Abstract

Malignant melanoma (MM) is potentially the most dangerous form of skin tumor. In the last few years, the so-called TAM receptors, a unique family of tyrosine kinase (TK) receptors, have become increasingly important. To evaluate Mer and Axl TAM receptor expression to find clinicopathological features that could explain the biological behavior of MM. Clinicopathological data were obtained from an MM electronic database at our Institute. We reviewed 24 cutaneous MM specimens. TAM receptor expression was assayed using immunohistochemistry. Combinative semiquantitative scoring was used for the evaluation of TAM receptor expression (MerTK and AxlTK). Appropriate statistical methods were used to evaluate a possible correlation between TAM receptor expression and the clinicopathological variables of the MM samples (univariate analysis and multivariate analysis). MerTK and AxlTK were expressed differently in the MM samples, with a major expression of the first receptor. The cells of the tumor microenvironment contributed to the majority of the total score. A significant association was found between AxlScore and the site of the tumor and between AxlScore and the variable ulceration; another correlation was found between MerScore and the following characteristics: pathological stage of the tumor (pT), sex, ulceration, and tumor-infiltrating lymphocytes. All correlations between the expression of MerTK and AxlTK with the clinical and histological variables of MM should be validated in a large group of people in order to increase the validity and the impact of our observations, with subsequently therapeutic implications in the era of the "targeted therapy."

Highlights

  • Malignant melanoma (MM) is potentially the most dangerous form of skin tumor, causing 90% of skin cancer mortality [1]

  • A significant association was found between AxlScore and the site of the tumor and between AxlScore and the variable ulceration; another correlation was found between MerScore and the fol

  • Mean progression-free survival (PFS) was 55.22 months in MerTK− lesions, while it was 93.58 in MerTK+ lesions (P = 0.004); in the long term, we found that overall survival (OS) was 62.9 in MerTK− and 93.76 in MerTK+ lesions (P = 0.02)

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Summary

Introduction

Malignant melanoma (MM) is potentially the most dangerous form of skin tumor, causing 90% of skin cancer mortality [1]. MM has more mutations than any other cancer type, and genome aberrations are present in the majority of them. In this regard, oncogenic mutations in c-KIT, NRAS, and BRAF components of the MAPK pathway have been identified in nearly 90% of cutaneous MM [3]; in particular, BRAF and NRAS mutations are the most frequently observed [4]. Malignant melanoma (MM) is potentially the most dangerous form of skin tumor. In the last few years, the so-called TAM receptors, a unique family of tyrosine kinase (TK) receptors, have become increasingly important

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