Primary cervical carcinomas show 2 common regions of deletion at 3P, 1 within the FHIT gene: Evaluation of allelic imbalance at FHIT, RB1 and TP53 inrelation to survival

Chromosome arm 3p is re-arranged in many tumor types, including cervical ca rcinomas. Putative tumor-suppressor genes on 3p have been proposed, includi ng the FHIT gene, which maps to chromosome band 3p14.2. We have analyzed 79 primary cervical carcinomas for allelic imbalance (AI) at 17 chromosome 3 loci, including 3 within the FHIT gene. Expression of the FHIT gene was eva luated after immunohistochemistry with an antibody against the pFHIT protei n. Previously determined human papillomavirus status, defined after in situ hybridization, showed type 16 or 18 in 56/77 tumors. Tumors were also anal yzed for AI at loci within the RB1 (chromosome band 13q14.2) and the TP53 ( 17p13) genes for AI. AI was found at 1 or more 3p loci in 50/79 tumors, at frequencies ranging from 30% to 52% at the individual loci. Two smallest re gions of overlapping deletion (SROs) were found, 1 including parts of the F HIT gene (SRO flanked by D3S1481 and D3S1313) and another more distal SRO b etween D3S32 and D3S1286, FHIT protein expression was reduced in 57/69 (83% ) tumors but not associated with AI at FHIT loci (p = 0.56). AI was found i n TP53 and RB1 in 18% and 29% of the samples, respectively. Relapse-free su rvival was associated with AI in the TP53 gene in both a univariate (p = 0. 0003) and a multivariate (p = 0.004) analysis. This study confirms a high f requency of Al at chromosome arm 3p in primary cervical carcinomas. The Al results and the reduced FHIT protein staining indicate that FHIT alteration s are important in cervical carcinogenesis. Int. J. Cancer 88:217-222, 2000 . (C) 2000 Wiley-Liss, Inc.