Molecular alterations of neuroendocrine tumours of the lung

Rossi, Giulio; Bertero, Luca; Marchiò, Caterina; Papotti, Mauro

doi:10.1111/his.13394

Cited by 39 publications

(29 citation statements)

References 85 publications

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“…The collective molecular data support this existing histological classification, with carcinoids and carcinomas displaying distinct mutational burdens and profiles (Swarts et al 2012, Simbolo et al 2017. For example, somatic TP53 mutations and loss of 3p are common in NE carcinomas, yet rare in carcinoids (Rossi et al 2018). These molecular differences are directly related to differences in tobacco exposure, which is known to cause TP53 and other mutations (Gibbons et al 2014).…”

Section: Lung Neuroendocrine Tumorssupporting

confidence: 67%

65 YEARS OF THE DOUBLE HELIX: Classification of endocrine tumors in the age of integrated genomics

Giordano

2018

Endocrine-Related Cancer

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The classification of human cancers represents one of the cornerstones of modern pathology. Over the last century, surgical pathologists established the current taxonomy of neoplasia using traditional histopathological parameters, which include tumor architecture, cytological features and cellular proliferation. This morphological classification is efficient and robust with high reproducibility and has served patients and health care providers well. The most recent decade has witnessed an explosion of genome-wide molecular genetic and epigenetic data for most cancers, including tumors of endocrine organs. The availability of this expansive multi-dimensional genomic data, collectively termed the cancer genome, has catalyzed a re-examination of the classification of endocrine tumors. Here, recent cancer genome studies of various endocrine tumors, including those of the thyroid, pituitary and adrenal glands, pancreas, small bowel, lung and skin, are presented with special emphasis on how genomic insights are impacting endocrine tumor classification.

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Section: Lung Neuroendocrine Tumorssupporting

confidence: 67%

65 YEARS OF THE DOUBLE HELIX: Classification of endocrine tumors in the age of integrated genomics

Giordano

2018

Endocrine-Related Cancer

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“…Notably, one study that used NGS to investigate carcinoids did not provide the original sequencing data and, consequently, the sequencing results were not summarized in Table III; however, it was reported in the study that FGFR1 was highly expressed in carcinoids (39). In addition, Rossi et al (40) also reported that ERBB4 alteration was detected in carcinoids. Recently, Asiedu et al (41) used mRNA expression, single nucleotide polymorphism genotyping and a combination of exome and whole-genome sequencing to detect genomic alterations in 31 TC and 11 AC tumors.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological characteristics and genetic analysis of pulmonary carcinoid tumors: A single‑center retrospective cohort study and literature review

Hou

Shi

et al. 2020

Oncol Lett

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Pulmonary carcinoid tumors, including typical and atypical carcinoids, are well-differentiated neuroendocrine tumors (NETs) that represent 1-2% of all lung cancer cases. In the present study, all cases of well-differentiated NETs diagnosed at Tianjin Medical University General Hospital (Tianjin, China) between 2006 and 2016 were reviewed, and 20 pulmonary carcinoid cases were identified. The clinical features of these cases were summarized, and the results of pathological and imaging examinations were collated. As a low-grade malignant pulmonary neoplasm, the molecular biological mechanism of pulmonary carcinoids is yet to be elucidated. To investigate the underlying molecular mechanisms behind pulmonary carcinoids and to determine an effective molecular targeted therapeutic strategy, next-generation sequencing (NGS) was performed using tissue samples from six patients to determine additional molecular biological characteristics that may help guide targeted therapy. A total of 27 somatic mutations in 21 genes were detected. Of note, mutations in the KIT proto-oncogene receptor tyrosine kinase, Erb-B2 receptor tyrosine kinase 4, MET proto-oncogene receptor tyrosine kinase and insulin-like growth factor 1 genes occurred in two out of six cases. Since treatments for advanced carcinoids are relatively ineffective, molecular profiling may contribute to the identification of novel treatments. In addition, the literature on mutations in pulmonary carcinoids was reviewed and available clinical information and features of this tumor type were summarized.

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“…Separate studies of DIPNECH are needed to define the role of the NETest in the delineation of this ill-understood pathobiological condition. This lack of difference may reflect the current understanding of DIPNECH as a subset of peripheral carcinoid tumors with low malignant potential [26]. …”

Section: Discussionmentioning

confidence: 99%

NETest Liquid Biopsy Is Diagnostic of Lung Neuroendocrine Tumors and Identifies Progressive Disease

et al. 2019

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Background: There are no effective biomarkers for the management of bronchopulmonary carcinoids (BPC). We examined the utility of a neuroendocrine multigene transcript “liquid biopsy” (NETest) in BPC for diagnosis and monitoring of the disease status. Aim: To independently validate the utility of the NETest in diagnosis and management of BPC in a multicenter, multinational, blinded study. Material and Methods: The study cohorts assessed were BPC (n = 99), healthy controls (n = 102), other lung neoplasia (n = 101) including adenocarcinomas (ACC) (n = 41), squamous cell carcinomas (SCC) (n = 37), small-cell lung cancer (SCLC) (n = 16), large-cell neuroendocrine carcinoma (LCNEC) (n = 7), and idiopathic pulmonary fibrosis (IPF) (n = 50). BPC were histologically classified as typical (TC) (n = 62) and atypical carcinoids (AC) (n = 37). BPC disease status determination was based on imaging and RECIST 1.1. NETest diagnostic metrics and disease status accuracy were evaluated. The upper limit of normal (NETest) was 20. Twenty matched tissue-blood pairs were also evaluated. Data are means ± SD. Results: NETest levels were significantly increased in BPC (45 ± 25) versus controls (9 ± 8; p < 0.0001). The area under the ROC curve was 0.96 ± 0.01. Accuracy, sensitivity, and specificity were: 92, 84, and 100%. NETest was also elevated in SCLC (42 ± 32) and LCNEC (28 ± 7). NETest accurately distinguished progressive (61 ± 26) from stable disease (35.5 ± 18; p < 0.0001). In BPC, NETest levels were elevated in metastatic disease irrespective of histology (AC: p < 0.02; TC: p = 0.0006). In nonendocrine lung cancers, ACC (18 ± 21) and SCC (12 ± 11) and benign disease (IPF) (18 ± 25) levels were significantly lower compared to BPC level (p < 0.001). Significant correlations were evident between paired tumor and blood samples for BPC (R: 0.83, p < 0.0001) and SCLC (R: 0.68) but not for SCC and ACC (R: 0.25–0.31). Conclusions: Elevated NETest levels are indicative of lung neuroendocrine neoplasia. NETest levels correlate with tumor tissue and imaging and accurately define clinical progression.

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Molecular alterations of neuroendocrine tumours of the lung

Cited by 39 publications

References 85 publications

65 YEARS OF THE DOUBLE HELIX: Classification of endocrine tumors in the age of integrated genomics

65 YEARS OF THE DOUBLE HELIX: Classification of endocrine tumors in the age of integrated genomics

Clinicopathological characteristics and genetic analysis of pulmonary carcinoid tumors: A single‑center retrospective cohort study and literature review

NETest Liquid Biopsy Is Diagnostic of Lung Neuroendocrine Tumors and Identifies Progressive Disease

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