Evaluation of Proliferation Index by Ki-67 and ProEx-C in Malignant Melanoma and Benign Melanocytic Nevi.
Bryan N Coffing, Shaofeng Yan. Dartmouth Hitchcock Medical Center, Lebanon, NH
Background: The correct classification of melanocytic lesions as benign nevi versus malignant melanoma is a high risk endeavor for patients and Pathologists alike. In diagnostically challenging cases, the proliferative rate of these lesions is considered a helpful distinguishing feature. The Ki-67 immunohistochemical proliferation index has been used to quantify proliferative activity in melanocytic lesions. ProEx-C is an immunohistochemical marker consisting of a cocktail of two antibodies that target minichromosome maintenance protein and topoisomerase II alpha protein, both of which are overexpressed in the nucleus during various phases of the cell cycle in proliferating cells. Moreover, ProEx-C has been shown to be a more sensitive marker of proliferation than Ki-67 in squamous lesions. Therefore, we hypothesize that ProEx-C will be a useful marker of proliferation in melanocytic lesions.
Design: We analyzed 199 melanocytic lesions (140 melanomas and 59 benign nevi) in a tissue microarray using an immunohistochemical method with antibodies directed against Ki-67 and ProEx-C. Melanocytes were counted at 400x magnification. Depending on the number of cells available in the core, 100 to 500 dermal melanocytes were counted (average per core: 307). Any positive staining within the nucleus was considered a positive cell.
Results: The average proliferative index of melanomas and benign nevi by Ki-67 staining was 16.9% and 0.3%, respectively (p < 0.001). By ProEx-C staining, the averages were 37% and 0.9%, respectively (p < 0.001). Comparison of primary melanomas with and without evidence of metastasis on follow-up did not show a statistically significant difference with either stain. However, the proliferative index by Ki-67 staining in primary melanomas (15.2%) was significantly different (p < 0.05) from that of metastatic melanomas (23.3%); statistically significant differentiation of these two groups by ProEx-C was not observed. Immunohistochemical proliferation rates for both markers paralleled mitotic activity.
Conclusions: ProEx-C staining index is a discriminating marker of proliferative activity in melanocytic lesions and may be useful in the diagnosis of melanoma and other difficult melanocytic lesions.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 113, Tuesday Morning