Clinicopathological characteristics and prognostic significance of HER2 status evaluation in patients with urothelial carcinoma: a retrospective single-center experience in China.

Due to the lack of an in-depth evaluation of urothelial carcinoma (UC) HER2 expression in both primary and recurrent UC, we examined possible clinical and pathological variables associated with altered UC HER2 expression. The HER2 status and clinicopathological features of primary UCs and matched recurrences from 2015 to 2023 (n = 1352) were compared by evolution category (stable or altered). In 1352 UC patients, HER2 protein expression was linked with age, histological grade, and recurrence. HER2 was expressed in 794 UC patients (58.7%) (1 + , 2 + , and 3 +). High-level (HER2 scored 2 + and 3 +) HER2 expression does not correlate with gene amplification. Significant differences in HER2 expression exist between initial and recurrent tumors (p < 0.05), including a shift from positive to negative expression. Recurrent UC patients showed associations between HER2 expression, histological grade (p < 0.05), and time to surgical recurrence (p = 0.008). HER2 expression in high-grade UC correlated positively with PD-L1 expression in tumor cells (TC) (rs = 0.222, p = 0.047) and tumor-associated immune cells (IC) (rs = 0.238, p = 0.032), especially in recurrent patients (rs = 0.464, p = 0.022). HER2 expression was associated with the biological behavior and prognosis of UC patients. Increased HER2 expression in recurrent UC indicates a poorer prognosis. Consequently, retesting for HER2 is essential in cases of recurrent UC. The association between HER2 and PD-L1 expression in high-grade, recurrent UC suggests the potential for utilizing ADC alongside immunotherapy.