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Molecular alterations of neuroendocrine tumours of the lung
Author(s) -
Rossi Giulio,
Bertero Luca,
Marchiò Caterina,
Papotti Mauro
Publication year - 2018
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13394
Subject(s) - men1 , carcinoid tumour , pathology , neuroendocrine tumors , lung , small cell lung carcinoma , multiple endocrine neoplasia , lung cancer , large cell , biology , carcinoid tumors , carcinoma , cancer research , small cell carcinoma , medicine , cancer , adenocarcinoma , gene , biochemistry
Neuroendocrine tumours of the lung comprise low [typical carcinoid ( TC )], intermediate [atypical carcinoid ( AC )] and high‐grade [small‐cell lung cancer ( SCLC ) and large‐cell neuroendocrine carcinoma ( LCNEC )] malignancies, while a pre‐invasive lesion [diffuse idiopathic pulmonary neuroendocrine cell hyperplasia ( DIPNECH )] may generate a subset of peripheral carcinoid tumours. These neoplasms are differentiated conventionally based on mitotic rate, presence of necrosis and cytological details, according to the 2015 World Health Organisation ( WHO ) classification. Clinical data and molecular alterations distinguish carcinoids and high‐grade carcinomas into two separate categories. Previous studies have demonstrated a significantly higher rate of chromosomal aberrations in carcinomas (e.g. 3p and 17p deletions), but restriction of multiple endocrine neoplasia type 1 ( MEN 1 ) mutations to carcinoids. High‐grade carcinomas are also characterised by TP 53 and RB 1 gene inactivation. In this review, a critical analysis of the diagnostic and prognostic role of Ki67 labelling index and a concise discussion of the most relevant findings regarding molecular characterisation of lung neuroendocrine neoplasms are reported. In addition, we illustrate how the development of promising therapeutic strategies based on the identification of molecular targets ( mTOR inhibitors in carcinoids and targeting of the Notch ligand DLL 3 in SCLC ) may require the assessment of predictive biomarkers, even in the group of neuroendocrine tumours of the lung.