title: Visual and automated assessment of matrix metalloproteinase-14 tissue expression for the evaluation of ovarian cancer prognosis.
abstract: The purpose of this study was to evaluate whether the membrane type 1 matrix metalloproteinase-14 (or MT1-MMP) tissue expression, as assessed visually on digital slides and by digital image analysis, could predict outcomes in women with ovarian carcinoma. Tissue microarrays from a cohort of 211 ovarian carcinoma women who underwent a debulking surgery between 1993 and 2006 at the CHU de Québec (Canada) were immunostained for matrix metalloproteinase-14. The percentage of MMP-14 staining was assessed visually and with the Calopix software. Progression was evaluated using the CA-125 and/or the RECIST criteria according to the GCIG criteria. Dates of death were obtained by record linkage with the Québec mortality files. Adjusted hazard ratios of death and progression with their 95% confidence intervals were estimated using the Cox model. Comparisons between the two modalities of MMP-14 assessment were done using the box plots and the Kruskal-Wallis test. The highest levels of MMP-14 immunostaining were associated with nonserous histology, early FIGO stage, and low preoperative CA-125 levels (P<0.05). In bivariate analyses, the higher level of MMP-14 expression (>40% of MMP-14-positive cells) was inversely associated with progression using visual assessment (hazard ratio=0.39; 95% confidence interval: 0.18-0.82). A similar association was observed with the highest quartile of MMP-14-positive area assessed by digital image analysis (hazard ratio=0.48; 95% confidence interval: 0.28-0.82). After adjustment for standard prognostic factors, these associations were no longer significant in the ovarian carcinoma cohort. However, in women with serous carcinoma, the highest quartile of MMP-14-positive area was associated with progression (adjusted hazard ratio=0.48; 95% confidence interval: 0.24-0.99). There was no association with overall survival. The digital image analysis of MMP-14-positive area matched the visual assessment using three categories (>40% vs 21-40 vs <20%). Higher levels of MMP-14 immunostaining were associated with standard factors of better ovarian carcinoma prognosis. In women with serous carcinoma, high expression of MMP-14 was associated with lower progression.
authors.affiliation: 1] Laval University Cancer Research Center and Research Center of the Centre Hospitalier Universitaire (CHU) de Québec, Québec, Canada [2] Department of Pathology/Applied Molecular Oncology, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Dominique
authors.initials: D
authors.lastname: Trudel
authors.affiliation: Anatomic Pathology and Cytology Department, Hôpital du St-Sacrement, Centre Hospitalier Universitaire (CHU) de Québec, Laval University, Québec, Canada.
authors.forename: Patrice
authors.initials: P
authors.lastname: Desmeules
authors.affiliation: Laval University Cancer Research Center and Research Center of the Centre Hospitalier Universitaire (CHU) de Québec, Québec, Canada.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Turcotte
authors.affiliation: 1] Laval University Cancer Research Center and Research Center of the Centre Hospitalier Universitaire (CHU) de Québec, Québec, Canada [2] Gynecologic Oncology Division, Centre Hospitalier Universitaire (CHU) de Québec, Québec, Canada.
authors.forename: Marie
authors.initials: M
authors.lastname: Plante
authors.affiliation: Gynecologic Oncology Division, Centre Hospitalier Universitaire (CHU) de Québec, Québec, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Grégoire
authors.affiliation: Gynecologic Oncology Division, Centre Hospitalier Universitaire (CHU) de Québec, Québec, Canada.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Renaud
authors.affiliation: Anatomic Pathology and Cytology Department, Hôpital du St-Sacrement, Centre Hospitalier Universitaire (CHU) de Québec, Laval University, Québec, Canada.
authors.forename: Michèle
authors.initials: M
authors.lastname: Orain
authors.affiliation: Laval University Cancer Research Center and Research Center of the Centre Hospitalier Universitaire (CHU) de Québec, Québec, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bairati
authors.affiliation: 1] Laval University Cancer Research Center and Research Center of the Centre Hospitalier Universitaire (CHU) de Québec, Québec, Canada [2] Anatomic Pathology and Cytology Department, Hôpital du St-Sacrement, Centre Hospitalier Universitaire (CHU) de Québec, Laval University, Québec, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Têtu
mesh_terms: D000328:Adult; D000368:Aged; D001331:Automation; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000201:enzymology / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D053511:Matrix Metalloproteinase 14 / Q000032:analysis / Q000096:biosynthesis*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14