Expression of HER2 in bladder urothelial carcinoma and its clinical significance
Objective:To investigate the expression and clinical significance of human epidermal growth factor receptor 2(HER2)in bladder urothelial carcinoma.Methods:Clinical data and surgical pathological specimens were collected from 497 bladder urothelial carcinoma patients who underwent surgery at West China Hospital,Si-chuan University,from April 2021 to April 2023.The expression of HER2 protein was analyzed,and a prospec-tive cohort analysis was conducted to explore the correlation between HER2 expression and clinical characteristics as well as prognosis.Results:A total of 497 bladder urothelial carcinoma patients were included in the study,a-mong which 324 had non-muscle-invasive bladder cancer(NMIBC)and 173 had muscle-invasive bladder cancer(MIBC).The overall HER2 positivity rate was 52.8％in NMIBC and 49.1％in MIBC,with no statistically sig-nificant difference between the two groups(P=0.44).In NMIBC,the HER2 positivity rate in T1 stage(63.1％,99/157)was significantly higher than that in Ta stage(43.1％,72/167)(P＜0.05).Significant differences in HER2 expression were observed among different histological subtypes in both NMIBC and MIBC(P＜0.05):the HER2 positivity rate was 100％(4/4)in the micropapillary subtype of NMIBC and 80.0％(8/10)in MIBC,26.7％(4/15)in the squamous differentiation of NMIBC and 25.8％(8/31)in MIBC,and 37.5％(3/8)in the glandular differentiation of NMIBC and 64.3％(9/14)in MIBC.Multivariate logistic regression analysis indicated that in NMIBC,T stage and tumor multiplicity were independent risk factors in HER2 positivity,with statistical-ly significant differences(P＜0.05).A total of 12 patients received the HER2-targeted antibody-drug conjugate RC-48 treatment;among these,58.3％(7/12)converted from HER2-positive to negative after treatment,25％(3/12)had consistent HER2 expression levels before and after treatment,and 8.3％(1/12)converted from HER2 1+to 2+.Conclusion:In NMIBC,HER2 expression is associated with tumor T stage and tumor multi-plicity,but not with pathological grade,EAU risk score,tumor location,presence of carcinoma in situ,or ureter-al involvement.In MIBC,HER2 expression is associated with tumor histological subtype,but not with T stage,lymph node metastasis,vascular invasion,or neural invasion.
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