PAX-8 Expression in Urothelial Neoplasia – An Immunohistochemical Study of 236 Cases
R Albadine, L Schultz, DA Fajardo, R Sharma, PB Illei, S Jadallah, JI Epstein, GJ Netto. Johns Hopkins University, Baltimore, MD
Background: PAX-8 is a transcription factor crucial for lineage commitment in thyroid, Mullerian duct and nephric development. For its role in ontogenesis and oncogenesis in the genitourinary tract, PAX-8 has recently gained great utility as a marker of renal and ovarian lineage. In the current study, we investigate PAX-8 expression in a large cohort of invasive and non-invasive urothelial neoplasms of upper and lower urinary tract, to further validate its utility in resolving the differential diagnosis of urothelial vs renal differentiation.
Design: Tissue microarrays (TMA) were constructed from archival tissues of urothelial neoplasms retrieved from our institution (1985-2005). The cohort of 236 tumors included 200 bladder tumors: 6 Papillary Urothelial Neoplasm of Low Malignant Potential (PUNLMP), 43 non-invasive urothelial carcinoma (10 high grade) and 151 invasive urothelial carcinoma (UrCa). The cohort also included 36 urothelial carcinoma of the upper urinary tract (UUC), including 2 non-invasive tumors. Triplicate tumor samples were spotted from each case. Immunohistochemistry for PAX-8 was performed using standard protocol and appropriate controls. Tumors were evaluated for extent of nuclear staining, categorized as focal (<25%), multifocal (25-75%) or diffuse (>75%) and assigned an incremental 0 to 3+ intensity score. The UUC subset of the cohort was further evaluated for p63 immunostaining (NeoMarkers), using a similar approach.
Results: Overall, 224/236 (95%) of urothelial neoplasms were negative for PAX-8. All 6 (100%) PUNLMP and 151 (100%) invasive UrCa of the bladder were negative for PAX-8. PAX-8 staining was encountered in 7/43 (16%) non-invasive bladder UrCa. In UUC, 3 (8%) invasive tumors were positive for PAX-8, all with weak/moderate intensity (1+/2+). Both cases of non-invasive UUC were negative for the PAX-8. p63 was positive in 33/36 (92%) UUC. The 3 negative cases included 2 non-invasive and 1 pT1 tumor and all were also negative for PAX-8.
Conclusions: For all practical purposes, urothelial neoplasms of the bladder lack PAX-8 expression. All invasive UrCa of bladder origin were negative for PAX-8. Although rare PAX-8 positivity was encountered in non invasive tumors, their urothelial nature is evident by their architecture. In UUC, where the differential diagnosis includes RCC, PAX-8 was rarely expressed by invasive UUC (8%), the urothelial nature of the latter subset of cases can be resolved by their co-expression of p63.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 148, Wednesday Afternoon