Increased expression of connexin 26 in the invasive component of lung squamous cell carcinoma: Significant correlation with poor prognosis

Reduced expression of connexins (Cxs), gap junction proteins, is frequently reported in malignant cell lines and tumors, whereas recent studies suggested that Cx26, a subtype of Cxs, might help tumor cells acquire malignant phenotypes. To examine this suggestion in the clinical setting, 50 lung squamous cell carcinomas (SCCs) were stained with the anti-Cx26 antibody. No Cx26-specific signals were detectable in 34 tumors (group I; 68%), whereas the remaining 16 were judged positive for Cx26 (group II; 32%). In 14 tumors of group II, Cx26-specific signals were detected not in all SCC cells but in SCC cells facing the tumor stroma or capsule, in which the signals were localized on the plasma membrane. Involved lymph nodes of group-II patients often contained metastatic foci consisting of all Cx26-positive cells. The proportion of Cx26-positive to Cx26-negative SCC cells in the metastatic nodes was larger than that in the corresponding primary tumors. Cx26-positive SCC cells seemed to be more invasive and metastatic than negative ones. Consistently, the 5-year cancer-specific survival rate of group-II patients was significantly lower than that of group-I patients (12.5 vs 38.9%; P=0.0391). Multivariate analysis demonstrated that Cx26 expression (P=0.0448) as well as pathological stage (P=0.0338) and vascular invasion (P=0.0191) were independent, significant prognostic predictors. These results suggest that Cx26 may represent an essential effector for controlling the biological aggressiveness of lung SCC tumor.