Prognostic Significance of Epidermal Growth Factor Receptor Overexpression and Chromosome 7 Polysomy in Clear Cell Renal Cell Carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cell carcinoma. In patients with ccRCC several prognostic markers have been suggested, enclosing epidermal growth factor receptor (EGFR) expression and chromosome 7 polysomy (C7p). Cancer cells addicted to EGFR bear activated mutations in the EGFR gene, and these mutations are useful in predicting susceptibility of ccRCC to EGFR inhibitors. The aim of this study was to evaluate the prognostic value of EGFR overexpression and C7p. Patients and methods: Archival specimens, coupled with clinical and survival data of 34 patients (20 men, 14 women, median age 58, range 42–79 years) who had undergone radical nephrectomy for ccRCC were analyzed. Immunohistochemistry and fluorescence in situ hybridization (FISH) specimens were sections of formalin-fixed paraffin-embedded tissue. EGFR expression was detected as membranous and cytoplasmic staining of neoplastic cells > 1%, and a ratio between gene/centromeric signals of more than two was considered to indicate gene amplification. Mean number of centromeric signals per nucleus was also scored to evaluate C7p. The log-rank test was used to examine the relationship between gender, EGFR overexpression, C7p and survival. Kaplan-Meyer analysis was performed to compare parameters with survival. Results: The age did not differ significantly (p = 0.79) between men and women. Overall, the median survival was 46 months (range 5-150 months). C7p was observed in 21 (61.8%) cases. The log-rank test showed a significantly (p = 0.01) shorter survival among men in respect of women. We did not find any relationship between survival and membranous (p = 0.32) or cytoplasmic (p = 0.51) EGFR overexpression, while C7p significantly (p = 0.02) correlated with survival. Similarly, no correlation was found (Cox’s regression) between EGFR overexpression and survival (R = 0.41, p = 0.21), while the relationship with gender (R = 0.87, p < 0.01) was confirmed. Conclusions: In our preliminary study, women with ccRCC had an overall better survival than men. EGFR was not a useful predictor of outcome, while C7p may have a prognostic significance.