Expression of GATA3, p63, E-cadherin and Her2Neu Immunohistochemical Stains in Urothelial Carcinoma and their Relationship with Histological Grading and Prognosis- A Cross-sectional Study

Abstract

Introduction: Urinary bladder cancer is the 10th most common cancer worldwide. Cystoscopy and biopsy/Transurethral Resection of Bladder Tumour (TURBT) are the best techniques for diagnosing and staging urinary bladder cancers. Urothelial Carcinomas (UC), particularly in transurethral resection biopsies, can pose diagnostic difficulties due to limited material. Immunohistochemistry (IHC) plays a valuable role in these settings, and many immunostains are being utilised for diagnostic evaluation. However, the relationship of these immunomarkers with histological grade and their prognostic utility has not been adequately explored. Aim: To analyse expression of Her2Neu, E-cadherin, p63, and GATA3 in UC and its relation with histological grading and prognosis. Materials and Methods: This was an observational crosssectional study conducted in the Pathology Department of IPGMER and SSKM Hospital, Kolkata, West Bengal, India over two years (November 2020-October 2022). Samples of 100 bladder carcinoma patients with predominant TURBT specimens were included in the study. The histopathological reports and tumour grading were done according to the World Health Organisation (WHO) classification of urinary bladder tumours. The Formalin Fixed Paraffin-embedded (FFPE) sections of the tumour blocks were subjected to IHC staining, and the results were interpreted accordingly. Statistical analysis was performed with the help of the Statistical Package for Social Sciences (SPSS), IBM (version 25.0). Unpaired t-test and Z-test (Standard Normal Deviate) were used to test the significant difference between two proportions. Results: The mean age of the study population was 59.69±14.53 years, and there was a male preponderance (male: female=3.54:1). Histopathological examination revealed 55% to be of low-grade morphology. Overall, 53% of cases were in T1 stage, and the rest were in T2 stage. On IHC analysis, E-cadherin showed a statistically significant decrease in intensity with increasing grade (p-value <0.001) and T stage of UC (p-value <0.001), but there was no statistically significant relationship between Her2Neu expression and tumour grade/ stage (p-value 0.5764 and 0.5663, respectively). A statistically significant relationship was observed between GATA3 and p63 scores with the grade and T stage of the tumour, i.e., GATA3 positivity increased with increasing grade and T stage of the tumour (p-value <0.001 in both), and there was a loss of p63 with advancing grade and stage of the tumour (p-value <0.001 in both). Conclusion: GATA3, p63, and E-cadherin can be used as prognostic markers in UCs. No significant relationship was found between Her2Neu expression and tumour grade in UC.