HtrA1 expression and the prognosis of high-grade serous ovarian carcinoma: a cohort study using digital analysis
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. Methods We evaluated the impact of HtrA1 downregulation in tumoral tissues on cancer progression and death in women with...
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| Published in | Diagnostic pathology Vol. 13; no. 1; pp. 57 - 9 |
|---|---|
| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
BioMed Central
21.08.2018
BioMed Central Ltd BMC |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1746-1596 1746-1596 |
| DOI | 10.1186/s13000-018-0736-6 |
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| Abstract | 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.
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).
Conclusion
Altogether, our results demonstrate that nuclear downregulation of HtrA1 is associated with a better prognosis in women with high grade serous ovarian carcinoma. |
|---|---|
| AbstractList | 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. 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 [greater than or equai to]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 [greater than or equai to] 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). Conclusion Altogether, our results demonstrate that nuclear downregulation of HtrA1 is associated with a better prognosis in women with high grade serous ovarian carcinoma. Keywords: Ovarian high grade serous carcinoma, High temperature requirement factor A1, Immunohistochemistry, Digital image analysis, Prognosis 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. 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). Conclusion Altogether, our results demonstrate that nuclear downregulation of HtrA1 is associated with a better prognosis in women with high grade serous ovarian carcinoma. 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. 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. 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). Conclusion Altogether, our results demonstrate that nuclear downregulation of HtrA1 is associated with a better prognosis in women with high grade serous ovarian carcinoma. 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 [greater than or equai to]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 [greater than or equai to] 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. Abstract 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. 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). Conclusion Altogether, our results demonstrate that nuclear downregulation of HtrA1 is associated with a better prognosis in women with high grade serous ovarian carcinoma. The expression of high temperature requirement factor A1 (Htra1) has been reported to be decreased in ovarian carcinoma, but its prognostic effect remains undetermined.BACKGROUNDThe 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.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.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).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).Altogether, our results demonstrate that nuclear downregulation of HtrA1 is associated with a better prognosis in women with high grade serous ovarian carcinoma.CONCLUSIONAltogether, our results demonstrate that nuclear downregulation of HtrA1 is associated with a better prognosis in women with high grade serous ovarian carcinoma. |
| ArticleNumber | 57 |
| Audience | Academic |
| Author | Renaud, Marie-Claude Gagné, Andréanne Têtu, Bernard Bairati, Isabelle Plante, Marie Trudel, Dominique Orain, Michèle Turcotte, Stéphane Grégoire, Jean |
| Author_xml | – sequence: 1 givenname: Andréanne surname: Gagné fullname: Gagné, Andréanne organization: Laval University Cancer Research Center, Hôtel-Dieu-de-Québec, Centre Hospitalier Universitaire (CHU) de Québec – sequence: 2 givenname: Bernard surname: Têtu fullname: Têtu, Bernard email: bernard.tetu@fmed.ulaval.ca organization: Laval University Cancer Research Center, Hôtel-Dieu-de-Québec, Centre Hospitalier Universitaire (CHU) de Québec, Anatomic Pathology and Cytology Department, Hôpital du St-Sacrement, Centre Hospitalier Universitaire (CHU) de Québec, Laval University, Department of Pathology, Hôpital du St-Sacrement, Centre Hospitalier Universitaire de Québec – sequence: 3 givenname: Michèle surname: Orain fullname: Orain, Michèle organization: Laval University