Biomarker Landscape in Neuroendocrine Tumors With High-Grade Features: Current Knowledge and Future Perspective
Neuroendocrine tumors (NETs) are classified based on morphology and are graded based on their proliferation rate as either well-differentiated low-grade (G1) to intermediate (G2–G3) or poorly differentiated high-grade neuroendocrine carcinomas (NEC G3). Recently, in gastroenteropancreatic (GEP) NETs...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.780716/full |
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| author | Michele Prisciandaro Michele Prisciandaro Maria Antista Alessandra Raimondi Francesca Corti Federica Morano Giovanni Centonze Giovanna Sabella Alessandro Mangogna Giovanni Randon Filippo Pagani Natalie Prinzi Monica Niger Salvatore Corallo Erica Castiglioni di Caronno Marco Massafra Maria Di Bartolomeo Filippo de Braud Filippo de Braud Massimo Milione Sara Pusceddu |
| author_facet | Michele Prisciandaro Michele Prisciandaro Maria Antista Alessandra Raimondi Francesca Corti Federica Morano Giovanni Centonze Giovanna Sabella Alessandro Mangogna Giovanni Randon Filippo Pagani Natalie Prinzi Monica Niger Salvatore Corallo Erica Castiglioni di Caronno Marco Massafra Maria Di Bartolomeo Filippo de Braud Filippo de Braud Massimo Milione Sara Pusceddu |
| author_sort | Michele Prisciandaro |
| collection | DOAJ |
| description | Neuroendocrine tumors (NETs) are classified based on morphology and are graded based on their proliferation rate as either well-differentiated low-grade (G1) to intermediate (G2–G3) or poorly differentiated high-grade neuroendocrine carcinomas (NEC G3). Recently, in gastroenteropancreatic (GEP) NETs, a new subgroup of well-differentiated high-grade tumors (NET G3) has been divided from NEC by WHO due to its different clinical–pathologic features. Although several mutational analyses have been performed, a molecular classification of NET is an unmet need in particular for G3, which tends to be more aggressive and have less benefit to the available therapies. Specifically, new possible prognostic and, above all, predictive factors are highly awaited, giving the basis for new treatments. Alteration of KRAS, TP53, and RB1 is mainly reported, but also druggable alterations, including BRAF and high microsatellite instability (MSI-H), have been documented in subsets of patients. In addition, PD-L1 demonstrated to be highly expressed in G3 NETs, probably becoming a new biomarker for G3 neuroendocrine neoplasm (NEN) discrimination and a predictive one for immunotherapy response. In this review, we describe the current knowledge available on a high-grade NET molecular landscape with a specific focus on those harboring potentially therapeutic targets in the advanced setting. |
| first_indexed | 2024-12-19T21:23:35Z |
| format | Article |
| id | doaj.art-7ae310bd6e49495dab2ddb83e0cd4b26 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-19T21:23:35Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-7ae310bd6e49495dab2ddb83e0cd4b262022-12-21T20:05:11ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-02-011210.3389/fonc.2022.780716780716Biomarker Landscape in Neuroendocrine Tumors With High-Grade Features: Current Knowledge and Future PerspectiveMichele Prisciandaro0Michele Prisciandaro1Maria Antista2Alessandra Raimondi3Francesca Corti4Federica Morano5Giovanni Centonze6Giovanna Sabella7Alessandro Mangogna8Giovanni Randon9Filippo Pagani10Natalie Prinzi11Monica Niger12Salvatore Corallo13Erica Castiglioni di Caronno14Marco Massafra15Maria Di Bartolomeo16Filippo de Braud17Filippo de Braud18Massimo Milione19Sara Pusceddu20Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyDepartment of Oncology and Hemato-Oncology, University of Milan, Milan, ItalyMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyFirst Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyFirst Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyInstitute for Maternal and Child Health, IRCCS Burlo Garofalo, Trieste, ItalyMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyDepartment of Oncology and Hemato-Oncology, University of Milan, Milan, ItalyFirst Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyNeuroendocrine tumors (NETs) are classified based on morphology and are graded based on their proliferation rate as either well-differentiated low-grade (G1) to intermediate (G2–G3) or poorly differentiated high-grade neuroendocrine carcinomas (NEC G3). Recently, in gastroenteropancreatic (GEP) NETs, a new subgroup of well-differentiated high-grade tumors (NET G3) has been divided from NEC by WHO due to its different clinical–pathologic features. Although several mutational analyses have been performed, a molecular classification of NET is an unmet need in particular for G3, which tends to be more aggressive and have less benefit to the available therapies. Specifically, new possible prognostic and, above all, predictive factors are highly awaited, giving the basis for new treatments. Alteration of KRAS, TP53, and RB1 is mainly reported, but also druggable alterations, including BRAF and high microsatellite instability (MSI-H), have been documented in subsets of patients. In addition, PD-L1 demonstrated to be highly expressed in G3 NETs, probably becoming a new biomarker for G3 neuroendocrine neoplasm (NEN) discrimination and a predictive one for immunotherapy response. In this review, we describe the current knowledge available on a high-grade NET molecular landscape with a specific focus on those harboring potentially therapeutic targets in the advanced setting.https://www.frontiersin.org/articles/10.3389/fonc.2022.780716/fullneuroendocrine tumorsneuroendocrine carcinoma (NEC)next-generation sequencing (NGS)PD-L1high microsatellite instability (MSI-H) |
| spellingShingle | Michele Prisciandaro Michele Prisciandaro Maria Antista Alessandra Raimondi Francesca Corti Federica Morano Giovanni Centonze Giovanna Sabella Alessandro Mangogna Giovanni Randon Filippo Pagani Natalie Prinzi Monica Niger Salvatore Corallo Erica Castiglioni di Caronno Marco Massafra Maria Di Bartolomeo Filippo de Braud Filippo de Braud Massimo Milione Sara Pusceddu Biomarker Landscape in Neuroendocrine Tumors With High-Grade Features: Current Knowledge and Future Perspective Frontiers in Oncology neuroendocrine tumors neuroendocrine carcinoma (NEC) next-generation sequencing (NGS) PD-L1 high microsatellite instability (MSI-H) |
| title | Biomarker Landscape in Neuroendocrine Tumors With High-Grade Features: Current Knowledge and Future Perspective |
| title_full | Biomarker Landscape in Neuroendocrine Tumors With High-Grade Features: Current Knowledge and Future Perspective |
| title_fullStr | Biomarker Landscape in Neuroendocrine Tumors With High-Grade Features: Current Knowledge and Future Perspective |
| title_full_unstemmed | Biomarker Landscape in Neuroendocrine Tumors With High-Grade Features: Current Knowledge and Future Perspective |
| title_short | Biomarker Landscape in Neuroendocrine Tumors With High-Grade Features: Current Knowledge and Future Perspective |
| title_sort | biomarker landscape in neuroendocrine tumors with high grade features current knowledge and future perspective |
| topic | neuroendocrine tumors neuroendocrine carcinoma (NEC) next-generation sequencing (NGS) PD-L1 high microsatellite instability (MSI-H) |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.780716/full |
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