Department of Pathology, Christian-Albrechts-University, Arnold-Heller-Str. 3, Haus 14, 24105, Kiel, Germany.
Virchows Arch. 2019 Nov;475(5):563-571. doi: 10.1007/s00428-019-02624-7. Epub 2019 Jul 22.
Gastric cancer (GC) is frequently diagnosed and treated in advanced tumour stages with poor prognosis. Recent studies have identified isoform 2 of the tight junction protein claudin-18 (CLDN18.2) as a promising target in GC therapy. In this study, we aimed to outline the expression of CLDN18.2 and its correlation with clinico-pathological patient characteristics in a large and well-characterized cohort of GC patients. The expression of CLDN18.2 was studied in 481 GCs by immunohistochemistry on whole tissue sections. Immunostained GCs were evaluated using the histoscore (H-score) and subsequently divided into two groups: tumours showing any or no expression. CLDN18.2 expression was investigated for correlation with various clinico-pathological patient characteristics, including survival. CLDN18.2 expression was found in 203 GCs (42.2%). Of these tumours, 71 (14.8%) showed solely weak immunostaining. CLDN18.2 expression correlated with mucin phenotype, EBV status, the integrin αvβ5, the EpCAM extracellular domain EpEX, and lysozyme. We found no correlation with survival, Laurén phenotype, or any other clinico-pathological patient characteristic. In conclusion, we demonstrate frequently decreased expression of CLDN18.2 in a GC cohort of appropriate size. Correlating CLDN18.2 expression with clinico-pathological patient characteristics reveals new linkages to αvβ5, EpEX, and lysozyme, which may pave the way for further investigations regarding the role of tight junction proteins in GC progression. Though CLDN18.2 continues to pose an attractive target candidate, we conclude that a rather low overall expression rate challenges its significance in advanced GC therapy and indicates the need for further investigations across different populations.
胃癌（GC）常被诊断和治疗处于晚期且预后较差的肿瘤阶段。最近的研究已经确定紧密连接蛋白 claudin-18（CLDN18.2）的同工型 2 是 GC 治疗中有前途的靶点。在这项研究中，我们旨在概述 CLDN18.2 的表达及其与大量特征明确的 GC 患者临床病理患者特征的相关性。通过免疫组织化学在全组织切片上研究了 481 例 GC 中的 CLDN18.2 表达。使用组织评分（H 评分）评估免疫染色的 GC，并随后将其分为两组：显示任何表达或无表达的肿瘤。研究了 CLDN18.2 表达与各种临床病理患者特征的相关性，包括生存情况。在 203 例 GC 中发现了 CLDN18.2 表达（42.2%）。在这些肿瘤中，71 例（14.8%）仅显示微弱的免疫染色。CLDN18.2 表达与粘蛋白表型、EBV 状态、整合素αvβ5、EpCAM 细胞外结构域 EpEX 和溶菌酶相关。我们没有发现与生存、Laurén 表型或任何其他临床病理患者特征相关。总之，我们在适当大小的 GC 队列中证明了 CLDN18.2 表达的频繁降低。将 CLDN18.2 表达与临床病理患者特征相关联揭示了与αvβ5、EpEX 和溶菌酶的新联系，这可能为进一步研究紧密连接蛋白在 GC 进展中的作用铺平道路。尽管 CLDN18.2 仍然是一个有吸引力的靶标候选者，但我们的结论是，总体表达率较低，这对其在晚期 GC 治疗中的意义构成了挑战，并表明需要在不同人群中进行进一步研究。
