Correlation of MET and PD-L1 Expression in Malignant Melanoma

Abstract

<jats:p>The proto-oncogene MET, the hepatocyte growth factor (HGF) receptor, is a transmembrane receptor tyrosine kinase (RTK) with a prominent role in tumor metastasis and resistance to anti-cancer therapies. Melanoma demonstrates relatively frequent MET aberrations, including MET gene amplification. Concurrently, programmed death-ligand 1 (PD-L1), with its ability to evade anti-tumor immune responses, has emerged as a prominent therapeutic target in melanoma and other malignancies and its expression is used as a predictive biomarker of response to immunotherapy. We performed immunohistochemistry analysis of MET and PD-L1 in 18 human melanoma cell lines derived from both primary and metastatic lesions, and in a human melanoma tissue microarray containing one hundreds melanocytic lesions, including primary cutaneous melanomas, primary mucosal melanomas, metastatic melanomas and benign melanocytic nevi as controls. After color deconvolution, each core was segmented to isolate staining and calculate the percentage of positive cells. Overall, MET expression was higher in tumors with increased PD-L1 expression. Moreover, a robust correlation between MET and PD-L1 expression was found in samples from metastatic melanoma and not in primary cutaneous or mucosal melanoma. These data suggest that relative expression levels of these proteins in combination is a marker of advanced disease and testing for expression of these markers should be considered in patients with melanoma.</jats:p>

Case Report: Durable complete pathologic response and organ preservation following ipilimumab and nivolumab for locally advanced primary vaginal mucosal melanoma

“…Our patient’s melanoma had an NRAS mutation where MEK inhibitors may have a role as systemic therapy, although a modest and short-lived responses are generally expected based on the experience with metastatic cutaneous melanoma. Furthermore, MET aberrations have been frequently demonstrated in melanoma and an interplay between MET and PD-L1 expression has been reported in cutaneous and mucosal melanoma ( 22 ), supporting experimental strategies involving combinatorial approaches of MET inhibition and immunotherapy that may have a role in this disease ( 23 ).…”

MACC1 and MET as markers associated with progression and metastasis in cutaneous melanoma

“…Prior studies using melanoma cell lines or patient FFPE tissue demonstrated a wide range of MET expression in both nevi and melanomas. There is a significantly higher proportion and expression level in melanomas than in nevi, while the expression levels are comparable in primary and metastatic melanomas ( 3 , 20 ). MET expression data in our study is consistent with prior studies in the literature.…”

Prognostic value of receptor tyrosine kinases in malignant melanoma patients: A systematic review and meta-analysis of immunohistochemistry

“…Our findings are consistent with their conclusions as the pooled HRs of survival data concerning VEGFR overexpression are relatively higher than other RTKs. Hepatocyte growth factor receptor (cmesenchymal-epithelial transition factor, c-Met) is a transmembrane protein encoded by the Mesenchymalepithelial transition factor (Met) gene, which is usually abnormally expressed in melanoma due to increased copy number, exon skipping, and gene mutations (19,44). Several studies also found that c-MET may represent a potential biomarker and therapeutic target for melanoma, which warrants further exploration (45,46).…”