Diagnostic Relevance of GATA 3 Expression in Urinary Bladder Carcinoma of Divergent Differentiation and Other Histological Variants

GATA binding protein 3, a zinc finger transcription factor, has now been demonstrated as a valuable and sensitive marker for conventional urothelial carcinoma with sparse literature related to its expression in various histological variants. It is a prospective study where 74 consecutive cases of bladder carcinoma were included between August 2016 and January 2017 followed by immunohistochemistry to assess GATA 3 expression in conventional as well as different urothelial carcinoma (UC) variants. Overall, 57 of the 74 lesions (77%) demonstrated nuclear staining for GATA 3. GATA 3 expression significantly correlated with histological grade (P < 0.001) and muscle invasion (P = 0.005). Divergent differentiation was observed in 54% (40/74) of the total cases. The study included 12 different variants of urothelial carcinoma. All or majority of the cases of clear cell (6/6, 100%), glandular (6/8, 75%), and sarcomatoid (4/6, 66.7%) variants expressed GATA 3 in a moderate to strong fashion and belonged to group III or IV. Nested variant, small cell carcinoma, pure squamous cell carcinoma, and squamous component of urothelial carcinoma with squamous differentiation do not show any GATA 3 expression. GATA 3 was expressed more intensely as well as in greater number of tumor cells at lymph node metastatic tumor deposits as compared to the primary tumor. GATA 3 expression was not significantly associated with tumor stage or patients’ clinical outcomes. GATA 3 is expressed in majority of variants of UC albeit with variable staining; however, situation is challenging in some variants known to be associated with poor prognosis like nested variant, small cell carcinoma, and squamous cell carcinoma where it is not expressed. Hence, the sensitivity of this determinant is diminished in these variants, which may affect the interpretation of GATA 3 stains at metastatic sites as well as their distinction from secondary bladder involvement, by tumors of non-urothelial origin.