Connexin26 expression is associated with lymphatic vessel invasion and poor prognosis in human breast cancer

Abstract

Cx26, which is a constituent of the connexin family, has recently been shown to promote metastasis through enhancing the vascular invasion in mouse melanoma cells. In this study, we have investigated whether or not Cx26 expression is associated with vascular invasion and recurrences in human breast cancers. Cx26 expression was studied in 152 invasive breast cancers by immunohistochemistry. In order to investigate the blood vessel invasion and lymphatic vessel invasion with precision, immunohistochemical staining of blood vessels and lymphatic vessels was carried out using anti-CD34 and anti-D2-40 antibodies, respectively. Cx26 was positive in 51.3% (78/152) of the breast tumors. A statistically significant association was observed between Cx26 expression and large tumor size (P = 0.013) or high histological grade (P = 0.043). Frequency of blood vessel invasion was higher in Cx26-positive tumors (5.1%, 4/78) than in Cx26-negative tumors (1.4%, 1/74) though not statistically significant (P = 0.210). Lymphatic vessel invasion was significantly (P = 0.001) more frequent in Cx26-positive tumors (39.7%) than in Cx26-negative tumors (14.9%). Patients with Cx26-positive tumors showed a significantly (P < 0.001) poorer prognosis than those with Cx26-negative tumors. Multivariate analysis showed that Cx26 (P < 0.05) expression was an independent prognostic factor. Cx26 expression is associated with lymphatic vessel invasion, large tumor size, high histological grade, and poor prognosis in human breast cancers. Cx26 seems to enhance the metastasis probably through promoting the lymphatic vessel invasion. Cx26 might be clinically useful as a new prognostic factor.