Role of GATA3, CK7, CK20 and CK14 in distinguishing urinary bladder squamous cell carcinoma and urothelial carcinoma with squamous differentiation

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Abstract

Urothelial carcinomas (UC) can demonstrate a broad spectrum of morphology and frequently demonstrate squamous differentiation. Urothelial neoplasms with squamous morphology raise the differential diagnosis between pure primary squamous cell carcinoma (SCC) and UC with squamous differentiation. Accurate identification between these entities is critical due to differing prognosis and therapeutic strategies. GATA3-binding protein 3 (GATA3) is a novel immunohistochemical marker for UC; however, few studies have investigated the role of GATA3 as a marker for urinary bladder SCC. The purpose of this study was to investigate the expression of a selected panel of antibodies (GATA3, CK14, CK7 and CK20) in SCC, and to investigate its utility to aid in the diagnosis of urinary bladder SCC and its differentiation from UC with squamous differentiation. We evaluated immunohistochemically the selected panel of GATA3 (a urothelial-associated antibody) and CK14 (squamous-associated antibody), CK7 and CK20 in 75 primary urinary bladder neoplasms: 10 pure UC (conventional), 55 pure SCCs and 10 UC with squamous differentiation. Squamous differentiation was defined by intercellular bridges or evidence of keratinization. Pure SCCs were strongly positive for CK14 (100%), showing a significant difference from the conventional UC (P=0.001), and were constantly negative for CK20 (100%), with a significant difference from UC with squamous differentiation and conventional UC (P=0.001). An overall 5% of the well-differentiated SCCs were positive for GATA3, whereas none of the poorly differentiated cases (0%) showed any positivity for GATA3, with a significant difference from UC with squamous differentiation and conventional UC (P=0.001). UC with squamous differentiation expressed urothelial and squamous-associated markers. GATA3 showed 70% positivity, with a significant difference from well-differentiated and poorly differentiated SCC (P=0.001) and conventional UC (P=0.01); CK14 showed 100% positivity, with a significant difference from conventional UC (P=0.001); CK7 showed 100% positivity, with a significant difference from well-differentiated and poorly differentiated SCC (P=0.01); and CK20 showed 70% positivity, with a significant difference from well-differentiated and poorly differentiated SCC (P=0.001) and was significantly different from conventional UC (P=0.01). The present study confirmed that CK14 is expressed in SCC and in UC with squamous differentiation. We postulated that the combination of CK14 positivity and CK20 negativity are diagnostic markers for pure squamous differentiation in bladder tumours. GATA3 can be used in differentiating UC from SCC.

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