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Howat WJ, Blows FM, Provenzano E, et al. Performance of automated scoring of ER, PR, HER2, CK5/6 and EGFR in breast cancer tissue microarrays in the Breast Cancer Association Consortium. J Pathol Clin Res. 2014;1(1):18-32doi: 10.1002/cjp2.3.
Howat, W. J., Blows, F. M., Provenzano, E., Brook, M. N., Morris, L., Gazinska, P., Johnson, N., McDuffus, L. A., Miller, J., Sawyer, E. J., Pinder, S., van Deurzen, C. H., Jones, L., Sironen, R., Visscher, D., Caldas, C., Daley, F., Coulson, P., Broeks, A., Sanders, J., Wesseling, J., Nevanlinna, H., Fagerholm, R., Blomqvist, C., Heikkilä, P., Ali, H. R., Dawson, S. J., Figueroa, J., Lissowska, J., Brinton, L., Mannermaa, A., Kataja, V., Kosma, V. M., Cox, A., Brock, I. W., Cross, S. S., Reed, M. W., Couch, F. J., Olson, J. E., Devillee, P., Mesker, W. E., Seyaneve, C. M., Hollestelle, A., Benitez, J., Perez, J. I., Menéndez, P., Bolla, M. K., Easton, D. F., Schmidt, M. K., Pharoah, P. D., Sherman, M. E., & García-Closas, M. (2015). Performance of automated scoring of ER, PR, HER2, CK5/6 and EGFR in breast cancer tissue microarrays in the Breast Cancer Association Consortium. The journal of pathology. Clinical research, 1(1), 18-32. https://doi.org/10.1002/cjp2.3
Howat, William J, et al. "Performance of automated scoring of ER, PR, HER2, CK5/6 and EGFR in breast cancer tissue microarrays in the Breast Cancer Association Consortium." The journal of pathology. Clinical research vol. 1,1 (2015): 18-32. doi: https://doi.org/10.1002/cjp2.3
Howat WJ, Blows FM, Provenzano E, Brook MN, Morris L, Gazinska P, Johnson N, McDuffus LA, Miller J, Sawyer EJ, Pinder S, van Deurzen CH, Jones L, Sironen R, Visscher D, Caldas C, Daley F, Coulson P, Broeks A, Sanders J, Wesseling J, Nevanlinna H, Fagerholm R, Blomqvist C, Heikkilä P, Ali HR, Dawson SJ, Figueroa J, Lissowska J, Brinton L, Mannermaa A, Kataja V, Kosma VM, Cox A, Brock IW, Cross SS, Reed MW, Couch FJ, Olson JE, Devillee P, Mesker WE, Seyaneve CM, Hollestelle A, Benitez J, Perez JI, Menéndez P, Bolla MK, Easton DF, Schmidt MK, Pharoah PD, Sherman ME, García-Closas M. Performance of automated scoring of ER, PR, HER2, CK5/6 and EGFR in breast cancer tissue microarrays in the Breast Cancer Association Consortium. J Pathol Clin Res. 2014 Dec 04;1(1):18-32. doi: 10.1002/cjp2.3. eCollection 2015 Jan. PMID: 27499890; PMCID: PMC4858117.
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J Pathol Clin Res. 2014 Dec 04;1(1):18-32. doi: 10.1002/cjp2.3. eCollection 2015 Jan.

Performance of automated scoring of ER, PR, HER2, CK5/6 and EGFR in breast cancer tissue microarrays in the Breast Cancer Association Consortium.

The journal of pathology. Clinical research

William J Howat, Fiona M Blows, Elena Provenzano, Mark N Brook, Lorna Morris, Patrycja Gazinska, Nicola Johnson, Leigh-Anne McDuffus, Jodi Miller, Elinor J Sawyer, Sarah Pinder, Carolien H M van Deurzen, Louise Jones, Reijo Sironen, Daniel Visscher, Carlos Caldas, Frances Daley, Penny Coulson, Annegien Broeks, Joyce Sanders, Jelle Wesseling, Heli Nevanlinna, Rainer Fagerholm, Carl Blomqvist, Päivi Heikkilä, H Raza Ali, Sarah-Jane Dawson, Jonine Figueroa, Jolanta Lissowska, Louise Brinton, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Angela Cox, Ian W Brock, Simon S Cross, Malcolm W Reed, Fergus J Couch, Janet E Olson, Peter Devillee, Wilma E Mesker, Caroline M Seyaneve, Antoinette Hollestelle, Javier Benitez, Jose Ignacio Arias Perez, Primitiva Menéndez, Manjeet K Bolla, Douglas F Easton, Marjanka K Schmidt, Paul D Pharoah, Mark E Sherman, Montserrat García-Closas

