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Invasive lobular carcinoma of the breast: assessment of proliferative activity using automated Ki-67 immunostaining

  • Benjamin Dessauvagie
    Correspondence
    Address for correspondence: Dr Benjamin Dessauvagie, Division of Pathology and Laboratory Medicine, UWA Medical School, Crawley, WA 6009, Australia.
    Affiliations
    Breast Subspecialty Group, Department of Anatomical Pathology, PathWest Laboratory Medicine WA, Perth, WA, Australia

    School of Biomedical Science, University of Western Australia, Crawley, WA, Australia

    Division of Pathology and Laboratory Medicine, UWA Medical School, University of Western Australia, Crawley, WA, Australia
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  • Anitha Thomas
    Affiliations
    Breast Subspecialty Group, Department of Anatomical Pathology, PathWest Laboratory Medicine WA, Perth, WA, Australia

    Division of Pathology and Laboratory Medicine, UWA Medical School, University of Western Australia, Crawley, WA, Australia
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  • Carla Thomas
    Affiliations
    Breast Subspecialty Group, Department of Anatomical Pathology, PathWest Laboratory Medicine WA, Perth, WA, Australia

    School of Biomedical Science, University of Western Australia, Crawley, WA, Australia
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  • Cleo Robinson
    Affiliations
    Breast Subspecialty Group, Department of Anatomical Pathology, PathWest Laboratory Medicine WA, Perth, WA, Australia

    School of Biomedical Science, University of Western Australia, Crawley, WA, Australia
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  • Marais Combrink
    Affiliations
    Breast Subspecialty Group, Department of Anatomical Pathology, PathWest Laboratory Medicine WA, Perth, WA, Australia

    School of Biomedical Science, University of Western Australia, Crawley, WA, Australia
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  • Vanitha Budhavaram
    Affiliations
    Department of Surgery, Sir Charles Gairdner Hospital, Nedlands, WA, Australia
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  • Bindu Kunjuraman
    Affiliations
    Department of Surgery, Sir Charles Gairdner Hospital, Nedlands, WA, Australia
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  • Katie Meehan
    Affiliations
    School of Biomedical Science, University of Western Australia, Crawley, WA, Australia
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  • Greg Sterrett
    Affiliations
    Breast Subspecialty Group, Department of Anatomical Pathology, PathWest Laboratory Medicine WA, Perth, WA, Australia

    School of Biomedical Science, University of Western Australia, Crawley, WA, Australia

    Division of Pathology and Laboratory Medicine, UWA Medical School, University of Western Australia, Crawley, WA, Australia
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  • Jennet Harvey
    Affiliations
    Breast Subspecialty Group, Department of Anatomical Pathology, PathWest Laboratory Medicine WA, Perth, WA, Australia

    School of Biomedical Science, University of Western Australia, Crawley, WA, Australia

    Division of Pathology and Laboratory Medicine, UWA Medical School, University of Western Australia, Crawley, WA, Australia
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Published:October 17, 2019DOI:https://doi.org/10.1016/j.pathol.2019.08.004

      Summary

      Invasive lobular carcinoma (ILC) is almost always classified as Nottingham histological grade 2. Despite this, prognosis is markedly varied, with some ILCs behaving more akin to grade 3 invasive ductal carcinoma (IDC). Methods to separate these aggressive ILCs are needed. Digital image analysis (DIA) of the Ki-67 biomarker has potential in this regard; thus, we sought to determine the feasibility of its use for automated evaluation of ILC. An initial pilot study demonstrated no ILC specific changes were required to our Ki-67 DIA algorithm for reproducible results. Subsequently, 42 consecutive cases of ILC were evaluated by visual mitosis counting in H&E stained sections and by DIA on Ki-67 stained sections. Ki-67 proliferative index (PI) DIA showed significant correlation with visual mitosis counting on H&E stained sections (rs=0.63; p<0.05), significant strong correlation (rs=0.78; p<0.05) and substantial agreement (κ=0.62) with manual/visual Ki-67 assessment and significant positive associations with grade, nodal status and ‘pleomorphic’ ILC subtype, and a wide stratification of values in classical/grade 2 ILC. In conclusion, DIA of Ki-67 PI in ILC is feasible, correlates with mitotic index, manual/visual Ki-67 PI and clinico-pathological variables. The broad stratification of Ki-67 PI in classical/grade 2 ILC supports its practicability as a biomarker with prognostic and predictive potential, although large studies with outcome data are required for validation.

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