Kolla Surendra B, Seth Amlesh, Singh Manoj K, Gupta Narmada P, Hemal Ashok K, Dogra Prem N, Kumar Rajeev
Department of Urology, All India Institute of Medical Sciences, New Delhi 110029, India.
Int Urol Nephrol. 2008;40(2):321-7. doi: 10.1007/s11255-007-9283-x.
The aim of the study was to evaluate the status of Her2/neu protein expression in patients with muscle-invasive urothelial carcinomas of the bladder treated with radical cystectomy and to determine its prognostic significance.
We retrospectively analyzed the data of 90 patients who had undergone cystectomy for invasive transitional cell carcinoma of the urinary bladder. Immunohistochemical analysis for Her2/neu was done on paraffin-fixed tissues with CB11 antibodies (BioGenex, San Ramon, CA, USA). Sections with grade 2 and grade 3 staining were considered positive for Her2/neu.
Over a median follow-up period of 46 months (24-96 months) 46 patients are living without disease recurrence and six with recurrent disease either at the local site or with distant metastases. The remaining 38 patients have died. The median overall survival time was 50 months, and median disease-free survival time was 40 months. The Her2/neu status was significantly related to the tumor stage (P = 0.001), lymph node involvement (77% in N+ vs 23% in N0; P = 0.001) and the grade of the disease (32% of grade 2 vs 71% of grade 3; P = 0.037). Kaplan-Meier curves showed a significantly worse disease-related survival period (log rank P = 0.011) for patients with Her2 overexpressing tumors than for those without overexpression. In addition to tumor stage [P = 0.001; relative risk (RR) = 2.62] and lymph node status (P = 0.0001; RR = 2.95), Her2 status (P = 0.020; RR = 2.22) was identified as an independent predictor for disease-related survival in a multivariate analysis.
These results suggest that Her2 expression might provide additional prognostic information for patients with muscle-invasive bladder cancer. Future studies on Her2 expression with chemosensitivity and the efficacy of Her2-targeted therapies in urothelial carcinomas are warranted.
本研究的目的是评估接受根治性膀胱切除术的肌层浸润性膀胱尿路上皮癌患者中Her2/neu蛋白表达状况,并确定其预后意义。
我们回顾性分析了90例因浸润性膀胱移行细胞癌接受膀胱切除术患者的数据。使用CB11抗体(美国加利福尼亚州圣拉蒙市BioGenex公司)对石蜡固定组织进行Her2/neu免疫组化分析。二级和三级染色切片被视为Her2/neu阳性。
在中位随访期46个月(24 - 96个月)内,46例患者无疾病复发存活,6例患者出现局部复发或远处转移。其余38例患者死亡。中位总生存时间为50个月,中位无病生存时间为40个月。Her2/neu状态与肿瘤分期(P = 0.001)、淋巴结受累情况(N + 组中为77%,N0组中为23%;P = 0.001)以及疾病分级(二级中为32%,三级中为71%;P = 0.037)显著相关。Kaplan - Meier曲线显示,Her2过表达肿瘤患者的疾病相关生存期明显差于无过表达患者(对数秩检验P = 0.011)。在多变量分析中,除肿瘤分期[P = 0.001;相对风险(RR)= 2.62]和淋巴结状态(P = 0.0001;RR = 2.95)外,Her2状态(P = 0.020;RR = 2.22)被确定为疾病相关生存的独立预测因素。
这些结果表明,Her2表达可能为肌层浸润性膀胱癌患者提供额外的预后信息。有必要对Her2表达与化疗敏感性以及Her2靶向治疗在尿路上皮癌中的疗效进行进一步研究。