Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Japan.
Gastric Cancer. 2019 Mar;22(2):335-343. doi: 10.1007/s10120-018-0853-7. Epub 2018 Jun 27.
Receptor tyrosine kinases (RTKs) play critical roles in gastric cancer (GC) progression and are potential targets for novel molecular-targeted agents or photo-immunotherapies. During patient selection, targeted biopsy is the first step. However, heterogeneous expression of RTKs based on the macroscopic appearance in GC has not been extensively addressed. Accordingly, in this study, we evaluated differences in RTK expression associated with macroscopic appearance in GC.
In total, 375 consecutive patients who had undergone gastrectomy at the National Cancer Center Hospital East and who had histologically proven adenocarcinoma, available archived tumor sample, and no history of chemotherapy were enrolled in this study. For these cases, tissue microarray (TMA) samples were examined using immunohistochemistry (IHC). Based on the results of IHC, cases were selected for detailed examination. We re-evaluated IHC scores in more than three tumor blocks per case and comparatively evaluated differences in IHC expression in RTKs between the mucosal portion (MuP) and invasive portion (InP).
Human epidermal growth factor receptor 2 (HER2)-, epidermal growth factor receptor (EGFR)-, and mesenchymal epithelial transition factor (c-MET)-positive rates were 6, 9, and 20%, respectively. Twenty-two cases were then analyzed to assess differences in IHC expression levels in the same lesion. Concordance rates of positive staining of HER2, EGFR, and MET between MuP and whole tumor were 100, 40, and 56% and those with InP were 46, 100, and 56%.
To avoid underestimating expression status, biopsies must be taken from MuP for HER2, InP for EGFR, and both proportions for c-MET.
受体酪氨酸激酶（RTKs）在胃癌（GC）的进展中起着关键作用，是新型分子靶向药物或光免疫疗法的潜在靶点。在患者选择过程中，靶向活检是第一步。然而，GC 基于宏观表现的 RTK 异质性表达尚未得到广泛研究。因此，在本研究中，我们评估了 GC 中与宏观表现相关的 RTK 表达差异。
本研究共纳入 375 例在国立癌症中心医院东部分院接受胃切除术且组织学证实为腺癌、有存档肿瘤样本且无化疗史的连续患者。对这些病例，使用免疫组织化学（IHC）检查组织微阵列（TMA）样本。根据 IHC 的结果选择病例进行详细检查。我们重新评估了每个病例超过三个肿瘤块的 IHC 评分，并比较了 RTKs 在黏膜部分（MuP）和浸润部分（InP）之间的 IHC 表达差异。
人表皮生长因子受体 2（HER2）、表皮生长因子受体（EGFR）和间质上皮转化因子（c-MET）的阳性率分别为 6%、9%和 20%。然后分析了 22 例病例以评估同一病变中 IHC 表达水平的差异。HER2、EGFR 和 MET 在 MuP 与整个肿瘤之间的阳性染色一致性率分别为 100%、40%和 56%，在 InP 之间的一致性率分别为 46%、100%和 56%。
为避免低估表达状态，必须从 MuP 取活检用于 HER2，从 InP 取活检用于 EGFR，同时从 MuP 和 InP 取活检用于 c-MET。
