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Inter-observer agreement for the histological diagnosis of invasive lobular breast carcinoma

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Inter-observer agreement for the histological diagnosis of invasive lobular breast carcinoma. / Christgen, Matthias; Kandt, Leonie Donata; Antonopoulos, Wiebke; Bartels, Stephan; Van Bockstal, Mieke R; Bredt, Martin; Brito, Maria Jose; Christgen, Henriette; Colpaert, Cecile; Cserni, Bálint; Cserni, Gábor; Daemmrich, Maximilian E; Danebrock, Raihanatou; Dedeurwaerdere, Franceska; van Deurzen, Carolien Hm; Erber, Ramona; Fathke, Christine; Feist, Henning; Fiche, Maryse; Gonzalez, Claudia Aura; Ter Hoeve, Natalie D; Kooreman, Loes; Krech, Till; Kristiansen, Glen; Kulka, Janina; Laenger, Florian; Lafos, Marcel; Lehmann, Ulrich; Martin-Martinez, Maria Dolores; Mueller, Sophie; Pelz, Enrico; Raap, Mieke; Ravarino, Alberto; Reineke-Plaass, Tanja; Schaumann, Nora; Schelfhout, Anne-Marie; De Schepper, Maxim; Schlue, Jerome; Van de Vijver, Koen; Waelput, Wim; Wellmann, Axel; Graeser, Monika; Gluz, Oleg; Kuemmel, Sherko; Nitz, Ulrike; Harbeck, Nadia; Desmedt, Christine; Floris, Giuseppe; Derksen, Patrick Wb; van Diest, Paul J; Vincent-Salomon, Anne; Kreipe, Hans.

In: J PATHOL CLIN RES, Vol. 8, No. 2, 03.2022, p. 191-205.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Christgen, M, Kandt, LD, Antonopoulos, W, Bartels, S, Van Bockstal, MR, Bredt, M, Brito, MJ, Christgen, H, Colpaert, C, Cserni, B, Cserni, G, Daemmrich, ME, Danebrock, R, Dedeurwaerdere, F, van Deurzen, CH, Erber, R, Fathke, C, Feist, H, Fiche, M, Gonzalez, CA, Ter Hoeve, ND, Kooreman, L, Krech, T, Kristiansen, G, Kulka, J, Laenger, F, Lafos, M, Lehmann, U, Martin-Martinez, MD, Mueller, S, Pelz, E, Raap, M, Ravarino, A, Reineke-Plaass, T, Schaumann, N, Schelfhout, A-M, De Schepper, M, Schlue, J, Van de Vijver, K, Waelput, W, Wellmann, A, Graeser, M, Gluz, O, Kuemmel, S, Nitz, U, Harbeck, N, Desmedt, C, Floris, G, Derksen, PW, van Diest, PJ, Vincent-Salomon, A & Kreipe, H 2022, 'Inter-observer agreement for the histological diagnosis of invasive lobular breast carcinoma', J PATHOL CLIN RES, vol. 8, no. 2, pp. 191-205. https://doi.org/10.1002/cjp2.253

APA

Christgen, M., Kandt, L. D., Antonopoulos, W., Bartels, S., Van Bockstal, M. R., Bredt, M., Brito, M. J., Christgen, H., Colpaert, C., Cserni, B., Cserni, G., Daemmrich, M. E., Danebrock, R., Dedeurwaerdere, F., van Deurzen, C. H., Erber, R., Fathke, C., Feist, H., Fiche, M., ... Kreipe, H. (2022). Inter-observer agreement for the histological diagnosis of invasive lobular breast carcinoma. J PATHOL CLIN RES, 8(2), 191-205. https://doi.org/10.1002/cjp2.253

Vancouver

Christgen M, Kandt LD, Antonopoulos W, Bartels S, Van Bockstal MR, Bredt M et al. Inter-observer agreement for the histological diagnosis of invasive lobular breast carcinoma. J PATHOL CLIN RES. 2022 Mar;8(2):191-205. https://doi.org/10.1002/cjp2.253

