Clear Cell Papillary Renal Cell Carcinoma (CCPAP): A Distinct Entity or a Variant of Clear Cell Renal Cell Carcinoma?
SM Rohan, ME Dudas, A Gopalan, SW Fine, VE Reuter, SK Tickoo. Memorial Sloan Kettering Cancer Center, NY, NY
Background: CCPAP, a recently described tumor, exhibits many differences from clear cell (CC) and papillary renal cell carcinoma (PAP). Utilizing fluorescence in situ hybridization (FISH), 3p deletion and trisomy 7 and/ or 17 were found to be lacking in CCPAP (Gobbo S. et. al., Am J Surg Pathol 2008). This cytogenetic datain conjunction with the morphologic features and unique immunohistochemical (IHC) profilehas been put forth as the basis for recognizing CCPAP as a distinct entity in future classification systems. We evaluated IHC expression of several markers, including hypoxia inducible factor (HIF)/ von Hippel Lindau (VHL) related proteins, in a cohort of CCPAP, CC and PAP.
Design: IHC staining for CD10, -methylacyl-coA racemase (AMACR), 34BE12, CK7, TFE3, HIF1-, and carbonic anhydrase IX (CA9) was performed, using a tissue microarray of 32 cases of renal cell carcinoma including 9 of CCPAP, 10 of CC and 13 of PAP. The staining was graded from 0 to 3+ (0, no staining; 1+, 1-25% cells positive; 2+; 26-50%; and 3+, >50%). Cytoplasmic / membranous expression of CD10, AMACR, CK7, and CA9 were considered positive. Only nuclear expression of TFE3 and HIF1- were considered positive.
Results: All 9 CCPAP cases showed strong co-expression (2-3+) of CK7, HIF-1- and CA9 with no or low (0-1+) expression of CD10 and AMACR. 34BE12 was strongly expressed (2-3+) in 5/9 CCPAP. All ten CC cases showed strong co-expression (2-3+) of HIF-1-, CA9 and CD10 with no or low (0-1+) expression of CK7, AMACR and 34BE12. The majority of PAP cases (11/13) showed strong (2-3+) co-expression of CK7 and AMACR. None of the PAP cases exhibited staining with HIF-1-, CA9, or 34BE12. All thirty-two cases were negative (0) for TFE3.
Conclusions: The morphological features and immunophentotype (CA9+, CK7+, 34BE12, CD10-, AMACR-) of CCPAP are sufficiently distinct to allow easy separation from CC and PAP. However, based on CA9 and HIF-1- expression it appears that CC and CCPAP both have activated HIF pathways. The expression of these antigens could be related to any number of genetic events. However, given the known role of the VHL gene in the activation of the HIF pathway the possibility of a close relationship between CC and CCPAP, at least at tumorigenesis level, cannot be excluded. Further molecular studies of the VHL locus, that include mutational analysis and promoter methylation in addition to 3p deletion studies are warranted.
Category: Genitourinary (including renal tumors)
Tuesday, March 10, 2009 1:45 PM
Platform Session: Section A, Tuesday Afternoon