ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
Next-Generation Sequencing of Pulmonary Large Cell Neuroendocrine Carcinoma Reveals Small Cell Carcinoma-like and Non-Small Cell Carcinoma-like Subsets.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 244 papers, 1 of them a synthesis that pooled it.
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Who cites it
244 citing papers in PubMed, 1 synthesis or guideline pooled it, 463 citations in OpenAlex.
- Prevalence of TP-53/Rb-1 Co-Mutation in Large Cell Neuroendocrine Carcinoma.Frontiers in oncology · 2021Pooled it
- TROP2 immunoreactivity in pulmonary large cell neuroendocrine carcinoma.Histopathology · 2026Article
- Distinct Molecular Pathways Driving Thymic and Pulmonary Neuroendocrine Neoplasms: Organ of Origin Defines Molecular Identity and Yields CD44 as a Marker of Pulmonary Neuroendocrine Tumors.Endocrine pathology · 2026Article
- Brief Report: Proposed Clinical Trial Guidelines Based on Clinicopathologic Heterogeneity of Metastatic Pulmonary Large Cell Neuroendocrine Carcinoma.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Article
- Divergent c-MYC Expression Patterns in NET and NEC: Insights from a Multicentre Cohort of 1380 Neuroendocrine Neoplasms.Endocrine pathology · 2026Article
- What's new in neoplastic pulmonary pathology 2026: updates on grading, staging and molecular testing.Journal of pathology and translational medicine · 2026Article
- De Novo Actionable Genomic Alterations in High-Grade Pulmonary Neuroendocrine Carcinomas: Therapeutic Implications of Targeted Treatment.Medical sciences (Basel, Switzerland) · 2026Article
- Proteogenomic characterization of pulmonary large-cell neuroendocrine carcinoma identifies molecular features and therapeutic strategy.Science advances · 2026Article
- Breast Neuroendocrine Carcinoma: Molecular Insights Beyond Histology.JCO precision oncology · 2026Article
- Utility of RB1 immunohistochemistry for prognostic subtyping of pulmonary large cell neuroendocrine carcinoma.Virchows Archiv : an international journal of pathology · 2026Article
- Hormone secretion predicts poor prognosis in lung neuroendocrine neoplasms.Endocrine-related cancer · 2026Article
- Clinical practice review of systemic treatment in large cell neuroendocrine carcinoma.Translational lung cancer research · 2026Review
- Deep learning based histomorphological phenotyping and prognostic stratification for combined SCLC and LCNEC.NPJ digital medicine · 2026Article
- Prognostic and therapeutic roles of specific genotypes through target-gene sequencing on gastroenteropancreatic neuroendocrine carcinoma.The oncologist · 2026Article
- Well-Differentiated Neuroendocrine Tumors of Lung: A Case Series Supporting the IARC/WHO Common Classification of Neuroendocrine Tumor Nomenclature and Grading.Endocrine pathology · 2026Article
- Identification of Actionable Gene Variants in Pulmonary Large-Cell Neuroendocrine Carcinoma: A Real-World Analysis of a Polish Cohort.International journal of molecular sciences · 2026Article
- Review
- Histomorphological and Molecular Features of Colonic Large-Cell Neuroendocrine Carcinoma in a Patient With Familial Adenomatous Polyposis: A Case Report and Review of Literature.International journal of surgical pathology · 2026Review
- Optimal Treatment Strategies for Pulmonary Large Cell Neuroendocrine Carcinoma Based on Molecular Subtypes.Journal of clinical medicine · 2026Article
- Clinical utility of molecular profiling in rare lung neuroendocrine neoplasms.Frontiers in oncology · 2026Review
184 more citing papers are in PubMed but not listed here.
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20 authors at 1 institution in 1 country.
Funding
Abstract
purposePulmonary large cell neuroendocrine carcinoma (LCNEC) is a highly aggressive neoplasm, whose biologic relationship to small cell lung carcinoma (SCLC) versus non-SCLC (NSCLC) remains unclear, contributing to uncertainty regarding optimal clinical management. To clarify these relationships, we analyzed genomic alterations in LCNEC compared with other major lung carcinoma types. EXPERIMENTAL
designLCNEC (n = 45) tumor/normal pairs underwent targeted next-generation sequencing of 241 cancer genes by Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) platform and comprehensive histologic, immunohistochemical, and clinical analysis. Genomic data were compared with MSK-IMPACT analysis of other lung carcinoma histologies (n = 242).
resultsCommonly altered genes in LCNEC included TP53 (78%), RB1 (38%), STK11 (33%), KEAP1 (31%), and KRAS (22%). Genomic profiles segregated LCNEC into 2 major and 1 minor subsets: SCLC-like (n = 18), characterized by TP53+RB1 co-mutation/loss and other SCLC-type alterations, including MYCL amplification; NSCLC-like (n = 25), characterized by the lack of coaltered TP53+RB1 and nearly universal occurrence of NSCLC-type mutations (STK11, KRAS, and KEAP1); and carcinoid-like (n = 2), characterized by MEN1 mutations and low mutation burden. SCLC-like and NSCLC-like subsets revealed several clinicopathologic differences, including higher proliferative activity in SCLC-like tumors (P < 0.0001) and exclusive adenocarcinoma-type differentiation marker expression in NSCLC-like tumors (P = 0.005). While exhibiting predominant similarity with lung adenocarcinoma, NSCLC-like LCNEC harbored several distinctive genomic alterations, including more frequent mutations in NOTCH family genes (28%), implicated as key regulators of neuroendocrine differentiation.
conclusionsLCNEC is a biologically heterogeneous group of tumors, comprising distinct subsets with genomic signatures of SCLC, NSCLC (predominantly adenocarcinoma), and rarely, highly proliferative carcinoids. Recognition of these subsets may inform the classification and management of LCNEC patients. Clin Cancer Res; 22(14); 3618-29. ©2016 AACR.
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