Automated quantitative analysis of estrogen receptor expression in breast carcinoma does not differ from expert pathologist scoring: A tissue microarray study of 3,484 cases

Dmitry A. Turbin, Samuel Leung, Maggie C U Cheang, Hagen A. Kennecke, Kelli D. Montgomery, Steven McKinney, Diana O. Treaba, Niki Boyd, Lynn C. Goldstein, Sunil Badve, Allen M. Gown, Matt Van De Rijn, Torsten O. Nielsen, C. Blake Gilks, David G. Huntsman

Research output: Contribution to journalArticle

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Abstract

Background: Estrogen receptor (ER) expression is routinely assessed by immunohistochemistry (IHC) in breast carcinoma. Our study compares visual scoring of ER in invasive breast cancer by histopathologists to quantitation of staining using a fully automated system. Materials and methods: A tissue microarray was constructed from 4,049 cases (3,484 included in analysis) of invasive breast carcinoma linked to treatment and outcome information. Slides were scored independently by two pathologists and scores were dichotomised, with ER positivity recognized at a cut-off of >1% positive nuclei. The slides were scanned and analyzed with an Ariol automated system. Results: Using data dichotomised as ER positive or negative, both visual and automated scores were highly consistent: there was excellent concordance between two pathologists (kappa = 0.918 (95%CI: 0.903-0.932)) and between two Ariol machines (kappa = 0.913 (95%CI: 0.897-0.928)). The prognostic significance of ER positivity was similar whether determined by pathologist or automated scoring for both the entire patient cohort and subsets of patients treated with tamoxifen alone or receiving no systemic adjuvant therapy. The optimal cut point for the automated scores using breast cancer disease-specific survival as an endpoint was >0.4% positive nuclei. The concordance between dextran-coated charcoal ER biochemical assay data and automated scores (kappa = 0.728 (95%CI: 0.69-0.75); 0.74 (95%CI: 0.71-0.77)) was similar to the concordance between biochemical assay and pathologist scores (kappa = 0.72 (95%CI: 0.70-0.75; 0.70 (95%CI: 0.67-0.72)). Conclusion: Fully automated quantitation of ER immunostaining yields results that do not differ from human scoring against both biochemical assay and patient outcome gold standards.

Original languageEnglish
Pages (from-to)417-426
Number of pages10
JournalBreast Cancer Research and Treatment
Volume110
Issue number3
DOIs
StatePublished - Aug 2008

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Estrogen Receptors
Breast Neoplasms
Breast Diseases
Charcoal
Tamoxifen
Pathologists
Dextrans
Immunohistochemistry
Staining and Labeling
Survival

Keywords

  • Automated scoring
  • Breast cancer
  • Estrogen receptor
  • Immunohistochemistry
  • Pathology
  • Tissue microarray

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Automated quantitative analysis of estrogen receptor expression in breast carcinoma does not differ from expert pathologist scoring : A tissue microarray study of 3,484 cases. / Turbin, Dmitry A.; Leung, Samuel; Cheang, Maggie C U; Kennecke, Hagen A.; Montgomery, Kelli D.; McKinney, Steven; Treaba, Diana O.; Boyd, Niki; Goldstein, Lynn C.; Badve, Sunil; Gown, Allen M.; Van De Rijn, Matt; Nielsen, Torsten O.; Gilks, C. Blake; Huntsman, David G.

In: Breast Cancer Research and Treatment, Vol. 110, No. 3, 08.2008, p. 417-426.

Research output: Contribution to journalArticle

Turbin, DA, Leung, S, Cheang, MCU, Kennecke, HA, Montgomery, KD, McKinney, S, Treaba, DO, Boyd, N, Goldstein, LC, Badve, S, Gown, AM, Van De Rijn, M, Nielsen, TO, Gilks, CB & Huntsman, DG 2008, 'Automated quantitative analysis of estrogen receptor expression in breast carcinoma does not differ from expert pathologist scoring: A tissue microarray study of 3,484 cases', Breast Cancer Research and Treatment, vol. 110, no. 3, pp. 417-426. https://doi.org/10.1007/s10549-007-9736-z
Turbin, Dmitry A. ; Leung, Samuel ; Cheang, Maggie C U ; Kennecke, Hagen A. ; Montgomery, Kelli D. ; McKinney, Steven ; Treaba, Diana O. ; Boyd, Niki ; Goldstein, Lynn C. ; Badve, Sunil ; Gown, Allen M. ; Van De Rijn, Matt ; Nielsen, Torsten O. ; Gilks, C. Blake ; Huntsman, David G. / Automated quantitative analysis of estrogen receptor expression in breast carcinoma does not differ from expert pathologist scoring : A tissue microarray study of 3,484 cases. In: Breast Cancer Research and Treatment. 2008 ; Vol. 110, No. 3. pp. 417-426.
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abstract = "Background: Estrogen receptor (ER) expression is routinely assessed by immunohistochemistry (IHC) in breast carcinoma. Our study compares visual scoring of ER in invasive breast cancer by histopathologists to quantitation of staining using a fully automated system. Materials and methods: A tissue microarray was constructed from 4,049 cases (3,484 included in analysis) of invasive breast carcinoma linked to treatment and outcome information. Slides were scored independently by two pathologists and scores were dichotomised, with ER positivity recognized at a cut-off of >1{\%} positive nuclei. The slides were scanned and analyzed with an Ariol automated system. Results: Using data dichotomised as ER positive or negative, both visual and automated scores were highly consistent: there was excellent concordance between two pathologists (kappa = 0.918 (95{\%}CI: 0.903-0.932)) and between two Ariol machines (kappa = 0.913 (95{\%}CI: 0.897-0.928)). The prognostic significance of ER positivity was similar whether determined by pathologist or automated scoring for both the entire patient cohort and subsets of patients treated with tamoxifen alone or receiving no systemic adjuvant therapy. The optimal cut point for the automated scores using breast cancer disease-specific survival as an endpoint was >0.4{\%} positive nuclei. The concordance between dextran-coated charcoal ER biochemical assay data and automated scores (kappa = 0.728 (95{\%}CI: 0.69-0.75); 0.74 (95{\%}CI: 0.71-0.77)) was similar to the concordance between biochemical assay and pathologist scores (kappa = 0.72 (95{\%}CI: 0.70-0.75; 0.70 (95{\%}CI: 0.67-0.72)). Conclusion: Fully automated quantitation of ER immunostaining yields results that do not differ from human scoring against both biochemical assay and patient outcome gold standards.",
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author = "Turbin, {Dmitry A.} and Samuel Leung and Cheang, {Maggie C U} and Kennecke, {Hagen A.} and Montgomery, {Kelli D.} and Steven McKinney and Treaba, {Diana O.} and Niki Boyd and Goldstein, {Lynn C.} and Sunil Badve and Gown, {Allen M.} and {Van De Rijn}, Matt and Nielsen, {Torsten O.} and Gilks, {C. Blake} and Huntsman, {David G.}",
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T1 - Automated quantitative analysis of estrogen receptor expression in breast carcinoma does not differ from expert pathologist scoring

