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<p>Although Claudin18.2 (CLDN18.2) is a promising therapeutic target in gastric and gastroesophageal junction cancer (G/GEJ), its expression profile based on histological subtypes remains unclear. This study aimed to investigate CLDN18.2 expression across various histological subtypes and its associations with clinicopathological features and crucial biomarkers. Tissue sample from 937 patients with G/GEJ was collected. Immunohistochemistry for CLDN18 (43-14A), PD-L1, HER2, and MMR proteins was performed on whole-section slides. EBER was detected by in situ hybridization. The overall positivity rate of CLDN18.2 was 25.8% (242/937). The highest CLDN18.2 positivity rate was observed in adenocarcinoma (AC) at 32.9% (211/641), followed by neuroendocrine neoplasms (NENs) at 12.8% (28/218), with a lower rate in adenosquamous carcinoma (ASC) at 6.3% (3/48), but CLDN18.2 was negative in squamous cell carcinoma (SCC) and undifferentiated carcinoma (<i>P</i> &lt; 0.001). Analysis of AC histomorphology revealed that the highest positivity rate was observed in gastric carcinoma with lymphoid stroma (83.3%), whereas mucinous and hepatoid adenocarcinoma showed lower positivity rates (10.0% and 11.5%, <i>P</i> &lt; 0.001). In ASC, the squamous component demonstrated CLDN18.2 expression in one case, which was characterized by EBV positivity and extensive stromal lymphocytic infiltration. In AC, CLDN18.2 positivity was significantly higher in EBV-positive compared to EBV-negative tumors (70.2% vs. 29.4%, <i>P</i> &lt; 0.001). CLDN18.2 was not significantly associated with PD-L1 or HER2 status regardless of histological subtype (<i>P</i> &gt; 0.05). This study characterized the histological profile of CLDN18.2-positive G/GEJ and broadened our understanding of subgroups likely to benefit from CLDN18.2-targeted therapy.</p>

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Histological and biomarker landscape of Claudin18.2-positive gastric and gastroesophageal junction cancers: a study of 937 cases

  • 期刊论文

  • 发表日期：

    2025年11月26日

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  • Qingxia Zhang,
  • Xinya Zhao,
  • Xiaozheng Huang,
  • Yajie Hu,
  • Ran Wang,
  • Lisha Yin,
  • Binyan Wu,
  • Ziyu Li,
  • Yu Sun

摘要

Although Claudin18.2 (CLDN18.2) is a promising therapeutic target in gastric and gastroesophageal junction cancer (G/GEJ), its expression profile based on histological subtypes remains unclear. This study aimed to investigate CLDN18.2 expression across various histological subtypes and its associations with clinicopathological features and crucial biomarkers. Tissue sample from 937 patients with G/GEJ was collected. Immunohistochemistry for CLDN18 (43-14A), PD-L1, HER2, and MMR proteins was performed on whole-section slides. EBER was detected by in situ hybridization. The overall positivity rate of CLDN18.2 was 25.8% (242/937). The highest CLDN18.2 positivity rate was observed in adenocarcinoma (AC) at 32.9% (211/641), followed by neuroendocrine neoplasms (NENs) at 12.8% (28/218), with a lower rate in adenosquamous carcinoma (ASC) at 6.3% (3/48), but CLDN18.2 was negative in squamous cell carcinoma (SCC) and undifferentiated carcinoma (P < 0.001). Analysis of AC histomorphology revealed that the highest positivity rate was observed in gastric carcinoma with lymphoid stroma (83.3%), whereas mucinous and hepatoid adenocarcinoma showed lower positivity rates (10.0% and 11.5%, P < 0.001). In ASC, the squamous component demonstrated CLDN18.2 expression in one case, which was characterized by EBV positivity and extensive stromal lymphocytic infiltration. In AC, CLDN18.2 positivity was significantly higher in EBV-positive compared to EBV-negative tumors (70.2% vs. 29.4%, P < 0.001). CLDN18.2 was not significantly associated with PD-L1 or HER2 status regardless of histological subtype (P > 0.05). This study characterized the histological profile of CLDN18.2-positive G/GEJ and broadened our understanding of subgroups likely to benefit from CLDN18.2-targeted therapy.