Revista de diagnóstico y biomarcadores moleculares

MITF Expression in Cutaneous Malignant Melanoma

Abstract

Margrét Agnarsdóttir, Fredrik Ponten, Hans Garmo, Gunnar Wagenius, Lorelei Mucci, Kristina Magnusson, Lars Holmberg and Sonja Eaker-Fält

The MITF protein has a central role in the differentiation and survival of melanocytes. The aim of the study was to investigate whether MITF can be employed as a prognostic marker in patients operated on for cutaneous malignant melanoma. A cohort study design, based on information collected from population-based registries, was employed. For included patients (n=264) tissue microarrays were stained with immunohistochemistry to study the protein expression of MITF in primary malignant melanoma tumors by estimating the fraction of positive tumor cells and the staining intensity. Most of the tumors (84%) expressed MITF in >25% of the tumor cells and for 87% of the tumors the staining intensity was strong. Tumors with cell fraction >75% had a better prognosis compared with those with <75% (HR 0.44, 95% CI: 0.20-1.0, P=0.05). Tumors with a strong staining intensity tended to have a better prognosis compared with the weaker staining ones (HR 0.59, 95% CI: 0.26 -1.36, P=0.22). When cell fraction and intensity were combined, a high-risk group dying of malignant melanoma was identified as those patients with 25- 75% of tumor cells staining with weak intensity (HR 2.9, 95% CI: 0.94-8.7, P=0.06) and those with <25% of tumor cells staining with strong intensity (HR 2.5, 95% CI: 1.1- 6.1, P=0.04). However, the majority of deaths occurred in the lower risk groups. In conclusion, a high-risk group for death in malignant melanoma was identified but MITF is not suitable as a prognostic marker due to the distribution of that particular expression in the population.