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.