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Absence of Nuclear p16 From Epstein‐Barr Virus‐Associated Undifferentiated Nasopharyngeal Carcinomas
Author(s) -
Shibosawa Eriko,
Tsutsumi Kouichiro,
Koizuka Izumi,
Hoshikawa Masahiro,
Takakuwa Toshifumi
Publication year - 2000
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1097/00005537-200001000-00017
Subject(s) - retinoblastoma protein , carcinogenesis , biology , nasopharyngeal carcinoma , cancer research , cyclin d1 , epstein–barr virus , retinoblastoma , in situ hybridization , cell cycle , virus , gene , virology , microbiology and biotechnology , gene expression , medicine , genetics , radiation therapy
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 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 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. Conclusion: Our data suggest that loss of p16‐related cell cycle regulation plays an important role in the development of EBV‐associated UNPCs.