PAX8 (+)/p63 (-) Immunostaining Pattern in Renal Collecting Duct Carcinoma (CDC): A Useful Immunoprofile in the Differential Diagnosis of CDC vs Urothelial Carcinoma of Upper Urinary Tract
GJ Netto, W Wang, NA Brownlee, A Osunkoya, J Hicks, R Sharma, R Albadine. Johns Hopkins, Baltimore
Background: Collecting duct carcinomas (CDC) are rare aggressive tumors with variable morphologic features, at time making for a difficult dx. One of the WHO diagnostic criteria for CDC is the exclusion of urothelial carcinoma of renal pelvis (UrCa) from the differential diagnosis (DDx). PAX8 is a novel lineage restricted transcription factor expressed in renal tubules. We investigated the expression pattern of PAX8 in CDC and its utility, in combination with p63, in resolving the DDx of CDC vs upper tract UrCa.
Design: Archival tissues from 10 CDCs and 11 UrCa were retrieved from our institutional files. Immunohistochemistry of PAX8 (Protein tech group, Inc. IL.) and p63 (NeoMarkers) were performed on routine sections with Bond-Leica automated stainer using a standard immunohistochemistry protocol. Intensity of PAX8 and p63 nuclear staining was evaluated and assigned an incremental 0,1+,2+,3+ score. Extent of staining was categorized as focal (<25%), multifocal (25-75%) or diffuse (>75%).
Results: CDC: All 10 (100%) CDC were positive for PAX8. Furthermore, staining for PAX8 was moderate in intensity (2+) and diffuse in extent (>75% of cells) in 9/10 (90%) cases. p63 was positive in 2/10 (20%) CDC cases (PAX8 +/p63+). p63 staining was multifocal in both cases. UrCa: The 11 upper tract UrCa included 2 pTa, 3 pT2, 4 pT3 and 2 pT4 tumors. All were negative for PAX8 while 9/11 (82%) were p63 positive. The p63 positivity was generally of moderate intensity and multifocal in extent. The 2 p63 negative UrCa were low grade pTa tumors and were also negative for PAX8 (PAX8 -/p63-).
Conclusions: We suggest a panel including PAX8 and p63 in the differential diagnosis of poorly differentiated renal sinus epithelial neoplasms where the DDx includes CDC vs UrCa. The immuoprofile PAX8+/p63- supports the diagnosis of CDC with a sensitivity of 80% and a specificity of 100%. On the other hand, a (PAX8-/p63+) profile supports the diagnosis of UrCa with a sensitivity of 82% and a specificity of 100%. The inverse PAX8/p63 profiles seen in CDC and UrCa in our study further support a renal tubular rather than a urothelial differentiation in renal CDC given the lineage restriction of PAX8.
Category: Genitourinary (including renal tumors)
Monday, March 9, 2009 1:45 PM
Platform Session: Section A, Monday Afternoon