| Worldwide, cervical carcinoma (CC) remains the second most common malignancy of women in both incidence and mortality. There are approximately 131,500 new cases diagnosed annually in China ,and it leans to threaten the younger women nowdays. Hence, people have concerned on the early diagnosis of CC. It is thought that cervical intraepithelial neoplasia (CIN), especially grade II and III lesions, is the precursor lesion for invasive CC. But, while most of CIN will persist or regress, only a partial of CIN will progress to ICC if left untreated. Unfortunately, morphological examination alone does not allow distinction of those lesions likely to progress from those that will regress or simply persist. With molecular technique developing, recent attention has focused on molecular markers to aid in this distinction and to enhance diagnosis of early cervical lesions.Although numerous studies have strongly implicated that certain "high-risk" HPV infection clearly play an important role in cervical carcinogenesis, several lines of evidence suggest that HPV infection alone is insufficient for cervical tumor development. Thus, other genetic events are likely to be critical in the pathogenesis of cervical cancer. Inactivation or deletion of multiple tumor suppressor genes (TSG) is thought to be one of the most important mechanisms of carcinogenesis. Analysis of allelic losses of specific chromosomal regions offers an available method to reveal TSGs associated with development of cancer. A high frequency of allelic deletions on the short arm of chromosome 3 (3p14-21) has been noted in primary CC andpreneoplastic lesions. This observation indicates that some tumor suppressor genes may be located in this region and play a role in cervical carcinogenesis. Recently, a candidate tumor suppressor gene, fragile histidine triad (FHIT), was identified at 3p14.2. FHIT abnormalities have been observed frequently in a variety of human malignant tumors, predominantly of organs directly exposed to environmental carcinogens. Studies on transcription and expression of FHIT in primary cervical carcinomas and preneoplastic lesions have come to conflicting conclusions. Up to now, it remains controversial about the role of FHIT gene in cervical carcinogenesis. Moreover the relationship between FHIT gene deletion and protein expression, and the mechanism of FHIT inactivation has been unclear.In this study, we investigated the profiles of abnormal Fhit expression and allelic losses of FHIT gene by immunohistochemical staining and LOH (loss of heterozygosity) analysis on microdissected archival tissues in primary CC and CIN, in order to evaluate the role of FHIT gene deletion in cervical carcinogenesis, and the potential value of FHIT as a molecular marker of progression risk of CIN. MethodsOne hundred and thirteen paraffin-embedded tissues of cervical lesions enrolled in this study were collected from Women's hospital, school of medicine, Zhejiang University dating from January 2000 to December 2001, including 56 primary invasive CCs (42 squamous cell carcinomas, 14 adenocarcinomas ) and 57 CINs (15 CIN I, 8 CIN II, 34 CIN III). Fhit expression was detected by immunohistochemmical staining. Microdissected tumor and corresponding normal tissues were evaluated for FHIT gene LOH by polymerase chain reaction using intragenic microsatellite markers D3S1300 and D3S1234. PCR products were electrophoresed in denature polyacrylamide gels and silver stained to determine allele loss. ResultsThirty-two of 56 (57%) invasive CC showed reduced or absent Fhit staining comparing to the intensity of staining of corresponding normal cervical epithelial cell.Sixty-nine percent of squamous cell carcinomas and 21% of adenocarcinomas showed abnormal Fhit expression. There was a significant difference between the two types (P<0.01). The loss of Fhit expression in squamous cell carcinomas was found to be independent of differentiation or FIGO stage (P>0.05). Of the total 57 CINs, 13 (23%) CIN exhibited reduced or absent Fhit expression, with a si...
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