The Role of GATA3 in the Differential Diagnosis of Upper Tract Urothelial and Collecting Duct Carcinomas
Nilda Gonzalez-Roibon, Alcides Chaux, Rajni Sharma, Mohamad E Allaf, George J Netto. Johns Hopkins Hospital, Baltimore, MD
Background: Collecting duct carcinoma (CDC) is a rare entity with poor prognosis, often presenting with advanced disease stage. Differential diagnosis from invasive upper tract urothelial carcinoma (UTUC) can be challenging. PAX8 and p63 are two markers often used in this setting. GATA3 is a newer marker of urothelial differentiation. We investigated the expression of GATA3 in UTUC and CDC and its utility in the differential diagnosis of these two entities.
Design: Archival tissues from 18 cases of CDC and 25 cases of UTUC were used to build 2 tissue microarrays. GATA3, p63 and PAX8 nuclear expression were evaluated using standard immunohistochemistry (GATA3: clone L50-823, BioCare Medical, CA; p63: NeoMarkers, Fremont, CA; PAX8: Protein Tech Group, Chicago, IL). For each marker, staining intensity and percentage of positive cells were assessed. Sensitivity, specificity and positive predictive value of the markers and their combination were evaluated.
Results: We found GATA3 positivity in 22/25 (88%) UTUC and 1/18 (5.6%) CDC. Median GATA3 extent of expression was higher in UTUC than in CDC (74% vs 0%, p=0.00). We found p63 positivity in 23/25 (92%) UTUC and 2/18 (11%) CDC. PAX8 was positive in 3/25 (12%) UTUC and all (100%) CDC. GATA 3 sensitivity and specificity for UTUC were 88% and 94%; p63 sensitivity and specificity for UTUC were 92% and 89%. Individually, GATA3 and p63 positivity had a positive predictive value for UTUC of 96% and 92%, respectively. PAX8 expression had a positive predictive value for CDC of 86%. The p63+/PAX8- combination profile showed higher sensitivity for UTUC than GATA3+/PAX8- profile (80% vs 76%). Both showed a specificity of 100% for UTUC. GATA3+/PAX8- and/or p63+/PAX8- sensitivity and specificity for UTUC were 84% and 100% respectively.
Conclusions: Immunohistochemical expression of GATA3 was higher in UTUC, suggesting a role in distinguishing UTUC from CDC. Adding this marker to the combination panel of p63 and PAX8 could improve its performance in the diagnosis of poorly differentiated renal sinus epithelial neoplasms where the differential diagnosis includes these two entities.
Category: Genitourinary (including renal tumors)
Monday, March 4, 2013 8:30 AM
Proffered Papers: Section A, Monday Morning