Expressions Of VEGF And Its Receptor Flk-1 In Gallbladder Carcinomas And Their Association With MVC

ObjectiveTumor growth, invasion and metastases are closely associated with angio-genesis. Some studies showed that tumor angiogenesis is the net effect of several angiogenic and antiangiogenic factors and their receptors among which vascular endothelial growth factor (VEGF) is one of the most important angiogenic regulators so far. VEGF is the only highly specific vascular endothelial cell mitogen which plays a central role in tumor angiogenesis, invision and metastases by increasing microvessels permeability, stimulating endotheliocytes division and proliferation, changing some endotheliocyte genes expressions and promiting endothelial cells to secrete histic factors and collagenases. Fetal liver kinase - 1 ( Flk - 1) is a crucial high - affinity tyrosine kinase receptor for VEGF in physiological and pathological vasculogenesis, which locates in vessel endotheliocytes and ' tumor cells. Flk - 1 induces tumor angiogenesis by up - regulating the expression of VEGF. A gallbladder carcinoma is one of the most lethal tumors in biliary system. Some data established that its incidence was only inferior to that of gastric, rectal, esophageal, hepatic and pancealic cancer in alimentary system. Most patients had low operation excision rates, short - term postoperation survival and poor prognoses because local diffusion and metastases had occurred, which was due to nonspecific clinical manifestation and insidious course at the early stage. Extensive previous reports demonstrated that expressions of VEGF and its receptor Flk - 1 were highly related to biological behavior in many malignant neoplasms. However, no information is available about expressions of VEGF and Flk - 1 in gallbladder carcinomas and their association with MVC. Inthis study, we detected VEGF, Flk - 1 expressions and MVC by immunohisto-chemical method to analyze the angiogenesis action of VEGF, Flk - 1 and the relationships between VEGF, Flk - 1, MVC and clinicopathological parameters, and therefor to supply the basis for VEGF and its receptor Flk - 1 dependent an-tiangiogenic therapy.MethodsForty - nine specimens of gallbladder carcinomas were randomly selected from the First and the Second Hospitals of China Medical University from March 1999 to December 2002, and these specimens were all stained by hematoxylin and eosin and diagnosed pathologically. No antianiogenic therapy was used prior to surgery. The stains of VEGF, Flk - 1 and MV were completed by the Strepta-vidin - Peroxidase complex immunohistochemical method.ResultsThe value of MVC was (34. 5 + 11. 8)/HP in 49 cases with gallbladder carcinomas, and it was closely correlated with Nevin staging, lymph node metas-tases and tumor differentiation ( P <0.05). The positive rate of VEGF in 49 cases with gallbladder cacinomas was 63. 3% (31/49) , and its expression was significantly lower in cases of Nevin staging SI - S3 and without metastases than that of Nevin staging S4 - S5 and with metastases respectively ( P <0.05) , but was not correlated with tumor differentiation ( P > 0. 05 ). The expression of VEGF was markedly correlated with MVC (t = 2. 061, P < 0. 05 ). The positive rate of Flk - 1 in 49 cases with gallbladder cacinomas was 67. 3% (33/49) , and it was correlated with VEGF ( P < 0. 05 ) , but there were no relationships between Flk - 1 and Nevin staging, lymph node metastases, tumor differentiation or MVC (P >0.05). The percentage of the cases with both positive VEGF and Flk - 1 expressions was 49. 0% (24/49) , and their MVC value was markedly higher (t = 2.480, P < 0.05 ) , most of them were Nevin staging S4 -S5 and with lymph node metastases.ConclusionsI. The expression of VECF and MVC had closely correlation with Nevin staging and lymph node metastases, so they may be used as the important parameters to reflect the malignant degree of gallbladder carcionmas.II. The expression of VEGF was markedly related to MVC, which illuminates VEGF expression is consistent with angiogenic position.lH. There were no relationships between Flk - 1 and Nevin staging,...