Abstract
BackgroundThe expression of high temperature requirement factor A1 (Htra1) has been reported to be decreased in ovarian carcinoma, but its prognostic effect remains undetermined.MethodsWe 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.ResultsBy 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).ConclusionAltogether, our results demonstrate that nuclear downregulation of HtrA1 is associated with a better prognosis in women with high grade serous ovarian carcinoma.
Highlights
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 have previously shown that many matrix metalloproteinases (MMPs) are associated with the prognosis of ovarian carcinoma [5,6,7]
Immunohistochemistry We demonstrated that the anti-high temperature requirement factor A1 (HtrA1) antibody was specific (Fig. 2)
Summary
The expression of high temperature requirement factor A1 (Htra1) has been reported to be decreased in ovarian carcinoma, but its prognostic effect remains undetermined. Ovarian carcinoma is the second most frequent neoplasm of the female genital system [1, 2]. In the United States, ovarian carcinoma was the most lethal neoplasm of the female genital system in 2017 [3]. We have previously shown that many matrix metalloproteinases (MMPs) are associated with the prognosis of ovarian carcinoma [5,6,7]. Apart from MMPs, other proteases have been proposed for prognostic potential in ovarian carcinoma. The protease high temperature requirement factor A1 (HtrA1) is expressed in the vast majority of healthy tissues in the human body, including gynecologic tissues and the ovary [8].
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