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Open Access 09-05-2024 | Gastric Cancer | Original Article

Claudin-18 status and its correlation with HER2 and PD-L1 expression in gastric cancer with peritoneal dissemination

Authors: Haruki Ogawa, Hiroyuki Abe, Koichi Yagi, Yasuyuki Seto, Tetsuo Ushiku

Published in: Gastric Cancer | Issue 4/2024

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Abstract

Background

Gastric cancer with peritoneal dissemination (PD) has a dismal prognosis, and current treatments have shown little efficacy. CLDN18.2-targeted therapies have shown promising efficacy against gastric cancers that express high levels of CLDN18. Because of the limited information regarding CLDN18.2 status in PD, we analyzed PD-positive gastric cancers for CLDN18 status in both primary and PD, along with HER2 and PD-L1 combined positive score (CPS).

Methods

Immunohistochemical analyses were performed on 84 gastric cancer cases using paired primary and PD tissue samples.

Results

At 40% cut-off, CLDN18 was positive in 57% (48/84) primary tumors and in 44% (37/84) PDs. At 75% cut-off, 28.6% (24/84) primary tumors and 20.2% (17/84) PDs were CLDN18-positive. The concordance rate between primary tumors and PD was 79.8% at 40% cut-off and 75% at 75% cut-off. When comparing biopsy and surgical specimens, the concordance rates were 87.5% at 40% cut-off and 81.3% at 75% cut-off. Within a tumor, the superficial area tended to have a higher CLDN18-positive rate than the invasive front (P = 0.001). Although HER2 -positivity was only 11.9% in this cohort, CLDN18 positivity in HER2-negative tumors (n = 74) was relatively high: 60.8% at 40% cut-off and 28.4% at 75% cut-off. Among double-negative (HER2 − and PD-L1 CPS < 1) tumors, CLDN18 positivity was 67.6% at 40% cut-off and 26.5% at 75% cut-off.

Conclusions

CLDN18 expression is generally maintained in PD and is relatively high even in double-negative tumors, making it a promising therapeutic target for PD-positive gastric cancer.
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Literature
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go back to reference Shitara K, Lordick F, Bang Y-J, et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. The Lancet. 2023. https://doi.org/10.1016/S0140-6736(23)00620-7.CrossRefPubMed Shitara K, Lordick F, Bang Y-J, et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. The Lancet. 2023. https://​doi.​org/​10.​1016/​S0140-6736(23)00620-7.CrossRefPubMed
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Metadata
Title
Claudin-18 status and its correlation with HER2 and PD-L1 expression in gastric cancer with peritoneal dissemination
Authors
Haruki Ogawa
Hiroyuki Abe
Koichi Yagi
Yasuyuki Seto
Tetsuo Ushiku
Publication date
09-05-2024
Publisher
Springer Nature Singapore
Published in
Gastric Cancer / Issue 4/2024
Print ISSN: 1436-3291
Electronic ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-024-01505-6

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