PAX8 Expression in Clear Cell, Papillary and Chromphobe RCC and Urothelial Carcinoma of Renal Pelvis
S Jadallah, R Albadine, R Sharma, GJ Netto. Johns Hopkins, Baltimore
Background: PAX8 is a novel cell lineage restricted transcription factor expressed by renal tubules. The current study evaluated PAX8 immunoexpression pattern in primary and metastatic renal cell carcinomas (RCC) as well as in upper urinary tract urothelial carcinomas primary to renal pelvis (UT-UCa).
Design: PAX8 IHC staining was performed on Tissue microarray (TMA) constructed from 144 primary and 40 metastatic archival RCC specimens (2004-2006). Primary RCC tumors included 68 clear cell (cRCC), 45 papillary (papRCC) and 31 chromophobe (chRCC) cases. All metastatic RCC were of clear cell type. PAX8 IHC was also performed on 11 primary renal pelvis urothelial carcinoma (UT-UCa) using routine sections. IHC was performed using Bond-Leica automated stainer and a monoclonal Ab (Protein tech group, Inc.; IL). Nuclear staining intensity was assigned an incremental 0, 1+, 2+, 3+ score. Extent of staining was categorized as focal (<25% of cells), multifocal (25-75%) or diffuse (>75%).
Results: Primary RCC: PAX8 was most frequently expressed in papRCC (43/45; 96%) followed by cRCC (44/68; 65%) then chRCC (17/31; 55%). The difference in expression rates among histologic types was statistically significant (p=0.0001). Variability in staining intensity and extent was encountered from case to case in each of the three histologic types. However, PAX8 staining was generally multifocal to diffuse in nature in all three types and was focal in extent (<25% of cells) in only a minority of cases: 4/44 (9%) of positive cRCC, 1/43 (2%) of positive papRCC and 6/31 (19%) of positive chRCC. We found no correlation between Fuhrman grade and rate of PAX8 positivity, extent or intensity of PAX8 positivity in either cRCC or papRCC (p:NS). Metastatic cRCC: PAX8 expression was detected in 33/40 (83%) of metastatic cRCC. Extent of expression was focal in only 2/40 (5%) of cases. The difference in rate of expression between primary and metastatic cRCC in our cohort was statistically significant (p: 0.05). Renal Pelvis UCa: None of the 11 UT-UCa were positive for PAX8.
Conclusions: PAX8 is expressed by the three most common types of RCC. Expression rate is significantly different among RCC types and is lowest in ChRCC and highest in papRCC and cRCC. In positive cases, PAX8 expression is multifocal to diffuse in the majority of cases potentially increasing its utility in needle bx setting. PAX8 was negative in UT-UCa cases suggesting its potential utility in distinguishing RCC from UT-UCa in difficult needle bx of a renal mass.
Category: Genitourinary (including renal tumors)
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 139, Tuesday Afternoon