title: Midkine in plasma as a novel breast cancer marker.
abstract: Midkine, a heparin-binding growth factor, is up-regulated in many types of cancer. The aim of this study was to measure plasma midkine levels in patients with breast cancer and to assess its clinical significance. 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). 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 breast cancer patients, plasma midkine levels were increased above normal values. These elevated levels of midkine were seen in one (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 a 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. Midkine may be a useful novel tumor marker for detection of breast cancer, superior to conventional tumor markers.
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Ibusuki
authors.forename: Hiromi
authors.initials: H
authors.lastname: Fujimori
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Ota
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Ueda
authors.forename: Satoru
authors.initials: S
authors.lastname: Shinriki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Taketomi
authors.forename: Sadatoshi
authors.initials: S
authors.lastname: Sakuma
authors.forename: Masanori
authors.initials: M
authors.lastname: Shinohara
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Iwase
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology; D002272:Carcinoembryonic Antigen / Q000097:blood; D018270:Carcinoma, Ductal, Breast / Q000097:blood* / Q000556:secondary*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000097:blood* / Q000556:secondary; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D000078792:Midkine; D018396:Mucin-1 / Q000097:blood; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009414:Nerve Growth Factors / Q000097:blood*; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; C066254:MDK protein, human; D018396:Mucin-1; D009414:Nerve Growth Factors; D000078792:Midkine