Immunohistochemical (IHC) Expression of Carbonic Anhydrase IX (CA9) in Papillary (PRCC) and Chromophobe (CHRCC) Renal Cell Carcinoma Is Associated with Necrosis.
Rajen Goyal, Bing Zhu, Vamsi Parimi, Shreenath Bishu, Xiaoqi Lin, Ximing J Yang, Stephen M Rohan. Northwestern University, Chicago, IL
Background: The modern classification of renal cell carcinoma (RCC) recognizes numerous subtypes of which clear cell (CRCC), PRCC, and CHRCC are the most common. Many IHC markers useful in differentiating RCC subtypes have been described. CA9 protein expression is induced by hypoxia or in the case of CRCC abrogation of the VHL / HIF pathway. In a recent phase III clinical trial radiolabeled CA9 was used with imaging techniques to preoperatively identify CRCC with high specificity. In the pathology literature it has been suggested that CA9 expression is often seen in PRCC and other renal tumors. We evaluated CA9 IHC in different RCC subtypes focusing on tumors with necrosis.
Design: H&E sections of RCC were evaluated for necrosis. IHC for CA9 was performed on whole sections from 17 RCC with necrosis (10 PRCC, 7 CHRCC) and 17 RCC without necrosis (10 PRCC, 7 CHRCC). Ten CRCC were included as controls. Qualitative (intensity 0-3+) and quantitative (% of cells) CA9 labeling was evaluated. The distribution of staining within a tumor (peri-necrotic vs. viable areas) was recorded. Only membranous CA9 labeling was considered positive. Statistics were performed using the Student's t-test.
Results: CA9 staining was seen in a larger percentage of cells and was more intense in necrotic areas compared to non-necrotic areas in PRCC (necrotic mean cell % = 5%; non-necrotic mean cell % = 1% [p value = 0.03]; mean intensity in necrotic areas = 2.1; mean intensity in non-necrotic areas = 0; p value < .001). A difference was also seen between mean intensity CA9 staining in necrotic versus non-necrotic areas in CHRCC (1.17 vs 0; p value = 0.02). Necrotic areas of PRCC and CHRCC when compared to each other showed no significant differences in either percentage of cells staining or intensity of staining (p value = 0.17 and p value = 0.75 respectively). All of the CRCC evaluated exhibited >90% of cells staining with 3+ intensity.
Conclusions: PRCC and CHRCC can exhibit expression of CA9 albeit at a much lower level relative to CRCC. Non-clear cell carcinomas with areas of necrosis show greater and more intense CA9 staining compared to non-clear cell carcinomas without necrosis. Caution should be taken when interpreting CA9 IHC in difficult to classify RCC cases exhibiting necrosis, particularly in small biopsies. The relevance of CA9 expression in necrotic non-clear cell RCC renal tumors as it relates to new preoperative imaging modalities warrants further investigation.
Category: Genitourinary (including renal tumors)
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 115, Wednesday Morning