Gagné Andréanne, Têtu Bernard, Orain Michèle, Turcotte Stéphane, Plante Marie, Grégoire Jean, Renaud Marie-Claude, Bairati Isabelle, Trudel Dominique
Laval University Cancer Research Center, Hôtel-Dieu-de-Québec, Centre Hospitalier Universitaire (CHU) de Québec, 11 Côte du Palais, Québec, Québec, G1R 2J6, Canada.
Anatomic Pathology and Cytology Department, Hôpital du St-Sacrement, Centre Hospitalier Universitaire (CHU) de Québec, Laval University, 1050 Chemin Ste-Foy, Québec, Québec, G1S 4L8, Canada.
Diagn Pathol. 2018 Aug 21;13(1):57. doi: 10.1186/s13000-018-0736-6.
The expression of high temperature requirement factor A1 (Htra1) has been reported to be decreased in ovarian carcinoma, but its prognostic effect remains undetermined.
We evaluated the impact of HtrA1 downregulation in tumoral tissues on cancer progression and death in women with serous ovarian carcinoma. HtrA1 staining was performed on tissue microarrays (TMA) comprised of tumor samples from a cohort of 106 women who were diagnosed with primary high-grade serous ovarian carcinoma and receiving standard treatment at the Québec University Hospital between 1993 and 2006. HtrA1 expression was assessed visually (percentage of positive nuclei) and by digital image analysis (percentage of positive area). Cox regression multivariate models included standard prognostic factors and were used to estimate adjusted hazard ratios (aHR) for progression or death in the cohort.
By visual analysis, a low percentage of HtrA1-positive nuclei (< 10% vs ≥10%) tend to be associated with a lower risk of progression (aHR = 0.71; 95% Confidence interval (CI) = 0.46-1.09; P = 0.11) and mortality (aHR = 0.65; 95% CI = 0.41-1.04; P = 0.07). Low nuclear HtrA1 expression assessed by digital image analysis (< median % vs ≥ median %) showed a significant association with lower risk of progression (aHR = 0.62; 95% CI = 0.40-0.95; p = 0.03) and death (aHR = 0.60; 95% CI = 0.38-0.95; p = 0.03).
Altogether, our results demonstrate that nuclear downregulation of HtrA1 is associated with a better prognosis in women with high grade serous ovarian carcinoma.
据报道，高温需求因子A1（Htra1）在卵巢癌中的表达降低，但其预后作用仍未确定。
我们评估了肿瘤组织中HtrA1下调对浆液性卵巢癌女性患者癌症进展和死亡的影响。对组织微阵列（TMA）进行HtrA1染色，该组织微阵列由1993年至2006年间在魁北克大学医院被诊断为原发性高级别浆液性卵巢癌并接受标准治疗的106名女性的肿瘤样本组成。通过视觉评估（阳性细胞核百分比）和数字图像分析（阳性面积百分比）来评估HtrA1表达。Cox回归多变量模型纳入了标准预后因素，并用于估计该队列中进展或死亡的调整风险比（aHR）。
通过视觉分析，HtrA1阳性细胞核百分比低（<10% 对比≥10%）往往与较低的进展风险（aHR = 0.71；95%置信区间（CI）= 0.46 - 1.09；P = 0.11）和死亡率（aHR = 0.65；95% CI = 0.41 - 1.04；P = 0.07）相关。通过数字图像分析评估的低核HtrA1表达（<中位数百分比对比≥中位数百分比）显示与较低的进展风险（aHR = 0.62；95% CI = 0.40 - 0.95；p = 0.03）和死亡风险（aHR = 0.60；95% CI = 0.38 - 0.95；p = 0.03）显著相关。
总体而言，我们的结果表明，HtrA1的核下调与高级别浆液性卵巢癌女性患者的较好预后相关。
