{"doi":"10.1038/s41379-019-0209-9","title":"The molecular mechanisms underlying reduced E-cadherin expression in invasive ductal carcinoma of the breast: high throughput analysis of large cohorts","abstract":null,"journal":"Modern Pathology","year":2019,"id":623743,"datarank":1.7689007460360713,"base_score":4.110873864173311,"endowment":4.110873864173311,"self_citation_contribution":0.6166310796259968,"citation_network_contribution":1.1522696664100744,"self_endowment_contribution":0.6166310796259968,"citer_contribution":1.1522696664100744,"corpus_percentile":null,"corpus_rank":null,"citation_count":60,"citer_count":52,"citers_with_citation_signal":38,"citers_with_endowment":38,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":581628,"name":"Michael S. Toss","orcid":"0000-0002-9077-3984","position":1,"is_corresponding":false},{"id":34713,"name":"Chitra Joseph","orcid":"0000-0003-2631-9266","position":2,"is_corresponding":false},{"id":1612140,"name":"Mohammed Aleskandarany","orcid":null,"position":3,"is_corresponding":false},{"id":1612141,"name":"Sasagu Kurozumi","orcid":null,"position":4,"is_corresponding":false},{"id":1612142,"name":"Ibrahim Alshankyty","orcid":null,"position":5,"is_corresponding":false},{"id":1612143,"name":"Angela Ogden","orcid":null,"position":6,"is_corresponding":false},{"id":427089,"name":"Padmashree C.G. Rida","orcid":null,"position":7,"is_corresponding":false},{"id":290745,"name":"Ian O. Ellis","orcid":"0000-0001-5292-8474","position":8,"is_corresponding":false},{"id":371123,"name":"Ritu Aneja","orcid":"0000-0003-4489-5320","position":9,"is_corresponding":false},{"id":112301,"name":"Andrew R Green","orcid":"0000-0002-0488-5913","position":10,"is_corresponding":false},{"id":679677,"name":"Nigel P. Mongan","orcid":"0000-0001-5438-1126","position":11,"is_corresponding":false},{"id":320592,"name":"Emad A. Rakha","orcid":"0000-0002-5009-5525","position":12,"is_corresponding":false},{"id":350165,"name":"Mansour Alsaleem","orcid":"0000-0002-7689-2493","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The molecular mechanisms underlying reduced E-cadherin expression in invasive ductal carcinoma of the breast: high throughput analysis of large cohorts","abstract":"E-cadherin is a tumor suppressor gene in invasive lobular breast cancer. However, a proportion of high-grade ductal carcinoma shows reduced/loss of E-cadherin. In this study, we assessed the underlying mechanisms and molecular implications of E-cadherin loss in invasive ductal carcinoma. This study used large, well-characterized cohorts of early-stage breast cancer-evaluated E-cadherin expression via various platforms including immunohistochemistry, microarray analysis using Illumina HT-12 v3, copy number analysis using Affymetrix SNP 6.0 arrays, and next-generation sequencing for differential gene expression. Our results showed 27% of high-grade invasive ductal carcinoma showed reduced/loss of E-cadherin membranous expression. CDH1 copy number loss was in 21% of invasive ductal carcinoma, which also showed low CDH1 mRNA expression (p = 0.003). CDH1 copy number was associated with copy number loss of TP53, ATM, BRCA1, and BRCA2 (p < 0.001). Seventy-nine percent of invasive ductal carcinoma with reduced CDH1 mRNA expression showed elevated expression of E-cadherin transcription suppressors TWIST2, ZEB2, NFKB1, LLGL2, CTNNB1 (p < 0.01). Reduced/loss E-cadherin expression was associated with differential expression of 2143 genes including those regulating Wnt (FZD2, GNG5, HLTF, WNT2, and CER1) and PIK3-AKT (FGFR2, GNF5, GNGT1, IFNA17, and IGF1) signaling pathways. Interestingly, key genes differentially expressed between invasive lobular carcinoma and invasive ductal tumors did not show association with E-cadherin loss in invasive ductal carcinoma. We conclude that E-cadherin loss in invasive ductal carcinoma is likely a consequence of genomic instability occurring during carcinogenesis. Potential novel regulators controlling E-cadherin expression in invasive ductal carcinoma warrant further investigation.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"30760857","pmcid":null,"openalex_id":null,"authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"bronze","license":"cc-by","oa_locations":[{"url":"https://www.nature.com/articles/s41379-019-0209-9.pdf","host_type":"publisher"},{"url":"http://www.nature.com/articles/s41379-019-0209-9.pdf","host_type":"publisher"},{"url":"http://www.nature.com/articles/s41379-019-0209-9","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0893395222010456?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0893395222010456?httpAccept=text/plain","host_type":"publisher"},{"url":"https://nottingham-repository.worktribe.com/output/1450005","host_type":"repository"}],"fields_of_study":[],"mesh_terms":["Humans","Carcinoma, Ductal, Breast","Breast Neoplasms","Genomic Instability","Cadherins","Tissue Array Analysis","Immunohistochemistry","Adolescent","Adult","Aged","Aged, 80 and over","Middle Aged","Female","Young Adult","High-Throughput Nucleotide Sequencing"],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-04T01:11:17.018890Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}