Cutaneous melanoma: A model to study cancer metastasis

Leong, Stanley P. L.; Gershenwald, Jeffrey E.; Soong, Seng Jaw; Schadendorf, Dirk; Tarhini, Ahmad A.; Agarwala, Sanjiv S.; Hauschild, Axel; Soon, Christopher W. M.; Daud, Adil; Kashani‐Sabet, Mohammed

doi:10.1002/jso.21816

Cited by 42 publications

(27 citation statements)

References 125 publications

(136 reference statements)

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“…Studies of cutaneous melanoma provide a distinctive opportunity to gain further insight into the nature of human metastasis heterogeneity. Melanoma metastases have been shown to have a high mutation frequency (7, 8), diverse phenotype (4, 9), a clinically diffuse dissemination pattern (10), and a unique ability to elicit spontaneous antigen specific host immune responses (11, 12). As highly targeted immune therapies are currently in development for the treatment of metastatic melanoma, an improved understanding of metastasis heterogeneity is critical to assessing potential tumor susceptibility in future clinical studies.…”

Section: Introductionmentioning

confidence: 99%

Human Melanoma Metastases Demonstrate Nonstochastic Site-Specific Antigen Heterogeneity That Correlates with T-cell Infiltration

Bartlett

Fetsch

Filie

et al. 2014

Clinical Cancer Research

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Purpose Metastasis heterogeneity presents a significant obstacle to the development of targeted cancer therapeutics. In this study, we sought to establish from a large series of human melanoma metastases whether there exists a determined pattern in tumor cellular heterogeneity that may guide the development of future targeted immunotherapies. Experimental Design From a cohort of 1514 patients with metastatic melanoma, biopsies were procured over a 17 year period from 3086 metastatic tumors involving various anatomic sites. To allow specific tumor cell profiling, we utilized established immunohistochemical methods to perform semi-quantitative assessment for a panel of prototypic melanocyte differentiation antigens (MDAs) including gp100, MART-1, and tyrosinase (TYR). To gain insight into the endogenous host immune response against these tumors, we further characterized tumor cell expression of MHC I and MHC II and, also, the concomitant CD4+ and CD8+ T cell infiltrate. Results Tumor cell profiling for MDA expression demonstrated an anatomic site-specific pattern of antigen expression that was highest in brain, intermediate in soft tissues/lymph nodes, and lowest in visceral metastases. Hierarchical clustering analysis supported that melanoma metastases have a phylogenetically determined, rather than a stochastic, pattern of antigen expression that varies by anatomic site. Further, TYR expression was more frequently lost in metastatic sites outside of the brain and was uniquely correlated with both endogenous CD8+ and CD4+ T cell infiltrate. Conclusion Site-specific antigen heterogeneity represents a novel attribute for human melanoma metastases that should be considered in future therapy development and when assessing the responsiveness to antigen specific immunotherapies.

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Section: Introductionmentioning

confidence: 99%

Human Melanoma Metastases Demonstrate Nonstochastic Site-Specific Antigen Heterogeneity That Correlates with T-cell Infiltration

Bartlett

Fetsch

Filie

et al. 2014

Clinical Cancer Research

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“…Melanoma is an aggressive tumor and has a propensity to metastasize to lymph nodes, lungs, liver and virtually any other site of the body [1,2]. An early and accurate diagnosis of the tumor at the site of recurrence or metastasis is necessary owing to the poor prognosis of the tumor.…”

Section: Introductionmentioning

confidence: 99%

Spindle Cell Melanoma: A Comparison of the Cytomorphological Features with the Epithelioid Variant

et al. 2013

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Objectives: Fine-needle aspiration cytology serves as a rapid and cost-effective tool for the diagnosis of melanoma, especially in the recurrent and metastatic cases. The diagnosis poses a challenge due to the varied morphological patterns. Spindle cell melanoma mimics other sarcomas and carcinomas on morphology. This study highlights the cytomorphological features of spindle cell melanoma and compares them with the conventional epithelioid type. Study Design: Cytology smears of 55 aspirates from 45 diagnosed cases of melanoma from various sites were reviewed. Histopathology correlation was done in spindle and mixed cell tumors. Results: Melanomas with a pure or mixed spindle cell component occurred in 31% of the cases and in a slightly higher age group. These demonstrated prominent cellular cohesion (p < 0.0001), mild to moderate nuclear atypia and inconspicuous to small nucleoli as compared to the epithelioid variant. The presence of melanin pigment was a useful clue to the diagnosis. Most of the cases correlated well with the histomorphology. Conclusion: Spindle cell melanoma is a morphological variant which can be readily misinterpreted due to a lack of classical cytological features of melanoma. Hence, these are vulnerable to be misinterpreted as other neoplasms. An awareness of clinical and cytological features is important to reach the correct diagnosis.

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“…The integrin facilitated the migration of the melanoma cells and also was found to interact with Thy-1 on activated endothelial cells with resultant intravasation of the tumor cells [21]. Furthermore, N-cadherin is expressed on the melanoma cells that allows for connection via gap junctions with fibroblasts and endothelial cells [6]. The production of metalloproteinases results in the digestion of matrix with resultant ease of invasion for the melanoma cells [22].…”

Section: Progression From the Primary Site To The Metastatic Deposit:mentioning

confidence: 99%

“…Cutaneous melanoma is an excellent model to study cancer metastasis [6]. In this review, we emphasize the proliferation of melanoma at its inception and progression through the lymphatics as in-transit metastases as well as sentinel lymph nodes (SLN) in the regional nodal basin to distant sites.…”

Section: Introductionmentioning

confidence: 99%

Progression of cutaneous melanoma: implications for treatment

Leong

Mihm

Murphy

et al. 2012

Clin Exp Metastasis

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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.

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Cutaneous melanoma: A model to study cancer metastasis

Cited by 42 publications

References 125 publications

Human Melanoma Metastases Demonstrate Nonstochastic Site-Specific Antigen Heterogeneity That Correlates with T-cell Infiltration

Human Melanoma Metastases Demonstrate Nonstochastic Site-Specific Antigen Heterogeneity That Correlates with T-cell Infiltration

Spindle Cell Melanoma: A Comparison of the Cytomorphological Features with the Epithelioid Variant

Progression of cutaneous melanoma: implications for treatment

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