Evaluation of the proliferation marker MIB-1 in the prognosis of cutaneous malignant melanoma

Abstract

Background: The proliferation marker MIB-1, which recognizes the Ki-67 antigen, provides independent prognostic information in several tumor types. Its utility in melanoma has been evaluated mostly in studies of thick primary tumors. Its usefulness in thinner lesions has not been assessed adequately.

Methods: A well characterized cohort of 137 patients diagnosed with primary cutaneous melanoma at the New York University School of Medicine between 1972 and 1982 was studied based on the availability of representative tissues and adequate clinical follow-up. Twenty-one tumors were less than or equal to 1.0 mm thick, 94 were between 1.01 and 4.0 mm thick, and 22 were thicker than 4.0 mm. Tumor cell proliferation was assessed by immunohistochemistry using the monoclonal antibody MIB-1. MIB-1 expression was correlated with baseline clinicopathologic parameters, as well as recurrence (RR), disease-free (DFS), and overall survival (OS) rates. Median follow-up among survivors was 6.5 years (range, 5.6-17.5).

Results: High proliferative index, defined as 20% or more of tumor cells showing nuclear immunoreactivity, was observed in 65 of 137 (47.4%) cases. High proliferative index was significantly correlated with increased tumor thickness (P < 0.001) and higher stage (P = 0.03). Trends approaching statistical significance were observed with ulceration of the primary tumor (P = 0.09), male gender (P = 0.06), and shorter DFS (P = 0.12). No significant associations were seen between high proliferative index and RR or OS. In multivariate analyses, tumor thickness was the strongest predictor of clinical outcome.

Conclusions: In primary cutaneous melanoma, a high proliferative index is associated with clinicopathologic parameters predictive of worse clinical outcomes. However, it was not an independent predictor of clinical outcome.