A Study On The Angiogenesis And Detection Of Micrometastases In Syrian Hamster Intrahepatic Cholangiocarcinoma Carcinogenesis

Intrahepatic cholangiocarcinoma (ICC) is a devastating neoplasm that is usually associated with a poor prognosis. As the second most common intrahepatic neoplasm, ICC presents differently from extrahepatic cholangiocarcinoma.Angiogenesis is an essential step in the progression of tumor formation and development. Tumor growth is angiogenesis dependent. Angiogenesis is driven by a balance between different positive and negative molecules influencing the growth rate of capillaries. As one of the most important angiogenic factor, the expression of VEGF ( vascular endothelial growth factor) or bFGF (basic fibroblast growth factor) can be found in many solid tumors such as mammary cancer , hepatocarcinoma , gastric carcinoma, rectal cancer, carcinoma of bladder, et al.For most solid tumors, surgery remains the most effective primary treatment. Despite apparently curative resection, significant numbers of patients develop secondary disease due to growth of undetected micrometastases. Recent advances in the detection of both isolated tumor cells and micrometastases in distant organs by means of immunocytochemical and molecular biological techniques have brought a new paradigm for the understanding of cancer biology. Immunocytochemical detection of isolated tumor cells in bone marrow (BM) is currently the most established method for monitoring micrometastases in epithelial cancer.Objective:1. To elucidate the expression of VEGF in the progression of syrian hamster ICC carcinogenesis. 2. To investigate the synergetic expression of VEGF and bFGF (basic fibroblast growth factor) in the progression of syrian hamster ICC carcinogenesis. 3. To investigate the frequency of bone marrow micrometastases and their relationship with the expression of VEGF and bFGF in the progression of syrian hamster ICC carcinogenesis.Methods:ICC was induced in syrian hamsters by aminopyrine and nitrite .On the base of the animal model which we established, the pathological changes were observed dynamically, the expression of VEGF, bFGF, cytokeratin AE1/AE3 were detected dynamically by immunohistochemistry during the progression of syrian hamster ICC carcinogenesis. Results :VEGF expression was found in 72.0% of tumour tissue , in 0.0% of control bile duct tissue(P<0.01 ). bFGF expression was found in 48.0% of tumour tissue ,in 0.0% of control bile duct tissue(P<0.01 ). The two factors (VEGF ,bFGF) expression were found in 44.0% of cancer tissue simultaneously, in 0.0% of control bile duct tissue (P<0.01 ).Cytokeratin AE1/AE3 positive cells were observed in 64.0% of ICC. When the expression of VEGF or bFGF were found in ICC, the frenquency of bone marrow micrometastases was greater than the sum of those unfounded with either factor. (p<0.01).Conclusion :VEGF and bFGF may be highly related to carcinogenesis of ICC and probably promotes its angiogenesis; At same time, there may be a synergetic effect between VEGF and bFGF in ICC carcinogenesis. VEGF and bFGF may play an important role in the pathogenesis and progression of ICC. Individual carcinoma cells present in bone marrow can be detected by sensitive immunohistochemistry. The ability of ICC to metastasize is probably related to the expression of VEGF and bFGF. Because the goal of adjuvant therapy is theeradication of occult micrometastatic tumor cells before metastatic disease becomes clinically evident, the early detection of micrometastases could identify those ICC patients who might benefit from adjuvant therapy.