Cancer Research Center, Hôtel-Dieu-de-Québec, Centre Hospitalier Universitaire (CHU) de Québec, Anatomic Pathology and Cytology Department, Hôpital du St-Sacrement, Centre Hospitalier Universitaire (CHU) de Québec, Laval University – sequence: 4 givenname: Stéphane surname: Turcotte fullname: Turcotte, Stéphane organization: Laval University Cancer Research Center, Hôtel-Dieu-de-Québec, Centre Hospitalier Universitaire (CHU) de Québec – sequence: 5 givenname: Marie surname: Plante fullname: Plante, Marie organization: Laval University Cancer Research Center, Hôtel-Dieu-de-Québec, Centre Hospitalier Universitaire (CHU) de Québec, Gynecologic Oncology Division, Centre Hospitalier Universitaire (CHU) de Québec, L’Hôtel-Dieu-de-Québec – sequence: 6 givenname: Jean surname: Grégoire fullname: Grégoire, Jean organization: Laval University Cancer Research Center, Hôtel-Dieu-de-Québec, Centre Hospitalier Universitaire (CHU) de Québec, Gynecologic Oncology Division, Centre Hospitalier Universitaire (CHU) de Québec, L’Hôtel-Dieu-de-Québec – sequence: 7 givenname: Marie-Claude surname: Renaud fullname: Renaud, Marie-Claude organization: Laval University Cancer Research Center, Hôtel-Dieu-de-Québec, Centre Hospitalier Universitaire (CHU) de Québec, Gynecologic Oncology Division, Centre Hospitalier Universitaire (CHU) de Québec, L’Hôtel-Dieu-de-Québec – sequence: 8 givenname: Isabelle surname: Bairati fullname: Bairati, Isabelle organization: Laval University Cancer Research Center, Hôtel-Dieu-de-Québec, Centre Hospitalier Universitaire (CHU) de Québec – sequence: 9 givenname: Dominique surname: Trudel fullname: Trudel, Dominique organization: Laval University Cancer Research Center, Hôtel-Dieu-de-Québec, Centre Hospitalier Universitaire (CHU) de Québec, Department of Pathology, Hôpital Saint-Luc, Centre Hospitalier Universitaire de Montréal, The Research Centre of the University of Montreal Teaching Hospital (CR-CHUM)/Montreal Cancer Institute, Department of Pathology and Cellular Biology, University of Montreal |
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| Keywords | Immunohistochemistry Ovarian high grade serous carcinoma Prognosis Digital image analysis High temperature requirement factor A1 |
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The expression of high temperature requirement factor A1 (Htra1) has been reported to be decreased in ovarian carcinoma, but its prognostic effect... The expression of high temperature requirement factor A1 (Htra1) has been reported to be decreased in ovarian carcinoma, but its prognostic effect remains... Background The expression of high temperature requirement factor A1 (Htra1) has been reported to be decreased in ovarian carcinoma, but its prognostic effect... Abstract Background The expression of high temperature requirement factor A1 (Htra1) has been reported to be decreased in ovarian carcinoma, but its prognostic... |
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| SubjectTerms | Aged Apoptosis Biomarkers, Tumor - analysis Cancer therapies Cell Nucleus - chemistry Cell Nucleus - pathology Chemotherapy Clinical trials Cohort analysis Cohort Studies Confidence intervals Death Diagnosis Digital image analysis Digital imaging Down-Regulation Female Gene expression Genetic aspects Gynecology High temperature High temperature requirement factor A1 High-Temperature Requirement A Serine Peptidase 1 - analysis Humans Image analysis Image Interpretation, Computer-Assisted Image processing Immunohistochemistry Medical prognosis Medicine Medicine & Public Health Middle Aged Mortality Neoplasm Grading Neoplasms, Cystic, Mucinous, and Serous - chemistry Neoplasms, Cystic, Mucinous, and Serous - mortality Neoplasms, Cystic, Mucinous, and Serous - pathology Neoplasms, Cystic, Mucinous, and Serous - therapy Nuclei Ovarian cancer Ovarian carcinoma Ovarian high grade serous carcinoma Ovarian Neoplasms - chemistry Ovarian Neoplasms - mortality Ovarian Neoplasms - pathology Ovarian Neoplasms - therapy Pathology Predictive Value of Tests Prognosis Proteins Regression analysis Risk Assessment Risk Factors Statistical analysis Temperature requirements Time Factors Tissue Array Analysis Treatment Outcome Tumors Womens health |
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| Title | HtrA1 expression and the prognosis of high-grade serous ovarian carcinoma: a cohort study using digital analysis |
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