Affiliations

  1. Cancer Research UK Cambridge Institute, University of Cambridge Cambridge UK.
  2. Centre for Cancer Genetic Epidemiology, Department of Oncology University of Cambridge Cambridge UK.
  3. Breast Pathology Addenbrookes Hospital Cambridge UK.
  4. Division of Genetics and Epidemiology The Institute of Cancer Research London UK.
  5. Cancer Research UK Cambridge Institute, University of CambridgeCambridgeUK; Department of OncologyUniversity of CambridgeCambridgeUK.
  6. Breakthrough Breast Cancer Research Unit, Division of Cancer Studies King's College London, Guy's Hospital London UK.
  7. Division of Cancer Studies, NIHR Comprehensive Biomedical Research Centre Guy's & St. Thomas' NHS Foundation Trust in partnership with King's College London London UK.
  8. Research Oncology, Division of Cancer Studies King's College London, Guy's Hospital London UK.
  9. Department of Pathology Erasmus University Medical Center Rotterdam The Netherlands.
  10. Centre for Tumour BiologyBarts Institute of CancerBartsUK; The London School of Medicine and DentistryLondonUK.
  11. School of Medicine, Institute of Clinical Medicine, Pathology and Forensic MedicineCancer Center of Eastern Finland, University of Eastern FinlandKuopioFinland; Imaging Center, Department of Clinical PathologyKuopio University HospitalKuopioFinland.
  12. Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN USA.
  13. Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research The Institute of Cancer Research London UK.
  14. Core Facility for Molecular Pathology and Biobanking Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital Amsterdam The Netherlands.
  15. Department of Pathology, Division of Diagnostic Oncology Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital Amsterdam The Netherlands.
  16. Department of Obstetrics and Gynecology University of Helsinki and Helsinki University Central Hospital Helsinki Finland.
  17. Department of Oncology Helsinki University Central Hospital Helsinki Finland.
  18. Department of Pathology Helsinki University Central Hospital Helsinki Finland.
  19. Division of Cancer Epidemiology and Genetics National Cancer Institute Rockville Maryland USA.
  20. Department of Cancer Epidemiology and Prevention M. Sklodowska-Curie Memorial Cancer Center & Institute of Oncology Warsaw Poland.
  21. Kuopio University Hospital, Cancer CenterKuopioFinland; School of Medicine, Institute of Clinical MedicineUniversity of Eastern Finland, Oncology and Central Hospital of Central Finland, Central Finland Hospital DistrictKuopioFinland.
  22. CRUK/YCR Sheffield Cancer Research Centre, Department of Oncology University of Sheffield Sheffield UK.
  23. Academic Unit of Pathology, Department of Neuroscience University of Sheffield Sheffield UK.
  24. Department of Health Sciences Research Mayo Clinic Rochester MN USA.
  25. Department of Human Genetics & Department of Pathology Leiden University Medical Center Leiden The Netherlands.
  26. Department of Surgical Oncology Leiden University Medical Center RC Leiden The Netherlands.
  27. Family Cancer Clinic, Department of Medical Oncology Erasmus MC Cancer Institute Rotterdam The Netherlands.
  28. Human Genetics Group, Human Cancer Genetics ProgramSpanish National Cancer Research Centre (CNIO)MadridSpain; Centro de Investigación en Red de Enfermedades Raras (CIBERER)ValenciaSpain.
  29. Servicio de Cirugía General y Especialidades Hospital Monte Naranco Oviedo Spain.
  30. Servicio de Anatomía Patológica Hospital Monte Naranco Oviedo Spain.
  31. Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care University of Cambridge Cambridge UK.
  32. Centre for Cancer Genetic Epidemiology, Department of OncologyUniversity of CambridgeCambridgeUK; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary CareUniversity of CambridgeCambridgeUK.
  33. Division of Molecular Pathology Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital Amsterdam The Netherlands.
  34. Division of Genetics and EpidemiologyThe Institute of Cancer ResearchLondonUK; Breakthrough Breast Cancer Research Centre, Division of Breast Cancer ResearchThe Institute of Cancer ResearchLondonUK.

