title: Prognostic value of tissue protein expression levels of MIB-1 (Ki-67) in Danish ovarian cancer patients. From the 'MALOVA' ovarian cancer study.
abstract: The primary objective of this study was to assess the expression of MIB-1 (Ki-67) in tumour tissues from 808 patients with epithelial ovarian tumours. The second was to evaluate, whether MIB-1 (Ki-67) tissue expression levels correlate with clinicopathological parameters and prognosis of the disease. Using tissue arrays (TA), we analysed the MIB-1 (Ki-67) expression levels in tissues from 202 women with borderline ovarian tumours (BOT) (177 stage I, 5 stage II, 19 stage III, 1 stage IV) and 606 ovarian cancer (OC) patients (177 stage I, 64 stage II, 311 stage III, 54 stage IV). Using a 10% cut-off level for MIB-1 (Ki-67) overexpression, 12% of the BOTs and 51% of the OCs were positive for MIB-1 (Ki-67) expression. The frequency of MIB-1 (Ki-67) expression-positive OC increased with increasing FIGO stage (p = 0.003), increasing histological grade (p ≤ 0.0001), and a significantly different distribution of MIB-1 (Ki-67) positive and negative tumours were found in adenocarcinoma NOS, serous adenocarcinomas, mucinous adenocarcinomas, endometrioid adenocarcinomas, non-epithelial and clear-cell carcinomas (p = 0.016). Univariate Kaplan-Meier survival analysis performed on all OC cases showed a significant shorter disease specific survival in patients with positive MIB-1 (Ki-67) expression in the tumour tissue (p ≤ 0.0001). In a Cox survival analysis including 606 FIGO stages I to IV OC cases, FIGO stage (II vs I: HR = 3.00, 95% CI: 1.81-4.99, III-I: HR = 6.41, 95% CI: 3.90-10.50, IV vs I: HR = 12.69, 95% CI: 7.21-22); age at diagnosis pr.10 years (HR = 1.27, 95% CI: 1.15-1.40), residual tumour after surgery (HR = 1.95, 95% CI: 1.40-2.73) and MIB-1 (Ki-67) expression (HR = 1.31, 95% CI: 1.08-1.60) had a significant independent impact on survival. Histological grade (p = 0.14) and histological tumour type (p = 0.35) had no significant independent impact on survival. In conclusion, our results predict that an increased level of MIB-1 (Ki-67) expression in tumour tissue, points to a less favourable outcome for OC patients.
authors.affiliation: Department of Pathology, Herlev Hospital, Aarhus, Denmark.
authors.forename: Mel C
authors.initials: MC
authors.lastname: Heeran
authors.forename: Claus K
authors.initials: CK
authors.lastname: Høgdall
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Kjaer
authors.forename: Lise
authors.initials: L
authors.lastname: Christensen
authors.forename: Allan
authors.initials: A
authors.lastname: Jensen
authors.forename: Jan
authors.initials: J
authors.lastname: Blaakaer
authors.forename: Ib Jarle
authors.initials: IJ
authors.lastname: Christensen
authors.forename: Estrid V S
authors.initials: EV
authors.lastname: Høgdall
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D000077216:Carcinoma, Ovarian Epithelial; D003718:Denmark; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen
keywords: MIB-1 (Ki-67); Tissue array; immunohistochemistry; ovarian cancer; prognosis