MOLECULAR EPIDEMIOLOGICAL STUDY FOR PREVENTION AND TREATMENT OF HPV-POSITIVE CERVICAL CANCER

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1) To investigate involvement of aberrant expression of the FHIT gene in development of cervical carcinoma, we examined the FHIT gene expression by the RT-PCR and cDNA sequence method in 32 cervical carcinomas and 18 its precursor lesions (CINs) and investigated relation of the FHIT gene expression to HPV infection and the other clinical characteristics. We detected the aberrant FHIT transcrtipts in 11 of 32 (34%) invasive cervical carcinoma and in 5 of 14 (36%) high-grade CINs (CIN 2/3). The alerations of the FHIT gene was identical in invasive carcinomas and CINs. The exons 5, 6 and 7 were commonly absent with or without loss of exon 4 and/or 8 in the aberrant FHIT transcripts. The alteration frequency of the FHIT gene was not related to HPV type and presence. Aberrant expression of the FHIT gene may have an important role in the early phase of development of cervical carcinoma.2) The p53 mutation has been found only in 0-6% of cervical carcinomas. In light of recent studies demonstr … More ating that mutation of p53 gene was found in over 20% of the patients with vulvar carcinoma, a disease of elder women and a known HPV-related malignancy, we analyzed mutation of p53 gene in 46 women with cervical carcinomas at the age of 60 or more (mean ; 71 years, range ; 60-96 years). Mutation of the p53 gene was analyzed by PCR-based single-strand conformation polymorphism (SSCP) and DNA sequencing technique. Point mutation of p53 gene was detected in 5 out of 46 (11%) cervical carcinomas : 1 of 17 (6%) samples associated with high-risk HPVs (HPV 16 and HPV 18) and 4 of 27 samples (15%) with intermediate-risk HPVs. The mutated residues resided in the selective sequence known as a DNA binding domain. All of the observed mutations of p53 gene were transition type, suggesting that the mutation may be caused by endogenous mutagenesis. These data imply that p53 gene mutation, particularly along with intermediate-risk HPV types, may constitute one of pathogenetic factors in cervical carcinoma affecting elderly women. Less