{"doi":"10.17615/2jpr-jy21","title":"Three Molecular Subtypes of Gastric Adenocarcinoma Have Distinct Histochemical Features Reflecting Epstein-Barr Virus Infection Status and Neuroendocrine Differentiation","abstract":"Current histopathologic classification schemes for gastric adenocarcinoma have limited clinical utility and are difficult to apply due to tumor heterogeneity. Elucidation of molecular subtypes of gastric cancer may contribute to our understanding of gastric cancer biology and to the development of new molecular markers that may lead to improved diagnosis, therapy, or prognosis. We previously demonstrated that Epstein-Barr virus infected gastric cancers have a distinct human gene expression profile compared to uninfected cancers. We now examine the histopathologic features characterizing infected (n=14) and uninfected (n=89) cancers, the latter of which are now further divided into two major molecular subtypes based on expression patterns of 93 RNAs. One uninfected gastric cancer subtype was distinguished by upregulation of three genes with neuroendocrine function (CHGA, GAST, and REG4 encoding chromogranin, gastrin and the secreted peptide REG4 involved in epithelial cell regeneration), implicating hormonal factors in the pathogenesis of a major class of gastric adenocarcinomas. Evidence of neuroendocrine differentiation (molecular, immunohistochemical, or morphologic) was mutually exclusive of EBV infection. EBV infected tumors tended to have solid-type morphology with lymphoid stroma. This study reveals novel molecular subtypes of gastric cancer and their associated morphologies that demonstrate divergent neuroendocrine features.","journal":"UNC Libraries","year":2020,"id":140890,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9613,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":605675,"name":"Michael O. Meyers","orcid":"0000-0003-4787-4752","position":1,"is_corresponding":false},{"id":263096,"name":"Douglas R. Morgan","orcid":"0000-0002-1136-0963","position":2,"is_corresponding":false},{"id":592334,"name":"Ricardo L. Domínguez","orcid":"0000-0001-5171-4415","position":3,"is_corresponding":false},{"id":264437,"name":"Pei Fen Kuan","orcid":"0000-0001-7861-916X","position":4,"is_corresponding":false},{"id":605676,"name":"Enrique Martı́nez","orcid":"0009-0003-8592-3989","position":5,"is_corresponding":false},{"id":429038,"name":"Margaret L. Gulley","orcid":"0000-0003-0222-4713","position":6,"is_corresponding":false},{"id":537674,"name":"Olga Speck","orcid":"0000-0002-8705-5121","position":7,"is_corresponding":false},{"id":528955,"name":"Weihua Tang","orcid":"0000-0002-7539-9322","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:20.701143Z","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":[]}