Minichromosome maintenance protein expression in benign nevi, dysplastic nevi, melanoma, and cutaneous melanoma metastases

Abstract

Minichromosome maintenance (MCM) proteins are a recently elucidated group of polypeptides intimately involved in DNA replication and appreciable only in cycling cells. In other organ systems their expression has proven more prognostically useful than cell proliferation markers such as Ki-67 and proliferating cell nuclear antigen. To date, the evaluation of MCM proteins in melanocytic neoplasms has not been undertaken. We sought to determine whether MCM protein 2 (the most extensively evaluated of the MCM protein family) is present in melanocytes from benign nevi, dysplastic nevi, primary cutaneous melanomas, and cutaneous melanoma metastases and, if so, whether there exists a significant difference in expression among the 3 groups. Immunohistochemical staining for MCM 2 was performed on tissue sections from 10 benign nevi, dysplastic nevi, and primary cutaneous melanomas and from 5 cutaneous melanoma metastases. Approximately 200 cells were evaluated microscopically in 5 separate fields for each specimen and the number of positively staining nuclei was counted. After a percentage was calculated for each lesion, the data were pooled and statistically analyzed. Melanocyte nuclear staining was readily visible microscopically. The percentage of positively staining nuclei in benign nevi (1.2%), dysplastic nevi (6.1%), primary cutaneous melanomas (49.1%), and cutaneous melanoma metastases (40.9%) was significantly different (P < .0001) among the 4 groups. Using paired comparisons, statistically significant differences were found between benign nevi and melanoma, dysplastic nevi and melanoma, benign nevi and cutaneous melanoma metastases, and dysplastic nevi and cutaneous melanoma metastases. There was no statistically significant difference between cutaneous melanoma metastases and primary cutaneous melanoma. This is a small pilot study without blinded evaluation of the tissue sections and lacking correlation with patient clinical outcome or accepted histologic prognostic factors. MCM protein expression appears to differ significantly in melanocytic neoplasms and potentially provides an additional tool for distinguishing benign tumors from their malignant counterparts. Further evaluation of this expression may prove useful in delineating the biologic behavior of these tumors and warrants additional research.