Role of E-cadherins in development of lymphatic tumor emboli.

Abstract

E-cadherin (E-cad) is a cell adhesion molecule that is expressed in normal breast tissue. While loss of E-cad expression is a characteristic feature of lobular carcinoma, it also is observed in infiltrating ductal carcinoma (IDC). The presence of peritumoral intralymphatic emboli also is a poor prognostic feature in IDC. Invasive lobular carcinoma rarely is associated with intralymphatic emboli. In the current study, the authors assessed E-cad expression in cases of IDC with and without intralymphatic tumor emboli to examine the potential role played by these molecules in the development of lymphatic emboli. Fifty patients with high-grade invasive ductal carcinoma--25 with prominent lymphatic invasion (LVI) and intralymphatic tumor emboli and 25 without LVI--were tested for expression of E-cad. For both groups, the intensity and frequency of E-cad expression was evaluated in tumor cells and lymphatic emboli; normal lobules were used as internal controls. Membranous expression of E-cad was observed in normal lobules and tumor cells in all patients, with the tumor cells exhibiting varying degrees of loss of expression. In the 25 LVI-positive patients, the majority of tumor cells (including intralymphatic emboli) expressed E-cad with an intensity and distribution similar to what was seen in normal lobules. In the LVI-negative patients, the intensity and the distribution of E-cad staining varied significantly. Tumor cells at the tumor-stroma interface showed a greater frequency and intensity of E-cad expression than did cells in the central region of the tumor. Strong expression of E-cad was observed in LVI-positive patients with high-grade IDC but not in LVI-negative patients. Emboli also exhibited high-intensity expression. These findings, taken in conjunction with the knowledge that intralymphatic tumor emboli in lobular carcinoma (which is E-cad-negative) are rare, suggest that E-cad plays an important role in tumor development and growth within the lymphatics.