Study On The Correlation Between Microsatellite Instability And Angiogenesis In Gastric Adenocarcinoma

Objective:It is now widely recognized that MSI, a form of genome instability, plays a very important role in the development of a tumor. MSI occurs in many types of carcinomas ,such as colorectal carcinoma, gastric cancer and so on. Meanwhile a unique clinical and pathological phenotype is identified for tumors with MSI-H.W hereas tumor angiogenesis as a main factor in the development of carcinoma has shown to be an independent prognostic marker in several types of human tumors.In this study ,we investigated the correlation between the MSI and the expression of vascular endothelial growth factor(VEGF) and microvessel density(MVD) in gastric adenocarcinoma in order to deduce the correlation between MSI and angiogenesis in gastric adenocarcinoma, in addition to the possibility of the two types of distinct pathway(MSI-H and MSS pathway) in tumor angiogenesis and tumor development in gastric adenocarcinoma.Methodsa) Thirty primary gastric adenocarcinoma tissues and their corresponding normal mucosa were obtained from patients atJiangSu Province Hospital from June 2002 to April 2003.b) PCR-SSCP method was used to detect MSI of thirty gastric adenocarcinoma at five microsatellite loci(BAT-26,BAT-40,D2S123,D17S250 and TP53).And thirty cases were divided into three groups(MSI-H,MSI-L and MSS) in according to the MSI analysis.Meanwhile the correlation among these three groups and relationship between MSI and clinic pathological characteristic were studied.c) Expression of VEGF and MVD were examined in these thirty cases by immunohistochemistry. The correlation between VEGF and MVD and relationship between VEGF and clinic pathological characteristic were studied.d) The correlation between MSI and VEGF , MVD was studied respectively in order to analyze the relationship between MSI and angiogenesis in human tumors.Resultsa) MSI was 43.3 percent in gastric adenocacinomas, 17 (56.7%) cases were classified as microsatellite stable (MSS).Within the remaining 13 cases ,we found that 7 (23.3%) cases were designated as MSI-L, while 6 (20.0%) cases were designated as MSI-H. There is no distinguish between MSI-H and MSI-L inclinic pathological characteristic(p>0.05) and the same as the group of MSI-L and MSS (p>0.05) .Combining the group of MSI-L and MSS ,however, they showed significant distinguish from the group MSI-H in several clinic pathological characteristics. Most MSI-H gastric cancer are detected in cases of pTNM stage 1,11, Meddle / High Differentiation and no serosa invasion(p<0.05).b) The result of the MVD was range form 29 to 82 and mean was 55+14 in thirty samples. Positive VEGF Immunostaining were detected in 18 patients ( 60.0% ) .There was a significant relationship between VEGF and MVD(p<0.01).While positive VEGF expression was higher in pTNM stage III,IV and serosa invasion positive gastric cancer(p<0.01).c) MVD among group MSI-H,MSI-L and MSS was 60+13,50+13 and 47+11 respectively.And there was no significant association among these three groups, which was similar to the group of MSI-H and combining group of MSI-L and MSS. The frequency of the positive VEGF expression was 1/6 (16.7%), 4/7(57.1%) and 13/17 (76.5%) in MSI-H,MSI-L and MSS gastric cancer respectively. The group MSI-H and MSS showed significant distinguish in VEGF expression(p<0.05) . Comparing with the group MSI-H and combining group of MSI-L and MSS the VEGFexpression also manifested significant difference (p<0.05).Conclusion:1. There is a distinguish between MSI-H gastric cancer and MSI-L&MSS gastric cancer in several clinic pathological characteristics and the same as the group of MSI-L and MSS. Most MSI-H gastric cancer are detected in cases of pTNM stage 1,11, Meddle / High Differentiation and no serosa invasion(p<0.05).2. There was a significant positive relationship between VEGF and MVD. Meanwhile the expression of VEGF indicates angiogenesis of gastric...