Insights into Novel Prognostic and Possible Predictive Biomarkers of Lung Neuroendocrine Tumors

doi:10.21873/cgp.20073

Cited by 8 publications

(6 citation statements)

References 86 publications

(101 reference statements)

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“…Several molecular alterations in thoracic neuroendocrine tumors interfere with cell-cycle regulation, chromatin remodeling, apoptosis, intracellular cascades, and cell–cell interactions. However, molecular alterations in thoracic neuroendocrine tumors that might be considered as targets for treatment are very scarce, and treatment of pulmonary and thymic carcinoids on a personalized basis is still an unmet goal, despite a list of hypothetical biomarkers [ 101 ]. Among those, rovalpituzumab tesirine, which targets the inhibitory Notch ligand Delta-like protein 3 (DLL3), has been shown to be a promising therapeutic agent in pulmonary neuroendocrine carcinomas.…”

Section: Implications For Therapymentioning

confidence: 99%

Molecular Pathology of Well-Differentiated Pulmonary and Thymic Neuroendocrine Tumors: What Do Pathologists Need to Know?

et al. 2021

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Thoracic (pulmonary and thymic) neuroendocrine tumors are well-differentiated epithelial neuroendocrine neoplasms that are classified into typical and atypical carcinoid tumors based on mitotic index cut offs and presence or absence of necrosis. This classification scheme is of great prognostic value but designed for surgical specimens, only. Deep molecular characterization of thoracic neuroendocrine tumors highlighted their difference with neuroendocrine carcinomas. Neuroendocrine tumors of the lung are characterized by a low mutational burden, and a high prevalence of mutations in chromatin remodeling and histone modification-related genes, whereas mutations in genes frequently altered in neuroendocrine carcinomas are rare. Molecular profiling divided thymic neuroendocrine tumors into three clusters with distinct clinical outcomes and characterized by a different average of copy number instability. Moreover, integrated histopathological, molecular and clinical evidence supports the existence of a grey zone category between neuroendocrine tumors (carcinoid tumors) and neuroendocrine carcinomas. Indeed, cases with well differentiated morphology but mitotic/Ki-67 indexes close to neuroendocrine carcinomas have been increasingly recognized. These are characterized by specific molecular profiles and have an aggressive clinical behavior. Finally, thoracic neuroendocrine tumors may arise in the background of genetic susceptibility, being MEN1 syndrome the well-defined familial form. However, pathologists should be aware of rarer germline variants that are associated with the concurrence of neuroendocrine tumors of the lung or their precursors (such as DIPNECH) with other neoplasms, including but not limited to breast carcinomas. Therefore, genetic counseling for all young patients with thoracic neuroendocrine neoplasia and/or any patient with pathological evidence of neuroendocrine cell hyperplasia-to-neoplasia progression sequence or multifocal disease should be considered.

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Section: Implications For Therapymentioning

confidence: 99%

Molecular Pathology of Well-Differentiated Pulmonary and Thymic Neuroendocrine Tumors: What Do Pathologists Need to Know?

et al. 2021

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“…One of the reasons for this is the low prevalence of this disease. MiRNA expression among patients with NEN of the pancreas, small intestine, stomach and lung cancer have been studied [7,16,18,21,22,24,25,28,35,36,40,46,[48][49][50].…”

Section: Localization Of Nen Increased Expression Decreased Expression Citationmentioning

confidence: 99%

“…Molecular markers based mainly on the functional characteristics of genes are widely studied, and the results are summarized, for example, in [7]. Much remains to be studied and analyzed regarding miRNA.…”

Section: Introductionmentioning

confidence: 99%

MiRNA Expression in Neuroendocrine Neoplasms of Frequent Localizations

Korotaeva

Mansorunov

Apanovich

et al. 2021

ncRNA

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Neuroendocrine neoplasms (NEN) are infrequent malignant tumors of a neuroendocrine nature that arise in various organs. They occur most frequently in the lungs, intestines, stomach and pancreas. Molecular diagnostics and prognosis of NEN development are highly relevant. The role of clinical biomarkers can be played by microRNAs (miRNAs). This work is devoted to the analysis of data on miRNA expression in NENs. For the first time, a search for specificity or a community of their functional characteristics in different types of NEN was carried out. Their properties as biomarkers were also analyzed. To date, more than 100 miRNAs have been characterized as differentially expressed and significant for the development of NEN tumors. Only about 10% of the studied miRNAs are expressed in several types of NEN; differential expression of the remaining 90% was found only in tumors of specific localizations. A significant number of miRNAs have been identified as potential biomarkers. However, only a few miRNAs have values that characterized their quality as markers. The analysis demonstrates the predominant specific expression of miRNA in each studied type of NEN. This indicates that miRNA’s functional features are predominantly influenced by the tissue in which they are formed.

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“…Interestingly, some studies have showed how the genetic alterations of TC differ from those of AC [ 13 , 14 ]. A study conducted with next generation sequencing (NGS) on 148 lung NENs, including 88 TC and AC, demonstrated that MEN1 alterations were almost exclusive to WD Lu-NETs, whereas alterations of TP53 and RB1 genes were significantly enriched in SCLC and LCNECs [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of laterality in lung neuroendocrine tumors

Salvia

Persano

Siciliani³

et al. 2022

Endocrine

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Purpose: Well-differentiated lung neuroendocrine tumors (Lu-NET) are classified as typical (TC) and atypical (AC) carcinoids, based on mitotic counts and necrosis. However, prognostic factors, other than tumor node metastasis (TNM) stage and the histopathological diagnosis, are still lacking. The current study is aimed to identify potential prognostic factors to better stratify lung NET, thus, improving patients’ treatment strategy and follow-up. Methods: A multicentric retrospective study, including 300 Lung NET, all surgically removed, from Italian and Spanish Institutions. Results: Median age 61 years (13–86), 37.7% were males, 25.0% were AC, 42.0% were located in the lung left parenchyma, 80.3% presented a TNM stage I-II. Mitotic count was ≥2 per 10 high-power field (HPF) in 24.7%, necrosis in 13.0%. Median overall survival (OS) was 46.1 months (0.6–323), median progression-free survival (PFS) was 36.0 months (0.3–323). Female sex correlated with a more indolent disease (T1; N0; lower Ki67; lower mitotic count and the absence of necrosis). Left-sided primary tumors were associated with higher mitotic count and necrosis. At Cox-multivariate regression model, age, left-sided tumors, nodal (N) positive status and the diagnosis of AC resulted independent negative prognostic factors for PFS and OS. Conclusions: This study highlights that laterality is an independent prognostic factors in Lu-NETs, with left tumors being less frequent but showing a worse prognosis than right ones. A wider spectrum of clinical and pathological prognostic factors, including TNM stage, age and laterality is suggested. These parameters could help clinicians to personalize the management of Lu-NET.

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Insights into Novel Prognostic and Possible Predictive Biomarkers of Lung Neuroendocrine Tumors

Abstract: The mammalian target of rapamycin (mTOR) pathway plays a key role in cellular processes by regulating protein synthesis, cell growth and metabolic systems. Deregulation 153

Cited by 8 publications

References 86 publications

Molecular Pathology of Well-Differentiated Pulmonary and Thymic Neuroendocrine Tumors: What Do Pathologists Need to Know?

Molecular Pathology of Well-Differentiated Pulmonary and Thymic Neuroendocrine Tumors: What Do Pathologists Need to Know?

MiRNA Expression in Neuroendocrine Neoplasms of Frequent Localizations

Prognostic significance of laterality in lung neuroendocrine tumors

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