Utility of GATA-3 and associated immunohistochemical markers in the differential diagnosis of poorly differentiated urothelial carcinoma.

Aims: The aims are to study the utility of GATA-3 along with panel of immunohistochemical (IHC) markers in the differential diagnosis of primary and metastatic poorly differentiated urothelial carcinoma (UC). Settings and Design: This is a prospective and retrospective observational study. Subjects and Methods: Poorly differentiated carcinomas of urinary tract and metastatic sites from January 2016 to December 2017 were subjected to a panel of four IHC markers including GATA-3, p63, Cytokeratin (CK) 7, and CK20. Additional markers such as p16, an enzyme called alpha-methylacyl-CoA racemase, CDX2, and thyroid transcription factor 1 were also done depending on the morphology and site. Statistical Analysis Used: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of GATA-3 in making the diagnosis of UC were calculated. Results: Forty-five cases were included in the study and after appropriate IHC, the diagnosis was resolved as UC in 24 cases. GATA-3 was positive in 83.33% of UC; all the four markers positive in 33.33% and all negative in 4.17% of UC. However, at least one of the four markers was present in 95.83% of UC, except in sarcomatoid UC. GATA-3 had 100% specificity in differentiating from prostate adenocarcinoma. Conclusion: GATA-3 is a useful marker in the diagnosis of UC in the primary and metastatic sites with a sensitivity of 83.33%. GATA-3 along with other IHC markers in correlation with clinical and imageological features is necessary for making specific diagnosis of poorly differentiated carcinoma.

GATA-3 Expression in all Grades and Different Variants of Primary and Metastatic Urothelial Carcinoma.

Urothelial carcinoma has a varied and wide histological spectrum posing a diagnostic challenge in H&E examination alone. Immunohistochemical markers like GATA-3 along with other appropriate panel of IHC can be used. However, the percentage positivity and its intensity may vary in different variants and grades of primary and metastatic urothelial carcinoma. To observe the GATA-3 expression patterns in all the grades and different variants of primary and metastatic urothelial carcinomas. It is a prospective and retrospective observational study. All the clinically suspected urothelial carcinoma (UC) during January 2016 to December 2017 were included in the study. Depending on the differential diagnosis considered, immunohistochemistry (IHC) markers including CK7, CK20, p63, AMACR, CDX2, and p16 were done to differentiate UC from other primary carcinomas. The tumors confirmed as UC were analyzed further for GATA-3 expression by Chi-square test. The number of UC in the present study was 126 including 122 (bladder in 107, ureter in 7, renal pelvis in 5, and urethra in 3) primary and 4 metastatic UC (3 in lung and 1 in liver). Age of the patients ranged from 29 to 80 (mean 61.28) years with male/female ratio 4:1. GATA-3 showed positivity in 97 (79.5%) primary UC. GATA-3 was positive in all normal urothelium and non-invasive UC (100%), while it was positive in 69/94 (73.4%) invasive UC including variants. GATA-3 was positive in 35/39 LP invasive (89.74%) and 34/55 (61.81%) MP invasive UC. GATA-3 was positive in 39/40 papillary cases (97.5%) and 45/59 (76.27%) cases of non-papillary UC. GATA-3 showed strong expression in all metastatic UC (100%). GATA-3 expression was seen in 101/126 (80.15%) of UC including primary and metastatic carcinomas and hence was a useful marker in diagnosing UC. The GATA-3 positivity decreased from normal urothelium to UC; low-grade UC to high-grade UC; non-invasive to invasive UC; lamina propria invasive to muscle invasive UC; papillary to non-papillary UC.