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, Jahrgang 8, Nr. 2, 03.2022, S. 191-205.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -