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Integration of Pathological Criteria and Immunohistochemical Evaluation for Invasive Lobular Carcinoma Diagnosis: Recommendations From the European Lobular Breast Cancer Consortium.
- Source :
-
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2024 Jul; Vol. 37 (7), pp. 100497. Date of Electronic Publication: 2024 Apr 17. - Publication Year :
- 2024
-
Abstract
- Invasive lobular carcinoma (ILC) is the second most frequent type of breast cancer (BC) and its peculiar morphology is mainly driven by inactivation of CDH1, the gene coding for E-cadherin cell adhesion protein. ILC-specific therapeutic and disease-monitoring approaches are gaining momentum in the clinic, increasing the importance of accurate ILC diagnosis. Several essential and desirable morphologic diagnostic criteria are currently defined by the World Health Organization, the routine use of immunohistochemistry (IHC) for E-cadherin is not recommended. Disagreement in the diagnosis of ILC has been repeatedly reported, but interpathologist agreement increases with the use of E-cadherin IHC. In this study, we aimed to harmonize the pathological diagnosis of ILC by comparing 5 commonly used E-cadherin antibody clones (NCH-38, EP700Y, Clone 36, NCL-L-E-cad [Clone 36B5], and ECH-6). We determined their biochemical specificity for the E-cadherin protein and IHC staining performance according to type and location of mutation on the CDH1 gene. Western blot analysis on mouse cell lines with conditional E-cadherin expression revealed a reduced specificity of EP700Y and NCL-L-E-cad for E-cadherin, with cross-reactivity of Clone 36 to P-cadherin. The use of IHC improved interpathologist agreement for ILC, lobular carcinoma in situ, and atypical lobular hyperplasia. The E-cadherin IHC staining pattern was associated with variant allele frequency and likelihood of nonsense-mediated RNA decay but not with the type or position of CDH1 mutations. Based on these results, we recommend the indication for E-cadherin staining, choice of antibodies, and their interpretation to standardize ILC diagnosis in current pathology practice.<br /> (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Female
Antigens, CD metabolism
Animals
Mice
Carcinoma, Lobular diagnosis
Carcinoma, Lobular pathology
Carcinoma, Lobular metabolism
Carcinoma, Lobular genetics
Breast Neoplasms pathology
Breast Neoplasms diagnosis
Breast Neoplasms genetics
Immunohistochemistry
Cadherins metabolism
Cadherins analysis
Biomarkers, Tumor analysis
Biomarkers, Tumor genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1530-0285
- Volume :
- 37
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
- Publication Type :
- Academic Journal
- Accession number :
- 38641322
- Full Text :
- https://doi.org/10.1016/j.modpat.2024.100497