Does HER2/neu expression provide prognostic information in patients with advanced urothelial carcinoma?
Does HER2/neu expression provide prognostic information in patients with advanced urothelial carcinoma?
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DOI：
10.1002/cncr.10808
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发表时间：
2002-09-01
期刊：
影响因子：
6.2
通讯作者：
DeVere-White, R
中科院分区：
文献类型：
--
作者：
Gandour-Edwards, R;Lara, PN;DeVere-White, R
背景肌层浸润性膀胱尿路上皮癌是一种高致死性的恶性肿瘤，特别是在局部晚期或转移性疾病的情况下。先前关于膀胱癌中HER 2/neu（c-erbB-2或HER 2）表达的报道是混合的;因此，在这种肿瘤类型中，其在预测转移或治疗反应方面的价值尚未确定。因此，作者评估了高级别、肌层浸润性膀胱尿路上皮癌患者的HER 2表达与接受紫杉醇化疗患者的预后之间可能存在的相关性。通过免疫组织化学（IHC）分析了入组两项基于紫杉醇的化疗方案临床试验的晚期尿路上皮癌患者的存档肿瘤组织的HER 2/neu表达。作者使用单变量分析将IHC检测的HER 2表达与临床结局（如缓解率、无进展生存期和总生存期）相关联。评估了39份肿瘤标本的HER 2表达，其中大部分（70%）采集自转移性疾病患者。所有病例均为高级别尿路上皮癌（移行细胞癌，3级）。在28例患者（71%）中观察到强HER 2表达（2+/3+）。有缓解疾病的患者的HER 2表达率为78%，与稳定疾病患者的表达率（75%）相似。相比之下，进展性疾病患者的HER 2表达率为50%，尽管这种差异没有达到统计学显著性。然而，单变量分析显示，HER 2表达增加可预测无进展生存期和总生存期的改善。当HER 2状态作为二分变量时，HER 2阳性表达的肿瘤与缓解或无进展生存期无任何相关性;然而，HER 2阳性状态与死亡风险降低显著相关（P = 0.03）。这项膀胱癌中HER 2表达的研究重点关注以标准化方式进行前瞻性治疗的患者，而不像以前的研究那样评估了库存的存档标本。作者证实了其他研究结果，即高级别、肌肉浸润性膀胱尿路上皮癌的HER 2表达率显著（71%）。然而，与其他报道相反，目前的研究发现，在基于紫杉醇的化疗背景下，HER 2表达显著降低了死亡风险。需要进一步研究HER 2表达与尿路上皮癌化疗敏感性的可能相关性，以及HER 2靶向治疗（如曲妥珠单抗）对高级别肌肉浸润性膀胱尿路上皮癌患者的疗效。
BACKGROUND. Muscle-invasive urothelial carcinoma of the bladder is a highly lethal malignancy, particularly in the setting of locally advanced or metastatic disease. Prior reports of HER2/neu (c-erbB-2 or HER2) expression in bladder carcinoma have been mixed; therefore, its value in predicting metastasis or response to therapy has not been established in this tumor type. Thus, the authors evaluated a possible correlation between HER2 expression in patients with high-grade, muscle-invasive urothelial carcinoma of the bladder and outcome in patients who received paclitaxel-based chemotherapy.METHODS. Archival tumor tissues from patients with advanced urothelial carcinoma who were enrolled on two clinical trials of paclitaxel-based chemotherapy regimens were analyzed for HER2/neu expression by immunohistochemistry (IHC). The authors correlated HER2 expression by IHC with clinical outcomes, such as response rate, progression free survival, and overall survival, using univariate analysis.RESULTS. Thirty-nine tumor specimens were assessed for HER2 expression, most of which (70%) were collected from patients with metastatic disease. All were high-grade urothelial carcinomas (transitional cell carcinomas, Grade 3). Strong HER2 expression (2+/3+) was seen in 28 patients (71%). Patients with responding disease had an HER2 expression rate of 78%, similar to the rate seen in patients with stable disease (75%). In contrast, patients with progressive disease had an HER2 expression rate of 50%, although this difference did not reach statistical significance. However, univariate analysis showed that increased HER2 expression predicted an improvement in progression free and overall survival. When HER2 status was used as a dichotomous variable, tumors with positive HER2 expression did not have any association with response or with progression free survival; however, positive HER2 status was associated significantly with a decreased risk of death (P = 0.03).CONCLUSIONS. This study of HER2 expression in bladder carcinoma focused on patients who were treated prospectively in a standardized fashion, unlike prior studies that have evaluated banked, archival specimens. The authors confirmed the findings of others that high-grade, muscle-invasive urothelial carcinoma of the bladder has a significant rate of HER2 expression (71%). However, contrary to other reports, the current study found that HER2 expression in the context of paclitaxel-based chemotherapy decreased the risk of death significantly. Further research is warranted on the possible association of HER2 expression with chemosensitivity in urothelial carcinoma as well as the efficacy of HER2-targeted therapies (such as trastuzumab) for patients with high-grade, muscle-invasive urothelial carcinoma of the bladder.