Loss or reduction of Fhit expression in renal neoplasias: Correlation withhistogenic class

Involvement of the 3p14.2 region of chromosome 3 in kidney cancers was sugg ested 20 years ago, when a reciprocal constitutional translocation, t(3;8)( p14.2;q24), was shown to segregate with bilateral clear cell renal carcinom a in 3 generations of 1 family. The FHIT gene that is interrupted at 3p14.2 by the t(3;8) translocation has been isolated, characterized, and shown to be frequently altered, mainly by internal deletion, in carcinomas or cance r-derived cell lines of the lung, stomach, pancreas, esophagus, cervix, and colon. Although up to 90% of sporadic clear cell renal carcinomas, represe nting similar to 70% of adult renal carcinomas, exhibit loss of FTIT allele s, FHIT gene alterations have been documented for only a few renal cell car cinoma-derived cell lines. Nevertheless, more than 50% of clear cell carcin omas were recently shown to express little or no Fhit protein, unlike the n ormal kidney tubule epithelium, which is uniformly strongly positive for Fh it expression. We have extended our immunohistochemical study of expression of Fhit protein to the spectrum of histopathologic subtypes of adult renal tumors. There is an apparent continuum of Fhit expression from the 100% st rongly positive oncocytomas through mostly positive papillary and chromopho be to the mostly negative clear cell and sarcomatoid to the negative or pre dominantly negative collecting duct renal carcinomas. This pattern of dimin ishing Fhit expression correlates with reported frequency of 3p allele loss in renal carcinomas and may parallel the potential for aggressive behavior of tumors, as suggested by the abundant Fhit expression in the benign onco cytomas and the near absence of Fhit expression in sarcomatoid and collecti ng duct RCCs. Copyright (C) 1999 by W.B. Saunders Company.