High proliferative activity may predict early metastasis of thin melanomas

Metastasis of thin melanomas is uncommon and unpredictable. We prospectively investigated the clinical course of 167 thin melanomas (<1 mm thickness) over a median observation period of 4 years (18 to 87 months). In addition to Breslow thickness, Clark level, and growth phase characteristics, we assessed cellular proliferation by counting mitoses and immunohistochemically using the monoclonal antibody Ki-S5 (Ki-67). Mitotic and Ki-S5 indices were correlated to tumor thickness, Clarks level, and radial/vertical growth phase (RGP/VGP). However, 5 tumors had proliferation indices above 25% (outside the range of a theoretical normal distribution). Four of these tumors metastasized, and none of the melanomas with lower proliferative activity progressed during the observation period. The metastatic behavior was independent of tumor thickness and Clark level and did not unconditionally coincide with VGP or high mitotic counts. It is concluded that the immunohistochemical proliferation index may be a powerful predictor of early systemic progression in thin melanomas, which may be helpful in making therapeutic decisions. Further investigations are needed to determine the value of proliferation measurements for the long-term prognosis of thin melanomas.