The prognostic significance of epidermal growth factor receptor expression in clear-cell renal cell carcinoma: A call for standardized methods for immunohistochemical evaluation

Background: Epidermal growth factor receptor (EGFR) is overexpressed in the majority of clear-cell renal cell carcinomas (RCCs). The prognostic significance of EGFR overexpression after nephrectomy, however, is controversial because of different methods used in the immunohistochemical (IHC) evaluation of EGFR expression. Patients and Methods: In this study, we evaluated EGFR expression and its prognostic significance using 3 IHC evaluation methods. A tissue microarray composed of 44 cases of clear-cell RCC was stained for the patterns of EGFR overexpression, including membranous, cytoplasmic (EGFR-c), and total (membranous and cytoplasmic), and the percentage of cells positive for EGFR overexpression were recorded. An EGFR composite score was calculated by multiplying the total EGFR overexpression score (0-3) and percentage of positive cells. Results: Membranous EGFR overexpression was detected in 38 of 44 cases (93.2%), with moderate to strong staining (scores 2 and 3) in 35 cases (79.5%). EGFR-c was detected in 28 cases (63.6%), with moderate to strong staining (scores 2 and 3) in 16 cases (36.4%). EGFR-c was significantly associated with pathologic stage (P = 0.003) and Fuhrman nuclear grade (P = 0.042). Epidermal growth factor receptor composite score correlated with pathologic stage (P = 0.045) but not Fuhrman nuclear grade. However, EGFR expression did not correlate with overall survival or disease recurrence. Conclusion: This study demonstrates that the prognostic value of EGFR overexpression differs significantly when different methods are used to evaluate EGFR expression by IHC. Future studies should use standardized methods to evaluate the EGFR staining pattern and intensity and the percentage of positive cells in order to clarify the prognostic significance of EGFR overexpression in clear-cell RCC.