Utility of GATA3, Uroplakin-II, and p40 Markers in the Diagnosis of Urothelial Carcinoma.

Background, aim, and objectives: Accurate diagnosis of urothelial carcinoma (UC), particularly in high-grade and limited biopsy specimens, may be challenging on morphology alone. Immunohistochemistry (IHC) markers such as GATA3, uroplakin II (UPII), and p40 may improve diagnostic confidence. This study aimed to evaluate the diagnostic utility of GATA3, UPII, and p40, individually and as a combined panel, in urothelial carcinoma, and to correlate marker expression with tumor grade and invasion status. This cross-sectional study was conducted in the Department of Pathology, Sri Siddhartha Medical College (SSMC), Tumkur, Karnataka, India, over a period of 24 months from February 2024 to January 2026. The study included 35 consecutive histopathologically confirmed cases of urothelial carcinoma received in the Department of Pathology during the study period, diagnosed on transurethral resection of bladder tumor (TURBT) specimens and bladder biopsy specimens. Formalin-fixed paraffin-embedded tissue sections were stained with hematoxylin and eosin and subjected to IHC for GATA3, UPII, and p40. Positivity rates and staining intensity were assessed. Associations with grade and invasion were analyzed statistically. Data were entered into Microsoft Excel and analyzed using SPSS Statistics (IBM Corp., Armonk, NY, USA). Categorical variables were expressed as frequencies and percentages, while continuous variables were summarized as mean ± standard deviation. Associations between marker expression, tumor grade, and invasion status were analyzed using the chi-square test. The mean age of the study population was 67.09 ± 5.77 years, with a male predominance (25/35, 71.4%). Low-grade urothelial carcinomas constituted 18/35 (51.4%) cases, while 17/35 (48.6%) were high-grade. Positive IHC expression was observed in 34/35 (97.1%) cases for UPII, 33/35 (94.3%) for GATA3, and 32/35 (91.4%) for p40. No statistically significant association was found between the expression of any marker and tumor grade or invasion status (p > 0.05). Triple-marker positivity was observed in 30/35 (85.7%) cases, dual-marker positivity in 4/35 (11.4%), and single-marker positivity in 1/35 (2.9%). No case was negative for all three markers, resulting in 100% diagnostic coverage with the combined IHC panel. GATA3, UPII, and p40 are highly useful IHC markers in urothelial carcinoma. While each marker performed well individually, the combined panel demonstrated positivity in all cases in this cohort, suggesting complementary diagnostic value. This three-marker panel may be useful in difficult primary and metastatic cases requiring confirmation of urothelial differentiation.