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. 2025 Feb 28;16(1):67-76.
doi: 10.21037/jgo-24-743. Epub 2025 Feb 26.

Expression of Claudin18.2 in metastatic lesions in peritoneum of gastric cancer

Akira Saito  1 , Hideyuki Ohzawa  2 , Rie Kawashima  3 , Shiro Matsumoto  1 , Kentaro Kurashina  1 , Shin Saito  1 , Hideyo Miyato  1 , Yoshinori Hosoya  1 , Naohiro Sata  1 , Joji Kitayama  1 , Hironori Yamaguchi  1   2
Affiliations

Expression of Claudin18.2 in metastatic lesions in peritoneum of gastric cancer

Akira Saito et al. J Gastrointest Oncol. .

Abstract

Background: Patients with advanced gastric cancer (GC) with peritoneal involvement have a dismal prognosis. Recent clinical trials have shown that anti-Claudin18.2 (CLDN18.2) antibody (zolbetuximab) enhances survival in patients with GC expressing high levels of CLDN18.2. However, the effectiveness of the zolbetuximab in patients with peritoneal metastases (PMs) remains unclear. In this study, we aimed to evaluate the expression of CLDN18.2 in disseminated lesions to assess the clinical utility of zolbetuximab in the treatment of GC with PM.

Methods: In 42 patients diagnosed with stage IV GC with PM, biopsy samples from the primary tumors and peritoneal metastatic nodules were collected and immunostained using the specific antibody (43-14A, Ventana). The expression of CLDN18.2 was comparatively evaluated based on staining intensity and the proportion of positive cells.

Results: Positive immunoreactivity of CLDN18.2 was observed in 37 (88%) of the primary tumors. Specifically, CLDN18.2 positivity was identified in 26 (62%) or 12 (29%) patients based on moderate to strong membrane staining in at least 40% or 75% of tumor cells, respectively. In comparison, the staining intensity in tumor cells was consistently reduced in PM across all patients. CLDN18.2 expression was absent in PM of 29 (69%) patients, while 3 (7.1%) cases were determined to be CLDN18.2-positive based on a cutoff value of 40% for high staining. This trend was particularly pronounced in cases with undifferentiated type and human epidermal growth factor receptor 2 (HER-2) negative primary tumors.

Conclusions: Although CLDN18.2 expression in PM mirrored that in primary lesions, the levels were generally reduced. When zolbetuximab is used for GC patients with peritoneal involvement, it is preferable to assess the expression of CLDN18.2 in the disseminated lesions.

Keywords: Claudin18.2 (CLDN18.2); gastric cancer (GC); immunohistochemistry; peritoneal metastasis (PM); zolbetuximab.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-743/coif). H.Y. reports payment from Astellas Pharma Inc. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
The scoring of staining intensity for CLDN18.2 was conducted on primary gastric cancer tissues using the anti-Claudin18.2 monoclonal antibody (43-14A, Ventana). Representative micrographs illustrate cases with varying staining intensities, categorized as score 0 (no reactivity), score 1+ (weak staining), score 2+ (moderate staining), and score 3+ (strong staining). Scale bar: 50 micrometers (CLDN18.2 immunohistochemistry, 200×). CLDN18.2, Claudin18.2.
Figure 2
Figure 2
Comparison of staining intensity of CLDN18.2 in primary tumors and metastatic nodules in the peritoneum (PM) from the same patients is presented. The y-axis represents the total number of cases (A) as well as the number of cases in each group categorized by the staining intensity of CLDN18.2 in the primary tumor, ranging from 0 to 3+ (B). CLDN18.2, Claudin18.2; PM, peritoneal metastasis.
Figure 3
Figure 3
Expression of CLDN18.2 in primary tumors and 3 metastatic nodules in the peritoneum (PM) is demonstrated in 3 representative cases. The bar represents a length of 50 micrometers (CLDN18.2 immunohistochemistry, 200×). CLDN18.2, Claudin18.2; PM, peritoneal metastasis.
See this image and copyright information in PMC

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