Midkine in plasma as a novel breast cancer marker.
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.
Ibusuki
Mutsuko
M
Department of Breast and Endocrine Surgery, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
Fujimori
Hiromi
H
Yamamoto
Yutaka
Y
Ota
Kazutoshi
K
Ueda
Mitsuharu
M
Shinriki
Satoru
S
Taketomi
Masahiro
M
Sakuma
Sadatoshi
S
Shinohara
Masanori
M
Iwase
Hirotaka
H
Ando
Yukio
Y
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
D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; C066254:MDK protein, human; D018396:Mucin-1; D009414:Nerve Growth Factors; D000078792:Midkine