Imunohistochemical Profiles of Urothelial Carcinomas from Upper Urogenital Tract Versus Lower Tract. Does PAX8 Have Any Role?
John Schwartz, Rajwant Malhotra, Ping Zhang, Mitual Amin. William Beaumont Hospital, Royal Oak, MI
Background: Metastatic urothelial carcinoma (UCa) is diagnosed by histologic features and sometimes with the aid of immunohistochemical (IHC) markers such as CK7 and CK20. PAX2 and PAX8 are recent markers that have shown expression in renal tumors. PAX8 in addition has been shown to be positive in 8-23% of UCas of kidney suggesting possible role in differentiating from lower tract UCas. While most studies showed negative PAX-8 IHC staining in UCa of bladder, a recent single study showed 10% cases positive. We wished to evaluate the role of PAX8 in combination with other IHC markers in the diagnosis of UCa in a metastatic setting.
Design: A representative paraffin block was selected from 60 cases of UCa of kidney/ureter (n=20), urinary bladder (n=20) and metastatic UCa (n=20). Six immunostains were performed on these cases - PAX-2, PAX8, CK7, CK20, p-63 and uroplakin. Immunostains were graded visually for extent of staining 0 (0%), 1+ (1-33%), 2+ (34-66%) and 3+ (>67%); and for intensity of staining as 1+ (weak), 2+ (moderate) and 3+ (strong).
Results: There was no PAX2 staining noted in any urothelial carcinoma. PAX8 positivity was noted in 12% (2/17) of UCa from kidney/ureter. No PAX-8 staining was noted in UCa of bladder. PAX8 staining was noted in 5% (1/19) in metastatic UCa, presumably from bladder primary. UCa from the kidney/ureters showed positivity for CK7 in 95% (19/20), CK20 in 71% (12/17), p63 100% (17/17) and uroplakin 18% (2/11). UCa from the urinary bladder showed positivity for CK7 in 95% (19/20), CK20 65% (13/20), p63 94% (17/18) and uroplakin 36% (4/11). Metastatic UCa showed positivity for CK7 in 100% (11/11), CK20 100% (7/7), p63 78% (7/9) and uroplakin 39% (5/13). PAX-8 immunostaining was noted in normal urothelium of the renal pelvis and in collecting tubules of kidney. Staining in normal mucosa is absent in bladder except for rare foci of basal cells.
Conclusions: PAX-2 positivty is not a feature of urothelial carcinoma and positivity should exclude urothelial primary. PAX8 on the other hand is positive in 17% in our hand. PAX8 positivity when present is invariably present as weak staining in rare isolated cells, suggesting little utility. While positivity of the more classic markers p-63, CK7 and CK20 has great value in determining urothelial tumors in a metastatic setting, this does not differentiate upper tract tumors from lower tract tumors. The positivity for PAX8 noted in normal urothelium of upper urogenital tract was confirmed in our study, however, this did not translate into positivity in UCas arising from this site.
Category: Genitourinary (including renal tumors)
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 100, Tuesday Afternoon