Expression of tissue factor pathway inhibitor (TFPI) in human breast and colon cancer tissue

Abstract

Activation of blood coagulation, a phenomenon frequently observed in breast and colon cancer patients, contributes to tumour progression. The principal initiator of blood coagulation activation in cancer patients is tissue factor (TF), while tissue factor pathway inhibitor (TFPI) is the main inhibitor of the TF-dependent pathway of blood coagulation. Previous immunohistochemical studies revealed no expression of TFPI in human cancer cells. The aim of the study was to evaluate the expression of TFPI protein and mRNA in breast and colon cancer tissues. A total of 108 cancer tissues (from primary tumours and metastatic lymph nodes) were obtained from 87 patients during surgical treatment. Immunohistochemical studies using a polyclonal anti-TFPI antibody were performed including a semiquantitative analysis. The in situ hybridisation method employed single-stranded DNA oligonucleotide (probe sequence: 5'Biotin-CCACCATACTTGAAACGTTCACACT-Biotin3') directed against TFPI mRNA. Strong or medium expression of TFPI protein was observed in cancer cell bodies in all breast cancers and in most (39/66 cases) colon cancers examined. Weaker expression of TFPI was detected in cancer cells localised in lymph node metastatic foci of breast cancer. Endothelial cells were also TFPI-positive. TFPI mRNA was demonstrated in all cases of breast and in approximately 80% cases of colon cancer cells. TFPI mRNA and protein are present in association with colon and breast cancer cells, suggesting that the protein may play a role in cancer biology. The presence of TFPI in association with breast cancer cells localised in regional lymph nodes may indicate its role in lymphatic spread.