The Relationship between Plasminogen Acti- vator Inhibitor-1 and Bone Marrow Microme- tastases in Breast Cancer

ABSTRACT

PURPOSE: Plasminogen Activator Inhibitor-1 (PAI-1) is the principal physiological urokinase-type plasminogen activator and is thought to regulate the overall invasive and metastatic behaviors of cancer cells. Although the occurrence of bone marrow micrometastases is an independent prognostic factor in breast cancer, its pathomechanism is not yet fully revealed until. We hypothesize that PAI-1 has a major role in the development of bone marrow micrometastases in breast cancer. Accordingly, we attempted to establish a correlation between PAI-1 activity in tumor tissues and bone marrow micrometastases in breast cancer. Additionally, we studied the relationship between PAI-1 level and selected clinicopathological characteristics such as tumor size, lymph node metastases, and steroid receptor positivity. METHODS: we used the RT-PCR targeting mRNA of cytokeratin 19 to detect bone marrow micrometastases and an ELISA kit to estimate PAI-1 activity in frozen tumor tissues. RESULTS: (1) The median PAI-1 level was 13.55 ng/ml 16.38 in the cases with bone marrow metastases, and 6.02 ng/ml 10.85 in the cases without bone marrow micrometastases. The difference was statistically significant (p-value=0.0165). (2) PAI-1 levels did not show any significant differences according to lymph node status, variation of tumor size or the expression status of the steroid receptors. CONCLUSION: PAI-1 is considered to have a role to hematogenous metastases of breast cancer cells. However, further study is recommended to reveal its significance as an independent prognstic factor for breast cancer.