The oncogeneERBB2, also known asHER2orc-ERB2, is located on chromosome 17 (q12). It encodes a tyrosine kinase receptor, the human epidermal growth factor receptor 2 (HER2), involved in neoplastic proliferation, tumor angiogenesis, and invasiveness. Over the past years, the introduction of various anti-HER2 therapies has significantly improved outcomes for patients with HER2-positive breast and gastroesophageal carcinomas. More recently, the introduction of a new antibody–drug conjugate, that is trastuzumab deruxtecan, expanded the therapeutic options to low-HER2 breast and gastroesophageal tumors. HER2 protein overexpression is investigated using immunohistochemistry, gene amplification using fluorescence in situ hybridization, and gene mutation using next-generation sequencing. This review evaluated the predictive and prognostic role of HER2 status in various types of epithelial malignant cancers beyond breast and gastroesophageal cancers. We critically analyzed the key published studies, focusing on utilized scoring systems and assays used, and analyzed clinical parameters and therapeutic approaches. Although the evidence about prognostic and predictive roles of HER2 in carcinomas other than breast and gastroesophageal has been widely increasing over the last decade, it still remains investigational, revealing a tumor site-related prognostic and predictive value of the different types of HER2 alterations. However, standardized and validated scoring system assays have not been well-established for many organs.
癌基因ERBB2，亦称HER2或c-ERB2，定位于17号染色体（q12区）。该基因编码一种酪氨酸激酶受体——人表皮生长因子受体2（HER2），该受体参与肿瘤增殖、血管生成及侵袭过程。近年来，多种抗HER2疗法的应用显著改善了HER2阳性乳腺癌及胃食管癌患者的临床结局。最新引入的抗体偶联药物——德曲妥珠单抗，更将治疗选择扩展至低HER2表达的乳腺及胃食管肿瘤。目前临床实践中，HER2蛋白过表达通过免疫组化检测，基因扩增通过荧光原位杂交技术评估，基因突变则采用新一代测序技术进行鉴定。本综述系统评估了HER2状态在乳腺及胃食管以外多种上皮源性恶性肿瘤中的预测与预后价值。通过批判性分析已发表的关键研究，重点考察了不同评分体系与检测方法的应用，并对临床参数及治疗策略进行解析。尽管近十年来关于HER2在乳腺及胃食管以外癌种中预后及预测价值的证据不断积累，其临床意义仍处于探索阶段，研究显示不同类型的HER2改变具有肿瘤部位特异性的预后及预测价值。然而针对多数器官，目前尚未建立标准化且经过验证的评分检测体系。
Prognostic and Predictive Roles of HER2 Status in Non-Breast and Non-Gastroesophageal Carcinomas
肿瘤(癌症)患者之家