Expression Pattern of Epidermal Growth Factor Receptor (EGFR) in Clear Cell Renal Cell Carcinoma (CRCC): Association with Clinicopathological Features and Clinical Outcome
S Kiremitci, D Kankaya, O Tulunay, S Baltaci. Medical School of Ankara University, Ankara, Turkey
Background: CRCC is the most common malignancy involving the adult kidney, and generally presents as a metastatic disease. Molecular markers to identify patients at risk for poor disease-specific survival (DSS) would benefit in such situations where additional therapeutic modalities are imperative.
Design: Immunohistochemistry was performed on 100 cases of CRCC using antibody against EGFR. Tumors were grouped by nuclear grade (NG) as low NG (LNG; NG1,2) or high NG (HNG; NG3,4), and by pathological stage as localized (LC; pT1,2), or locally invasive (IS; pT3,4). Clinical stage was grouped as early stage (ES; cTI,II), or late stage (LS; cTIII,IV). Lymphovascular, renal vein, perirenal, and regional lymph node invasions (LVI, RVI, PRI, RLN, respectively), and metastasis (Mx) were noted. Evaluation of EGFR is based on the pattern of staining; cytoplasmic (EGFRCyt), membranous (EGFRMem), and cytoplasmic and/or membranous (EGFRGroup). EGFR analysis was based on intensity and distribution of EGFR.
Results: HNG tumors were larger (>7 cm). Local invasiveness correlated with larger size (p=0.003), HNG (p=0.006). Mx correlated with HNG (p=0.001), and older age (>57 yrs, p=0.045). Median follow-up was 24 months (range=1-144 months). While NG (p=0.001), LVI (p=0.042), RVI (p=0.001), PRI (p=0.012), pT (p=0.006), RLN (p=0.001), Mx (p=0.001), cT (p=0.001) correlated with DSS, only cT (p=0.010) was an independent predictor of survival. EGFRCyt overexpression correlated with HNG (p=0.001), LVI (p=0.028), RLN involvement (p=0.027), Mx (p=0.001), LS (p=0.003), and DSS (p=0.009), and was a predictor for DSS (p=0.012). EGFRMem overexpression correlated with IS tumor (p=0.021), PRI (p=0.009), but not DSS. Cytoplasmic dominant EGFRGroup overexpression correlated with multifocal tumor (p=0.018), HNG (p=0.001), IS tumor (p=0.047), LVI (p= 0.035), RLN involvement (p=0.009), Mx (p=0.022), and DSS (p=0.012).
Conclusions: This study demonstrates the importance of the assessment methods of EGFR immunostaining, and explain the conflicting results in the literature. We demonstrate that, EGFR overexpression is an important prognostic factor in CRCC which is modified by the location of expression in tumor cells. EGFRCyt expression; either alone or as cytoplasmic dominat EGFRGroup, demonstrated powerful potential for the prediction of poor DSS. EGFRMem expression does not worsen clinical outcome and is associated with better prognosis.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 115, Wednesday Morning