Department of Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, Henan, China.
Department of Pathology, Heilongjiang Province Land Reclamation Headquarter General Hospital, Harbin 150086, Heilongjiang, China.
Pathol Res Pract. 2020 Nov;216(11):153229. doi: 10.1016/j.prp.2020.153229. Epub 2020 Sep 21.
Given the high heterogeneity of tumor tissue in gastric cancer (GC), inaccurate detection of tumor biomarkers will inevitably hamper a precise diagnosis and selection of patients for targeted therapies. Human epidermal growth factor receptor 2 (HER2) has been widely accepted as an underlying treatment biomarker of GC. The objective of this study is to investigate the heterogeneity (both intratumoral and intertumoral) of HER2 expression in GC, and the relationship between heterogeneity and the clinicopathological features.
A total of 618 patients with primary gastric adenocarcinoma were recruited, and two formalin-fixed paraffin-embedded (FFPE) tumor-containing blocks of each patient were selected for HER2 immunohistochemical (IHC) assay. Clinicopathological characteristics were recorded, and intratumoral and intertumoral heterogeneity of HER2 IHC expression was determined.
The results indicated that the dual-block assays significantly increased the HER2 overexpression (IHC 2+ and 3+) rate compared with the single paraffin block detection. Approximately 50 % of the cases showed intratumoral HER2 heterogeneity within a single tissue section, and 30.10 % of cases showed intertumoral heterogeneity between a patient's two blocks. Furthermore, intertumoral heterogeneity was associated with tumors of small size (P = 0.029) and distal location (P = 0.032) characters, while the intratumoral heterogeneity was correlated with poorly differentiated carcinomas. Laurén's diffuse type showed a notably higher intratumoral heterogeneity rate, and the mixed type exhibited higher intertumoral HER2 discordance between the dual-block cohorts (P < 0.001). Besides, HER2 heterogenous overexpression was not associated with age, gender, type of resection, lymphatic or venous invasion, perineural invasion or pTNM (P > 0.05) for both cohorts.
The research findings in this paper indicate that the intratumoral and intertumoral heterogeneity of HER2 overexpression is common in GC patients, and these variations are associated with certain clinicopathological features. We highly recommend multi-block HER2 assessment for accurate diagnosis of GC.
由于胃癌（GC）肿瘤组织具有高度异质性，因此肿瘤生物标志物的检测不准确不可避免地会阻碍对患者进行精确诊断和靶向治疗的选择。人表皮生长因子受体 2（HER2）已被广泛接受为 GC 的潜在治疗生物标志物。本研究旨在探讨 GC 中 HER2 表达的异质性（包括肿瘤内和肿瘤间），以及异质性与临床病理特征之间的关系。
共招募了 618 名原发性胃腺癌患者，为每位患者选择了两个含福尔马林固定、石蜡包埋（FFPE）肿瘤的组织块进行 HER2 免疫组化（IHC）检测。记录临床病理特征，并确定 HER2 IHC 表达的肿瘤内和肿瘤间异质性。
结果表明，双块检测与单块石蜡块检测相比，显著增加了 HER2 过表达（IHC 2+和 3+）率。在单个组织切片内，约有 50%的病例存在 HER2 异质性，30.10%的病例在患者的两个块之间存在肿瘤间异质性。此外，肿瘤间异质性与肿瘤体积小（P=0.029）和远端位置（P=0.032）特征有关，而肿瘤内异质性与低分化癌有关。Laurén 弥漫型显示出明显更高的肿瘤内异质性率，混合型在双块队列中表现出更高的肿瘤间 HER2 不一致性（P<0.001）。此外，HER2 异质过表达与年龄、性别、切除类型、淋巴或静脉浸润、神经周围浸润或 pTNM 无关（P>0.05）。
本文的研究结果表明，GC 患者中 HER2 过表达的肿瘤内和肿瘤间异质性很常见，这些变化与某些临床病理特征有关。我们强烈建议对多个肿瘤块进行 HER2 评估，以准确诊断 GC。
