Carbonic Anhydrase 9 (CA9) and Caspase-9 (CASP-9) Expression in Clear Cell Renal Cell Carcinoma (CRCC): Diagnostic, Prognostic and Therapeutic Implications
S Kiremitci, D Kankaya, O Tulunay, S Baltaci. Medical School of Ankara University, Ankara, Turkey
Background: Although clinicopathological parameters have proven their prognostic significance in primary CRCC, there is an utmost need of biological predictors for individual tumor behavior with respect to response to survival rate, progression to metastasis, and of biological candidates for targeted therapies.
Design: Immunohistochemistry (IHC) was performed on 100 cases of CRCC using antibodies against CASP-9 and CA9. Tumors were grouped by nuclear grade as low-grade (LNG; NG1,2) or high-grade (HNG; NG3,4), and by pathological stage as localized (LC; pT1,2), or locally invasive (IS; pT3,4). Clinically the tumors were staged as early stage (ES; cTI,II), or late stage (LS; cTIII,IV). Lymphovascular, renal vein, perirenal, regional lymph node invasions (LVI, RVI, PRI, RLN, respectively), and metastasis (Mx) were noted. IHC analysis was based on intensity and/or distribution of the markers. Prognostic factors and expression patterns (cyt/nuc) of markers were considered when developing a prognostic model for disease-specific survival (DSS).
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). 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 found to be an independent predictor of survival. Low expression of CA9 correlated with large tumor size (p=0.002), HNG (p=0.001), LVI (p=0.012), PRI (p=0.015), IS tumor (p=0.045), RLN invasion (p=0.007), Mx (p=0.013), and LS (p=0.003). More patients with low CA9 died of the disease (p=0.001) within shorter time (p=0.004). Low CA9 expression reflected increased aggressiveness for CRCC (OR 3.06, 95% CI 1.35 to 6.91, p=0.007). Loss of CASP-9Nuc correlated with large tumor size (p=0.026), HNG (p=0.001), LVI (p=0.018), Mx (p=0.047), but not with DSS. CASP-9Nuc and CA9 expressions correlated significantly (p=0.017, CC:0.239).
Conclusions: Co-expression of CA9, and CASP-9 reflects significant changes in tumor biology which correlates with survival in CRCC. A combination of CA9 and CASP-9 identify a group of patients with CRCC at high risk for Mx and poor survival. CA9 is a predictor of survival in CRCC and could be a potential tumor-associated antigen and a target for a novel therapeutic target for patients with CRCC.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 116, Wednesday Morning