Annals of Oncology Advance Access originally published online on March 5, 2008
Annals of Oncology 2008 19(7):1271-1277; doi:10.1093/annonc/mdn035
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gynecologic tumors |
Human tissue kallikrein 7, a novel biomarker for advanced ovarian carcinoma using a novel in situ quantitative method of protein expression
1 Department of Medical Oncology, Yale University School of Medicine, New Haven, CT 06520, USA
2 Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
3 Department of Pathology, University of Athens School of Medicine, Athens, Greece
4 Department of Pathology, Yale University School of Medicine, New Haven, USA
5 Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece
* Correspondence to: Dr A. Psyrri, Yale Cancer Center, PO Box 208032, New Haven, CT 06520, USA. Tel: +1-203-737-2476; Fax: +1-203-785-7531; E-mail: diamando.psyrri{at}yale.edu
Background: Kallikreins, a subgroup of the serine protease enzyme family, are considered important prognostic biomarkers in cancer. Here, we sought to determine the prognostic value of kallikrein 7 (hk7) in ovarian cancer using a novel method of compartmentalized in situ protein analysis.
Patients and methods: A tissue array composed of 150 advanced-stage ovarian cancers, uniformly treated with surgical debulking followed by platinum–paclitaxel (Taxol) combination chemotherapy, was constructed. For evaluation of kallikrein 7 protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis (AQUA).
Results: Mean follow-up time of the cohort was 34.35 months. One hundred and twenty eight of 150 cases had sufficient tissue for AQUA. In univariate survival analysis, low tumor hk7 expression was associated with better outcome for overall survival (OS) and disease-free survival in 3 years (P values 0.032 and 0.037, respectively). In multivariate survival analysis, adjusting for well-characterized prognostic variables, low tumor hk7 expression level was the most significant predictor variable for OS (95% confidence interval 0.125–0.729, P = 0.007).
Conclusions: High tumor hk7 protein expression is associated with inferior patient outcome in ovarian cancer. hk7 may represent a promising prognostic factor in ovarian cancer.
Key words: advanced ovarian cancer, AQUA, biomarker, hk7, prognosis
These authors contributed equally to this work. Received for publication June 14, 2007. Revision received December 10, 2007. Accepted for publication January 22, 2008.