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


  • P. Jurmeister
  • M. Bockmayr
  • C. Treese
  • U. Stein
  • D. Lenze
  • K. Jöhrens
  • F. Friedling
  • M. Dietel
  • F. Klauschen
  • W. Marsch
  • E. Fiedler
  • M. von Laffert


  • Journal der Deutschen Dermatologischen Gesellschaft


  • J Dtsch Dermatol Ges 17 (8): 800-808


  • 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.