT OPINION: Vemurafenib is an oral agent licensed for patients with BRAF V600E mutation-positive inoperable and metastatic melanoma. The most common adverse effects observed in Phase III clinical trials were dermatological events, arthralgia and fatigue. Specific dermatological toxicities included development of cutaneous squamous cell cancers and keratoacanthomas. Prolongation of the QT interval was also reported. Regular dermatological assessments and electrocardiograms are recommended. Ongoing trials are examining vemurafenib in both the adjuvant setting and metastatic setting in combination with ipilimumab and MEK inhibitors (mitogen-activated protein kinase\\/extracellular signal-regulated kinase). Understanding and overcoming mechanisms of resistance to BRAF inhibitors is the focus of ongoing research.

  15. Relevance of in vivo models in melanoma skin cancer

    Energy Technology Data Exchange (ETDEWEB)

    Setlow, R.B.

    1995-12-31

    A discussion of possible wavelength dependence of induction of cutaneous malignant melanoma (CMM) is provided. Strengths and weaknesses of various experimental approaches to better understanding of the prevalence of CMM in different human populations including latitude effects are compared. Further the advantages and limitations of the use of the laboratory opossum (Monodelphis domestic), transgenic mice containing SV40 ongogene sequences under tyrosinase promoter control, and a backcross hybrid fish of the genus Xenophorus are contrasted.

  16. [Molecular diagnostics in melanoma].

    Science.gov (United States)

    Lang, R; Bauer, J W; Laimer, M

    2015-04-01

    The molecular landscape of melanoma is changing more rapidly than ever since new molecular technology approaches have made it possible to examine human melanoma for genetic alterations underlying the disease. In recent years, these approaches have identified new familial melanoma susceptibility genes, most of them also conferring risk to other cancers. This has implications for clinical testing and surveillance. Furthermore, molecular testing of melanoma to determine therapeutic eligibility for targeted therapies is now standard of care and should be familiar to the dermatologist.

  17. Cytotoxic effects of local anesthesia through lidocaine/ropivacaine on human melanoma cell lines

    Directory of Open Access Journals (Sweden)

    Ding-Kun Kang

    Full Text Available Abstract Background: Local anesthetics (LAs are generally considered as safe, but cytotoxicity has been reported for several local anesthetics used in humans, which is not well investigated. In the present study, the cytotoxicity of lidocaine, ropivacaine and the combination of lidocaine and ropivacaine were evaluated on human melanoma cell lines. Melphalan, a nitrogen mustard alkylating agent, was used as a control agent for comparison of cytotoxic activity. Methods: Melanoma cell lines, A375 and Hs294T, were exposed to 1 h to different concentrations of above agents. Cell-viability after exposure was determined by flow cytometry. Results: Investigated LAs showed detrimental cytotoxicity on studied melanoma cell lines in time- (p < 0.001, concentration- (p < 0.001, and agent dependant. In both A375 and Hs294T cell lines, minimum cell viability rates were found after 72 h of exposure to these agents. Lidocaine 2% caused a reduction of vital cells to 10% ± 2% and 14% ± 2% in A375 and Hs294T, respectively after 72 h of exposure. Ropivacaine 0.75% after 72 h reduced viable cells to 15% ± 3% and 25% ± 3% in A375 and Hs294T, respectively. Minimum cell viability after 72 h exposure to the combination was 10% ± 2% and 18% ± 2% in A375 and Hs294T, respectively. Minimum cell viability after 72 h exposure to melphalan was 8% ± 1% and 12% ± 2%, in A375 and Hs294T, respectively. Conclusion: LAs have cytotoxic activity on human melanoma cell lines in a time-, concentration- and agent-dependant manner. Apoptosis in the cell lines was mediated through activity of caspases-3 and caspases-8.

