人乳头瘤病毒相关宫颈癌中FHIT、P53和错配修复基因之间的相关性

The correlation between FHIT, P53 and MMR genes in human papillomavirus-associated cervical carcinoma.

作者信息

Bahnassy Abeer A, Zekri Abdel Rahman N, Madbouly Maha S, El-Naggar Mervat, El-Khelany Zinab F, El-Merzebany Mahmoud M M

机构信息

Department of Pathology, National Cancer Institute, Cairo University, Egypt.

出版信息

J Egypt Natl Canc Inst. 2006 Sep;18(3):191-202.

PMID:17671528

Abstract

BACKGROUND AND AIM

High risk human papillomavirus (HR-HPV) types have been closely associated with cervical carcinoma. However, other genetic events are likely to be required, in addition to HPV infection, for the development of cervical cancer. We investigated 20 human cervical carcinomas and 15 normal cervical tissues for the correlation between aberrant expression of the FHIT, p53 and MMR genes and their prognostic impact.

METHODS AND RESULTS

The expression of p53, FHIT and MMR genes (hMSH2, hMLH1,GTBP/hMSH6,hPMS2, hPMS1) was assessed in relation to HPV infection by immunohistochemistry and PCR. HPV-16 and 18 DNA were detected in 95% and 25%, HPV m-RNA in 90% and 10% of cases; respectively. Homozygous deletion (HZD) and reduced FHIT protein was detected in 40% and 65% of cases, respectively; 25% of which showed abnormal gene transcripts. Reduced MMR gene expression was found in 19 cases. hMSH2 and hMLH1 showed the highest frequency (80% and 70%, respectively). p53 overexpression was present in 50% of cases with a single mutation in exon 7. There was a significant relation between FHIT aberrations, HPV-16 RNA, reduced hMLH-1 and hMSH- 2 expression; between reduced expression of hMSH-2 and p53 overexpression, GTPB-6, as well as between GTPB-6 and hMLH-1. Aberrant expression of p53, FHIT, hMLH1and GTPB-6 was significantly associated with recurrence.

CONCLUSIONS

Aberrations involving MMR genes, FHIT and p53 are frequent in HPV-associated cervical carcinoma with a significant correlation between them. However, only the FHIT, p53, hMLH1 and GTPB6 aberrations could be used as predictors of tumor recurrences.

摘要

背景与目的

高危型人乳头瘤病毒（HR-HPV）与宫颈癌密切相关。然而，除HPV感染外，宫颈癌的发生可能还需要其他基因事件。我们研究了20例人宫颈癌组织和15例正常宫颈组织，以探讨FHIT、p53和错配修复（MMR）基因的异常表达及其预后影响之间的相关性。

方法与结果

采用免疫组化和PCR技术评估p53、FHIT和MMR基因（hMSH2、hMLH1、GTBP/hMSH6、hPMS2、hPMS1）的表达与HPV感染的关系。分别在95%和25%的病例中检测到HPV-16和18 DNA，在90%和10%的病例中检测到HPV信使核糖核酸（mRNA）。分别在40%和65%的病例中检测到FHIT基因纯合缺失（HZD）和FHIT蛋白表达降低；其中25%表现为异常基因转录本。在19例病例中发现MMR基因表达降低。hMSH2和hMLH1的降低频率最高（分别为80%和70%）。50%的病例中存在p53过表达，其第7外显子有单个突变。FHIT基因异常、HPV-16 RNA、hMLH-1和hMSH-2表达降低之间存在显著相关性；hMSH-2表达降低与p53过表达、GTPB-6之间存在显著相关性，GTPB-6与hMLH-1之间也存在显著相关性。p53、FHIT、hMLH1和GTPB-6的异常表达与复发显著相关。