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Integration of computer-aided automated analysis algorithms in the development and validation of immunohistochemistry biomarkers in ovarian cancer
  1. Lucy Gentles1,
  2. Rachel Howarth1,
  3. Won Ji Lee1,
  4. Sweta Sharma-Saha1,
  5. Angela Ralte2,
  6. Nicola Curtin1,
  7. Yvette Drew1,3,
  8. Rachel Louise O'Donnell1,4
  1. 1 Translational and Clinical Institute, Newcastle Cancer Centre, Newcastle upon Tyne, UK
  2. 2 Department of Pathology, Queen Elizabeth Hospital Gateshead, Gateshead, UK
  3. 3 Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne, Newcastle upon Tyne, UK
  4. 4 Northern Centre for Gynaecological Surgery, Royal Victoria Infirmary, Newcastle upon Tyne, Newcastle upon Tyne, UK
  1. Correspondence to Dr Rachel Louise O'Donnell, Translational and Clinical Institute, Newcastle Cancer Centre, Newcastle upon Tyne, UK; rachel.o%E2%80%99donnell{at}


In an era when immunohistochemistry (IHC) is increasingly depended on for histological subtyping, and IHC-determined biomarker informing rapid treatment choices is on the horizon; reproducible, quantifiable techniques are required. This study aimed to compare automated IHC scoring to quantify 6 DNA damage response protein markers using a tissue microarray of 66 ovarian cancer samples. Accuracy of quantification was compared between manual H-score and computer-aided quantification using Aperio ImageScope with and without a tissue classification algorithm. High levels of interobserver variation was seen with manual scoring. With automated methods, inclusion of the tissue classifier mask resulted in greater accuracy within carcinomatous areas and an overall increase in H-score of a median of 11.5% (0%–18%). Without the classifier, the score was underestimated by a median of 10.5 (5.2–25.6). Automated methods are reliable and superior to manual scoring. Fixed algorithms offer the reproducibility needed for high-throughout clinical applications.

  • ovary
  • carcinoma
  • antibodies
  • cell biology
  • immunohistochemistry

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  • Handling editor Runjan Chetty.

  • Contributors LG acquired laboratory data, devised methodologies, curated data, undertook formal analysis, drafted and revised the manuscript; RH acquired laboratory data and devised methodologies; WJL acquired laboratory data; SS-S contributed to data analysis; AR acquired clinical data and devised methodologies; NC revised and provided final approval of manuscript; YD recruited participants, acquired clinical data and revised the manuscript; RLO recruited participants, acquired clinical data, undertook formal analysis, drafted, and revised and the manuscript, and provided final approval of the manuscript. RLO has full access to the data in the study and is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

  • Funding Work in this study was funded by the Newcastle uponon Tyne Hospitals NHS Charity (registered charity number 1057213).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.