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Different immunohistochemical patterns of Fhit protein expression in renal neoplasms
E J Eyzaguirre1, M Miettinen, B A Norris
1Department of Pathology, University of Texas Medical Branch at Galveston, 77555-0588, USA.
Background:
The FHIT gene on human chromosome 3p14.2 is deleted in a variety of malignant tumors, including clear cell renal carcinomas (RCCs) resulting in a loss of expression of Fhit protein. The Fhit expression in specific subtypes of renal carcinomas has not been characterized. We have investigated the association of Fhit expression with particular subtypes of renal tumors to determine the role and specificity of this putative tumor suppressor gene in renal neoplasia.
Material And Methods:
The immunohistochemical expression of Fhit was tested in normal kidneys and in 109 renal neoplasms consisting of 51 clear cell RCCs, 26 papillary RCCs, two chromophobe carcinomas, 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 (78%) of clear cell RCCs showed reduced or absent expression of Fhit, whereas the majority (74%) of papillary carcinomas, all chromophobe renal cell carcinomas, and oncocytomas were strongly positive. Sixty-eight percent of low-grade (G1 plus G2) but only 9% of high-grade (G3 plus G4) clear cell carcinomas were Fhit negative. Wilms' tumors demonstrated focal staining in the epithelial component in 8 of 20 cases (40%).
Conclusions:
The loss of Fhit expression in a high percentage of clear cell RCCs with conservation of Fhit in other types of tumors supports the proposed role of FHIT alterations in the genesis of clear cell carcinomas in contrast to other types of renal epithelial tumors. FHIT expression may play a role in epithelial differentiation of nephroblastomas (Wilms' tumors).
Insights
Loss of Fhit protein expression is common in clear cell renal cell carcinoma (RCC) but preserved in other renal tumors, suggesting FHIT gene alterations are specific to clear cell RCC development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The FHIT gene, located on chromosome 3p14.2, is frequently deleted in various cancers, leading to loss of Fhit protein expression.
- Fhit protein expression patterns in different renal carcinoma subtypes were previously uncharacterized.
- Investigated the role of Fhit as a tumor suppressor in renal neoplasia by examining its expression in specific tumor subtypes.
Purpose of the Study:
- To characterize Fhit expression in various renal tumor subtypes.
- To determine the association between Fhit expression and specific renal tumor types.
- To elucidate the role and specificity of the FHIT gene in renal neoplasia.
Main Methods:
- Immunohistochemical analysis of Fhit expression.
- Tested Fhit expression in normal kidney tissue and 109 renal neoplasms.
- Included clear cell RCCs, papillary RCCs, chromophobe carcinomas, oncocytomas, pelvic transitional cell carcinomas, and Wilms' tumors.
Main Results:
- Normal renal tubules exhibited strong and consistent Fhit expression.
- A majority of clear cell RCCs (78%) showed reduced or absent Fhit expression.
- Papillary RCCs (74%), chromophobe RCCs, and oncocytomas were predominantly Fhit positive, while Wilms' tumors showed focal staining.
Conclusions:
- Loss of Fhit expression is prevalent in clear cell RCCs but not in other renal epithelial tumors, supporting FHIT's role in clear cell carcinoma genesis.
- FHIT alterations appear specific to the development of clear cell renal carcinomas.
- Fhit expression may be involved in the epithelial differentiation of Wilms' tumors.