Expression of melan-a/MART-1 antigen as a prognostic factor in primary cutaneous melanoma

Berset, Magali; Cerottini, Jean‐Philippe; Guggisberg, D.; Romero, Pedro; Burri, Françoise; Rimoldi, Donata; Panizzon, Renato G.

doi:10.1002/1097-0215(20010120)95:1<73::aid-ijc1013>3.0.co;2-s

Cited by 37 publications

(8 citation statements)

References 24 publications

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“…We report a small series of melanomas showing clonal MelanA expression, defined as two distinct and different cell clones within one tumour section. In line with these findings, MelanA expression was linked to an increased likelihood of survival as shown partly by MelanA expression in both circulating tumour cells [12] and melanoma cell lines established from patients with metastatic melanoma [13] and partly by immunohistochemistry of primary human melanoma [14]. Furthermore, MelanA expression altered from an exclusively homogeneous pattern in the early stages of cancer development to a more heterogeneous pattern in the later stages [11].…”

Section: Discussionsupporting

confidence: 59%

MelanA-negative spindle-cell associated melanoma, a distinct inflammatory phenotype correlated with dense infiltration of CD163 macrophages and loss of E-cadherin

Bønnelykke-Behrndtz

Steiniche²,

Damsgaard

et al. 2015

Melanoma Research

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MelanA is a known melanocyte marker and is important in melanoma diagnostics. Some tumours, however, show loss of MelanA expression and may therefore be difficult to distinguish from tumours of mesenchymal origin. Pure spindle-cell melanoma is a rare event, and little is known about its biological background and prognosis. However, morphological changes towards a more mesenchymal shape and cellular dedifferentiation may correlate with reactivation of important developmental programmes (epithelial-to-mesenchymal transition) and disseminative tumour cell properties. Inflammation and CD163+ macrophages have been shown to be important inducers of E-cadherin and cell-to-cell adhesion loss, a pivotal and final event of epithelial-to-mesenchymal transition. In a cohort of 385 patients with melanoma, we located nine tumours with a clonal MelanA expression, defined as a tumour section with a distinct MelanA-negative clone next to a MelanA-positive clone. Interestingly, MelanA-negative clones correlated significantly with an augmented inflammatory response of tumour-infiltrating macrophages (CD163+), complete loss of E-cadherin and a spindle-shaped morphology, irrespective of ulcerated status. These cases show the inflammatory heterogeneity of melanoma, which may have important diagnostic, prognostic and therapeutic implications for the patients. We show that melanomas harbour cell clones that bear strong resemblance to tumour-associated macrophages, a pivotal player in a tumour-supporting microenvironment. Interestingly, this distinct inflammatory phenotype is associated with loss of MelanA expression, the presence of spindle-shape morphology and complete loss of E-cadherin, considered as possible markers of poorly differentiated and more invasive tumour cells.

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Section: Discussionsupporting

confidence: 59%

MelanA-negative spindle-cell associated melanoma, a distinct inflammatory phenotype correlated with dense infiltration of CD163 macrophages and loss of E-cadherin

Bønnelykke-Behrndtz

Steiniche²,

Damsgaard

et al. 2015

Melanoma Research

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“…We propose that this may be due to the presence of Wnt5A-positive tumor cells, prone to metastasis, which also express less MART-1 and other similar antigens. Indeed, overexpression of Wnt5A has been associated with poorer outcome for patients with both cutaneous and uveal melanoma (7, 27), where increased MART-1 expression in primary tumors is a predictor of more favorable outcome (28). In the present study, we have shown that the inverse relationship between the expression of Wnt5A and melanoma antigens is not simply a correlation, but is cause and effect.…”

Section: Discussionmentioning

confidence: 99%

Wnt5A Regulates Expression of Tumor-Associated Antigens in Melanoma via Changes in Signal Transducers and Activators of Transcription 3 Phosphorylation

Dissanayake¹,

Olkhanud²,

O’Connell³

et al. 2008

Cancer Research

115

135

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There are currently no effective therapies for metastatic melanoma and targeted immunotherapy results in the remission of only a very small percentage of tumors. In this study, we show that the noncanonical Wnt ligand, Wnt5A, can increase melanoma metastasis in vivo while down-regulating the expression of tumor-associated antigens important in eliciting CTL responses (e.g., MART-1, GP100, and tyrosinase). Melanosomal antigen expression is governed by MITF, PAX3, and SOX10 and is inhibited upon signal transducers and activators of transcription 3 (STAT3) activation, via decreases in PAX3 and subsequently MITF expression. Increasing Wnt5A in Wnt5A-low cells activated STAT3, and STAT3 was decreased upon Wnt5A knockdown. Downstream targets such as PAX3, MITF, and MART-1 were also affected by Wnt5A treatment or knockdown. Staining of a melanoma tissue array also highlighted the inverse relationship between MART-1 and Wnt5A expression. PKC activation by phorbol ester mimicked Wnt5A effects, and Wnt5A treatment in the presence of STAT3 or PKC inhibitors did not lower MART-1 levels. CTL activation studies showed that increases in Wnt5A correspond to decreased CTL activation and vice versa, suggesting that targeting Wnt5A before immunotherapy may lead to the enhancement of current targeted immunotherapy for patients with metastatic melanoma.

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“…It was reported that Melan-A/MART-1 was required for the maturation of melanosomes (Hoashi et al 2005), though the function of Melan-A/MART-1 in melanocyte development and differentiation still remains to be clarified. Melan-A/ MART-1 is expressed in normal immature melanocytes and in more than 90% of fresh melanoma tumors and melanoma cell lines (Berset et al 2001;van Dinten et al 2005). Many epitopes of Melan-A/MART-1 were reported and used for peptide vaccine therapy of melanoma in practice.…”

Section: Discussionmentioning

confidence: 99%

Establishment of a Screening System for Chemicals that Upregulate a Melanoma Antigen, Melan-A/MART-1

Song

Kono

Tomita

2009

Tohoku J. Exp. Med.

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Expression of melan-a/MART-1 antigen as a prognostic factor in primary cutaneous melanoma

Cited by 37 publications

References 24 publications

MelanA-negative spindle-cell associated melanoma, a distinct inflammatory phenotype correlated with dense infiltration of CD163 macrophages and loss of E-cadherin

MelanA-negative spindle-cell associated melanoma, a distinct inflammatory phenotype correlated with dense infiltration of CD163 macrophages and loss of E-cadherin

Wnt5A Regulates Expression of Tumor-Associated Antigens in Melanoma via Changes in Signal Transducers and Activators of Transcription 3 Phosphorylation

Establishment of a Screening System for Chemicals that Upregulate a Melanoma Antigen, Melan-A/MART-1

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