Department of Urology, Mayo Clinic, Rochester, MN, USA.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Mod Pathol. 2014 May;27(5):758-64. doi: 10.1038/modpathol.2013.201. Epub 2013 Nov 1.
Micropapillary urothelial carcinoma exhibits amplification of the human epidermal growth factor receptor, ERBB2(HER2), and overexpression of the ERBB2 protein product. The clinical significance of this has yet to be established. The objective of this study was to examine ERBB2 amplification and protein expression in micropapillary urothelial carcinoma and stage-matched typical urothelial carcinoma treated by radical cystectomy to assess the frequency of amplification and protein expression, and to determine the association with cancer-specific survival. Pathologic material and data from patients undergoing cystectomy at Mayo Clinic between 1980 and 2008 were reviewed. ERBB2 amplification by fluorescence in situ hybridization (FISH) and protein expression by immunohistochemistry were assessed. Univariate and multivariate Cox proportional hazards regression models were used to evaluate for associations of ERBB2 amplification and protein expression with survival. ERBB2 amplification was identified in 9 (15%) of 61 micropapillary carcinomas compared with 9 (9%) of 100 urothelial carcinomas. In patients with micropapillary carcinoma, ERBB2 amplification was associated with a nearly threefold increased risk of cancer death. ERBB2 amplification (hazard ratio 4.3; P=0.0008) remained associated with an increased risk of death from bladder cancer among patients with micropapillary urothelial carcinoma on multivariate analysis. The association of cancer-specific survival and ERBB2 amplification was not seen in patients with urothelial carcinoma. ERBB2 immunohistochemistry correlated with ERBB2 amplification but there was no association of ERBB2 protein expression and survival. ERBB2 amplification is more frequent in micropapillary urothelial carcinoma than typical urothelial carcinoma, and patients with micropapillary carcinoma who have ERBB2 amplification have worse cancer-specific survival than those who do not. Identification of ERBB2 amplification in micropapillary carcinoma could provide important prognostic information and possibly provide a role for ERBB2 targeted therapy.
微乳头状尿路上皮癌表现出人表皮生长因子受体（EGFR）、ERBB2（HER2）扩增和 ERBB2 蛋白产物过表达。但其临床意义尚未确定。本研究旨在检查根治性膀胱切除术治疗的微乳头状尿路上皮癌和匹配的典型尿路上皮癌中 ERBB2 扩增和蛋白表达，评估扩增和蛋白表达的频率，并确定与癌症特异性生存的关系。回顾了 1980 年至 2008 年在梅奥诊所接受膀胱切除术的患者的病理材料和数据。通过荧光原位杂交（FISH）评估 ERBB2 扩增，通过免疫组织化学评估蛋白表达。使用单变量和多变量 Cox 比例风险回归模型评估 ERBB2 扩增和蛋白表达与生存的关系。与 100 例尿路上皮癌相比，61 例微乳头状尿路上皮癌中发现 9（15%）例存在 ERBB2 扩增。在微乳头状尿路上皮癌患者中，ERBB2 扩增与癌症死亡风险增加近三倍相关。在多变量分析中，ERBB2 扩增（危险比 4.3；P=0.0008）与微乳头状尿路上皮癌患者膀胱癌死亡风险增加仍然相关。在尿路上皮癌患者中未发现癌症特异性生存与 ERBB2 扩增之间的关联。ERBB2 免疫组化与 ERBB2 扩增相关，但 ERBB2 蛋白表达与生存无关。与典型尿路上皮癌相比，微乳头状尿路上皮癌中 ERBB2 扩增更为常见，并且 ERBB2 扩增的微乳头状尿路上皮癌患者的癌症特异性生存比没有扩增的患者差。在微乳头状尿路上皮癌中鉴定出 ERBB2 扩增可能提供重要的预后信息，并可能为 ERBB2 靶向治疗提供作用。
