Immunohistochemical Expression of Phospho-mTOR Is Associated With Poor Prognosis in Patients With Gallbladder Adenocarcinoma

Leal P.; Garcia P.; Sandoval A.; Letelier P; Brebi P.; Ili C.; Alvarez H.; Tapia O.; Roa, JC

Abstract

Context.-Advanced gallbladder carcinoma (GBC) is a highly fatal disease with poor prognosis and few therapeutic alternatives. The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays a central role in cell growth and homeostasis. Its regulation is frequently altered in various tumors and is an attractive target for cancer therapy; however, its status in GBC remains unclear. Objective.-To characterize immunohistochemical expression and prognostic significance of phospho-mTOR in advanced gallbladder carcinoma. Design.-Phospho-mTOR expression was examined by immunohistochemistry in tissue microarrays containing 128 advanced GBCs and 99 cases of chronic cholecystitis, which were divided into 2 groups according to the presence or absence of metaplasia. To evaluate the association of the level of phospho-mTOR expression with clinical variables and patient survival, the advanced GBCs were classified as having low or high expression. Statistical analysis was performed by using a significance level of P < .05, and Kaplan-Meier curves were constructed for survival analysis. Results.-Immunostaining for phospho-mTOR was positive in 82 of 128 tumors (64.1%) and in 24% of chronic cholecystitis cases (16% nonmetaplasia and 32% with metaplasia) (P < .001). Survival analysis indicated that a high phospho-mTOR immunohistochemical expression was associated with poorer prognosis in patients with advanced GBC (P = .02). Conclusions.-Metaplasia is a common finding in chronic cholecystitis and is considered a precursor lesion of dysplasia. Our results suggest that the activation of mTOR occurs very early during the development of GBC, contributing to the carcinogenesis process. Phospho-mTOR expression is correlated with poor survival, supporting the potential of mTOR for targeted therapy.

Más información

Título según WOS: Immunohistochemical Expression of Phospho-mTOR Is Associated With Poor Prognosis in Patients With Gallbladder Adenocarcinoma
Título según SCOPUS: Immunohistochemical expression of phospho-mTOR is associated with poor prognosis in patients with gallbladder adenocarcinoma
Título de la Revista: Archives of Pathology and Laboratory Medicine
Volumen: 137
Número: 4
Editorial: American Medical Association
Fecha de publicación: 2013
Página de inicio: 552
Página final: 557
Idioma: English
URL: http://www.archivesofpathology.org/doi/abs/10.5858/arpa.2012-0032-OA
DOI:

10.5858/arpa.2012-0032-OA

Notas: ISI, SCOPUS