PRB AND P16 PROTEIN ALTERATIONS IN HUMAN ORAL TUMORIGENESIS

Cyclin dependent kinase inhibitor 2/multiple tumour suppressor gene 1 (CDKN2/MTS1) and retinoblastoma (Rb) tumour suppressor genes play impo rtant roles in the regulation of the cell cycle. The protein products of these genes p16(INK4) (p16) and pRb, respectively, like p53 protein inhibit progression from G(1) to S phase, p16 exerts its function thr ough inhibition of CDK4-mediated phosphorylation of pRb. The pRb/p16 p athway is a critical target for molecular aberration at the GI-S check point in a wide range of primary human tumours. The expression of p16 and pRb proteins was analyzed by immunohistochemistry in 35 eases of o ral squamous cell carcinomas (SCCs), 22 cases of premalignant oral les ions and 30 normal oral tissues. Lack of pRb expression was observed i n 23/35 (66%) oral SCCs and 14/22 (64%) premalignant lesions. Lack of p16 expression was observed in 22/35 (63%) oral SCCs and 13/22 (59%) p remalignant lesions. Weak p16 and pRb immunoreactivities were observed in normal oral mucosal epithelium. The status of p16 and pRb was corr elated with clinicopathological characteristics of the patients. Alter ation in p16 expression showed significant correlation with tumour sta ging and progression (P = 0.024). Alteration in pRb/p16 expression cor related with heavy consumption of betel and tobacco. Our results sugge st that alterations in the p16/pRb pathway are early events in oral tu morigenesis and may be involved in the development of betel- and tobac co-related oral malignancies. (C) 1998 Elsevier Science Ltd. All right s reserved.