OVSCORE ‑ a validated score to identify ovarian cancer patients not suitable for primary surgery

Dorn,Julia; Bronger,Holger; Kates,Ronald; Slotta‑Huspenina,Julia; Schmalfeldt,Barbara; Kiechle,Marion; Diamandis,Eleftherios  P.; Soosaipillai,Antoninus; Schmitt,Manfred; Harbeck,Nadia

doi:10.3892/ol.2014.2630

January-2015 Volume 9 Issue 1

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January-2015 Volume 9 Issue 1

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Article

OVSCORE ‑ a validated score to identify ovarian cancer patients not suitable for primary surgery

Authors:
- Julia Dorn
- Holger Bronger
- Ronald Kates
- Julia Slotta‑Huspenina
- Barbara Schmalfeldt
- Marion Kiechle
- Eleftherios P. Diamandis
- Antoninus Soosaipillai
- Manfred Schmitt
- Nadia Harbeck
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Affiliations: Department of Obstetrics and Gynecology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany, Department of Pathology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada, Department of Obstetrics and Gynecology, Breast Center, Klinikum Grosshadern, University of Munich, Munich, Germany
Pages: 418-424
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Published online on: October 24, 2014

https://doi.org/10.3892/ol.2014.2630
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Abstract

Following primary debulking surgery, the presence of a residual tumor mass is one of the most important prognostic factors in ovarian cancer. In a previous study, we established the OVSCORE, an algorithm to predict surgical outcome, based on the clinical factors of nuclear grading and ascitic fluid volume, plus the cancer biomarkers, kallikrein‑related peptidases (KLKs), KLK6 and KLK13. In the present study, OVSCORE performance was tested in an independent ovarian cancer patient cohort consisting of 87 patients. The impact of KLKs, KLK5, 6, 7 and 13 and other clinical factors on patient prognosis and outcome was also evaluated. The OVSCORE proved to be a strong and statistically significant predictor of surgical success in terms of area under the receiver operating characteristic curve (ROC AUC, 0.777), as well as positive and negative predictive value in this independent study group. KLK6 and 13 individually did not show clinical relevance in this cohort, but two other KLKs, KLK5 and KLK7, were associated with advanced FIGO stage, higher nuclear grade and positive lymph node status. In the multivariate Cox regression analysis for overall survival (OS), KLK7 had a protective impact on OS. This study confirms the role of KLKs in ovarian cancer for surgical success and survival, and validates the novel OVSCORE algorithm in an independent collective. As a key clinical application, the OVSCORE could aid gynecological oncologists in identifying those ovarian cancer patients unlikely to benefit from radical surgery who could be candidates for alternative therapeutic approaches.

