A possible involvement of aberrant expression of the FHIT gene in the carcinogenesis of squamous cell carcinoma of the uterine cervix

To investigate involvement of an aberrant expression of the FHIT(fragile hi stidine triad) gene in the process of carcinogenesis and progression in cer vical carcinoma, we examined its expression by the reverse transcriptase po lymerase chain reaction (RT-PCR) and cDNA sequence method in 32 cervical in vasive carcinomas (25 squamous cell carcinomas and seven adeno- or adenosqu amous carcinomas) and 18 of its precursor lesions [four low-grade and 14 hi gh-grade cervical intraepithelial[ neoplasias (CINs)]. We also examined a l ink between the occurrence of the aberrant expression and human papillomavi rus (HPV). We detected the aberrant FHIT transcripts in 11 of 25 (44%) cerv ical invasive squamous cell carcinomas and in 5 of 14 (36%) high-grade CINs (CIN 2 or 3), whereas they were not found in seven non-squamous type and f our low-grade CINs (CIN 1). The alteration patterns of the FHIT gene expres sion in high-grade CINs Ms were virtually similar to those found in invasiv e carcinomas, such that the exons 5-7 were consistently deleted associated or unassociated with loss of the exon 4 and/or 8. The incidence of the aber rant expression was not related to the presence of HPV and its type. These data indicate that the aberrant expression of the FHIT gene is observed in precursor lesions of cervical carcinoma as well as invasive carcinomas, wit h its incidence not increasing with advance of clinical stage. Given the sq uamous cell type dominant expression, the aberrant expression may play a cr itical role in the generation of squamous cell carcinoma of the uterine cer vix, but not the consequence of the progression of the cancer.