Prognostic value of tissue protein expression levels of MIB-1 (Ki-67) in Danish ovarian cancer patients. From the 'MALOVA' ovarian cancer study

Mel C Heeran; Claus K Høgdall; Susanne K Kjaer; Lise Christensen; Allan Jensen; Jan Blaakaer; Ib Jarle Christensen; Estrid V S Høgdall

doi:10.1111/apm.12071

Prognostic value of tissue protein expression levels of MIB-1 (Ki-67) in Danish ovarian cancer patients. From the 'MALOVA' ovarian cancer study

Mel C Heeran, Claus K Høgdall, Susanne K Kjaer, Lise Christensen, Allan Jensen, Jan Blaakaer, Ib Jarle Christensen, Estrid V S Høgdall

Department of Clinical Medicine

5 Citations (Scopus)

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.

Original language	English
Journal	APMIS : acta pathologica, microbiologica, et immunologica Scandinavica
Volume	121
Issue number	12
Pages (from-to)	1177-1186
Number of pages	10
ISSN	0903-4641
DOIs	https://doi.org/10.1111/apm.12071
Publication status	Published - Dec 2013

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10.1111/apm.12071

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Heeran, M. C., Høgdall, C. K., Kjaer, S. K., Christensen, L., Jensen, A., Blaakaer, J., Christensen, I. J., & Høgdall, E. V. S. (2013). Prognostic value of tissue protein expression levels of MIB-1 (Ki-67) in Danish ovarian cancer patients. From the 'MALOVA' ovarian cancer study. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica, 121(12), 1177-1186. https://doi.org/10.1111/apm.12071

Prognostic value of tissue protein expression levels of MIB-1 (Ki-67) in Danish ovarian cancer patients. From the 'MALOVA' ovarian cancer study. / Heeran, Mel C; Høgdall, Claus K ; Kjaer, Susanne K et al.

In: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica, Vol. 121, No. 12, 12.2013, p. 1177-1186.

Research output: Contribution to journal › Journal article › Research › peer-review

Heeran, MC, Høgdall, CK , Kjaer, SK, Christensen, L, Jensen, A, Blaakaer, J, Christensen, IJ & Høgdall, EVS 2013, 'Prognostic value of tissue protein expression levels of MIB-1 (Ki-67) in Danish ovarian cancer patients. From the 'MALOVA' ovarian cancer study', APMIS : acta pathologica, microbiologica, et immunologica Scandinavica, vol. 121, no. 12, pp. 1177-1186. https://doi.org/10.1111/apm.12071

@article{17f0afcdb8c14e28941735425fd77a5d,

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.",

author = "Heeran, {Mel C} and H{\o}gdall, {Claus K} and Kjaer, {Susanne K} and Lise Christensen and Allan Jensen and Jan Blaakaer and Christensen, {Ib Jarle} and H{\o}gdall, {Estrid V S}",

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language = "English",

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T1 - Prognostic value of tissue protein expression levels of MIB-1 (Ki-67) in Danish ovarian cancer patients. From the 'MALOVA' ovarian cancer study

AU - Heeran, Mel C

AU - Høgdall, Claus K

AU - Kjaer, Susanne K

AU - Christensen, Lise

AU - Jensen, Allan

AU - Blaakaer, Jan

AU - Christensen, Ib Jarle

AU - Høgdall, Estrid V S

PY - 2013/12

Y1 - 2013/12

N2 - 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.

AB - 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.

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DO - 10.1111/apm.12071

M3 - Journal article

C2 - 23594232

SN - 0903-465X

VL - 121

SP - 1177

EP - 1186

JO - APMIS. Supplementum

JF - APMIS. Supplementum

IS - 12

ER -

Prognostic value of tissue protein expression levels of MIB-1 (Ki-67) in Danish ovarian cancer patients. From the 'MALOVA' ovarian cancer study

Abstract

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