Improving the Diagnosis of Endometrial Hyperplasia Using Computerized Analysis and Immunohistochemical Biomarkers

Endometrial hyperplasia (EH) is a precursor lesion to endometrial carcinoma (EC). Risks for EC include genetic, hormonal and metabolic factors most notably those associated with obesity: rates are rising and there is concern that cases in pre-menopausal women may remain undetected. Making an accurat...

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Main Authors: Peter A. Sanderson, Arantza Esnal-Zufiaurre, Mark J. Arends, C. Simon Herrington, Frances Collins, Alistair R. W. Williams, Philippa T. K. Saunders
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-05-01
Series:Frontiers in Reproductive Health
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/frph.2022.896170/full
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author Peter A. Sanderson
Peter A. Sanderson
Arantza Esnal-Zufiaurre
Mark J. Arends
C. Simon Herrington
Frances Collins
Alistair R. W. Williams
Philippa T. K. Saunders
author_facet Peter A. Sanderson
Peter A. Sanderson
Arantza Esnal-Zufiaurre
Mark J. Arends
C. Simon Herrington
Frances Collins
Alistair R. W. Williams
Philippa T. K. Saunders
author_sort Peter A. Sanderson
collection DOAJ
description Endometrial hyperplasia (EH) is a precursor lesion to endometrial carcinoma (EC). Risks for EC include genetic, hormonal and metabolic factors most notably those associated with obesity: rates are rising and there is concern that cases in pre-menopausal women may remain undetected. Making an accurate distinction between benign and pre-malignant disease is both a challenge for the pathologist and important to the gynecologist who wants to deliver the most appropriate care to meet the needs of the patient. Premalignant change may be recognized by histological changes of endometrial hyperplasia (which may occur with or without atypia) and endometrial intraepithelial neoplasia (EIN). In this study we created a tissue resource of EH samples diagnosed between 2004 and 2009 (n = 125) and used this to address key questions: 1. Are the EIN/WHO2014 diagnostic criteria able to consistently identify premalignant endometrium? 2. Can computer aided image analysis inform identification of EIN? 3. Can we improve diagnosis by incorporating analysis of protein expression using immunohistochemistry. Our findings confirmed the inclusion of EIN in diagnostic criteria resulted in a better agreement between expert pathologists compared with the previous WHO94 criteria used for the original diagnosis of our sample set. A computer model based on assessment of stromal:epithelial ratio appeared most accurate in classification of areas of tissue without EIN. From an extensive panel of putative endometrial protein tissue biomarkers a score based on assessment of HAND2, PTEN, and PAX2 was able to identify four clusters one of which appeared to be more likely to be benign. In summary, our study has highlighted new opportunities to improve diagnosis of pre-malignant disease in endometrium and provide a platform for further research on this important topic.
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spelling doaj.art-3c61bc981068438db06b32f45a04921e2022-12-22T00:38:42ZengFrontiers Media S.A.Frontiers in Reproductive Health2673-31532022-05-01410.3389/frph.2022.896170896170Improving the Diagnosis of Endometrial Hyperplasia Using Computerized Analysis and Immunohistochemical BiomarkersPeter A. Sanderson0Peter A. Sanderson1Arantza Esnal-Zufiaurre2Mark J. Arends3C. Simon Herrington4Frances Collins5Alistair R. W. Williams6Philippa T. K. Saunders7Centre for Inflammation Research, Edinburgh Bioquarter, The University of Edinburgh, Edinburgh, United KingdomCancer Research UK Edinburgh Centre, Institute of Genetics and Cancer, Western General Hospital, The University of Edinburgh, Edinburgh, United KingdomCentre for Inflammation Research, Edinburgh Bioquarter, The University of Edinburgh, Edinburgh, United KingdomCancer Research UK Edinburgh Centre, Institute of Genetics and Cancer, Western General Hospital, The University of Edinburgh, Edinburgh, United KingdomCancer Research UK Edinburgh Centre, Institute of Genetics and Cancer, Western General Hospital, The University of Edinburgh, Edinburgh, United KingdomCentre for Inflammation Research, Edinburgh Bioquarter, The University of Edinburgh, Edinburgh, United KingdomDepartment of Pathology, Edinburgh BioQuarter, Royal Infirmary of Edinburgh, Edinburgh, United KingdomCentre for Inflammation Research, Edinburgh Bioquarter, The University of Edinburgh, Edinburgh, United KingdomEndometrial hyperplasia (EH) is a precursor lesion to endometrial carcinoma (EC). Risks for EC include genetic, hormonal and metabolic factors most notably those associated with obesity: rates are rising and there is concern that cases in pre-menopausal women may remain undetected. Making an accurate distinction between benign and pre-malignant disease is both a challenge for the pathologist and important to the gynecologist who wants to deliver the most appropriate care to meet the needs of the patient. Premalignant change may be recognized by histological changes of endometrial hyperplasia (which may occur with or without atypia) and endometrial intraepithelial neoplasia (EIN). In this study we created a tissue resource of EH samples diagnosed between 2004 and 2009 (n = 125) and used this to address key questions: 1. Are the EIN/WHO2014 diagnostic criteria able to consistently identify premalignant endometrium? 2. Can computer aided image analysis inform identification of EIN? 3. Can we improve diagnosis by incorporating analysis of protein expression using immunohistochemistry. Our findings confirmed the inclusion of EIN in diagnostic criteria resulted in a better agreement between expert pathologists compared with the previous WHO94 criteria used for the original diagnosis of our sample set. A computer model based on assessment of stromal:epithelial ratio appeared most accurate in classification of areas of tissue without EIN. From an extensive panel of putative endometrial protein tissue biomarkers a score based on assessment of HAND2, PTEN, and PAX2 was able to identify four clusters one of which appeared to be more likely to be benign. In summary, our study has highlighted new opportunities to improve diagnosis of pre-malignant disease in endometrium and provide a platform for further research on this important topic.https://www.frontiersin.org/articles/10.3389/frph.2022.896170/fullendometrial hyperplasiaintraepithelial neoplasiacarcinomaHAND2stromal to epithelial ratio
spellingShingle Peter A. Sanderson
Peter A. Sanderson
Arantza Esnal-Zufiaurre
Mark J. Arends
C. Simon Herrington
Frances Collins
Alistair R. W. Williams
Philippa T. K. Saunders
Improving the Diagnosis of Endometrial Hyperplasia Using Computerized Analysis and Immunohistochemical Biomarkers
Frontiers in Reproductive Health
endometrial hyperplasia
intraepithelial neoplasia
carcinoma
HAND2
stromal to epithelial ratio
title Improving the Diagnosis of Endometrial Hyperplasia Using Computerized Analysis and Immunohistochemical Biomarkers
title_full Improving the Diagnosis of Endometrial Hyperplasia Using Computerized Analysis and Immunohistochemical Biomarkers
title_fullStr Improving the Diagnosis of Endometrial Hyperplasia Using Computerized Analysis and Immunohistochemical Biomarkers
title_full_unstemmed Improving the Diagnosis of Endometrial Hyperplasia Using Computerized Analysis and Immunohistochemical Biomarkers
title_short Improving the Diagnosis of Endometrial Hyperplasia Using Computerized Analysis and Immunohistochemical Biomarkers
title_sort improving the diagnosis of endometrial hyperplasia using computerized analysis and immunohistochemical biomarkers
topic endometrial hyperplasia
intraepithelial neoplasia
carcinoma
HAND2
stromal to epithelial ratio
url https://www.frontiersin.org/articles/10.3389/frph.2022.896170/full
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