Bibtex

@article{6d59ccaf5faf4c30a41f9c0140a51f3f,
title = "Inter-observer agreement for the histological diagnosis of invasive lobular breast carcinoma",
abstract = "Invasive lobular breast carcinoma (ILC) is the second most common breast carcinoma (BC) subtype and is mainly driven by loss of E-cadherin expression. Correct classification of BC as ILC is important for patient treatment. This study assessed the degree of agreement among pathologists for the diagnosis of ILC. Two sets of hormone receptor (HR)-positive/HER2-negative BCs were independently reviewed by participating pathologists. In set A (61 cases), participants were provided with hematoxylin/eosin (HE)-stained sections. In set B (62 cases), participants were provided with HE-stained sections and E-cadherin immunohistochemistry (IHC). Tumor characteristics were balanced. Participants classified specimens as non-lobular BC versus mixed BC versus ILC. Pairwise inter-observer agreement and agreement with a pre-defined reference diagnosis were determined with Cohen's kappa statistics. Subtype calls were correlated with molecular features, including CDH1/E-cadherin mutation status. Thirty-five pathologists completed both sets, providing 4,305 subtype calls. Pairwise inter-observer agreement was moderate in set A (median κ = 0.58, interquartile range [IQR]: 0.48-0.66) and substantial in set B (median κ = 0.75, IQR: 0.56-0.86, p < 0.001). Agreement with the reference diagnosis was substantial in set A (median κ = 0.67, IQR: 0.57-0.75) and almost perfect in set B (median κ = 0.86, IQR: 0.73-0.93, p < 0.001). The median frequency of CDH1/E-cadherin mutations in specimens classified as ILC was 65% in set A (IQR: 56-72%) and 73% in set B (IQR: 65-75%, p < 0.001). Cases with variable subtype calls included E-cadherin-positive ILCs harboring CDH1 missense mutations, and E-cadherin-negative ILCs with tubular elements and focal P-cadherin expression. ILCs with trabecular growth pattern were often misclassified as non-lobular BC in set A but not in set B. In conclusion, subtyping of BC as ILC achieves almost perfect agreement with a pre-defined reference standard, if assessment is supported by E-cadherin IHC. CDH1 missense mutations associated with preserved E-cadherin protein expression, E- to P-cadherin switching in ILC with tubular elements, and trabecular ILC were identified as potential sources of discordant classification.",
keywords = "Biomarkers, Tumor/genetics, Breast Neoplasms/diagnosis, Carcinoma, Lobular/diagnosis, Female, Humans, Immunohistochemistry, Observer Variation",
author = "Matthias Christgen and Kandt, {Leonie Donata} and Wiebke Antonopoulos and Stephan Bartels and {Van Bockstal}, {Mieke R} and Martin Bredt and Brito, {Maria Jose} and Henriette Christgen and Cecile Colpaert and B{\'a}lint Cserni and G{\'a}bor Cserni and Daemmrich, {Maximilian E} and Raihanatou Danebrock and Franceska Dedeurwaerdere and {van Deurzen}, {Carolien Hm} and Ramona Erber and Christine Fathke and Henning Feist and Maryse Fiche and Gonzalez, {Claudia Aura} and {Ter Hoeve}, {Natalie D} and Loes Kooreman and Till Krech and Glen Kristiansen and Janina Kulka and Florian Laenger and Marcel Lafos and Ulrich Lehmann and Martin-Martinez, {Maria Dolores} and Sophie Mueller and Enrico Pelz and Mieke Raap and Alberto Ravarino and Tanja Reineke-Plaass and Nora Schaumann and Anne-Marie Schelfhout and {De Schepper}, Maxim and Jerome Schlue and {Van de Vijver}, Koen and Wim Waelput and Axel Wellmann and Monika Graeser and Oleg Gluz and Sherko Kuemmel and Ulrike Nitz and Nadia Harbeck and Christine Desmedt and Giuseppe Floris and Derksen, {Patrick Wb} and {van Diest}, {Paul J} and Anne Vincent-Salomon and Hans Kreipe",
note = "{\textcopyright} 2021 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland & John Wiley & Sons, Ltd.",
year = "2022",
month = mar,
doi = "10.1002/cjp2.253",
language = "English",
volume = "8",
pages = "191--205",
journal = "J PATHOL CLIN RES",
issn = "2056-4538",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "2",

}

RIS

TY - JOUR

T1 - Inter-observer agreement for the histological diagnosis of invasive lobular breast carcinoma

AU - Christgen, Matthias

AU - Kandt, Leonie Donata

AU - Antonopoulos, Wiebke

AU - Bartels, Stephan

AU - Van Bockstal, Mieke R

AU - Bredt, Martin

AU - Brito, Maria Jose

AU - Christgen, Henriette

AU - Colpaert, Cecile

AU - Cserni, Bálint

AU - Cserni, Gábor

AU - Daemmrich, Maximilian E

AU - Danebrock, Raihanatou

AU - Dedeurwaerdere, Franceska

AU - van Deurzen, Carolien Hm

AU - Erber, Ramona

AU - Fathke, Christine

AU - Feist, Henning

AU - Fiche, Maryse

AU - Gonzalez, Claudia Aura

AU - Ter Hoeve, Natalie D

AU - Kooreman, Loes

AU - Krech, Till

AU - Kristiansen, Glen

AU - Kulka, Janina

AU - Laenger, Florian

AU - Lafos, Marcel

AU - Lehmann, Ulrich

AU - Martin-Martinez, Maria Dolores

AU - Mueller, Sophie

AU - Pelz, Enrico

AU - Raap, Mieke

AU - Ravarino, Alberto

AU - Reineke-Plaass, Tanja

AU - Schaumann, Nora

AU - Schelfhout, Anne-Marie

AU - De Schepper, Maxim

AU - Schlue, Jerome

AU - Van de Vijver, Koen

AU - Waelput, Wim

AU - Wellmann, Axel

AU - Graeser, Monika

AU - Gluz, Oleg

AU - Kuemmel, Sherko

AU - Nitz, Ulrike

AU - Harbeck, Nadia

AU - Desmedt, Christine

AU - Floris, Giuseppe

AU - Derksen, Patrick Wb

AU - van Diest, Paul J

AU - Vincent-Salomon, Anne

AU - Kreipe, Hans

N1 - © 2021 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland & John Wiley & Sons, Ltd.

