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原发性肿瘤及其卵巢转移灶中Claudin 18.2的表达谱:对靶向治疗的意义

Claudin 18.2 expression profile in primary tumors and their ovarian metastases: implications for targeted therapy.

作者信息

Kim Nah Ihm, Koo Joo Yeon, Kim Sung Sun, Lee Ji Young, Lee Ji Shin, Bang Hyun Jin, Bae Woo Kyun, Yoon Tae Mi, Moon Kyung-Sub, Lee Jae-Hyuk, Lee Kyung-Hwa

机构信息

Department of Pathology, Chonnam National University Hwasun Hospital and Medical School, 264 Seoyang-ro, Hwasun-eup, Hwasun-gun, Jeollanam-do, 58128, Republic of Korea.

Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Hwasun Hospital and Medical School, Hwasun, Republic of Korea.

出版信息

BMC Cancer. 2025 Mar 25;25(1):540. doi: 10.1186/s12885-025-13940-4.

Abstract

BACKGROUND

Claudin 18.2 (CLDN18.2), a tight junction protein predominantly expressed in the normal gastric epithelium, has recently emerged as a potential therapeutic target in various solid tumors. Despite growing interest, comprehensive data on CLDN18.2 expression across primary tumors from different organs and their corresponding metastatic lesions remain limited.

METHODS

This study analyzed CLDN18.2 expression in 102 patients with primary adenocarcinomas from various organs and their corresponding ovarian metastatic carcinomas and in 81 cases of primary ovarian mucinous tumors using immunohistochemistry. We evaluated the association of CLDN18.2 expression with clinicopathologic features and survival outcomes.

RESULTS

The highest CLDN18.2 positivity rate was observed in gastric adenocarcinomas (40%, 12/30), followed by cervical adenocarcinomas (20%, 1/5) and colorectal adenocarcinomas (4%, 2/50). Notably, primary ovarian mucinous tumors showed remarkably high expression rates, reaching 77% overall and 100% in mucinous borderline tumors. In contrast, adenocarcinomas of the appendix and breast lacked CLDN18 expression. While CLDN18.2 expression was generally maintained during metastasis, some variations in expression patterns were observed, particularly in gastric cancers (13%, 4/30). Our analysis found no significant correlation between CLDN18.2 expression and overall survival in the patient cohort.

CONCLUSION

The preserved expression of CLDN18.2 in metastatic tumors underscores its potential utility as a target for therapeutic approaches. Our findings emphasize the importance of evaluating CLDN18.2 status in both primary and metastatic tumors to refine therapeutic strategies.

摘要

背景

Claudin 18.2(CLDN18.2)是一种主要在正常胃上皮中表达的紧密连接蛋白,最近已成为各种实体瘤的潜在治疗靶点。尽管人们对此的兴趣日益浓厚,但关于CLDN18.2在不同器官原发性肿瘤及其相应转移病灶中的表达的全面数据仍然有限。

方法

本研究采用免疫组织化学方法分析了102例来自不同器官的原发性腺癌患者及其相应的卵巢转移癌以及81例原发性卵巢黏液性肿瘤中CLDN18.2的表达情况。我们评估了CLDN18.2表达与临床病理特征及生存结果之间的关联。

结果

在胃腺癌中观察到最高的CLDN18.2阳性率(40%,12/30),其次是宫颈腺癌(20%,1/5)和结肠直肠腺癌(4%,2/50)。值得注意的是,原发性卵巢黏液性肿瘤显示出非常高的表达率,总体达到77%,在黏液性交界性肿瘤中达到100%。相比之下,阑尾和乳腺的腺癌缺乏CLDN18表达。虽然CLDN18.2表达在转移过程中通常保持,但观察到一些表达模式的变化,特别是在胃癌中(13%,4/30)。我们的分析发现,在患者队列中,CLDN18.2表达与总生存期之间无显著相关性。

结论

CLDN18.2在转移性肿瘤中的表达保留强调了其作为治疗靶点的潜在效用。我们的研究结果强调了评估原发性和转移性肿瘤中CLDN18.2状态以优化治疗策略的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c48/11934528/36a3585b44a8/12885_2025_13940_Fig1_HTML.jpg

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