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Thromb Haemost 2009; 101(03): 541-546
DOI: 10.1160/TH08-01-0052
Cellular Proteolysis and Oncology
Schattauer GmbH

Expression and prognostic significance of kallikrein-related peptidase 8 protein levels in advanced ovarian cancer by using automated quantitative analysis

Panteleimon Kountourakis   *
1   Department of Medical Oncology, Yale University, School of Medicine, New Haven, Connecticut, USA
,
Amanda Psyrri   *
1   Department of Medical Oncology, Yale University, School of Medicine, New Haven, Connecticut, USA
,
Andreas Scorilas
2   Department of Biology, University of Athens, School of Medicine, Athens, Greece
,
Sonia Markakis
3   Department of Pathology; University of Athens, School of Medicine, Athens, Greece
,
Diane Kowalski
4   Department of Pathology, Yale University, School of Medicine, New Haven, Connecticut, USA
,
Robert L. Camp
4   Department of Pathology, Yale University, School of Medicine, New Haven, Connecticut, USA
,
Eleftherios P. Diamandis
5   Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
,
Meletios A. Dimopoulos
6   Department of Clinical Therapeutics, University of Athens, School of Medicine, Athens, Greece
› Author Affiliations
Further Information

Publication History

Received: 26 January 2008

Accepted after major revision: 02 January 2008

Publication Date:
24 November 2017 (online)

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Summary

Kallikrein-related peptidases, a subgroup of the serine protease enzyme family, are considered to be important prognostic biomarkers in cancer. In this study we sought to determine the prognostic value of kallikrein-related peptidase 8 (KLK8,hK8,KLK-8) in ovarian cancer using a novel method of compartmentalised in situ protein analysis. A tissue array composed of 150 advanced stage ovarian cancers, uniformly treated with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For the evaluation of kallikrein-related peptidase 8 protein expression, we used an immunofluorescence-based method of automated in situ quantitative protein analysis (AQUA). Mean follow-up time of the cohort was 34.35 months. One hundred twenty-six of 150 cases had sufficient tissue for AQUA analysis. There were significant correlations between tumour mask KLK8 protein expression levels and clinicopathological variables, including grade (p=0.0011), residual disease (p=0.0063) and clinical response to chemotherapy(p=0.0346). In univariate survival analysis there was a significant correlation between KLK8 tumour mask expression and five years progression-free survival, meanwhile it was not associated with five-year overall survival (p =0.0694). Specifically, low KLK8 expression correlated with better outcome (top vs. bottom quartile, p=0.0319). In multivariate survival analysis, adjusting for well-characterised prognostic variables, tumour KLK8 expression level retained its prognostic significance for progression-free survival (95%CI: 0.341–1.027, p=0.045). The possibility that KLK8 may be a suitable candidate as a diagnostic and prognostic marker warrants further investigation.

Keywords

Kallikrein-related peptidase 8 - AQUA - advanced ovarian cancer - prognosis

* These authors contributed equally to this paper.


 

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