Establishment of a Personalized Medicine in Cholangocarcinoma Patients Based on Tissue Microarray

Backgrounds: The incidence of cholangiocarcinoma (ICC) is increasing worldwide, associated with a dismal prognosis irrespective to current management modalities including aggressive surgical resection, liver transplant, radiation therapy and chemotherapy. Along with the emergence and successful experience of target therapy for various cancer diseases, a molecular-based therapeutic strategy on cholangiocarcinoma patients appears desirable. In such scenario, a personalized medicine for cholangiocarcinoma patients based on tissue microarray is mandatory to screen and design the optimal therapeutic strategy, in turn, to reach a better outcome. Facility: We are one of the most experienced surgical and pathologic team for cholangiocarcinoma. We have accumulated hundreds of surgical specimens of cholangiocarcinoma in the archives of Pathology Department, CGMH, as well in Tissue Bank, CGMH (Figure 1). All these paraffin-embedded blocks and frozen tissues are precisely corresponding with invaluable clinicopathological data collected in our Cancer Center, CGMH. Tissue microarray (TMA) has been well run for two years in CGMH (Figure 2). Further, the confirmation work can be solidly completed using animal models in our Surgical Lab, CGMH (Figure 3A-C). The works we wish to achieve in the ongoing three years include: 1. To set-up tissue microarray of cholangiocarcinoma, including intrahepatic cholangiocarcinoma (n=200), hilar cholangiocarcinoma (n=50), and extrahepatic cholangiocarcinoma (n=250) (First-year). 2. To conduct immunohistochemical study on TMA of cholangiocarcinoma against six groups of molecular targets (self-sufficiency in growth signals, insensitivity to growth-inhibitory (antigrowth) signals, evasion of programmed cell death, limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis) (First-year, second-year). 3. To verify the most significant risk factors (the highest odd ratio for survival) using animal models treated by gene silencing method (Second-year, third-year). 4. To construct a cost-effective gene profile to predict the survival risk and to design optimal therapeutic strategy for cholangiocarcinoma patients (third-year). Preliminary dataD1 silencing at day 30 post-implant. Obviously, the tumors at left flank are larger than those at right flank on each subject. This data revealed that the technique using siRNA to knock-down specific gene is available in our Lab.

Project ID:PC10001-0213
External Project ID:NSC98-2314-B182A-091-MY3