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Prognostic value of tissue protein expression levels of MIB‐1 (Ki‐67) in Danish ovarian cancer patients. From the ‘MALOVA’ ovarian cancer study
Authors:Mel C. Heeran  Claus K. Høgdall  Susanne K. Kjaer  Lise Christensen  Allan Jensen  Jan Blaakaer  IB Jarle Christensen  Estrid V.S. Høgdall
Affiliation:1. Department of Pathology, Herlev Hospital, , Aarhus, Denmark;2. The Gynaecologic Clinic, The Juliane Marie Centre, Rigshospitalet, University of Copenhagen, , Aarhus, Denmark;3. Danish Cancer Society Research Center, Virus, Lifestyle and Genes, , Aarhus, Denmark;4. Department of Pathology, Rigshospitalet, University of Copenhagen, , Aarhus, Denmark;5. Department of Gynecology & Obstetrics, Aarhus University Hospital, , Aarhus, Denmark;6. The Finsen Laboratory, Rigshospitalet and Biotech Research and Innovation Centre (BRIC), University of Copenhagen, , Copenhagen, Denmark
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.
Keywords:Tissue array  ovarian cancer  MIB‐1 (Ki‐67)  prognosis  immunohistochemistry
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