Abstract | INTRODUCTION: METHODS: One hundred seven TNET (22 TC, 51 AC, 28 LCNEC, and 6 SCC) from 103 patients were classified according to the WHO, the European Neuroendocrine Tumor Society, and a grading-related PNET classification. Low coverage whole-genome sequencing and immunohistochemical studies were performed in 63 cases. A copy number instability (CNI) score was applied to compare tumors. Eleven LCNEC were further analyzed using targeted next-generation sequencing. Morphologic classifications were tested against molecular features. RESULTS: Whole-genome sequencing data fell into three clusters: CNIlow, CNIint, and CNIhigh. CNIlow and CNIint comprised not only TC and AC, but also six LCNECs. CNIhigh contained all SCC and nine LCNEC, but also three AC. No morphologic classification was able to predict the CNI cluster. Cases where primary tumors and metastases were available showed progression from low-grade to higher-grade histologies. Analysis of LCNEC revealed a subgroup of intermediate NET G3 tumors that differed from LCNEC by carcinoid morphology, expression of chromogranin, and negativity for enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2). CONCLUSIONS: TNETs fall into three molecular subgroups that are not reflected by the current WHO classification. Given the large overlap between TC and AC on the one hand, and AC and LCNEC on the other, we propose a morphomolecular grading system, Thy-NET G1-G3, instead of histologic classification for patient stratification and prognostication.
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Authors | Helen Dinter, Hanibal Bohnenberger, Julia Beck, Kirsten Bornemann-Kolatzki, Ekkehard Schütz, Stefan Küffer, Lukas Klein, Teri J Franks, Anja Roden, Alexander Emmert, Marc Hinterthaner, Mirella Marino, Luka Brcic, Helmut Popper, Cleo-Aron Weis, Giuseppe Pelosi, Alexander Marx, Philipp Ströbel |
Journal | Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
(J Thorac Oncol)
Vol. 14
Issue 8
Pg. 1472-1483
(08 2019)
ISSN: 1556-1380 [Electronic] United States |
PMID | 31042566
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2019 International Association for the Study of Lung Cancer. All rights reserved. |
Topics |
- Adolescent
- Adult
- Aged
- Child
- Female
- Humans
- Immunohistochemistry
(methods)
- Male
- Middle Aged
- Neuroendocrine Tumors
(classification, mortality, pathology)
- Survival Analysis
- Thymus Gland
- Young Adult
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