Midkine in the plasma as a novel breast cancer marker.

Abstract

1142 Background: Midkine, a heparin-binding growth factor, is up-regulated in many types of cancer. The aim of this study is to measure plasma midkine levels in patients with breast cancer and to assess its clinical significance in breast cancer. Methods: We examined plasma midkine levels in 95 healthy volunteers, 11 patients with ductal carcinoma in situ (DCIS), 111 patients with primary invasive breast cancer without distant metastasis (PIBC) and 25 patients with distant metastatic breast cancer (MBC), using an automatic immunoasssay analyzer (TOSOH AIA system). Results: In PIBC, we studied the correlation between plasma midkine levels and clinicopathological factors. Immunoreactive midkine was detectable in the plasma of healthy volunteers, and a cut-off level of 750 pg/ml was established. In patients with breast cancer, plasma midkine levels were increased above normal values. These elevated levels of midkine were seen in 1 (9.1%) of 11 patients with DCIS, 36 (32.4%) of 111 patients with PIBC, and 16 (64.0%) of 25 patients with MBC. Increased levels of midkine were correlated with menopausal status (p=0.0497) and nuclear grade (p=0.0343) in PIBC. Cancer detection rates based on midkine levels were higher than those based on three conventional markers including CA15-3 (p<0.0001), CEA (p=0.0077) and NCCST-439 (p<0.0001). Detection rates of breast cancer using combination of two conventional tumor markers (CA15-3/CEA, CA15-3/NCCST-439 or CEA/NCCST-439) with midkine is significantly higher than those using combination of three conventional tumor markers. Conclusions: Midkine may be a useful novel tumor marker for detection of breast cancer, superior to conventional tumor markers. No significant financial relationships to disclose.