Absence of nuclear p16 from Epstein-Barr virus-associated undifferentiated nasopharyngeal carcinomas.
OBJECTIVE
Epstein-Barr virus (EBV) is detected in the majority of undifferentiated nasopharyngeal carcinomas (UNPCs, World Health Organization type III). However, the exact mechanism involved in the carcinogenesis of EBV-associated UNPCs remains to be elucidated. An important unresolved question is: how is the normal cell cycle deregulated during EBV-associated UNPC development? The p16CDKN2 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 G1 cell cycle progression. The objective of this study was to determine whether p16 absence is involved in the development of EBV-associated UNPCs.


METHODS
We performed immunohistochemistry 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 p16 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.


CONCLUSIONS
Our data suggest that loss of p16-related cell cycle regulation plays an important role in the development of EBV-associated UNPCs.
Shibosawa
E
E
Department of Otolaryngology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
Tsutsumi
K
K
Koizuka
I
I
Hoshikawa
M
M
Takakuwa
T
T
D002277:Carcinoma / Q000209:etiology / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D020031:Epstein-Barr Virus Infections / Q000209:etiology / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods; D009303:Nasopharyngeal Neoplasms / Q000209:etiology / Q000378:metabolism*; D012342:RNA, Small Nuclear / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism
D019941:Cyclin-Dependent Kinase Inhibitor p16; D012342:RNA, Small Nuclear; D012367:RNA, Viral; D016160:Retinoblastoma Protein