Molecular alterations of neuroendocrine tumours of the lung

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 (MEN1) mutations to carcinoids. High-grade carcinomas are also characterised by TP53 and RB1 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 DLL3 in SCLC) may require the assessment of predictive biomarkers, even in the group of neuroendocrine tumours of the lung.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2yqq2BD