Urothelial carcinoma (UC) of the urinary bladder often presents as non-invasive (pTa) or invasive (pT1) tumours. The pTa tumours are prone to high recurrence rates. Despite several developments in diagnosis and management, the lack of reliable prognostic markers greatly limits the ability to accurately predict disease progression and recurrence. This reiterates the growing need to incorporate specific histological biomarkers that can facilitate better treatment strategies and improve patient outcomes. Our study explores the role of HER2 protein expression in UC. Establishing HER2 as a reliable biomarker could greatly augment diagnostic accuracy and predictive assessments. The objectives of this study are: 1. To study the potential role of immunohistochemical expression of HER2 in urothelial carcinoma (UC). 2. To study the association between HER2 positivity and overall survival. 3. To see if there is a prognostic potential for HER2 expression in predicting disease outcomes.

This prospective study was conducted in a tertiary care referral teaching institution in South India from January 2022 to August 2024. The study included 112 patients diagnosed with urothelial carcinoma and investigated the relationship between HER2 expression, tumour grade, and recurrence.

Among the patients, hematuria was the most common presenting symptom (52.5%), and the majority had tumours larger than 3 cm (55%). HER2 overexpression was observed in 72.5% of cases. HER2 positivity demonstrated a significant correlation with tumour recurrence, with 65% of recurrent cases being HER2 positive, compared to no recurrence in HER2-negative cases (p < 0.001).

HER2 expression represents a pivotal biomarker in urothelial carcinoma, with its positivity significantly associated with heightened tumour aggressiveness and an adverse prognostic trajectory. This study underscores the necessity of integrating HER2 status into routine diagnostic and prognostic protocols, thereby enabling refined risk stratification and the development of individualized therapeutic regimens to optimize clinical management and outcomes for patients with bladder cancer.