Immunohistochemical analysis of Bcl-2, nuclear S100A4, MITF and Ki67 for risk stratification of early-stage melanoma - A combined IHC score for melanoma risk stratification.

Philipp Jurmeister, Michael Bockmayr, Christoph Treese, Ulrike Stein, Dido Lenze, Korinna Jöhrens, Franziska Friedling, Manfred Dietel, Frederick Klauschen, Wolfgang Marsch, Eckhard Fiedler, Maximilian von Laffert

Journal: Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG 2020;17(8):800-808

PMID: 31437373

Abstract

BACKGROUND AND OBJECTIVES

Overall survival (OS) in patients with early-stage malignant melanoma differs. To date, there are no established prognostic markers. We aimed to contribute to a better understanding of potential prognostic immunohistochemical markers for risk stratification.

PATIENTS AND METHODS

161 surgically resected early-stage malignant melanomas (stage pT1 and pT2) were analyzed for expression of 20 different proteins using immunohistochemistry. The results were correlated with OS. The cohort was randomly split into a discovery and a validation cohort.

RESULTS

High Bcl-2 expression, high nuclear S100A4 expression as well as a Ki67 proliferation index of ≥ 20 % were associated with shorter OS. Strong MITF immunoreactivity was a predictor for favorable prognosis. A combination of these four markers resulted in a multi-marker score with significant prognostic value in multivariate survival analysis (HR: 3.704; 95 % CI 1.484 to 9.246; p = 0.005). Furthermore, the score was able to differentiate a low-risk group with excellent OS rates (five-year survival rate: 100 %), an intermediate-risk group (five-year survival rate: 81.8 %) and a high-risk group (five-year survival rate: 52.6 %). The prognostic value was confirmed within the validation cohort.

CONCLUSIONS

Combined immunohistochemical analysis of Bcl-2, nuclear S100A4, Ki67 and MITF could contribute to better risk stratification of early-stage malignant melanoma patients.

© 2019 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Address: Institute of Pathology, Charité - Universitätsmedizin Berlin, Berlin, Germany.; Charité Comprehensive Cancer Center, Berlin, Germany.; Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Berlin Institute of Health (BIH), Berlin, Germany.; Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany and Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.; Department of Gastroenterology, Infectious Diseases, Rheumatology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.; German Cancer Consortium (DKTK), Heidelberg, Germany.; Department of Dermatology and Venereology, University Hospital Halle (Saale), Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
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