Human tissue kallikrein 7, a novel biomarker for advanced ovarian carcinoma using a novel in situ quantitative method of protein expression.
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.


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.
Psyrri
A
A
Department of Medical Oncology, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: diamando.psyrri@yale.edu.
Kountourakis
P
P
Department of Medical Oncology, Yale University School of Medicine, New Haven, CT 06520, USA.
Scorilas
A
A
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
Markakis
S
S
Department of Pathology, University of Athens School of Medicine, Athens, Greece.
Camp
R
R
Department of Pathology, Yale University School of Medicine, New Haven, USA.
Diamandis
E P
EP
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
Dimopoulos
M A
MA
Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece.
Kowalski
D
D
D001331:Automation; D014408:Biomarkers, Tumor / Q000378:metabolism; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes / Q000378:metabolism; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007211:Indoles / Q000378:metabolism; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D005456:Fluorescent Dyes; D007211:Indoles; C007293:DAPI; C082472:KLK7 protein, human; D007610:Kallikreins