CAIX Immunohistochemical Expression in Epithelial Tumors.
Shreenath Bishu, Vamsi Parimi, Ximing J Yang. Northwestern University, Chicago, IL
Background: Carbonic Anhydrase IX (CA IX), a transmembrane protein regulated by the Von Hippel Lindau (VHL) gene, is involved in tumor genesis through regulation of cell adhesion, and pH via the HIF-1alpha activation cascade. CA IX is also a potential prognostic marker and chemotherapeutic target in renal cell carcinoma as high expression indicates a favorable prognosis and may predict response to interleukin-2 therapy. Although CAIX expression has been well documented in renal epithelial neoplasms, its expression in other epithelial tumors has not been well characterized.
Design: After IRB approval 183 in-house cases of viable (non-necrotic) epithelial malignancies were retrieved for construction of tissue microarrays, which were subsequently stained via immunohistochemistry using monoclonal antibody specific for CA IX. The cases include; renal cell carcinoma (RCC), clear cell type (ccRCC, n=37), chromophobe (chRCC, n=18), papillary (papRCC n=20), oncocytoma (n=16), and various carcinomas including urothelial (n=10), breast (ductal, n=8), colonic (n=10), endometrial (n=8), esophageal adenocarcinoma (n=9), hepatocellular (n=10), lung (NSCLC, n=10), pancreatic (n=9), prostatic (n=10), and ovarian epithelial (n=8). Transmembrane immunohistochemical expression on tumor cells was deemed a positive result. CAIX staining was further stratified for distribution (focal vs. diffuse), and intensity, on a scale from 1+ to 3+ (3+= strongest).
Results: CAIX expression was diffusely positive in all cases of ccRCC, with a majority showing strong staining (2+ or 3+) in 33/37 cases (89%). In contrast the large majority of other primary renal epithelial neoplasms were completely negative for CAIX (50/54 cases, 93%). The four positive cases were papillary RCC showing focal staining only (2 with 2+, and 2 with 1+). Of the other epithelial malignancies, only colonic adenocarcinoma showed a primarily positive pattern of staining (7/10, 70%,) with a majority of these being diffuse (5/7, 72%). Conversely, hepatocellular carcinoma (HCC) and prostatic adenocarcinoma showed absence of CA IX staining in all cases. All other epithelial malignancies showed variable staining patterns.
Conclusions: In the setting of evaluating primary renal epithelial neoplasms, CA IX is a very good marker for renal cell carcinoma, clear cell type. In the context of metastatic disease however, CA IX staining should be used with caution, as many tumors showed variable expression, with the exceptions being HCC and prostatic adenocarcinoma (which both showed none). This is particularly true with colonic adenocarcinoma, with the majority of cases showing positive and diffuse expression.
Category: Genitourinary (including renal tumors)
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 136, Wednesday Afternoon