Determination of Mammalian Target of Rapamycin Hyperactivation as Prognostic Factor in Well-Differentiated Neuroendocrine Tumors

Purpose. To evaluate the role of the activation of mTOR (phosphorylated mTOR, p-mTOR) and the expression SSTR2A and IGF-1R as prognostic factor in well-differentiated neuroendocrine tumors. Methods. A retrospective study was conducted on data from patients with diagnosis of neuroendocrine tumor orig...

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Main Authors: G. Lamberti, C. Ceccarelli, N. Brighi, I. Maggio, D. Santini, C. Mosconi, C. Ricci, G. Biasco, D. Campana
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Gastroenterology Research and Practice
Online Access:http://dx.doi.org/10.1155/2017/7872519
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author G. Lamberti
C. Ceccarelli
N. Brighi
I. Maggio
D. Santini
C. Mosconi
C. Ricci
G. Biasco
D. Campana
author_facet G. Lamberti
C. Ceccarelli
N. Brighi
I. Maggio
D. Santini
C. Mosconi
C. Ricci
G. Biasco
D. Campana
author_sort G. Lamberti
collection DOAJ
description Purpose. To evaluate the role of the activation of mTOR (phosphorylated mTOR, p-mTOR) and the expression SSTR2A and IGF-1R as prognostic factor in well-differentiated neuroendocrine tumors. Methods. A retrospective study was conducted on data from patients with diagnosis of neuroendocrine tumor originated from pancreas (pNET) or gastrointestinal tract (stomach, appendix, and ileus; GI-NET) made between January 2003 and December 2004 and followed up at our institution. Archival material should be available for revision according to WHO 2010 neuroendocrine tumor classification and for p-mTOR, SSTR2A, and IGF-1R immunostaining, calculating a quantitative score (QS). We evaluated clinical, pathological, and immunohistochemistry features for association with the presence of advanced disease at diagnosis and disease relapse in patients who have undergone radical surgery. Results. Archival material from 64 patients was analyzed (37 pNETs and 27 GI-NETs). In these patients, G2 grading, low SSTR2A QS, and high p-mTOR QS were associated with advanced disease at diagnosis at multivariate analysis. Risk of recurrence in 49 patients with R0-resected tumors was higher for G2 grading, stage IIIB-IV, low IGF-1R QS, and high p-mTOR QS at univariate analysis. Conclusions. With the limits of retrospective data, activation of m-TOR is correlated with advanced disease at diagnosis and with shorter disease-free survival after R0 resection. Validation through prospective studies is needed.
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spelling doaj-art-e49bb3fbae1a4484a482b4613b70b40e2025-02-03T01:32:06ZengWileyGastroenterology Research and Practice1687-61211687-630X2017-01-01201710.1155/2017/78725197872519Determination of Mammalian Target of Rapamycin Hyperactivation as Prognostic Factor in Well-Differentiated Neuroendocrine TumorsG. Lamberti0C. Ceccarelli1N. Brighi2I. Maggio3D. Santini4C. Mosconi5C. Ricci6G. Biasco7D. Campana8Department of Experimental, Diagnostic and Specialty Medicine, S.Orsola-Malpighi University Hospital, Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine, S.Orsola-Malpighi University Hospital, Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine, S.Orsola-Malpighi University Hospital, Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine, S.Orsola-Malpighi University Hospital, Bologna, ItalyDepartment of Diagnostic and Prevention Medicine, S.Orsola-Malpighi University Hospital, Bologna, ItalyDepartment of Diagnostic and Prevention Medicine, S.Orsola-Malpighi University Hospital, Bologna, ItalyDepartment of Medical and Surgical Sciences, S.Orsola-Malpighi University Hospital, Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine, S.Orsola-Malpighi University Hospital, Bologna, ItalyDepartment of Medical and Surgical Sciences, S.Orsola-Malpighi University Hospital, Bologna, ItalyPurpose. To evaluate the role of the activation of mTOR (phosphorylated mTOR, p-mTOR) and the expression SSTR2A and IGF-1R as prognostic factor in well-differentiated neuroendocrine tumors. Methods. A retrospective study was conducted on data from patients with diagnosis of neuroendocrine tumor originated from pancreas (pNET) or gastrointestinal tract (stomach, appendix, and ileus; GI-NET) made between January 2003 and December 2004 and followed up at our institution. Archival material should be available for revision according to WHO 2010 neuroendocrine tumor classification and for p-mTOR, SSTR2A, and IGF-1R immunostaining, calculating a quantitative score (QS). We evaluated clinical, pathological, and immunohistochemistry features for association with the presence of advanced disease at diagnosis and disease relapse in patients who have undergone radical surgery. Results. Archival material from 64 patients was analyzed (37 pNETs and 27 GI-NETs). In these patients, G2 grading, low SSTR2A QS, and high p-mTOR QS were associated with advanced disease at diagnosis at multivariate analysis. Risk of recurrence in 49 patients with R0-resected tumors was higher for G2 grading, stage IIIB-IV, low IGF-1R QS, and high p-mTOR QS at univariate analysis. Conclusions. With the limits of retrospective data, activation of m-TOR is correlated with advanced disease at diagnosis and with shorter disease-free survival after R0 resection. Validation through prospective studies is needed.http://dx.doi.org/10.1155/2017/7872519
spellingShingle G. Lamberti
C. Ceccarelli
N. Brighi
I. Maggio
D. Santini
C. Mosconi
C. Ricci
G. Biasco
D. Campana
Determination of Mammalian Target of Rapamycin Hyperactivation as Prognostic Factor in Well-Differentiated Neuroendocrine Tumors
Gastroenterology Research and Practice
title Determination of Mammalian Target of Rapamycin Hyperactivation as Prognostic Factor in Well-Differentiated Neuroendocrine Tumors
title_full Determination of Mammalian Target of Rapamycin Hyperactivation as Prognostic Factor in Well-Differentiated Neuroendocrine Tumors
title_fullStr Determination of Mammalian Target of Rapamycin Hyperactivation as Prognostic Factor in Well-Differentiated Neuroendocrine Tumors
title_full_unstemmed Determination of Mammalian Target of Rapamycin Hyperactivation as Prognostic Factor in Well-Differentiated Neuroendocrine Tumors
title_short Determination of Mammalian Target of Rapamycin Hyperactivation as Prognostic Factor in Well-Differentiated Neuroendocrine Tumors
title_sort determination of mammalian target of rapamycin hyperactivation as prognostic factor in well differentiated neuroendocrine tumors
url http://dx.doi.org/10.1155/2017/7872519
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