Claudin-18 status and its correlation with HER2 and PD-L1 expression in gastric cancer with peritoneal dissemination.

IF 6 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gastric Cancer Pub Date : 2024-07-01 Epub Date: 2024-05-09 DOI:10.1007/s10120-024-01505-6

Haruki Ogawa, Hiroyuki Abe, Koichi Yagi, Yasuyuki Seto, Tetsuo Ushiku

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引用次数: 0

Abstract

Background: Gastric cancer with peritoneal dissemination (PD) has a dismal prognosis, and current treatments have shown little efficacy. CLDN18.2-targeted therapies have shown promising efficacy against gastric cancers that express high levels of CLDN18. Because of the limited information regarding CLDN18.2 status in PD, we analyzed PD-positive gastric cancers for CLDN18 status in both primary and PD, along with HER2 and PD-L1 combined positive score (CPS).

Methods: Immunohistochemical analyses were performed on 84 gastric cancer cases using paired primary and PD tissue samples.

Results: At 40% cut-off, CLDN18 was positive in 57% (48/84) primary tumors and in 44% (37/84) PDs. At 75% cut-off, 28.6% (24/84) primary tumors and 20.2% (17/84) PDs were CLDN18-positive. The concordance rate between primary tumors and PD was 79.8% at 40% cut-off and 75% at 75% cut-off. When comparing biopsy and surgical specimens, the concordance rates were 87.5% at 40% cut-off and 81.3% at 75% cut-off. Within a tumor, the superficial area tended to have a higher CLDN18-positive rate than the invasive front (P = 0.001). Although HER2 -positivity was only 11.9% in this cohort, CLDN18 positivity in HER2-negative tumors (n = 74) was relatively high: 60.8% at 40% cut-off and 28.4% at 75% cut-off. Among double-negative (HER2 - and PD-L1 CPS < 1) tumors, CLDN18 positivity was 67.6% at 40% cut-off and 26.5% at 75% cut-off.

Conclusions: CLDN18 expression is generally maintained in PD and is relatively high even in double-negative tumors, making it a promising therapeutic target for PD-positive gastric cancer.

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腹膜扩散的胃癌中Claudin-18的状态及其与HER2和PD-L1表达的相关性。

背景：伴有腹膜播散（PD）的胃癌预后很差，目前的治疗方法疗效甚微。CLDN18.2靶向疗法对高水平表达CLDN18的胃癌有很好的疗效。由于有关PD中CLDN18.2状态的信息有限，我们分析了PD阳性胃癌原发和PD中的CLDN18状态，以及HER2和PD-L1联合阳性评分（CPS）：方法：使用配对的原发和PD组织样本对84例胃癌病例进行免疫组化分析：结果：以 40% 为临界值，57%（48/84）的原发肿瘤和 44%（37/84）的原发灶中 CLDN18 呈阳性。截断率为 75% 时，28.6%（24/84）的原发肿瘤和 20.2%（17/84）的原发灶中 CLDN18 呈阳性。原发性肿瘤和肺结核的一致性在 40% 截止值时为 79.8%，在 75% 截止值时为 75%。在比较活检和手术标本时，40%截断值的吻合率为87.5%，75%截断值的吻合率为81.3%。在肿瘤内部，浅表区域的 CLDN18 阳性率往往高于浸润前沿（P = 0.001）。虽然在这一队列中，HER2 阳性率仅为 11.9%，但在 HER2 阴性肿瘤（n = 74）中，CLDN18 阳性率相对较高：截断率为 40% 时为 60.8%，截断率为 75% 时为 28.4%。在双阴性（HER2 - 和 PD-L1 CPS）肿瘤中，CLDN18 的表达通常保持不变：CLDN18的表达在PD中通常保持不变，即使在双阴性肿瘤中也相对较高，这使其成为PD阳性胃癌的一个有希望的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gastric Cancer 医学-胃肠肝病学

CiteScore

14.70

自引率

2.70%

发文量

审稿时长

6-12 weeks

期刊介绍： Gastric Cancer is an esteemed global forum that focuses on various aspects of gastric cancer research, treatment, and biology worldwide. The journal promotes a diverse range of content, including original articles, case reports, short communications, and technical notes. It also welcomes Letters to the Editor discussing published articles or sharing viewpoints on gastric cancer topics. Review articles are predominantly sought after by the Editor, ensuring comprehensive coverage of the field. With a dedicated and knowledgeable editorial team, the journal is committed to providing exceptional support and ensuring high levels of author satisfaction. In fact, over 90% of published authors have expressed their intent to publish again in our esteemed journal.