Impact of Epidermal Growth Factor Receptor (EGFR), Gelsolin, NF-kB, and p53 Expression on Clinicopathological Parameters in Clear Cell Renal Cell Carcinoma (CRCC)
D Kankaya, S Kiremitci, O Tulunay, S Baltaci. Medical School of Ankara University, Ankara, Turkey
Background: CRCC has an unpredictable behavior and tendency for recurrence and metastasis (Mx). Novel markers are necessary to develop a prognostic profiling system for disease specific survival (DSS), and to design therapeutic regimens in CRCC.
Design: Immunohistochemistry was performed on 100 cases of CRCC using antibodies against EGFR, Gelsolin, NF-kB, and p53. Tumors were grouped by nuclear grade 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 disease was grouped by clinical stage as early stage (ES; cTI,II), or late stage (LS; cTIII,IV). Evaluation was based on cytoplasmic (EGFRCyt), and membranous (EGFRMem) expression for EGFR; cytoplasmic (NF-kBCyt), and nuclear (NF-kBNuc) expression for NF-kB.
Results: Mx correlated with HNG (p=0.001), and older age (>57 yrs, p=0.045). 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 was an independent predictor of DSS (p=0.010) . EGFRCyt correlated with HNG (p=0.001), LVI (p=0.028), RLN involvement (p=0.027), Mx (p=0.001), LS (p=0.003), and was a predictor for DSS (p=0.012). EGFRMem correlated with IS tumor (p=0.021), PRI (p=0.009). Gelsolin expression correlated with HNG (p=0.001), Mx (p=0.003), LS (p=0.008), DSS (p=0.006). NF-kBCyt expression correlated with HNG (p=0.002), PRI (p=0.010), IS tumor (p=0.020), LS (p=0.003). NF-kBNuc did not predict the prognosis of CRCC. p53 expression correlated with HNG (p=0.045), LVI (p=0.05), Mx (p=0.001), LS (p=0.028). Gelsolin correlated with EGFRCyt (p=0.005), p53 (p=0.045), and NF-κBCyt (p=0.028). p53 correlated with EGFRCyt. EGFRMem correlated with NF-κBCyt(p=0.044).
Conclusions: Expressions of Gelsolin, NF-κBCyt, and p53 associated with aggressive behavior of CRCC. EGFR and Gelsolin demonstrated to be an unfavourable prognostic factor in CRCC. Prognostic value of EGFR differed significantly with expression pattern. EGFRCyt expression associated with with short survival, while EGFRMem is not correlated with DSS. This study demonstrated a staining profile as a classifier of the high-risk group of patients with CRCC; overexpressions of EGFRCyt, Gelsolin, NF-kBCyt, and p53. EGFR seems an attractive target for therapeutic manipulation in patients with advanced CRCC.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 114, Wednesday Morning