Expression of phosphatase and tensin homolog and programmed cell death ligand 1 in adenosquamous carcinoma of the lung

Abstract Background Lung adenosquamous carcinoma (ASC) is a rare variant of non-small cell lung cancer (NSCLC) with poor prognosis. Certain biological differences may exist between these tumors and other common histological types of NSCLC, including adenocarcinoma (ADC) and squamous cell carcinoma (SCC). The phosphoinositide 3-kinase (PI3K) pathway, which links oncogenes and multiple receptor classes to essential cellular functions, is activated by phosphatase and tensin homolog (PTEN) loss. The PTEN loss has been suggested to induce programmed cell death ligand 1 (PD-L1) expression in various cancer types. Objective Here, we sought to determine the relationships between the expression of PTEN and PD-L1 in each component of ASC with ADC and SCC, and clinical parameters. Material and methods Tissue microarrays of 148 cases of surgically resected lung ADC and 102 cases of SCC, as well as full sections from 28 ASC cases, were analyzed immunohistochemically for the expression of PTEN and PD-L1. Results PD-L1 expression was similar between the adenocarcinoma component of ASC vs. lung ADC and between the squamous component of ASC vs. lung SCC. PTEN loss was higher in lung ADC than in the adenocarcinoma component of ASC and significantly higher in lung SCC than in the squamous component of ASC. PD-L1 expression was higher in the squamous component than in the glandular component of the 28 ASC cases, but PTEN loss was similar. Overall, PTEN loss was higher in lung SCC than in lung ADC and both components of ASC. In lung SCC and glandular portions of ASC, PD-L1 expression levels were significantly associated with those of PTEN. The loss of PTEN correlated with smoking status in patients with lung ADC. Conclusions Our results implied that both squamous and glandular components of ASC may share the same oncogenic driver pathway for carcinogenesis. However, the squamous cell components of ASC likely escape the immune surveillance better than the glandular components due to higher PD-L1 expression.