This 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. Immunohistochemistry 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. CLDN18.2 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). CLDN18.2 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.
Bian et al. (Tue,) studied this question.