Expression of G1/S phase modulators of cell cycle cyclin D1, CDK4, and pRb, and of proliferation marker Ki67 in primary mucosal melanoma of the head and neck

Abstract

Objective Overexpression of Cyclin D1 and CDK4 genes and loss of pRb function are frequent events in many malignant tumors. Interestingly, Cyclin D1 and CDK4 expression is infrequent in cutaneous melanomas, except for the acral melanomas, and pRb expression is retained. The objective of this study was to ascertain the expression of these G1/S phase modulators of the cell cycle and of the proliferation marker Ki67 in the nonUV-light-related primary mucosal melanoma of the head and neck using monoclonal antibodies to Cyclin D1, CDK4, pRb, and Ki67. Findings Archival tissue from 13 primary sinonasal and 4 oral mucosal melanomas from 12 men and 5 women (age range 60-86 years, median 76 years) were used for the study. Cyclin D1 expression was seen in 14 of 15 tumors ( 50% positive cells = 5 tumors). CDK4 expression was seen in all 17 cases (20% positive cells = 1, >50% positive cells = 16 tumors). pRb expression also was seen in all 17 tumors ( 50% positive cells = 14 tumors). The proliferation index as determined by Ki67 expression was 50% in 4 tumors and did not correlate with the expression of cyclin D1, CDK4, or pRb. Conclusion Frequent overexpression of Cyclin D1 and CDK4 suggests deregulation of the G1/S phase of the cell cycle. This may be a critical step in the pathogenesis of mucosal melanoma. Loss of pRb is infrequent in mucosal melanoma and does not appear to be an important factor in its pathogenesis.