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Published on: January 22, 2013
FHIT expression in clear cell renal carcinomas: versatility of protein levels and correlation with survival
1Institute of Pathology, Heinrich Heine University, 40225 Duesseldorf, Germany.
Abstract:
Clear cell renal cell carcinomas (RCCs) are characterized by a deletion of chromosome 3p, which might result in the inactivation of the FHIT (fragile histidine triad) gene, a putative tumour suppressor gene. To explore the relevance of FHIT aberrations for tumour progression and prognosis in clear cell RCCs, FHIT protein expression was analysed in formalin-fixed tissue from 149 clear cell RCCs by immunohistochemistry. FHIT protein expression was found to be markedly reduced in all RCCs, when compared with adjacent non-neoplastic tubule epithelia. Although remaining below the FHIT levels of normal tubule epithelia, a significant increase of FHIT expression became evident from well (G1) to poorly (G3) differentiated clear cell RCCs (p=0.0001) and from low (pT1) to advanced (pT3) tumour stages (p=0.001). The log-rank test demonstrated a significant inverse correlation (p=0.0074) between FHIT expression and tumour aggressiveness as indicated by patient survival. Cox regression analysis revealed that FHIT expression is an independent prognostic parameter (p=0.0139) in clear cell RCCs. In conclusion, clear cell RCCs show a marked reduction of FHIT protein expression when compared with their putative cells of origin. In contrast to other tumour types, however, loss of FHIT protein expression is significantly less pronounced in poorly differentiated RCCs or advanced tumour stages. This versatility of FHIT expression during tumour progression suggests a role for reversible mechanisms of FHIT inactivation during the initiation and progression of clear cell RCCs.
Insights
Clear cell renal cell carcinoma (RCC) shows reduced FHIT protein expression. However, increased FHIT levels correlate with less aggressive tumors and better patient survival, suggesting a complex role in RCC progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal cell carcinomas (RCCs) are linked to chromosome 3p deletions.
- The FHIT (fragile histidine triad) gene, a potential tumor suppressor, may be inactivated by these deletions.
Purpose of the Study:
- To investigate the role of FHIT gene aberrations in clear cell RCC tumor progression.
- To determine the prognostic significance of FHIT protein expression in clear cell RCC patients.
Main Methods:
- Immunohistochemistry was used to analyze FHIT protein expression in 149 clear cell RCC tissue samples.
- Statistical analyses including log-rank tests and Cox regression were performed.
Main Results:
- FHIT protein expression was significantly reduced in all RCCs compared to normal kidney tissue.
- Despite being reduced, FHIT expression increased with tumor dedifferentiation (G1 to G3) and advanced stages (pT1 to pT3).
- Lower FHIT expression inversely correlated with tumor aggressiveness and patient survival, and was an independent prognostic factor.
Conclusions:
- Clear cell RCCs exhibit reduced FHIT protein expression compared to their origin cells.
- Unlike other cancers, FHIT loss is less pronounced in advanced RCC stages, suggesting reversible inactivation mechanisms.
- FHIT expression serves as an independent prognostic marker for clear cell RCC.
