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

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.