Comparison of PAX-2 and PAX-8 in Distinguishing Hepatocellular Carcinomas with Clear-Cell Morphology from Renal Cell Carcinomas
AN Mattis, LW Browne, S Kakar, YY Chen, GE Kim, L Ferrell. UCSF, San Francisco, CA; Kaiser Permanente, Walnut Creek, CA
Background: Immunohistochemistry (IPOX) for PAX-2 and PAX-8, transcription factors important to renal development, are positive in the majority of clear-cell renal cell carcinomas (RCC). The IPOX profile of PAX-2 and PAX-8 in hepatocellular carcinomas (HCC) have not been compared. In adults, the differential diagnosis for hepatic neoplasms with clear-cell morphology includes metastatic RCC. The distinction between HCC with clear-cell morphology and metastatic RCC can be especially challenging on small tissue samples.
Design: We constructed tissue microarrays (TMAs) to investigate the IPOX patterns of PAX-2 and PAX-8 in HCC. The HCC TMAs contained 1.5-mm cores of 82 HCC tumors with a wide range of differentiation and morphologic subtypes including clear cell morphology. We also constructed a TMA containing 1.5-mm cores of 84 primary RCCs which included clear-cell, chromophobe, and papillary variants. We performed IPOX for PAX-2, PAX-8, as well as EMA and RCC antibodies to evaluate renal differentiation, and HepPar1 and glypican-3 to evaluate hepatocellular differentiation. Negative controls were performed. Neoplasms were interpreted as positive for PAX-2 or PAX-8 if they showed nuclear staining.
Results: Only 4(5%) of HCCs showed any PAX-2 focal or weak nuclear staining while none showed strong staining, and 2(3%) of HCCs (not the same cases which were positive for PAX-2) showed focal intermediate to strong positive nuclear staining for PAX-8. Additionally some scattered lymphocytes within HCCs showed strong PAX-8 staining which could be mistaken for positive nuclear staining. 98% of HCCs were negative for EMA and all were negative for RCC antibody. IPOX staining for HepPar1 and/or glypican-3 was seen in 94% of HCCs. Cytoplasmic or background staining was seen in 23% and 13% of HCCs for PAX-2 and PAX-8 respectively. Nuclear staining for PAX-2 was present in 83% and PAX-8 was present in 92% of RCCs.
Conclusions: PAX-2 and PAX-8 nuclear staining is absent in HCC over a wide range of morphologic subtypes but nuclear staining is present in a vast majority of RCC subtypes. PAX-2 and PAX-8 are both very useful in distinguishing between HCC and RCC, including HCC variants with clear cell morphology, comparable to other markers for RCC, including RCC antibody and EMA, and are helpful, particularly in combination with other markers such as HepPar 1 and GLy-3, in distinguishing HCC from RCC.
Category: Liver & Pancreas
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 236, Tuesday Morning