Absence of nuclear p16 from Epstein-Barr virus-associated undifferentiatednasopharyngeal carcinomas

Objective: Epstein-Barr virus (EBV) is detected in the majority of undiffer entiated nasopharyngeal carcinomas (UNPCs, World Health Organization type I II). However, the exact mechanism involved in the carcinogenesis of EBV-ass ociated UNPCs remains to be elucidated. An important unresolved question is : how is the normal cell cycle deregulated during EBV-associated UNPC devel opment? The p16(CDKN2) gene encodes a nuclear protein, p16, which inhibits the D-type cyclin/cyclin-dependent kinase complexes that phosphorylate the retinoblastoma gene product (pRb), thus blocking G(1) cell cycle progressio n, The objective of this study was to determine whether p16 absence is invo lved in the development of EBV-associated UNPCs, Methods: We performed immu nohistochemistry to detect p16 and pRb and in situ hybridization to detect EBV-encoded small RNA (EBER) in UNPCs from 28 patients, Results: No p16 was detected in 23 of 28 UNPCs (82.1%), whereas pRb was expressed in all those examined and EBER was detected in 22 of 28 (78.6%). The absence of pie was associated with the presence of EBER in UNPCs (P < .0001): none of the 22 EBER+ UNPCs expressed p16, whereas 5 of 6 EBER- UNPCs did, Conclusion: Our data suggest that loss of pie-related cell cycle regulation plays an import ant role in the development of EBV-associated UNPCs.