Different immunohistochemical patterns of Fhit protein expression in renalneoplasms

Background: The FHIT gene on human chromosome 3p14.2 is deleted in a variet y of malignant tumors, including clear cell renal carcinomas (RCCs) resulti ng in a loss of expression of Fhit protein. The Fhit expression in specific subtypes of renal carcinomas has not been characterized. We have investiga ted the association of Fhit expression with particular subtypes of renal tu mors to determine the role and specificity of this putative tumor suppresso r gene in renal neoplasia, Material and Methods: The immunohistochemical ex pression of Fhit was tested in normal kidneys and in 109 renal neoplasms co nsisting of 51 clear cell RCCs, 26 papillary RCCs, two chromophobe carcinom as, six oncocytomas, four pelvic transitional cell carcinomas and 20 Wilms' tumors from formalin fixed and routinely processed tissue. Results: Normal renal tubules expressed Fhit strongly and consistently, The majority (18%) of clear cell RCCs showed reduced or absent expression of Fhit, whereas th e majority (74%) of papillary carcinomas, all chromophobe renal cell carcin omas, and oncocytomas were strongly positive. Sixty-eight percent of low-gr ade (G1 plus G2) but only 9% of high-grade (G3 plus G4) clear cell carcinom as were Fhit negative. Wilms' tumors demonstrated focal staining in the epi thelial component in 8 of 20 cases (40%), Conclusions: The loss of Fhit exp ression in a high percentage of clear cell RCCs with conservation of Fhit i n other types of tumors supports the proposed role of FHIT alterations in t he genesis of clear cell carcinomas in contrast to other types of renal epi thelial tumors. FHIT expression may play a role int epithelial differentiat ion of nephroblastomas (Wilms' tumors).