T2 - A tissue microarray study of 3,484 cases

AU - Turbin, Dmitry A.

AU - Leung, Samuel

AU - Cheang, Maggie C U

AU - Kennecke, Hagen A.

AU - Montgomery, Kelli D.

AU - McKinney, Steven

AU - Treaba, Diana O.

AU - Boyd, Niki

AU - Goldstein, Lynn C.

AU - Badve, Sunil

AU - Gown, Allen M.

AU - Van De Rijn, Matt

AU - Nielsen, Torsten O.

AU - Gilks, C. Blake

AU - Huntsman, David G.

PY - 2008/8

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N2 - Background: Estrogen receptor (ER) expression is routinely assessed by immunohistochemistry (IHC) in breast carcinoma. Our study compares visual scoring of ER in invasive breast cancer by histopathologists to quantitation of staining using a fully automated system. Materials and methods: A tissue microarray was constructed from 4,049 cases (3,484 included in analysis) of invasive breast carcinoma linked to treatment and outcome information. Slides were scored independently by two pathologists and scores were dichotomised, with ER positivity recognized at a cut-off of >1% positive nuclei. The slides were scanned and analyzed with an Ariol automated system. Results: Using data dichotomised as ER positive or negative, both visual and automated scores were highly consistent: there was excellent concordance between two pathologists (kappa = 0.918 (95%CI: 0.903-0.932)) and between two Ariol machines (kappa = 0.913 (95%CI: 0.897-0.928)). The prognostic significance of ER positivity was similar whether determined by pathologist or automated scoring for both the entire patient cohort and subsets of patients treated with tamoxifen alone or receiving no systemic adjuvant therapy. The optimal cut point for the automated scores using breast cancer disease-specific survival as an endpoint was >0.4% positive nuclei. The concordance between dextran-coated charcoal ER biochemical assay data and automated scores (kappa = 0.728 (95%CI: 0.69-0.75); 0.74 (95%CI: 0.71-0.77)) was similar to the concordance between biochemical assay and pathologist scores (kappa = 0.72 (95%CI: 0.70-0.75; 0.70 (95%CI: 0.67-0.72)). Conclusion: Fully automated quantitation of ER immunostaining yields results that do not differ from human scoring against both biochemical assay and patient outcome gold standards.

AB - Background: Estrogen receptor (ER) expression is routinely assessed by immunohistochemistry (IHC) in breast carcinoma. Our study compares visual scoring of ER in invasive breast cancer by histopathologists to quantitation of staining using a fully automated system. Materials and methods: A tissue microarray was constructed from 4,049 cases (3,484 included in analysis) of invasive breast carcinoma linked to treatment and outcome information. Slides were scored independently by two pathologists and scores were dichotomised, with ER positivity recognized at a cut-off of >1% positive nuclei. The slides were scanned and analyzed with an Ariol automated system. Results: Using data dichotomised as ER positive or negative, both visual and automated scores were highly consistent: there was excellent concordance between two pathologists (kappa = 0.918 (95%CI: 0.903-0.932)) and between two Ariol machines (kappa = 0.913 (95%CI: 0.897-0.928)). The prognostic significance of ER positivity was similar whether determined by pathologist or automated scoring for both the entire patient cohort and subsets of patients treated with tamoxifen alone or receiving no systemic adjuvant therapy. The optimal cut point for the automated scores using breast cancer disease-specific survival as an endpoint was >0.4% positive nuclei. The concordance between dextran-coated charcoal ER biochemical assay data and automated scores (kappa = 0.728 (95%CI: 0.69-0.75); 0.74 (95%CI: 0.71-0.77)) was similar to the concordance between biochemical assay and pathologist scores (kappa = 0.72 (95%CI: 0.70-0.75; 0.70 (95%CI: 0.67-0.72)). Conclusion: Fully automated quantitation of ER immunostaining yields results that do not differ from human scoring against both biochemical assay and patient outcome gold standards.

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KW - Breast cancer

KW - Estrogen receptor

KW - Immunohistochemistry

KW - Pathology

KW - Tissue microarray

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