Differential expression of key cell cycle genes (p16/cyclin D1/pRb) in head and neck squamous carcinomas

Cyclin D1, p16, and Rb are key genes that play critical roles in the contro l of G1/S cell cycle progression and cellular homeostasis. To assess the di fferential expression of these genes in the biologic evaluation of head and neck squamous carcinoma (HNSC), we analyzed their protein expression in 11 cell lines and 46 primary tumors by Western blotting and correlated the re sults with clinicopathologic factors. In all cell lines, reciprocal express ion between p16 and cyclin-D1 and Rb proteins was noted; p16 protein was de tected in one (9%) cell line that lacked Rb and cyclin D1 and was absent in 10 of the cell lines (91%) that expressed both cyclin D1 and Rb proteins. Similar, albeit less striking, results were obtained in primary tumors: 30 tumors (65%) lacked p16 expression, and 33 tumors (72%) and 38 tumors (83%) expressed Rb and cyclin D1 proteins, respectively. p16 and Rb proteins wer e inversely expressed in 72% of tumors and in all cell lines. Except for ge nder and age, no significant correlation between protein expression and the clinicopathologic factors was found. Our results indicate that (1) loss of the p16 protein may constitute an early event in the development of these HNSC, (2) the reciprocal expression of p16 and Rb suggests a tight regulato ry interaction between these genes in HNSC tumorigenesis, and (3) alteratio n in at least one of these genes might be required for HNSC development and progression.