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Primary lung neuroendocrine tumors (NETs) consist of typical and atypical carcinoids, large-cell neuroendocrine carcinomas and small-cell lung carcinomas. NETs are highly heterogeneous in histological characteristics, clinical presentation and natural history. While there are morphological and immunohistochemical criteria to establish diagnosis, there is a lack of universal consensus for prognostic factors or therapeutic targets for personalized treatment of the disease. Thus, identifying potential markers of neuroendocrine differentiation and prognostic factors remains of high importance. This review provides an insight into promising molecules and genes that are implicated in NET carcinogenesis, cell-cycle regulation, chromatin remodeling, apoptosis, intracellular cascades and cell-cell interactions. Additionally it supports a basis for classifying these tumors into categories that distinct molecular characteristics and disease natural history, which may have a direct impact on treatment options. In light of the recent approval of everolimus, mammalian target of rapamycin pathway inhibition and related biomarkers may play a central role in the treatment of pulmonary NETs. Future clinical trials that integrate molecular profiling are deemed necessary in order to treat patients with NET on a personalized basis.

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