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1	du Bois A, Reuss A, Pujade-Lauraine E, et al: Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: by the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d’Investigateurs Nationaux Pour les Etudes des Cancers de l’Ovaire (GINECO). Cancer. 115:1234–1244. 2009. View Article : Google Scholar : PubMed/NCBI
2	Buys SS, Partridge E, Black A, et al; PLCO Project Team. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA. 305:2295–2303. 2011. View Article : Google Scholar : PubMed/NCBI
3	Panici BP, Maggioni A, Hacker N, et al: Systematic aortic and pelvic lymphadenectomy versus resection of bulky nodes only in optimally debulked advanced ovarian cancer: a randomized clinical trial. J Natl Cancer Inst. 97:560–566. 2005. View Article : Google Scholar : PubMed/NCBI
4	Crawford SC, Vasey PA, Paul J, et al: Does aggressive surgery only benefit patients with less advanced ovarian cancer? Results from an international comparison within the SCOTROC-1 Trial. J Clin Oncol. 23:8802–8811. 2005. View Article : Google Scholar : PubMed/NCBI
5	Borley J, Wilhelm-Benartzi C, Brown R and Ghaem-Maghami S: Does tumour biology determine surgical success in the treatment of epithelial ovarian cancer? A systematic literature review. Br J Cancer. 107:1069–1074. 2012. View Article : Google Scholar : PubMed/NCBI
6	Dowdy SC, Mullany SA, Brandt KR, et al: The utility of computed tomography scans in predicting suboptimal cytoreductive surgery in women with advanced ovarian carcinoma. Cancer. 101:346–352. 2004. View Article : Google Scholar : PubMed/NCBI
7	Axtell AE, Lee MH, Bristow RE, et al: Multi-institutional reciprocal validation study of computed tomography predictors of suboptimal primary cytoreduction in patients with advanced ovarian cancer. J Clin Oncol. 25:384–389. 2007. View Article : Google Scholar : PubMed/NCBI
8	Dorn J, Schmitt M, Kates R, et al: Primary tumor levels of human tissue kallikreins affect surgical success and survival in ovarian cancer patients. Clin Cancer Res. 13:1742–1748. 2007. View Article : Google Scholar : PubMed/NCBI
9	Dorn J, Bayani J, Yousef GM, et al: Clinical utility of kallikrein-related peptidases (KLK) in urogenital malignancies. Thromb Haemost. 110:408–422. 2013. View Article : Google Scholar : PubMed/NCBI
10	Dorn J, Milou V, Kulasingam V, et al: Clinical relevance of kallikrein-related peptidases in ovarian cancer. Kallikrein-Related Peptidases. Novel Cancer-Related Biomarkers. Magdolen V, Sommerhoff CP, Fritz H and Schmitt M: 2. deGruyter; Berlin: pp. 145–166. 2012
11	Diamandis EP, Borgono CA, Scorilas A, et al: Immunofluorometric quantification of human kallikrein 5 expression in ovarian cancer cytosols and its association with unfavorable patient prognosis. Tumour Biol. 24:299–309. 2003. View Article : Google Scholar
12	Kim H, Scorilas A, Katsaros D, et al: Human kallikrein gene 5 (KLK5) expression is an indicator of poor prognosis in ovarian cancer. Br J Cancer. 84:643–650. 2001. View Article : Google Scholar : PubMed/NCBI
13	Hoffman BR, Katsaros D, Scorilas A, et al: Immunofluorometric quantitation and histochemical localisation of kallikrein 6 protein in ovarian cancer tissue: a new independent unfavourable prognostic biomarker. Br J Cancer. 87:763–771. 2002. View Article : Google Scholar : PubMed/NCBI
14	Seiz L, Dorn J, Kotzsch M, et al: Stromal cell-associated expression of kallikrein-related peptidase 6 (KLK6) indicates poor prognosis of ovarian cancer patients. Biol Chem. 393:391–401. 2012. View Article : Google Scholar : PubMed/NCBI
15	Dorn J, Gkazepis A, Kotzsch M, et al: Clinical value of protein expression of kallikrein-related peptidase 7 (KLK7) in ovarian cancer. Biol Chem. 395:95–107. 2014. View Article : Google Scholar
16	Scorilas A, Borgoño CA, Harbeck N, et al: Human kallikrein 13 protein in ovarian cancer cytosols: a new favorable prognostic marker. J Clin Oncol. 22:678–685. 2004. View Article : Google Scholar : PubMed/NCBI
17	Dorn J, Harbeck N, Kates R, et al: Disease processes may be reflected by correlations among tissue kallikrein proteases but not with proteolytic factors uPA and PAI-1 in primary ovarian carcinoma. Biol Chem. 387:1121–1128. 2006. View Article : Google Scholar : PubMed/NCBI
18	Christopoulos TK and Diamandis EP: Enzymatically amplified time-resolved fluorescence immunoassay with terbium chelates. Anal Chem. 64:342–346. 1992. View Article : Google Scholar : PubMed/NCBI
19	Shan SJ, Scorilas A, Katsaros D, et al: Unfavorable prognostic value of human kallikrein 7 quantified by ELISA in ovarian cancer cytosols. Clin Chem. 52:1879–1886. 2006. View Article : Google Scholar : PubMed/NCBI
20	Kyriakopoulou LG, Yousef GM, Scorilas A, et al: Prognostic value of quantitatively assessed KLK7 expression in ovarian cancer. Clin Biochem. 36:135–143. 2003. View Article : Google Scholar : PubMed/NCBI
21	Dorn J, Magdolen V, Gkazepis A, et al: Circulating biomarker tissue kallikrein-related peptidase KLK5 impacts ovarian cancer patients’ survival. Ann Oncol. 22:1783–1790. 2011. View Article : Google Scholar : PubMed/NCBI
22	Psyrri A, Kountourakis P, Scorilas A, et al: Human tissue kallikrein 7, a novel biomarker for advanced ovarian carcinoma using a novel in situ quantitative method of protein expression. Ann Oncol. 19:1271–1277. 2008. View Article : Google Scholar : PubMed/NCBI
23	Dong Y, Tan OL, Loessner D, et al: Kallikrein-related peptidase 7 promotes multicellular aggregation via the alpha(5)beta(1) integrin pathway and paclitaxel chemoresistance in serous epithelial ovarian carcinoma. Cancer Res. 70:2624–2633. 2010. View Article : Google Scholar : PubMed/NCBI
24	Oikonomopoulou K, Li L, Zheng Y, et al: Prediction of ovarian cancer prognosis and response to chemotherapy by a serum-based multiparametric biomarker panel. Br J Cancer. 99:1103–1113. 2008. View Article : Google Scholar : PubMed/NCBI
25	Borgono CA and Diamandis EP: The emerging roles of human tissue kallikreins in cancer. Nat Rev Cancer. 4:876–890. 2004. View Article : Google Scholar : PubMed/NCBI
26	Holzscheiter L, Biermann JC, Kotzsch M, et al: Quantitative reverse transcription-PCR assay for detection of mRNA encoding full-length human tissue kallikrein 7: prognostic relevance of KLK7 mRNA expression in breast cancer. Clin Chem. 52:1070–1079. 2006. View Article : Google Scholar : PubMed/NCBI
27	Talieri M, Diamandis EP, Gourgiotis D, et al: Expression analysis of the human kallikrein 7 (KLK7) in breast tumours: a new potential biomarker for prognosis of breast carcinoma. Thromb Haemost. 91:180–186. 2004.