ArticleInternational journal of clinical oncology2026
Intratumoral heterogeneity of intermediate CLDN18.2 expression in gastric cancer.
Article in International journal of clinical oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundCLDN18.2-targeted therapies show promise in HER2-negative, CLDN18.2-positive advanced gastric cancer (GC); however, cutoffs defining CLDN18.2 positivity vary across studies. Tumors with high expression (moderate to strong membranous expression in ≥ 75% of tumor cells) generally exhibit intratumoral homogeneity and a uniform staining pattern, but intratumoral heterogeneity and staining pattern of CLDN18.2 at lower expression thresholds remains unclear. This study investigated intratumoral heterogeneity of CLDN18.2 by comparing inter-block concordance of expression levels and staining patterns in GC.
methodsEighty-six resected GC specimens were retrospectively analyzed using CLDN18.2 immunohistochemistry on two tissue blocks per tumor. CLDN18.2 expression was categorized as high (≥ 75%), intermediate (< 75% and ≥ 40%), or negative (< 40%), and staining patterns as uniform or variable. Inter-block concordance of expression levels and staining patterns and their influence on concordance and outcomes were assessed.
resultsOverall inter-block concordance of expression levels was high (77%, κ = 0.89). Discordance was substantially higher in intermediate expression tumors (63.5%) than in high (15.5%) or negative (19%) expression tumors. Uniform staining was observed exclusively in high expression tumors, whereas all intermediate expression tumors displayed variable staining (100%). Among high expression tumors, inter-block concordance was substantially higher with uniform staining (98.0%) than with variable staining (71.5%). CLDN18.2 expression and staining pattern heterogeneity were not associated with worse survival.
conclusionSignificant intratumoral heterogeneity of CLDN18.2 expression was observed in GC, particularly in intermediate expression tumors; however, this heterogeneity does not affect survival. These results highlight the importance of standardized assessment methods when applying lower thresholds for CLDN18.2-targeted therapies.
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