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Clinical Trial
. 2019 Sep 1;49(9):870-876.
doi: 10.1093/jjco/hyz068.

Comparison of Claudin 18.2 expression in primary tumors and lymph node metastases in Japanese patients with gastric adenocarcinoma

Christoph Rohde  1 , Rin Yamaguchi  2 , Svetlana Mukhina  1 , Ugur Sahin  3 , Kyogo Itoh  4 , Özlem Türeci  5
Affiliations
Clinical Trial

Comparison of Claudin 18.2 expression in primary tumors and lymph node metastases in Japanese patients with gastric adenocarcinoma

Christoph Rohde et al. Jpn J Clin Oncol. .

Abstract

Background: The monoclonal antibody zolbetuximab (formerly IMAB362), which is being developed as a potential treatment for gastric cancer (GC), targets Claudin 18.2 (CLDN18.2), a GC biomarker. This study aimed to determine the prevalence of CLDN18.2 in primary tumors and lymph node (LN) metastases of Japanese patients with GC.

Methods: CLDN18.2 expression was investigated in tissue samples from patients with gastric adenocarcinoma archived at Kurume University Medical Center, Japan, between 2000 and 2012. Expression of CLDN18.2 in tumor samples was evaluated by immunohistochemistry using the same detection antibody (43-14A) and assay used in the FAST clinical trial (NCT01630083), a phase 2 randomized trial that compared the safety and antitumor activity of the zolbetuximab-chemotherapy combination with chemotherapy alone. Samples showing any specific staining with ≥1+ intensity were defined as CLDN18.2-positive.

Results: Of 263 samples analyzed (134 primary gastric tumors and corresponding LN metastases; 128 primary tumors only; one LN metastases only), CLDN18.2 was detected in 87% (n = 228/262) of all primary tumors and 80% (n = 108/135) of LN metastases. Moderate-to-strong CLDN18.2 expression (≥2+ membrane staining intensity in ≥40% of tumor cells [FAST eligibility criterion]) was observed in 52% (n = 135/262) of primary tumors and 45% (n = 61/135) of (LN) metastases. CLDN18.2 expression was significantly higher in GCs of the diffuse histological subtype per Lauren classification and in high grade (G3) tumors.

Conclusions: The high prevalence of CLDN18.2 among Japanese patients with GC supports the therapeutic assessment of zolbetuximab in this population.

Keywords: Claudin; biomarkers; gastric cancer; immunohistochemistry; prevalence.

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Figures

Figure 1.
Figure 1.
Expression of CLDN18.2 in primary gastric tumors and LN metastases.

  1. Intra-individually matched pairs of samples from a patient with strong CLDN18.2 expression in both the primary tumor (a-c) and corresponding lymph node metastasis (d-f) at three different magnifications.

  2. The graph depicts the distribution of CLDN18.2 staining intensities in tumor cells from patient samples of primary tumor and LN metastases. CLDN18.2 staining intensity in tumor cells from each tissue sample analyzed were classified as 1+, 2+, and 3+ CLDN18.2 reactivity and are shown.

CLDN18.2, claudin 18.2; LN, lymph node. *Indicates normal stomach mucosal epithelium expressing CLDN18.2.
Figure 2.
Figure 2.
CLDN18.2 expression in matched pairs of primary tumors and corresponding LN metastases.

  1. The percentage of CLDN18.2-positive tumor cells in the primary tumor is indicated on the X axis, the percentage in the corresponding LN metastasis on the Y axis. Each ▾ represents one patient. Line shows Spearman’s correlation of stained tumor cells in primary tumors and LN.

  2. Difference in relative fraction of positive tumor cells for each case of intra-individually matched sample.

LN, lymph node.
See this image and copyright information in PMC

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