Claudin 18.2 expression in various tumor types and its role as a potential target in advanced gastric cancer.
Claudin 18.2 expression in various tumor types and its role as a potential target in advanced gastric cancer.
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Claudin 18.2在各种肿瘤类型中的表达及其在晚期胃癌中的潜在靶标。
DOI：
10.21037/tcr-19-1876
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发表时间：
2020-05
影响因子：
0.9
通讯作者：
Kim ST
中科院分区：
文献类型：
--
作者：
Hong JY;An JY;Lee J;Park SH;Park JO;Park YS;Lim HY;Kim KM;Kang WK;Kim ST
在一些上皮癌中，claudin表达的改变可损害紧密连接功能，影响信号通路，并作为肿瘤促进事件。最近，一种针对claudin 18.2的高效肿瘤细胞选择性治疗抗体zolbetuximab已被开发并在临床试验中进行研究。我们在2012年6月至2016年3月期间对430例连续的晚期胃肠道、泌尿生殖系统或罕见癌症患者进行了一项使用claudin 18.2免疫组织化学的前瞻性研究。免疫组化检测96.3%（414/430）患者的Claudin 18.2表达。总共有4.1%（17/414）的患者claudin 18.2阳性，包括胰腺（16.7%,1/6）、胃（14.1%,12/85）、胆道（6.3%,1/16）、泌尿生殖系统/其他（2.2%,1/46）和结直肠癌（0.9%,2/203）患者。17例claudin 18.2阳性患者中有12例胃癌（GCs）；该亚组在性别、年龄、疾病程度、原发肿瘤部位、病理分化、人表皮生长因子受体2或Epstein-Barr病毒状态是否表达claudin 18.2方面无统计学差异。然而，Lauren分类评估claudin 18.2在肠型中阳性的频率高于弥漫性型（P=0.026）。claudin 18.2表达与不表达患者的总生存期（OS）无显著差异（P=0.101）。我们的研究结果增加了关于claudin 18.2在各种癌症类型中的表达的新兴文献，并支持了唑贝妥昔单抗扩展临床探索的必要性。
Alterations in claudin expression can impair tight junction function, influence signaling pathways, and act as a tumor-promoting event in some epithelial cancers. Recently, zolbetuximab, a highly potent and tumor cell-selective therapeutic antibody against claudin 18.2, has been developed and investigated in clinical trials. We conducted a prospective study using claudin 18.2 immunohistochemistry in 430 consecutive patients with advanced gastrointestinal, genitourinary, or rare cancers between June 2012 and March 2016. Claudin 18.2 expression was evaluated in 96.3% of the patients (414/430) using immunohistochemistry. In total, 4.1% (17/414) of the patients were claudin 18.2-positive, including patients with pancreatic (16.7%, 1/6), gastric (14.1%, 12/85), biliary tract (6.3%, 1/16), genitourinary/miscellaneous (2.2%, 1/46), and colorectal (0.9%, 2/203) cancers. Twelve of 17 patients positive for claudin 18.2 had gastric cancers (GCs); this subgroup showed no statistical differences by gender, age, disease extent, primary tumor site, pathologic differentiation, human epidermal growth factor receptor 2, or Epstein-Barr virus status with or without claudin 18.2 expression. However, claudin 18.2 was more frequently positive in intestinal-type compared with diffuse-type as assessed by Lauren classification (P=0.026). There was no significant difference in overall survival (OS) between patients with and without claudin 18.2 expression (P=0.101). Our results add to the emerging literature about claudin 18.2 expression in various cancer types and support the need for extended clinical exploration of zolbetuximab.
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