  18. Cytotoxic effects of local anesthesia through lidocaine/ropivacaine on human melanoma cell lines.

    Science.gov (United States)

    Kang, Ding-Kun; Zhao, Li-Yan; Wang, Hong-Li

    Local anesthetics (LAs) are generally considered as safe, but cytotoxicity has been reported for several local anesthetics used in humans, which is not well investigated. In the present study, the cytotoxicity of lidocaine, ropivacaine and the combination of lidocaine and ropivacaine were evaluated on human melanoma cell lines. Melphalan, a nitrogen mustard alkylating agent, was used as a control agent for comparison of cytotoxic activity. Melanoma cell lines, A375 and Hs294T, were exposed to 1h to different concentrations of above agents. Cell-viability after exposure was determined by flow cytometry. Investigated LAs showed detrimental cytotoxicity on studied melanoma cell lines in time- (pLidocaine 2% caused a reduction of vital cells to 10%±2% and 14%±2% in A375 and Hs294T, respectively after 72h of exposure. Ropivacaine 0.75% after 72h reduced viable cells to 15%±3% and 25%±3% in A375 and Hs294T, respectively. Minimum cell viability after 72h exposure to the combination was 10%±2% and 18%±2% in A375 and Hs294T, respectively. Minimum cell viability after 72h exposure to melphalan was 8%±1% and 12%±2%, in A375 and Hs294T, respectively. LAs have cytotoxic activity on human melanoma cell lines in a time-, concentration- and agent-dependant manner. Apoptosis in the cell lines was mediated through activity of caspases-3 and caspases-8. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  19. Identification of Leishmania Species Isolated from Human Cutaneous Leishmaniasis in Mehran, Western Iran Using Nested PCR

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    Mohammad Hossein FEIZ HADDAD

    2016-03-01

    Full Text Available Background: The incidence of cutaneous leishmaniasis in the city of Mehran has risen sharply in recent years because the city borders Iraq, which has allowed entrance of different Leishmania strains. These strains have different shapes, periods of disease, and healing of lesions. The present study identified and determined cutaneous leishmaniasis species in this region. Methods: This cross-sectional study was carried out by preparing slides from 92 patients with suspected cutaneous leishmaniasis lesions from Mehran during 2012-2013. Parasite genomic DNA was extracted and CSB2XF and CSB1XR primers were used to amplify the Leishmania minicircle kDNA regions. The parasite species were detected by specific 13Z and LIR primers by applying nested PCR technique.Results: All banding patterns were diagnosed as L. major parasite by comparison of standard models with amplified fragments 560 bp in length from bands. The patients were 56.5% male and 43.5% female. The most frequently-infected age group was the 21-30 years group at a rate of 27.2%. About 56.3% of patients had a single lesion and a significant correlation was observed between age and number of lesions (P > 0.05. Conclusion: The nested PCR technique was shown to be an effective method with high sensitivity and specificity for identification of human Leishmania parasites. Molecular analysis revealed that parasites isolated from Mehran were identified as L. major and the disease was rural in form.

  20. RasGRP3, a Ras activator, contributes to signaling and the tumorigenic phenotype in human melanoma

    Science.gov (United States)

    Li, Luowei; Kedei, Noemi; Tóth, Zsuzsanna E.; Czap, Alexandra; Velasquez, Julia F.; Mihova, Daniela; Michalowski, Aleksandra M.; Yuspa, Stuart H.; Blumberg, Peter M.

    2014-01-01

    RasGRP3, an activator for H-Ras, R-Ras and Rap1/2, has emerged as an important mediator of signaling downstream from receptor coupled phosphoinositide turnover in B and T cells. Here, we report that RasGRP3 showed a high level of expression in multiple human melanoma cell lines as well as in a subset of human melanoma tissue samples. Suppression of endogenous RasGRP3 expression in these melanoma cell lines reduced Ras-GTP formation as well as c-Met expression and Akt phosphorylation downstream from HGF or EGF stimulation. RasGRP3 suppression also inhibited cell proliferation and reduced both colony formation in soft agar and xenograft tumor growth in immunodeficient mice, demonstrating the importance of RasGRP3 for the transformed phenotype of the melanoma cells. Reciprocally, overexpression of RasGRP3 in human primary melanocytes altered cellular morphology, markedly enhanced cell proliferation, and rendered the cells tumorigenic in a mouse xenograft model. Suppression of RasGRP3 expression in these cells inhibited downstream RasGRP3 responses and suppressed cell growth, c