Kinzler Maximilian N, Gretser Steffen, Schulze Falko, Bankov Katrin, Abedin Nada, Bechstein Wolf O, Finkelmeier Fabian, Zeuzem Stefan, Reis Henning, Wild Peter J, Walter Dirk
Goethe University Frankfurt, Medical Clinic 1, University Hospital, Frankfurt am Main, Germany.
Goethe University Frankfurt, Dr. Senckenberg Institute of Pathology, University Hospital, Frankfurt am Main, Germany.
Histopathology. 2025 Mar;86(4):640-646. doi: 10.1111/his.15407. Epub 2024 Dec 27.
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.
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).
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.
抗claudin-18.2（CLDN18.2）疗法最近被批准用于治疗胃癌或胃食管交界腺癌。本研究的目的是调查CLDN18.2在胆管癌（CCA）中的表达情况，以确定是否有一部分患者也可能从抗CLDN18.2治疗中获益。
对2005年8月至2021年12月在法兰克福大学医院接受根治性手术切除的所有CCA患者的组织微阵列（TMA）队列，使用VENTANA CLDN18（43-14A）抗体进行免疫组化评估。CLDN18.2的肿瘤阳性定义如下：≥75%的肿瘤细胞呈现中度至强的CLDN18膜染色。共有160例接受手术切除的CCA患者适合进行免疫组化（IHC）分析。其中，13.1%（n = 21）的患者显示VENTANA CLDN18抗体呈中度至强膜染色，而86.9%（n = 139）为阴性。亚型分析显示CLDN18表达存在显著差异。在肝门部（pCCA）和肝内（iCCA）亚组中，分别有26.5%（n = 34例中的9例）和7.4%（n = 95例中的7例）观察到CLDN18阳性染色。表达CLDN18的CCA患者术中发现远处转移（P = 0.002）、淋巴结转移（P = 0.008）和神经周围浸润阳性（Pn1）状态（P = 0.022）的情况更为常见。
本研究表明，一部分CCA患者表现出CLDN18.2的显著表达。这些发现强调了有必要开展一项临床研究，评估抗CLDN18.2疗法对CCA患者的疗效。
