Abnormal Fragile Histidine Triad (FHIT) Expression in Cervical Carcinomas / 대한산부인과학회잡지

ABSTRACT

OBJECTIVE: The fragile histidine triad (FHIT) gene is located at chromosome 3p14.2 and encompasses the common fragile site, FRA3B, which may contribute to chromosome breakage and rearrangement of cancer cells. In this study, we examined whether transcriptional alterations of FHIT gene play a role in the development of human cervical carcinomas and the possibility that hypermethylation of CpG islands serves for FHIT inactivation. We then analyzed FHIT expression status with clinical parameters to determine whether it has any prognostic significance. METHODS: The study group included 50 squamous carcinomas, 4 adenocarcinomas, 4 adenosquamous carcinomas, 7 noncancerous tissue and the clinical stage is composed of 4 Ia, 37 Ib and 17 II. Tissue specimens were snap-frozen in liquid N2 and stored at -70degrees C until used. To examine for abnormal transcripts of the FHIT gene, quantitative RT-PCR, genomic DNA-PCR and nonisotopic RT-PCR-SSCP analysis were performed using the standard method. The methylation status was determined by methylation specific PCR. RESULTS: The FHIT gene was down-regulated in 15 of 58 (25.9%) cervical carcinomas. FHIT promoter hypermethylation was detected in 15 of 15 (100%) abnormally expression in cervical carcinomas. CONCLUSION: In this study, gene mutation is not a main mechanism for FHIT inactivation, but the aberrant promoter hypermethylation may be correlated with decreased expression of the FHIT gene. The significance of decreased expression of FHIT does not appear to be an independent prognostic factor in cervical cancers, although a still larger sample of patients will be required to asses this issue definitively.