Expression of p-AKT and p-mTOR in a large series of bronchopulmonary neuroendocrine tumors

Alì,Greta; Boldrini,Laura; Capodanno,Alessandra; Pelliccioni,Serena; Servadio,Adele; Crisman,Giuliana; Picchi,Alessandro; Davini,Federico; Mussi,Alfredo; Fontanini,Gabriella

doi:10.3892/etm.2011.291

Expression of p-AKT and p-mTOR in a large series of bronchopulmonary neuroendocrine tumors

Authors:
- Greta Alì
- Laura Boldrini
- Alessandra Capodanno
- Serena Pelliccioni
- Adele Servadio
- Giuliana Crisman
- Alessandro Picchi
- Federico Davini
- Alfredo Mussi
- Gabriella Fontanini
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Affiliations: Department of Surgery, Division of Pathological Anatomy, University of Pisa, Pisa 56126, Italy, Laboratory Medicine and Molecular Diagnostics, University of Pisa, Pisa 56126, Italy, Department of Health Sciences, University of L'Aquila, L'Aquila 67010, Italy, Department of Cardio-Thoracic Surgery, Division of Thoracic Surgery, University of Pisa, Pisa 56124, Italy
Published online on: June 20, 2011 https://doi.org/10.3892/etm.2011.291
Pages: 787-792

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Abstract

Bronchopulmonary neuroendocrine tumors (BP-NETs) are separated into four subgroups: typical carcinoid tumor (TC), atypical carcinoid tumor (AC), large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung carcinoma (SCLC). The signaling pathway involving AKT/mammalian target of rapamycin (mTOR) is crucial to the regulation of cell growth, proliferation and survival, and is frequently activated in human cancers. Consequently, mTOR is considered an attractive target for anticancer agents. The present study aimed to evaluate the expression of phosphorylated AKT and mTOR in a series of BP-NETs, and to analyze the correlations with clinicopathological parameters. p-AKT and p-mTOR levels were determined by immunohistochemistry in a series of 210 BP-NETs, including 85 SCLCs, 17 LCNECs, 26 ACs, 75 TCs and 7 tumorlets. Higher p-AKT and p-mTOR expression levels were identified in the majority of tumorlets and carcinoids in comparison to the LCNECs (P=0.0001) and SCLCs (P=0.0002). Furthermore, a significant association was observed between p-mTOR expression and tumor size (T) in SCLCs (P=0.04) and LCNECs (P=0.03): T3-T4 tumors exhibited significantly lower p-mTOR expression compared to T1-T2 tumors. In conclusion, most of the BP-NETs examined in this study expressed p-AKT and p-mTOR, suggesting that the AKT/mTOR pathway plays an important role in these tumors. Additionally, our results confirm that low- to intermediate-grade tumors are more closely associated to each other than to high-grade tumors, despite sharing common classification and a common origin from neuroendocrine cells. These findings improve our knowledge of the biological characterization of these tumors and indicate new therapeutic opportunities for the treatment of BP-NETs.

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