Repositorio
Institucional

Roa, Juan C.

Leal, Pamela

Garcia, Patricia

Sandoval, Alejandra

Letelier, Pablo

Brebi, Priscilla

Ili, Carmen

Alvarez, Hector

Tapia, Oscar

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

COLL AMER PATHOLOGISTS

ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE

en

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.

Artículo original

We acknowledge the financial support provided for this research through the FONDECYT project No. 1090171 and DIUFRO project DI11-0039.

Agradecemos el apoyo financiero brindado para esta investigación a través del proyecto FONDECYT No. 1090171 y el proyecto DIUFRO DI11-0039.

10.5858/arpa.2012-0032-OA

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MAMMALIAN TARGET

BILIARY-TRACT

THERAPEUTIC TARGET

RAD001 EVEROLIMUS

CANCER-THERAPY

PI3K PATHWAY

RISK-FACTORS

CARCINOMA

PIK3CA

MUTATIONS

OBJETIVO EN MAMÍFEROS

VÍA BILIAR

OBJETIVO TERAPÉUTICO

RAD001 EVEROLIMUS

TERAPIA CONTRA EL CÁNCER

VÍA PI3K

FACTORES DE RIESGO

CARCINOMA

PIK3CA

MUTACIONES

MAMMALIAN TARGET

BILIARY-TRACT

THERAPEUTIC TARGET

RAD001 EVEROLIMUS

CANCER-THERAPY

PI3K PATHWAY

RISK-FACTORS

CARCINOMA

PIK3CA

MUTATIONS

OBJETIVO EN MAMÍFEROS

VÍA BILIAR

OBJETIVO TERAPÉUTICO

RAD001 EVEROLIMUS

TERAPIA CONTRA EL CÁNCER

VÍA PI3K

FACTORES DE RIESGO

CARCINOMA

PIK3CA

MUTACIONES

Oncología

Patología

Biología Molecular

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

ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE

dorada

verde

acceso abierto

acceso abierto

PMID 23544944

en

Artículo original

versión publicada

ANID CONICYT FONDECYT 1090171#UFRO DI11-0039

ANID CONICYT FONDECYT 1090171

UFRO DI11-0039

COLL AMER PATHOLOGISTS

0003-9985

552

557

Tecnología de laboratorio médico

Medicina, investigación y experimentación

Patología

Medical Laboratory Technology

Medicine, Research & Experimental

Pathology

pdf

WOS:000319777200015