HtrA1 expression and the prognosis of high-grade serous ovarian carcinoma: a cohort study using digital analysis

HtrA1 表达与高级别浆液性卵巢癌的预后:一项使用数字分析的队列研究

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作者:Andréanne Gagné, Bernard Têtu, Michèle Orain, Stéphane Turcotte, Marie Plante, Jean Grégoire, Marie-Claude Renaud, Isabelle Bairati, Dominique Trudel

Background

The expression of high temperature requirement factor A1 (Htra1) has been reported to be decreased in ovarian carcinoma, but its prognostic effect remains undetermined.

Conclusion

Altogether, our results demonstrate that nuclear downregulation of HtrA1 is associated with a better prognosis in women with high grade serous ovarian carcinoma.

Methods

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.

Results

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).

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