Kunz Pamela L, Mojtahed Amirkaveh, Fisher George A, Ford James M, Chang Daniel T, Balise Raymond R, Bangs Charles D, Cherry Athena M, Pai Reetesh K
Department of Medicine/Oncology, Stanford University, Stanford, CA 94305, USA.
Appl Immunohistochem Mol Morphol. 2012 Jan;20(1):13-24. doi: 10.1097/PAI.0b013e31821c821c.
Recent evidence suggests that trastuzumab, a monoclonal antibody which targets HER2, in combination with chemotherapy is a therapeutic option in patients with HER2-positive gastric or gastroesophageal junction cancer. Widely accepted guidelines for HER2 testing in gastric and gastroesophageal junction cancer have not been established. The purpose of this study was to analyze the incidence and patterns of HER2 expression in gastric and gastroesophageal junction cancer using a tissue microarray approach, which closely simulates small biopsies routinely tested for HER2. One hundred sixty-nine patients, including 99 primary gastric adenocarcinomas and 70 primary gastroesophageal junction carcinomas were analyzed for HER2 overexpression by immunohistochemistry and HER2 gene amplification by fluorescence in situ hybridization using scoring schemes proposed by both American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) and the results of the recently published Trastuzumab for Gastric Cancer (ToGA) trial. In our analysis, 19 adenocarcinomas were HER2 positive, defined as either a HER2/CEP17 ratio >2.2 and/or a 3+ HER2 immunohistochemistry score with either the ASCO/CAP or ToGA scoring schemes. Of the 19 HER2-positive adenocarcinomas, 8 (42%) exhibited a characteristic strongly intense basolateral membranous staining pattern which would be interpreted as negative (1+) using the accepted ASCO/CAP scoring scheme for HER2 assessment in breast carcinoma, but were correctly labeled as 3+ positive using the proposed ToGA scoring scheme. Of the 19 HER2-positive adenocarcinomas, 8 (42%) demonstrated heterogeneous HER2 protein expression by immunohistochemistry. Twelve of 99 (12%) gastric carcinomas were positive for HER2. Of these, HER2 was more often identified in intestinal-type adenocarcinomas (10 of 52, 19%) compared with diffuse (2 of 34, 6%) adenocarcinoma. Seven of 70 (10%) gastroesophageal junction carcinomas were positive for HER2 of which all were intestinal type (7 of 58, 12%). HER2 status or primary tumor site did not correlate with patient survival. Gastric and gastroesophageal junction adenocarcinomas typically display a characteristic basolateral membranous pattern of HER2 expression which is often heterogeneous rendering routine evaluation of HER2 status on small tissue samples challenging.
近期证据表明，曲妥珠单抗（一种靶向HER2的单克隆抗体）联合化疗是HER2阳性胃癌或胃食管交界癌患者的一种治疗选择。目前尚未建立广泛接受的胃癌和胃食管交界癌HER2检测指南。本研究的目的是使用组织微阵列方法分析胃癌和胃食管交界癌中HER2表达的发生率和模式，该方法紧密模拟常规检测HER2的小活检。采用美国临床肿瘤学会/美国病理学家学会（ASCO/CAP）提出的评分方案以及最近发表的曲妥珠单抗治疗胃癌（ToGA）试验的结果，通过免疫组织化学分析169例患者（包括99例原发性胃腺癌和70例原发性胃食管交界癌）的HER2过表达情况，并通过荧光原位杂交分析HER2基因扩增情况。在我们的分析中，19例腺癌为HER2阳性，根据ASCO/CAP或ToGA评分方案，定义为HER2/CEP17比值>2.2和/或HER2免疫组织化学评分为3+。在这19例HER2阳性腺癌中，8例（42%）表现出特征性的强烈基底外侧膜染色模式，按照用于乳腺癌HER2评估的公认ASCO/CAP评分方案，这种模式会被判定为阴性（1+），但按照提议的ToGA评分方案则被正确标记为3+阳性。在这19例HER2阳性腺癌中，8例（42%）通过免疫组织化学显示HER2蛋白表达异质性。99例胃癌中有12例（12%）HER2阳性。其中，肠型腺癌（52例中的10例，19%）比弥漫型腺癌（34例中的2例，6%）更常检测到HER2。70例胃食管交界癌中有7例（10%）HER2阳性，其中所有均为肠型（58例中的7例，12%）。HER2状态或原发肿瘤部位与患者生存率无关。胃癌和胃食管交界腺癌通常表现出特征性的HER2基底外侧膜表达模式，且这种模式往往是异质性的，这使得对小组织样本进行HER2状态的常规评估具有挑战性。
