Department of Pathology, The Jikei University School of Medicine, Tokyo, Japan; Present address: Department of Pathology, Kyorin University School of Medicine, Tokyo, Japan.
Department of Pathology, The Jikei University School of Medicine, Tokyo, Japan.
Clin Genitourin Cancer. 2020 Aug;18(4):e443-e449. doi: 10.1016/j.clgc.2019.12.003. Epub 2019 Dec 13.
Erb-b2 receptor tyrosine kinase 2 (ERBB2, also known as HER2) gene amplification or protein overexpression occurs in certain types of urothelial carcinomas. Molecular pathologic classification of urinary bladder cancer using immunohistochemistry has identified basal and luminal subtypes with differing prognoses, but the HER2 status of these subtypes has not been investigated. In addition, research on urothelial carcinoma of the renal pelvis and ureter (UCRPU) has not progressed because of its rarity, though its prognosis is worse than that of bladder cancer. In this study, we evaluated the clinical significance of HER2 status in molecular subtypes of UCRPU.
HER2 status (protein overexpression and/or gene amplification) and molecular subtyping were determined for 148 cases of UCRPU (83 and 65 cases in the renal pelvis and ureter, respectively), using immunohistochemistry and fluorescent in situ hybridization, and compared with clinicopathologic factors.
Subtype analysis revealed that the cases were 46% basal and 54% luminal. HER2 protein overexpression and/or gene amplification was observed in 14% of UCRPU cases and was significantly more frequent in the luminal subtype than in the basal (22% vs. 4%; P = .0030). Univariate analysis showed that the overall survival of patients with HER2-positive UCRPU was significantly shorter than those with HER2-negative tumors.
HER2 protein overexpression and gene amplification were specifically observed in the luminal subtype of UCRPU, suggesting that these cases may respond to HER2-targeted therapies like trastuzumab.
表皮生长因子受体 2 基因（ERBB2，也称为 HER2）扩增或蛋白过表达发生在某些类型的尿路上皮癌中。使用免疫组织化学对膀胱癌进行分子病理分类，已经确定了具有不同预后的基底和腔面亚型，但这些亚型的 HER2 状态尚未得到研究。此外，由于肾盂和输尿管尿路上皮癌（UCRPU）的罕见性，其研究进展缓慢，尽管其预后比膀胱癌差。在这项研究中，我们评估了 HER2 状态在 UCRPU 分子亚型中的临床意义。
使用免疫组织化学和荧光原位杂交技术，对 148 例 UCRPU 病例（肾盂和输尿管分别为 83 例和 65 例）的 HER2 状态（蛋白过表达和/或基因扩增）和分子亚型进行了测定，并与临床病理因素进行了比较。
亚型分析显示，病例中有 46%为基底型，54%为腔面型。UCRPU 病例中观察到 HER2 蛋白过表达和/或基因扩增的比例为 14%，在腔面亚型中明显高于基底型（22%比 4%；P=0.0030）。单因素分析显示，HER2 阳性 UCRPU 患者的总生存率明显短于 HER2 阴性肿瘤患者。
HER2 蛋白过表达和基因扩增特异性地出现在 UCRPU 的腔面亚型中，提示这些病例可能对曲妥珠单抗等 HER2 靶向治疗有反应。
