人乳头瘤病毒（HPV）分型与宫颈肿瘤中G2细胞周期调节因子状态之间的关系

Relationship between HPV typing and the status of G2 cell cycle regulators in cervical neoplasia.

作者信息

Hashiguchi Yasunori, Tsuda Hiroshi, Nishimura Sadako, Inoue Takeshi, Kawamura Naoki, Yamamoto Kumio

机构信息

Department of Obstetrics and Gynecology, Osaka City General Hospital, 2-13-22 Miyako-jimahondori Miyakojima, Osaka 534-0021, Japan.

出版信息

Oncol Rep. 2004 Sep;12(3):587-91.

PMID:15289842

Abstract

We examined human papillomavirus (HPV) typing and the status of ATM, chk2, CDC25C, cdc2 and cyclinB1 in cervical intraepithelial neoplasia (CIN) and invasive cancer (IC). A total of 93 samples [normal: 10; CIN: 34 (CINI:9, CINII:12, CINIII:13); IC: 49 (stage I:10, stage II:21, stage III:15, stage IV:3)] were included in this study. HPV status was evaluated by the PCR non-radioactive HPV detection system. We analyzed ATM, chk2, CDC25C, cdc2 and cyclinB1 protein expression by immunohistochemistry. HPV DNA was detected in 73.5% of 34 CINs and 89.8% of 49 ICs. Detection of HPV subtypes 16 and 18 was more frequent in ICs (46.9%) than in CINs (23.5%) (p=0.0387). Abnormal expression of ATM, chk2, CDC25C, cdc2 and cyclinB1 were 2.9%, 32.4%, 2.9% 20.6% and 0% in CINs and 8.2%, 30.6%, 10.2%, 46.9% and 12.2% in ICs. The alteration of cdc2 was higher in ICs than in CINs (p=0.0198). Altered expression of cdc2 was higher in HPV16 and 18 cases (69.6%) than in other cases (26.9%) (p=0.0042). However, the relationship between HPV typing and ATM, chk2, CDC25C and cyclinB1 expression was not significant. Cdc2 is implicated in cervical carcinogenesis and may be related to p53 inactivation by HPV.

摘要

我们检测了人乳头瘤病毒（HPV）分型以及宫颈上皮内瘤变（CIN）和浸润性癌（IC）中ATM、chk2、CDC25C、cdc2和细胞周期蛋白B1的状态。本研究共纳入93份样本[正常：10份；CIN：34份（CINI：9份，CINII：12份，CINIII：13份）；IC：49份（I期：10份，II期：21份，III期：15份，IV期：3份）]。通过PCR非放射性HPV检测系统评估HPV状态。我们采用免疫组织化学分析ATM、chk2、CDC25C、cdc2和细胞周期蛋白B1的蛋白表达。在34份CIN样本中有73.5%检测到HPV DNA，在49份IC样本中有89.8%检测到HPV DNA。IC中HPV 16和18亚型的检出率（46.9%）高于CIN（23.5%）（p = 0.0387）。CIN中ATM、chk2、CDC25C、cdc2和细胞周期蛋白B1的异常表达分别为2.9%、32.4%、2.9%、20.6%和0%，IC中分别为8.2%、30.6%、10.2%、46.9%和12.2%。IC中cdc2的改变高于CIN（p = 0.0198）。HPV 16和18病例中cdc2的表达改变（69.6%）高于其他病例（26.9%）（p = 0.0042）。然而，HPV分型与ATM、chk2、CDC25C和细胞周期蛋白B1表达之间的关系并不显著。Cdc2与宫颈癌发生有关，可能与HPV导致的p53失活有关。