title: Expression of insulin-like growth factor I receptor as a biomarker for predicting prognosis in biliary tract cancer patients.
abstract: Carcinomas of the gallbladder (GBCa) and bile ducts are aggressive tumors with poor survival and it is, therefore, essential to elucidate the molecular mechanisms of the various signaling pathways in order to develop effective therapies. In this study, tumor specimens from 40 GBCa patients, 12 extrahepatic bile duct carcinoma patients and 26 intrahepatic bile duct carcinoma patients from the USA and Japan were investigated for insulin-like growth factor I receptor (IGF-IR), mammalian target of rapamycin (mTOR) and rapidly accelerated fibrosarcoma-1 (Raf-1) expression by immunohistochemistry; in addition, the correlations with histological type, pathological stage and patient outcome were analyzed. Positive expression of IGF-IR, mTOR and Raf-1 were identified in 68, 73 and 85% of the specimens, respectively. There was no association with histological type and pathological stage, although the positive expression rate of Raf-1 was higher in advanced-stage GBCa. Moreover, patients with positive expression of IGF-IR exhibited significantly reduced survival compared to those with negative IGF-IR expression. In conclusion, IGF-IR, mTOR and Raf-1 were highly expressed in biliary tract cancer and targeted therapy against IGF-IR may be an effective strategy. Among these molecules, IGF-IR expression was found to be a useful biomarker for identifying patients who may benefit from additional treatment.
authors.affiliation: Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Molecular Pathology Laboratory, Department of Pathology, Pontifical Catholic University of Chile, Santiago 8320000, Chile.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Roa
authors.affiliation: Minato Shiba Clinic, Tokyo 105-0014, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kawamoto
authors.affiliation: Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ishige
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Donghui
authors.initials: D
authors.lastname: Li
authors.affiliation: Medical University of South Carolina, Hollings Cancer Center, Charleston, SC 29425, USA.
authors.forename: Melanie B
authors.initials: MB
authors.lastname: Thomas
authors.affiliation: Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Shoda
keywords: biliary tract cancer; insulin-like growth factor I receptor; mammalian target of rapamycin; rapidly accelerated fibrosarcoma-1