Philipp Jurmeister1,2, Michael Bockmayr1,3, Christoph Treese4,5,6, Ulrike Stein5,7, Dido Lenze1, Korinna Jöhrens1, Franziska Friedling8, Manfred Dietel1, Frederick Klauschen1, Wolfgang Marsch8, Eckhard Fiedler8, Maximilian von Laffert1,4. 1. Institute of Pathology, Charité - Universitätsmedizin Berlin, Berlin, Germany. 2. Charité Comprehensive Cancer Center, Berlin, Germany. 3. Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 4. Berlin Institute of Health (BIH), Berlin, Germany. 5. Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany and Max-Delbrück-Center for Molecular Medicine, Berlin, Germany. 6. Department of Gastroenterology, Infectious Diseases, Rheumatology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany. 7. German Cancer Consortium (DKTK), Heidelberg, Germany. 8. Department of Dermatology and Venereology, University Hospital Halle (Saale), Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
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.
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 melanomapatients.