ArticleThe journal of pathology. Clinical research2022
Inter-observer agreement for the histological diagnosis of invasive lobular breast carcinoma.
Article in The journal of pathology. Clinical research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 49 citations in OpenAlex.
- Impact of Neoadjuvant Chemotherapy on Surgical Outcomes and Conversion to Node-Negativity in Invasive Lobular Breast Cancer: Analysis of Molecularly High-Risk Tumors by Histologic Subtype on the I-SPY2 Clinical Trial.Annals of surgical oncology · 2025Trial
- Breast cancer ovarian metastases show increased activity of GPCR pathways.bioRxiv : the preprint server for biology · 2026Article
- The association between parity, age of first full term pregnancy and invasive lobular breast cancer: a case-only analysis.Cancer treatment and research communications · 2026Article
- NMD-insensitive CDH1 mutation as a mechanism for retained E-cadherin protein expression in lobular carcinoma in situ (LCIS).Histopathology · 2025Article
- Pitfalls in the Histological Diagnosis of Morphologic Variants of Invasive Lobular Carcinoma of the Breast.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2025Review
- A pooled analysis evaluating prognostic significance of Residual Cancer Burden in invasive lobular breast cancer.NPJ breast cancer · 2025Article
- E-cadherin staining in the diagnosis of lobular versus ductal neoplasms of the breast: the emperor has no clothes.Histopathology · 2025Review
- Review
- Unraveling complexity and leveraging opportunities in uncommon breast cancer subtypes.NPJ breast cancer · 2025Review
- Comprehensive characterization of invasive mammary carcinoma with lobular features: integrating morphology and E-cadherin immunohistochemistry patterns.Breast cancer (Tokyo, Japan) · 2025Article
- Review
- A Genomics-Driven Artificial Intelligence-Based Model Classifies Breast Invasive Lobular Carcinoma and Discovers CDH1 Inactivating Mechanisms.Cancer research · 2024Article
- Spatial molecular profiling of mixed invasive ductal and lobular breast cancers reveals heterogeneity in intrinsic molecular subtypes, oncogenic signatures, and mutations.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- International survey on invasive lobular breast cancer identifies priority research questions.NPJ breast cancer · 2024Article
- Histological Patterns and Mammographic Presentation of Invasive Lobular Carcinoma Show No Obvious Associations.Cancers · 2024Article
- Is There a Special Role for Ovarian Hormones in the Pathogenesis of Lobular Carcinoma?Endocrinology · 2024Review
- Microenvironment-induced restoration of cohesive growth associated with focal activation of P-cadherin expression in lobular breast carcinoma metastatic to the colon.The journal of pathology. Clinical research · 2024Article
- Histologic tumor type as a determinant of survival in hormone receptor-positive, HER2-negative, pT1-3 invasive ductal and lobular breast cancer.Breast cancer research : BCR · 2023Article
- Review
- Defining features of hereditary lobular breast cancer due to CDH1 with magnetic resonance imaging and tumor characteristics.NPJ breast cancer · 2023Article
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Authors and funding
52 authors at 20 institutions in 10 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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