Immunohistochemical expression of GATA3, CK5/6 and snail-1 in intrinsic subtypes of bladder carcinoma

Abstract

Author(s): Nehal K. Naga, Samir N. Mina, Ayman M. El-Saka, Safinaz H. El-Shorbagy and Alaa I. Amer*

Background: GATA3 binding protein has been described as a diagnostic immunomarker for urothelial carcinoma with high sensitivity and specificity. The purpose of this study was the evaluation of immunohistochemical based molecular classification of bladder cancer employing GATA3 and CK5/6, the relation between different subtypes and the available prognostic parameters of bladder cancer, correlation of the immunohistochemical expression of Snail-1 with various types of bladder carcinoma. Expression of GATA3, CK5/6 and Snail-1 immunohistochemistry was assessed in 80 formalin fixed embedded in paraffin blocks from selected cases of UBC (Trans Urethral Resection of bladder tumour 62 and Radical Cystectomy 18 specimens). Results: GATA3 showed positive nuclear expression in 75% of urothelial carcinoma cases, while all the studied cases of squamous cell carcinoma, adenocarcinoma and the neuroendocrine carcinoma small cell type were GATA3 negative. There was a significant relation between CK5/6 expression and high grade tumours as 100% of high scores were high grade with presence of muscle invasion. Moreover, by using CK5/6 and GATA3 cases were classified into three intrinsic molecular subtypes. Additionally, 62.5% of urothelial carcinoma cases showed positive nuclear and/or cytoplasmic Snail-1 expression, while most of studied cases of non-urothelial carcinoma (87.5%) were Snail-1 positive. Conclusions: GATA3 is considered as a specific marker for excluding nonurothelial tumours in primary urinary bladder carcinoma. GATA3 and CK5/6 could classify urothelial carcinoma cases into intrinsic molecular subtypes. Since, Snail-1 and CK5/6 expression was correlated significantly to high grade and muscle invasive tumours, we speculated that Snail-1 and CK5/6 considered as independent poor prognostic markers.

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