Immunohistochemical Expression of Renal Markers in Matched Primary and Metastatic Renal Cell Carcinomas.
Zenggang Pan, William E Grizzle, Omar Hameed. University of Alabama at Birmingham
Background: The diagnosis of metastatic renal cell carcinoma (RCC) may be challenging, especially due to its broad morphologic spectrum and potential histologic mimicry of other tumors. Thus immunohistochemistry (IHC) has become an invaluable tool for the diagnosis. Recent studies, however, have found that many proteins are up- or down-regulated in metastasis and it is unknown whether this affects the utility of IHC in the diagnosis of metastatic RCC.
Design: A retrospective review was performed to identify RCCs in which materials from both primary and metastatic sites were present. After histologic review, the primary and metastatic tumors were punched (1.0 mm) in triplicate and plated on tissue microarrays. IHC was then performed with antibodies directed against the RCC antigen (RCCA), kidney-specific cadherin (KSC), carbonic anhydrase-IX (CA-IX), PAX2, and PAX8. The intensity (0-3) and percentage of positive cells (0-100%) were used to calculate the H-score for each immunostain.
Results: Our search identified 16 cases. There was significant variation (P<0.0001; paired ANOVA) in marker expression when primary and metastatic RCCs were grouped together (Fig 1) with RCCA having the lowest average H-score (P value <0.001; paired t-test). In comparing primary and metastatic tumors there was also significant variation (P<0.0001; ANOVA) with greater CA-IX, PAX2 and PAX8 expression in metastases (Fig 2). Moreover, out of 8 originally PAX8-ve tumors (H-score < 10), 7 expressed this marker in corresponding metastases. The expression of KSC was very similar in primary and metastatic RCCs, whereas a significant proportion of originally RCCA+ve tumors lost such expression in metastases (44% vs. 2% for all other markers; P<0.0001; X2).
Conclusions: Although there is significant variation in the expression of renal markers in primary and metastatic RCC, loss of RCCA expression in metastatic lesions appears to be the only finding of potential clinical consequence.
Category: Genitourinary (including renal tumors)
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 112, Wednesday Morning