Comparative Analysis of Coagulation System Proteins Distribution in Breast Cancer Primary Lesions and Lymph Node Metastases.

Abstract

Breast cancer is the most frequent cause of morbidity and mortality due to cancer in women. Thromboembolic episodes are relatively common complication during the course of the disease. It was widely documented, that components of blood coagulation play a role in tumor progression and metastasis formation. Presence of hemostatic proteins was observed in primary lesions of different malignant tumors. However, information on expression and role of coagulation system components in regional lymph node metastases is scanty. The purpose of the study was to assess and compare the distribution of selected coagulation proteins - in primary versus metastatic lesions of breast cancer. Specimens of primary tumor of different degree of malignancy and metastatic lesions localized in regional lymph nodes were obtained during surgical treatment of previously untreated twenty five breast cancer patients and fixed in formalin. Immunohistochemical procedure was employed using monoclonal and polyclonal antibodies against tissue factor (TF), tissue factor pathway inhibitor (TFPI), factor IX, factor X, fibrinogen and fibrin. A strong expression of TF was demonstrated in cancer cells of both primary tumors and lymph node metastases. Coagulation factors IX and X were also present in primary and metastatic breast cancer lesions. However, the expression of the proteins was weaker in regional lymph node metastases than in primary tumor. Strong staining for fibrinogen was detected in the stroma of primary breast cancer, particularly at the area adjacent to the cancer foci. Stroma of metastatic lesions was characterized by much weaker staining for fibrinogen. Strong expression of fibrin and TFPI was demonstrated in cancer cells of primary tumor while much weaker expression of the antigens was visualized in cancer cells localized in lymph node metastatic lesions. Furthermore, the presence of all examined proteins was observed in small blood vessel walls and in macrophages infiltrating both primary tumor tissue as well as metastatic lesions. The results of the study indicate extravascular activation of blood coagulation in loco in breast cancer, both in the primary tumor and in the regional lymph node metastatic lesions. The presence of coagulation system proteins in cancer tissue (primary tumor and metastatic foci) suggests that they may play a role in the biology of breast cancer growth as well as they may modulate breast cancer metastatic dissemination.