Claudin18.2 expression in pulmonary mucinous adenocarcinoma

Pulmonary invasive mucinous adenocarcinoma (IMA) is a unique type of lung adenocarcinoma with a high recurrence rate and limited treatment strategies. The tight-junction-associated protein claudin18.2 is a new therapeutic target for several solid tumors. This study aimed to detect the expression of claudin18.2 in IMA and its clinicopathological association with the disease.

The expression of claudin18.2 was immunohistochemically evaluated in an IMA cohort of 84 patients, who underwent partial pneumonectomy between January 2017 and December 2021. Positive staining for claudin18.2 was defined as ≥ 10% of tumor cells showing ≥ 1 + membrane staining or any ≥ 2 + membrane staining.

Claudin18.2 was detected in 76.2% (64/84) of IMA patients, significantly higher than that in non-mucinous adenocarcinoma (NMA). 46.4% (39/84) of the IMA patients met the enrollment criteria of the clinical trials of monoclonal antibodies (≥ 75% of tumor cells demonstrating ≥ 2 + staining intensity). Positive staining for claudin18.2 was significantly associated with smaller tumor size (p = 0.010), less pleural invasion (p = 0.019), and earlier pN stage (p < 0.001). Expression of claudin18.2 was not related to prognosis in multivariate analysis.

To summarize, in this study we found that claudin18.2 was remarkably highly expressed in IMA and the overexpression was associated with low invasive capacity. Thus, this protein appears to be a promising therapeutic target and deserves further investigation in IMA patients.