Trudel Dominique, Desmeules Patrice, Turcotte Stéphane, Plante Marie, Grégoire Jean, Renaud Marie-Claude, Orain Michèle, Bairati Isabelle, Têtu Bernard
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.
Anatomic Pathology and Cytology Department, Hôpital du St-Sacrement, Centre Hospitalier Universitaire (CHU) de Québec, Laval University, Québec, Canada.
Mod Pathol. 2014 Oct;27(10):1394-404. doi: 10.1038/modpathol.2014.32. Epub 2014 Mar 7.
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.
本研究的目的是评估通过数字切片上的视觉评估和数字图像分析所测定的1型膜基质金属蛋白酶-14（MT1-MMP）组织表达，是否能够预测卵巢癌女性患者的预后。对1993年至2006年间在加拿大魁北克大学中心医院接受肿瘤细胞减灭术的211例卵巢癌女性患者的组织微阵列进行基质金属蛋白酶-14免疫染色。通过视觉评估和Calopix软件评估MMP-14染色的百分比。根据GCIG标准，使用CA-125和/或RECIST标准评估疾病进展情况。通过与魁北克省死亡率档案进行记录链接获取死亡日期。使用Cox模型估计死亡和进展的校正风险比及其95%置信区间。使用箱线图和Kruskal-Wallis检验对MMP-14评估的两种方式进行比较。MMP-14免疫染色的最高水平与非浆液性组织学、国际妇产科联盟（FIGO）早期分期以及术前低CA-125水平相关（P<0.05）。在双变量分析中，使用视觉评估时，较高水平的MMP-14表达（>40%的MMP-14阳性细胞）与疾病进展呈负相关（风险比=0.39；95%置信区间：0.18-0.82）。通过数字图像分析评估的MMP-14阳性面积的最高四分位数也观察到类似的相关性（风险比=0.48；95%置信区间：0.28-0.82）。在对标准预后因素进行校正后，这些相关性在卵巢癌队列中不再显著。然而，在浆液性癌女性患者中，MMP-14阳性面积的最高四分位数与疾病进展相关（校正风险比=0.48；95%置信区间：0.24-0.99）。与总生存期无相关性。MMP-14阳性面积的数字图像分析与使用三个类别（>40%对21%-40%对<20%）的视觉评估结果相符。较高水平的MMP-14免疫染色与卵巢癌较好预后的标准因素相关。在浆液性癌女性患者中，MMP-14的高表达与较低的疾病进展相关。
