Evidence map›Paper›PMID 42415061›Full record

ArticleDiagnostic pathology2026

CLDN18.2 expression identifies a gastric-type phenotype and a potential therapeutic target in pulmonary invasive mucinous adenocarcinoma.

Tingting Bian, Xiaoyu Ren, Daishan Jiang, Jianguo Zhang, Sheng Xiao, Yuan Li, Yifei Liu

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Article in Diagnostic pathology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1 citing paper in PubMed.

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5 · Who and what money

Authors and funding

7 authors.

Tingting Bian *Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, China.
Xiaoyu Ren *Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, China.
Daishan JiangDepartment of Emergency Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, China.
Jianguo ZhangDepartment of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, China.
Sheng XiaoAdvanced Molecular Pathology, Institute of Soochow University and SANO, Suzhou, China.
Yuan LiDepartment of Pathology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.
Yifei LiuDepartment of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, China. ntdxliuyifei@sina.com.

Funding

Jiangsu Provincial Research Hospital YJXYY202204-YSC01, YJXYY202204-YSB01Nantong Basic Research Plan Project MS2023067National Natural Science Foundation of China No. 82273422
6 · The paper itself

Abstract

aimsThis study aimed to investigate the clinicopathological and immunophenotypic significance of Claudin18.2 (CLDN18.2) in pulmonary invasive mucinous adenocarcinoma (IMA), with particular focus on its association with gastric-type differentiation and potential implications for diagnosis and targeted therapy.

methodsImmunohistochemistry for CLDN18.2, MUC5AC, MUC6, and PD-L1 (22C3-TPS) was performed in 117 surgically resected lung IMAs. Associations with clinicopathological parameters and overall survival were analysed. Correlation analyses among CLDN18.2, MUC5AC, and MUC6 expression were conducted using Spearman's rank coefficients to assess the relationship between CLDN18.2 and gastric-type mucin phenotype.

resultsCLDN18.2 expression was detected in 71 of 117 tumors (60.7%), including 42 with high (35.9%) and 29 with low (24.8%) expression. MUC5AC and MUC6 positivity was observed in 75.2% and 34.2% of cases, respectively, while all tumors were PD-L1 negative. Spread through air spaces (STAS) was less frequent in CLDN18.2-positive (40.8% vs. 60.9%, P = 0.034) and MUC5AC-positive tumors (42% vs. 69%, P = 0.012). High CLDN18.2 expression was associated with earlier pathological stage (81% vs. 68%) and fewer nodal metastases (4.8% vs. 18%). CLDN18.2 expression correlated positively with MUC5AC (ρ = 0.469, P < 0.0001) and MUC6 (ρ = 0.43, P < 0.0001). Neither CLDN18.2 nor MUC5AC had prognostic impact, whereas MUC6 positivity tended to indicate shorter overall survival (P = 0.088).

conclusionsCLDN18.2 is frequently expressed in lung IMA and is closely associated with gastric-type mucin differentiation and reduced aerogenous spread. Although not prognostic, its consistent expression in PD-L1-negative tumors suggests a distinct biological subset and supports the potential use of CLDN18.2 as a biomarker for molecular stratification and therapeutic exploration in this rare subtype of lung adenocarcinoma.

Indexed as

Adenocarcinoma, MucinousAdenocarcinoma of LungBiomarkers, TumorClaudinsLung NeoplasmsAdultAgedAged, 80 and overFemaleHumansImmunohistochemistryMaleMiddle AgedMucin 5ACMucin-6PhenotypeBiomarkers, TumorClaudinsCLDN18 protein, humanMUC5AC protein, humanMUC6 protein, humanMucin 5ACMucin-6CLDN18.2Gastric-type differentiationLung mucinous adenocarcinomaMUC5ACMUC6Targeted therapy

Identifiers

PMID42415061
PMCPMC13625313

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