Ki 67 immunostaining in melanocytic skin tumors. Correlation with histologic parameters

A total of 145 melanocytic tumors (nevus, 38; primary malignant melanoma, 72; metastatic malignant melanoma, 35) were stained with Ki 67 monoclonal antibody using a three-step immunoperoxidase technique. For each case, mean numerical density and maximum numerical density of Ki 67 positive nuclei (number per mm3) were quantitatively evaluated using interactive image analysis. Maximum numerical densities revealed highly significant differences. Within the group of primary malignant melanomas, there was a significant correlation between proliferative activity and maximum tumor thickness. Further, a 'Ki 67-prognostic index' was assessed in each case of primary malignant melanoma, calculating the product of the Breslow index and maximum numerical density/1000 (103 +/- 12; range 1-694). In a prospective, short-term evaluation of primary malignant melanomas, there was a significant difference concerning 'Ki 67-prognostic index' between disease-free survival and occurrence of metastases. After a follow-up time of 24 months, only 63% of the patients with a 'Ki 67-prognostic index' greater than 25 were disease-free, whereas no patient with a 'Ki 67-prognostic index' less than 25 was found to have metastases. We conclude: assessment of the maximum numerical density of Ki 67 reflects the degree of malignancy in melanocytic skin tumors; within primary malignant melanomas, maximum numerical density of Ki 67 positive cells correlates with well-established prognostic parameters (tumor thickness, level of invasion, mitotic rate); assessment of the 'Ki 67-prognostic index' may be of additional prognostic value for patients with primary malignant melanoma.