Expression of claudin-18.2 in cholangiocarcinoma: a comprehensive immunohistochemical analysis from a German tertiary centre

IF 3.9 2区医学 Q2 CELL BIOLOGY

Histopathology Pub Date : 2024-12-27 DOI:10.1111/his.15407

Maximilian N Kinzler, Steffen Gretser, Falko Schulze, Katrin Bankov, Nada Abedin, Wolf O Bechstein, Fabian Finkelmeier, Stefan Zeuzem, Henning Reis, Peter J. Wild, Dirk Walter

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Abstract

Aims

Anti-claudin-18.2 (CLDN18.2) therapy was recently approved for the treatment of gastric or gastro-oesophageal junction adenocarcinoma. The aim of the present study was to investigate the expression of CLDN18.2 in cholangiocarcinoma (CCA) to determine whether there is a subgroup of patients who might also benefit from anti-CLDN18.2 therapy.

Methods and results

A tissue microarray (TMA) cohort of all CCA patients who underwent surgical resection with curative intent between August 2005 and December 2021 at University Hospital Frankfurt were immunohistochemically evaluated using the VENTANA^® CLDN18 (43-14A) antibody. Tumour positivity for CLDN18.2 was determined as follows: ≥ 75% of tumour cells with moderate-to-strong CLDN18 membranous staining. In total, 160 patients with surgically resected CCA were suitable for immunohistochemistry (IHC) analysis. Of the patients, 13.1% (n = 21) showed moderate to strong membranous staining of VENTANA^® CLDN18 antibody, while 86.9% (n = 139) were negative. Subtype analysis revealed strong differences in CLDN18 expression. Positive staining of CLDN18 could be observed in 26.5% (n = nine of 34) and 7.4% (n = seven of 95) of the perihilar (pCCA) and intrahepatic (iCCA) subgroup, respectively. CCA patients with CLDN18 expression had a more frequently intraoperative finding of distant metastasis (P = 0.002), lymph node metastasis (P = 0.008) and positive perineural invasion (Pn1) status (P = 0.022).

Conclusions

The present study suggests that a subset of patients with CCA exhibited a marked expression of CLDN18.2. These findings underline the need to perform a clinical study evaluating the efficacy of anti-CLDN18.2 therapy in patients suffering from CCA.

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claudin-18.2在胆管癌中的表达：来自德国三级中心的全面免疫组织化学分析。

目的：抗CLDN18.2 （CLDN18.2）疗法最近被批准用于治疗胃或胃-食管交界处腺癌。本研究的目的是研究CLDN18.2在胆管癌（CCA）中的表达，以确定是否存在一个亚组患者也可能从抗CLDN18.2治疗中获益。方法和结果：2005年8月至2021年12月在法兰克福大学医院接受手术切除的所有CCA患者的组织微阵列（TMA）队列使用VENTANA®CLDN18 （43-14A）抗体进行免疫组织化学评估。CLDN18.2的肿瘤阳性确定如下：≥75%的肿瘤细胞具有中至强CLDN18膜染色。总共有160例手术切除的CCA患者适合进行免疫组织化学（IHC）分析。13.1% （n = 21）的患者显示VENTANA®CLDN18抗体中至强膜性染色，86.9% （n = 139）的患者呈阴性。亚型分析显示CLDN18表达存在明显差异。肝门周（pCCA）亚组和肝内（iCCA）亚组CLDN18阳性分别为26.5% （n = 9 / 34）和7.4% （n = 7 / 95）。CLDN18表达的CCA患者术中发现远端转移（P = 0.002）、淋巴结转移（P = 0.008）和周围神经浸润（Pn1）阳性（P = 0.022）的频率更高。结论：目前的研究表明，一部分CCA患者表现出明显的CLDN18.2表达。这些发现强调需要进行临床研究，评估抗cldn18.2治疗对CCA患者的疗效。

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来源期刊

Histopathology 医学-病理学

CiteScore

10.20

自引率

4.70%

发文量

239

审稿时长

1 months

期刊介绍： Histopathology is an international journal intended to be of practical value to surgical and diagnostic histopathologists, and to investigators of human disease who employ histopathological methods. Our primary purpose is to publish advances in pathology, in particular those applicable to clinical practice and contributing to the better understanding of human disease.