Molecular subtypes of neuroendocrine carcinomas: A cross-tissue classification framework based on five transcriptional regulators.

Neuroendocrine carcinomas (NECs) are extremely lethal malignancies that can arise at almost any anatomic site. Characterization of NECs is hindered by their rarity and significant inter- and intra-tissue heterogeneity. Herein, through an integrative analysis of over 1,000 NECs originating from 31 various tissues, we reveal their tissue-independent convergence and further unveil molecular divergence driven by distinct transcriptional regulators. Pan-tissue NECs are therefore categorized into five intrinsic subtypes defined by ASCL1, NEUROD1, HNF4A, POU2F3, and YAP1. A comprehensive portrait of these subtypes is depicted, highlighting subtype-specific transcriptional programs, genomic alterations, evolution trajectories, therapeutic vulnerabilities, and clinicopathological presentations. Notably, the newly discovered HNF4A-dominated subtype-H exhibits a gastrointestinal-like signature, wild-type RB1, unique neuroendocrine differentiation, poor chemotherapeutic response, and prevalent large-cell morphology. The proposal of uniform classification paradigm illuminates transcriptional basis of NEC heterogeneity and bridges the gap across different lineages and cytomorphological variants, in which context-dependent prevalence of subtypes underlies their phenotypic disparities.

Estudo da correlação entre a incidência de metástases em tumores carcinóides típicos broncopulmonares e biomarcadores teciduais, variáveis clínicas e índice de risco / Study of the correlation between metastasis incidence in typical bronchopulmonary carcinoid tumors and clinical features, tissue biomarkers and index risk

Tumores carcinóides broncopulmonares são proliferações celulares com baixo grau de malignidade. Porém, reltatos de metástases são cada vez mais comuns. Estudo de características clínicas e de biomarcadores teciduais tumorais nos casos referentes a 55 pacientes operados determinou fatores prognósticos para o desenvolvimento de metástases, e permitiu o estabelecimento de um Índice de Risco numérico relacionado com o fenômeno. Gênero masculino, idade acima de 40 anos, margem cirúrgica comprometida, hiperexpressão imunohistoquímica de p53, Ki67 e microvasos, hipodensidade de fibras estromais no tumor e o índice de risco estão correlacionados com maior incidência de metástases/Bronchopulmonary carcinoid tumors are low grade malignancy proliferations, although reports of metastatic behavior has been became more common. The study of clinical and tumoral histologic profiles in the group of 55 pacients underwent to surgical treatment stablished prognostic factors for the metastatic behavior, and a numeric risk index. Male gender, age above 40 years, residual tumor in surgical margin, imunohistochemical hiperexpression for p53, Ki67 and microvessels, hipodensity of estromal fibers in tumoral tissue, and risk index are correlated with increased incidence of metastasis...