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. 2024 Jul 31;14(1):17648.
doi: 10.1038/s41598-024-68411-w.

Heterogeneity of claudin 18.2 expression in metastatic gastric cancer

Eugene Choi  1 , Jinho Shin  1 , Min-Hee Ryu  2 , Hyung-Don Kim #  3 , Young Soo Park #  4
Affiliations

Heterogeneity of claudin 18.2 expression in metastatic gastric cancer

Eugene Choi et al. Sci Rep. .

Abstract

Claudin 18.2 has emerged as a viable therapeutic target in gastric cancer (GC), but little is known about the heterogeneity of its expression in GC. This study investigated the heterogeneity of claudin 18.2 expression in 166 patients with metastatic GC whose surgical or paired primary-metastatic specimens were available. The prevalence of claudin 18.2 positivity (moderate-to-strong expression in ≥ 75% by the 43-14A clone) was 47.0%. Claudin 18.2-positive tumors exhibited more frequent peritoneal metastasis and a lower incidence of hepatic and distant lymph node involvement. Survival outcomes were comparable between patients with claudin 18.2-positive and -negative tumors. Intratumoral heterogeneity was noted in 38.5% of surgical specimens. Paired primary-metastatic site analysis revealed that 25.2% of patients had discordant results for claudin 18.2 positivity. Across different metastatic organ categories, peritoneal lesions showed the highest positivity rate (44.3%) and positive concordance rate (31.4%), whereas liver lesions had the lowest positivity rate (17.9%) and concordance rate (12.8%). In conclusion, claudin 18.2 expression exhibits intratumoral and intrapatient spatial heterogeneity in metastatic GC. Claudin 18.2 positivity is associated with more frequent peritoneal metastasis, and peritoneal lesions are more likely to have positively concordant claudin 18.2 results with the primary site than other metastatic sites.

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Conflict of interest statement

M-H.R. received honoraria from DAEHWA Pharmaceutical, Bristol Myers Squibb, Lilly, Ono Pharmaceutical, MSD, Taiho Pharmaceutical, Novartis, Daiichi Sankyo and AstraZeneca, and served as a consultant for DAEHWA Pharmaceutical, Bristol Myers Squibb, Lilly and Ono Pharmaceutical. H-D.K. received honoraria from AstraZeneca, Bristol Myers Squibb, Ono Pharmaceuticals, Boryung Pharmaceuticals, and Boostimmune; and served as a consultant for Mustbio. E.C., J.S, and Y.S.P. declare no competing interests.

Figures

Figure 1
Figure 1
Scheme of the study population. (A) Clinical characteristics and prognostic value of claudin 18.2 positivity in the overall study population (n = 166). (B) Intratumoral heterogeneity of claudin 18.2 expression was investigated among those who underwent surgical resection of the primary tumor (n = 39). (C) Intrapatient spatial heterogeneity of claudin 18.2 expression across different metastatic sites in paired cases of primary and metastatic tumors (n = 135).
Figure 2
Figure 2
Survival outcomes with respect to claudin 18.2 expression status. (A) Progression-free survival and (B) overall survival.
Figure 3
Figure 3
Categorization of paired cases into 4 groups based on the concordance of claudin 18.2 expression determined by immunohistochemical (IHC) staining. (A) Representative examples of immunohistochemical staining for each group. (B) Percentage of tumor cells exhibiting moderate-to-strong staining patterns for claudin 18.2 in each group.
Figure 4
Figure 4
Concordance of claudin 18.2 expression between primary and metastatic sites across different metastatic sites.
See this image and copyright information in PMC

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