title: The serum concentration of human kallikrein 10 represents a novel biomarker for ovarian cancer diagnosis and prognosis.
abstract: Human kallikrein 10 (hK10) is a secreted serine protease that is highly expressed in ovarian tissue. We hypothesized that hK10 might represent a novel serological marker for ovarian cancer. We quantified by immunoassay, hK10 in sera from 97 normal women (controls), 141 patients with benign gynecologic diseases, and 146 patients with ovarian cancer. We then examined the diagnostic and prognostic value of this measurement in ovarian cancer. We found that normal serum hK10 ranged from 50 to 1040 ng/liter (mean = 439 ng/liter). hK10 concentration is significantly elevated in serum of presurgical ovarian cancer patients (range: 106-11,746 ng/liter; mean = 1067 ng/liter) but not in serum of patients with benign gynecologic diseases (range: 120-1200 ng/liter; mean = 447 ng/liter). When a cutoff of 700 ng/liter was selected (diagnostic specificity = 90%), the diagnostic sensitivity for ovarian cancer is 54%. About 35% of CA125-negative ovarian cancer patients (CA125 < 23 kU/liter) were hK10 positive at 90% specificity. In patients with stage I/II ovarian cancer, use of these two markers in combination results in a 21% increase in sensitivity, at 90% specificity, compared with CA125 alone. High serum hK10 was strongly associated with serous epithelial type, late-stage, advanced grade, large residual tumor (>1 cm), suboptimal debulking, and no response to chemotherapy (all Ps < 0.001). In univariate Cox survival analysis, high serum hK10 is associated with increased risk for relapse and death (hazard ratio = 2.59 and 3.15, respectively, P </= 0.003). This prognostic value remains significant for overall survival in the multivariate analysis. Kaplan-Meier survival curves demonstrated similar findings. Serum hK10 represents a novel biomarker for ovarian cancer. We conclude that preoperative serum hK10 concentration is a strong and independent unfavorable prognostic marker for ovarian cancer.
authors.affiliation: Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5 Canada.
authors.forename: Liu-Ying
authors.initials: LY
authors.lastname: Luo
authors.forename: Dionyssios
authors.initials: D
authors.lastname: Katsaros
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
authors.forename: Stefano
authors.initials: S
authors.lastname: Fracchioli
authors.forename: Roberto
authors.initials: R
authors.lastname: Bellino
authors.forename: Marleen
authors.initials: M
authors.lastname: van Gramberen
authors.forename: Henk
authors.initials: H
authors.lastname: de Bruijn
authors.forename: Alfthan
authors.initials: A
authors.lastname: Henrik
authors.forename: Ulf-Hakan
authors.initials: UH
authors.lastname: Stenman
authors.forename: Marco
authors.initials: M
authors.lastname: Massobrio
authors.forename: Ate G J
authors.initials: AG
authors.lastname: van der Zee
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Diamandis
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D005260:Female; D015200:Fluoroimmunoassay; D006801:Humans; D007610:Kallikreins / Q000097:blood*; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000097:blood* / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C100936:KLK10 protein, human; D007610:Kallikreins