Researchers found that CLDN18.2 may be frequently expressed in pulmonary invasive mucinous adenocarcinoma and could be associated with gastric-type differentiation, potentially helping to define a distinct tumor phenotype for biomarker-based stratification.
In a retrospective, single-center study, researchers evaluated 117 pulmonary invasive mucinous adenocarcinomas in patients who underwent curative-intent surgical resection between 2018 and 2020. Clinicopathologic characteristics and overall survival were assessed and immunohistochemistry was performed for CLDN18.2, MUC5AC, MUC6, and PD-L1. Patients were followed for a median of 32 months.
The primary objectives were to determine the prevalence of CLDN18.2 expression and its relationship with gastric-type mucin differentiation. Secondary analyses examined associations with spread through air spaces (STAS), pathologic features, PD-L1 expression, and overall survival.
CLDN18.2 expression was identified in 61% (n = 71) of the tumors, including high expression in 36% (n = 42) of them. MUC5AC and MUC6 expression was observed in 75% (n = 88) and 34% (n = 40) of the tumors, respectively. All tumors were negative for PD-L1 expression using the predefined tumor proportion score cutoff.
CLDN18.2 expression closely tracked with gastric-type mucin differentiation. Further, 90% vs. 52% of CLDN18.2-positive tumors expressed MUC5AC compared with CLDN18.2-negative tumors, while MUC6 expression was present in 52% vs. 7%, respectively. The researchers reported positive correlations between CLDN18.2 expression and both gastric mucin markers, supporting a gastric-type phenotype in this adenocarcinoma subset.
Clinicopathologic analyses also showed that STAS occurred less frequently in CLDN18.2-positive tumors compared with in CLDN18.2-negative tumors (41% vs. 61%). While patients with high CLDN18.2 expression demonstrated numerical trends toward earlier disease staging and fewer nodal metastases compared with those with low expression, the differences were not statistically significant.
Neither CLDN18.2 expression nor MUC5AC expression were associated with overall survival. MUC6 positivity showed a trend toward shorter overall survival, but the finding did not reach statistical significance.
The researchers acknowledged several limitations, including the retrospective single-center design, the relatively small cohort, inclusion of only surgically resected tumors, incomplete molecular profiling, limited characterization of the tumor immune microenvironment beyond PD-L1 assessment, and the absence of treatment-response or functional validation data. They noted that additional multicenter prospective studies are needed to determine the therapeutic relevance of CLDN18.2.
The findings suggested that CLDN18.2 may define a distinct gastric-type phenotype in pulmonary invasive mucinous adenocarcinoma rather than serve as a prognostic marker, supporting its further investigation as a biomarker for molecular stratification.
"These findings provide a basis for further studies to clarify the biological significance and possible therapeutic relevance of CLDN18.2 in clinically and molecularly well-characterized cohorts," wrote lead study authors Tingting Bian, of the Department of Pathology at the Affiliated Hospital of Nantong University in China, and colleagues.
The study authors reported no conflicts of interest.
Source: Diagnostic Pathology