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

Benjamin Dessauvagie, Anitha Thomas, Carla Thomas, Cleo Robinson, Marais Combrink, Vanitha Budhavaram, Bindu Kunjuraman, Katie Meehan, Greg Sterrett, Jennet Harvey

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)681-687
Number of pages7
JournalPathology
Volume51
Issue number7
DOIs
Publication statusPublished - 1 Dec 2019

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Lobular Carcinoma
Breast
Mitosis
Biomarkers
Ductal Carcinoma
Mitotic Index
Outcome Assessment (Health Care)

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Dessauvagie, Benjamin ; Thomas, Anitha ; Thomas, Carla ; Robinson, Cleo ; Combrink, Marais ; Budhavaram, Vanitha ; Kunjuraman, Bindu ; Meehan, Katie ; Sterrett, Greg ; Harvey, Jennet. / Invasive lobular carcinoma of the breast : assessment of proliferative activity using automated Ki-67 immunostaining. In: Pathology. 2019 ; Vol. 51, No. 7. pp. 681-687.
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abstract = "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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Invasive lobular carcinoma of the breast : assessment of proliferative activity using automated Ki-67 immunostaining. / Dessauvagie, Benjamin; Thomas, Anitha; Thomas, Carla; Robinson, Cleo; Combrink, Marais; Budhavaram, Vanitha; Kunjuraman, Bindu; Meehan, Katie; Sterrett, Greg; Harvey, Jennet.

In: Pathology, Vol. 51, No. 7, 01.12.2019, p. 681-687.

Research output: Contribution to journalArticle

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T1 - Invasive lobular carcinoma of the breast

T2 - assessment of proliferative activity using automated Ki-67 immunostaining

AU - Dessauvagie, Benjamin

AU - Thomas, Anitha

AU - Thomas, Carla

AU - Robinson, Cleo

AU - Combrink, Marais

AU - Budhavaram, Vanitha

AU - Kunjuraman, Bindu

AU - Meehan, Katie

AU - Sterrett, Greg

AU - Harvey, Jennet

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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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KW - cell proliferation

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DO - 10.1016/j.pathol.2019.08.004

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