PY - 2022/3

Y1 - 2022/3

N2 - Invasive lobular breast carcinoma (ILC) is the second most common breast carcinoma (BC) subtype and is mainly driven by loss of E-cadherin expression. Correct classification of BC as ILC is important for patient treatment. This study assessed the degree of agreement among pathologists for the diagnosis of ILC. Two sets of hormone receptor (HR)-positive/HER2-negative BCs were independently reviewed by participating pathologists. In set A (61 cases), participants were provided with hematoxylin/eosin (HE)-stained sections. In set B (62 cases), participants were provided with HE-stained sections and E-cadherin immunohistochemistry (IHC). Tumor characteristics were balanced. Participants classified specimens as non-lobular BC versus mixed BC versus ILC. Pairwise inter-observer agreement and agreement with a pre-defined reference diagnosis were determined with Cohen's kappa statistics. Subtype calls were correlated with molecular features, including CDH1/E-cadherin mutation status. Thirty-five pathologists completed both sets, providing 4,305 subtype calls. Pairwise inter-observer agreement was moderate in set A (median κ = 0.58, interquartile range [IQR]: 0.48-0.66) and substantial in set B (median κ = 0.75, IQR: 0.56-0.86, p < 0.001). Agreement with the reference diagnosis was substantial in set A (median κ = 0.67, IQR: 0.57-0.75) and almost perfect in set B (median κ = 0.86, IQR: 0.73-0.93, p < 0.001). The median frequency of CDH1/E-cadherin mutations in specimens classified as ILC was 65% in set A (IQR: 56-72%) and 73% in set B (IQR: 65-75%, p < 0.001). Cases with variable subtype calls included E-cadherin-positive ILCs harboring CDH1 missense mutations, and E-cadherin-negative ILCs with tubular elements and focal P-cadherin expression. ILCs with trabecular growth pattern were often misclassified as non-lobular BC in set A but not in set B. In conclusion, subtyping of BC as ILC achieves almost perfect agreement with a pre-defined reference standard, if assessment is supported by E-cadherin IHC. CDH1 missense mutations associated with preserved E-cadherin protein expression, E- to P-cadherin switching in ILC with tubular elements, and trabecular ILC were identified as potential sources of discordant classification.

AB - Invasive lobular breast carcinoma (ILC) is the second most common breast carcinoma (BC) subtype and is mainly driven by loss of E-cadherin expression. Correct classification of BC as ILC is important for patient treatment. This study assessed the degree of agreement among pathologists for the diagnosis of ILC. Two sets of hormone receptor (HR)-positive/HER2-negative BCs were independently reviewed by participating pathologists. In set A (61 cases), participants were provided with hematoxylin/eosin (HE)-stained sections. In set B (62 cases), participants were provided with HE-stained sections and E-cadherin immunohistochemistry (IHC). Tumor characteristics were balanced. Participants classified specimens as non-lobular BC versus mixed BC versus ILC. Pairwise inter-observer agreement and agreement with a pre-defined reference diagnosis were determined with Cohen's kappa statistics. Subtype calls were correlated with molecular features, including CDH1/E-cadherin mutation status. Thirty-five pathologists completed both sets, providing 4,305 subtype calls. Pairwise inter-observer agreement was moderate in set A (median κ = 0.58, interquartile range [IQR]: 0.48-0.66) and substantial in set B (median κ = 0.75, IQR: 0.56-0.86, p < 0.001). Agreement with the reference diagnosis was substantial in set A (median κ = 0.67, IQR: 0.57-0.75) and almost perfect in set B (median κ = 0.86, IQR: 0.73-0.93, p < 0.001). The median frequency of CDH1/E-cadherin mutations in specimens classified as ILC was 65% in set A (IQR: 56-72%) and 73% in set B (IQR: 65-75%, p < 0.001). Cases with variable subtype calls included E-cadherin-positive ILCs harboring CDH1 missense mutations, and E-cadherin-negative ILCs with tubular elements and focal P-cadherin expression. ILCs with trabecular growth pattern were often misclassified as non-lobular BC in set A but not in set B. In conclusion, subtyping of BC as ILC achieves almost perfect agreement with a pre-defined reference standard, if assessment is supported by E-cadherin IHC. CDH1 missense mutations associated with preserved E-cadherin protein expression, E- to P-cadherin switching in ILC with tubular elements, and trabecular ILC were identified as potential sources of discordant classification.

KW - Biomarkers, Tumor/genetics

KW - Breast Neoplasms/diagnosis

KW - Carcinoma, Lobular/diagnosis

KW - Female

KW - Humans

KW - Immunohistochemistry

KW - Observer Variation

U2 - 10.1002/cjp2.253

DO - 10.1002/cjp2.253

M3 - SCORING: Journal article

C2 - 34889530

VL - 8

SP - 191

EP - 205

JO - J PATHOL CLIN RES

JF - J PATHOL CLIN RES

SN - 2056-4538

IS - 2

ER -