Loss of TSLC1 expression in lung adenocarcinoma: Relationships with histological subtypes, sex and prognostic significance

The TSLC1 (tumor suppressor in lung cancer 1) gene is a tumor suppressor recently identified through functional complementation in a lung adenocarcinoma cell line A549. In this study we immunohistochemically examined the loss of TSLC1 expression in 93 cases of surgically resected lung adenocarcinoma, and investigated its correlation with clinicopathological parameters, including histological subtypes of tumors. The prognostic significance of loss of TSLC1 expression was analyzed by univariate and multivariate analyses, in parallel with other prognostic markers such as p53, p27, and Ki-67. In non-cancerous lung tissue, TSLC1 was weakly positive in bronchial and bronchiolar epithelial cells, type II pneumocytes and bronchial glands. Overall, TSLC1 was negative in 60 of 93 lung adenocarcinomas. TSLC1 was mainly localized in the cytoplasm of the cells, but cell membrane staining was also observed, especially at sites of cell-cell adhesion. TSLC1-negative tumors were more frequently observed in male cases (41/54 cases, 70.0%) than in female cases (19/39 cases, 48.7%) (P<0.01). Notably, TSLC1 expression was preserved in a non-invasive, bronchiolo-alveolar histological pattern of tumor cells (P<0.0001). Survival analyses showed that loss of TSLC1 expression was associated with lower patient survival in univariate and multivariate analyses (P<0.05 and P=0.059, respectively). Subset analyses further showed that the prognostic impact of loss of TSLC1 was significant for male patients (P=0.0089), but not for female patients. We conclude that TSLC1 is expressed in a subset of lung adenocarcinomas, especially in those with bronchiolo-alveolar spread pattern. Loss of TSLC1 is associated with lower patient survival, supporting its role as a tumor suppressor.