Expression of c-met tyrosine kinase receptor is biologically and prognostically relevant for primary cutaneous malignant melanomas

Abstract

Objectives: The c-met tyrosine-kinase receptor and its ligand hepatocyte growth factor are involved in cell survival, proliferation, motility, and invasion. Experimental data have suggested a putative role in melanomagenesis and progression of cutaneous malignant melanoma (CMM). We sought to evaluate c-met expression in a cohort of 62 primary CMM patients diagnosed and primarily treated at the same institution.

Methods: Sixty-two cases of CMM were retrospectively retrieved from the archives of the Department of Pathology, Hospital São João, Porto, Portugal. All classical clinicopathological features were reviewed. Only those patients in whom representative paraffin blocks were available and the diagnosis of primary CMM was confirmed, and who were followed up after the primary diagnosis were included in the study. Immunohistochemistry for c-met was performed in 59 cases, and semiquantitatively and qualitatively (membranous and cytoplasmic, M+C, or cytoplasmic) evaluated. Statistical analysis was performed using chi(2), ANOVA and Kaplan-Meier/log-rank tests.

Results: M+C pattern of c-met expression was significantly associated with presence of vertical growth phase (p = 0.0198), thick tumors (p = 0.0006), ulceration (p = 0.0386), high mitotic index (p = 0.0008), lymphatic (p = 0.0086) and vascular (p = 0.0080) invasion, and nodal (p = 0.0422) and combined (nodal and/or visceral) metastases (p = 0.0234). M+C pattern of c-met expression also proved to be a significant prognostic factor for overall survival in univariate analysis (p = 0.0125).

Conclusions: Our findings suggest that the pattern of c-met expression is a relevant prognostic factor for overall survival and is associated with more aggressive behavior of primary CMMs.