PMID: 27499890 PMCID: PMC4858117 DOI: 10.1002/cjp2.3

Abstract

Breast cancer risk factors and clinical outcomes vary by tumour marker expression. However, individual studies often lack the power required to assess these relationships, and large-scale analyses are limited by the need for high throughput, standardized scoring methods. To address these limitations, we assessed whether automated image analysis of immunohistochemically stained tissue microarrays can permit rapid, standardized scoring of tumour markers from multiple studies. Tissue microarray sections prepared in nine studies containing 20 263 cores from 8267 breast cancers stained for two nuclear (oestrogen receptor, progesterone receptor), two membranous (human epidermal growth factor receptor 2 and epidermal growth factor receptor) and one cytoplasmic (cytokeratin 5/6) marker were scanned as digital images. Automated algorithms were used to score markers in tumour cells using the Ariol system. We compared automated scores against visual reads, and their associations with breast cancer survival. Approximately 65-70% of tissue microarray cores were satisfactory for scoring. Among satisfactory cores, agreement between dichotomous automated and visual scores was highest for oestrogen receptor (Kappa = 0.76), followed by human epidermal growth factor receptor 2 (Kappa = 0.69) and progesterone receptor (Kappa = 0.67). Automated quantitative scores for these markers were associated with hazard ratios for breast cancer mortality in a dose-response manner. Considering visual scores of epidermal growth factor receptor or cytokeratin 5/6 as the reference, automated scoring achieved excellent negative predictive value (96-98%), but yielded many false positives (positive predictive value = 30-32%). For all markers, we observed substantial heterogeneity in automated scoring performance across tissue microarrays. Automated analysis is a potentially useful tool for large-scale, quantitative scoring of immunohistochemically stained tissue microarrays available in consortia. However, continued optimization, rigorous marker-specific quality control measures and standardization of tissue microarray designs, staining and scoring protocols is needed to enhance results.

Keywords: automated scoring; breast tumours; digital pathology; immunohistochemistry; tissue microarrays

References

  1. Sci Transl Med. 2011 Nov 9;3(108):108ra113 - PubMed
  2. J Clin Oncol. 1999 May;17(5):1474-81 - PubMed
  3. Cancer Epidemiol Biomarkers Prev. 2010 Apr;19(4):992-9 - PubMed
  4. Histopathology. 2013 May;62(6):827-39 - PubMed
  5. Clin Cancer Res. 2004 Aug 15;10(16):5367-74 - PubMed
  6. BMC Cancer. 2007 Mar 27;7:55 - PubMed
  7. Br J Cancer. 2013 Feb 19;108(3):602-12 - PubMed
  8. Nature. 2000 Aug 17;406(6797):747-52 - PubMed
  9. Br J Cancer. 2012 Aug 21;107(5):800-7 - PubMed
  10. J Clin Pathol. 2013 Mar;66(3):169-77 - PubMed
  11. Breast Cancer Res. 2008;10(5):R89 - PubMed
  12. Histopathology. 2009 Nov;55(5):587-93 - PubMed
  13. PLoS Med. 2010 May 25;7(5):e1000279 - PubMed
  14. J Clin Oncol. 2011 Nov 10;29(32):4273-8 - PubMed
  15. J Pathol Inform. 2010 Dec 23;1:29 - PubMed
  16. Clin Cancer Res. 2010 Nov 1;16(21):5222-32 - PubMed
  17. Cancer Epidemiol Biomarkers Prev. 2010 Apr;19(4):966-72 - PubMed
  18. Am J Clin Pathol. 2005 Jan;123(1):21-7 - PubMed
  19. Nat Med. 1998 Jul;4(7):844-7 - PubMed
  20. Philos Trans A Math Phys Eng Sci. 2010 Aug 28;368(1925):3937-52 - PubMed
  21. Nature. 2012 Apr 18;486(7403):346-52 - PubMed
  22. Breast Cancer Res Treat. 2012 Feb;132(1):41-9 - PubMed
  23. BMC Clin Pathol. 2011 Jan 25;11:3 - PubMed
  24. Breast Cancer Res Treat. 2008 Aug;110(3):417-26 - PubMed
  25. J Natl Cancer Inst. 2005 Dec 21;97(24):1808-15 - PubMed
  26. Arch Pathol Lab Med. 2011 Jul;135(7):896-902 - PubMed
  27. J Clin Oncol. 2001 Feb 15;19(4):980-91 - PubMed
  28. Virchows Arch. 2009 Mar;454(3):241-8 - PubMed
  29. Am J Clin Pathol. 1988 Sep;90(3):233-9 - PubMed
  30. Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10869-74 - PubMed

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