HER2在膀胱尿路上皮癌中的表达情况及临床意义

Expression of HER2 in bladder urothelial carcinoma and its clinical significance

目的探究人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)在膀胱尿路上皮癌中的表达及临床意义。方法收集2021年4月—2023年4月于四川大学华西医院接受手术治疗的497例膀胱尿路上皮癌患者的临床资料以及手术病理标本HER2蛋白的表达情况,并通过前瞻性队列分析HER2的表达与临床特征和预后的相关性。结果本研究共纳入497例膀胱尿路上皮癌患者,其中非肌层浸润性膀胱癌(non-muscle-invasive bladder cancer,NMIBC)患者324例,肌层浸润性膀胱癌(muscle-invasive bladder cancer,MIBC)患者173例。NMIBC总体HER2阳性率为52.8%,MIBC总体HER2阳性率为49.1%,2组比较差异无统计学意义(P=0.44)。NMIBC中T1期HER2阳性率(63.1%,99/157)显著高于Ta期(43.1%,72/167)(P<0.05)。在NMIBC和MIBC中均观察到不同组织亚型间HER2表达情况的显著差异(P<0.05):HER2阳性率在微乳头型中分别为100%(4/4,NMIBC)和80.0%(8/10,MIBC),在伴鳞状分化亚型中分别为26.7%(4/15,NMIBC)和25.8%(8/31,MIBC);在伴腺样分化亚型中分别为37.5%(3/8,NMIBC)和64.3%(9/14,MIBC)。多因素logistic回归分析结果显示,在NMIBC中T分期以及肿瘤多发是HER2表达阳性的独立风险因素,差异有统计学意义(P<0.05)。共12例患者接受了靶向HER2的抗体-药物偶联物RC-48治疗,其中58.3%(7/12)的患者治疗后由HER2阳性转为阴性,25.0%(3/12)的患者HER2表达水平与用药前一致,8.3%(1/12)的患者用药后HER2表达水平由1+转为2+。结论NMIBC HER2表达情况与肿瘤T分期以及肿瘤是否多发相关,但与病理分级、EAU风险评分、肿瘤部位、是否伴原位癌、是否侵犯输尿管等无关;MIBC HER2表达情况与肿瘤组织学亚型相关,与T分期、是否淋巴结转移、是否合并脉管内癌栓、是否神经侵犯等无关。

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,Sichuan University,from April 2021 to April 2023.The expression of HER2 protein was analyzed,and a prospective 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,among 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 significant 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 statistically 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 HER21+to 2+.Conclusion In NMIBC,HER2 expression is associated with tumor T stage and tumor multiplicity,but not with pathological grade,EAU risk score,tumor location,presence of carcinoma in situ,or ureteral involvement.In MIBC,HER2 expression is associated with tumor histological subtype,but not with T stage,lymph node metastasis,vascular invasion,or neural invasion.