AIM:To investigate the expression of PTEN/MMAC_1/TEP_1and vascular endothelial growth factor(VEGF),their rolesin biologic behavior and angiogenesis and their associationin gastric cancer.METHODS:Immunohistochemical staining was used toevaluate the expression of PTEN,VEGF and microvasculardensity(MVD)on paraffin-embedded sections in 70 patientswith primary gastric cancer and 24 patients with chronicsuperficial gastritis(CSG).Expression of PTEN,VEGF andMVD were compared with clinicopathological features ofgastric cancer.The relationship between expression ofPTEN,VEGF and MVD as well as the relationship betweenPTEN and VEGF expression in caner cells were investigated.RESULTS:PTEN expression significantly decreased(t=3.98,P<0.01)whereas both VEGF expression and MVD significantincreased(t=4.29 and 4.41,respectively,both P<0.01)in gastric cancer group compared with CSG group.PTENexpression was significantly down-regulated(t=1.95,P<0.05)whereas VEGF expression(t=2.37,P<0.05)andMVD(t=3.28,P<0.01)was significantly up-regulated inadvanced gastric cancer compared with early-stage gastriccancer.PTEN expression in gastric cancer showed a negativeassociation with lymph node metastasis(t=3.91,P<0.01),invasion depth(t=1.95,P<0.05)and age(t=4.69,P<0.01).MVD in PTEN-negative gastric cancer was significantlyhigher than that in PTEN-positive gastric cancer(t=3.69,P<0.01),and there was a negative correlation betweenPTEN expression and MVD(γ=-0.363,P<0.05).VEGFexpression was positively associated with invasion depth(especially with serosa invasion,t=4.69,P<0.01),lymphnode metastasis(t=2.31,P<0.05)and TNM stage(t=3.04,P<0.01).MVD in VEGF-positlve gastric cancer was significantlyhigher than that in VEGF-negative gastric cancer(t=4.62,P<0.01),and there was a positive correlation betweenVEGF expression of and MVD(γ=0.512,P<0.05).VEGFexpression in PTEN-negative gastric cancer was significantlystronger than that in PTEN-positive gastric cancer(t=2.61,P<0.05),and there was a significantly negative correlationbetween the expression of VEGF and PTEN(γ=-0.403,P<0.O5). CONCLUSION:Our results imply that inactivation of PTENgene and over-expression of VEGF contribute to theneovascularization and progression of gastric cancer.PTEN-related angiogenesis might be attributed to its up-regulationof VEGF expression.PTEN and VEGF could be used as themarkers reflecting the biologic behaviors of tumor and viabletargets in therapeutic approaches to inhibit angiogenesis ofgastric cancers.Zhou YJ,Xiong YX,Wu XT,Shi D,Fan W,Zhou T,Li YC,Huang X.Inactivation of PTEN is associated with increasedangiogenesis and VEGF overexpression in gastric cancer.WorldJ Gastroenterol 2004;10(21):3225-3229http://www.wjgnet.com/1007-9327/10/3225.asp AIM: To investigate the expression of PTEN / MMAC_1 / TEP_1 and vascular endothelial growth factor (VEGF), their roles in biologic behavior and angiogenesis and their association in gastric cancer. METHODS: Immunohistochemical staining was used to evaluate the expression of PTEN, VEGF and microvasculardensity (MVD) on paraffin-embedded sections in 70 patients with primary gastric cancer and 24 patients with chronicsuperficial gastritis (CSG). Expression of PTEN, VEGF and MVD were compared with clinicopathological features of gastric cancer. The relationship between expression of PTEN, VEGF and MVD as well as the relationship between PTEN and VEGF expression in caner cells were investigated. RESULTS: PTEN expression significantly decreased (t = 3.98, P <0.01) both in VEGF and MVD significantly increased (t = 4.29 and 4.41, respectively, both P <0.01) with CSG group. PTENexpression was significantly down-regulated (t = 1.95, P <0.05) VEGFexpression (t = 2.37, 01) was significantly up-regulated in gastric cancer compared with early-stage gastriccancer. PTEN expression in gastric cancer showed a negative association with lymph node metastasis (t = 3.91, P <0.01) and age (t = 4.69, P <0.01) .MVD in PTEN-negative gastric cancer was significantlyhigher than that in PTEN-positive gastric cancer (t = 3.69, P <0.01), and there was a negative correlation between PTEN expression and MVD γ = -0.363, P <0.05) .VEGFexpression was positively associated with invasion depth (especially with serosa invasion, t = 4.69, P <0.01), lymphnode metastasis , P <0.01) .MVD in VEGF-positlve gastric cancer was significantlyhigher than that in VEGF-negative gastric cancer (t = 4.62, P <0.01), and there was a positive correlation between VEGF expression of and MVD <0.05). VEGF expression in PTEN-negative gastric cancer was significantlystronger than that in PTEN-positive gastric cancer (t = 2.61, P <0.05), and there was a significant neg ative correlation between the expression of VEGF and PTEN (γ = -0.403, P <0.O5). CONCLUSION: Our results imply that inactivation of PTENgene and over-expression of VEGF contribute to the neovascularization and progression of gastric cancer. PTEN-related angiogenesis might be attributed to its up-regulation of VEGF expression. PTEN and VEGF could be used as the markers reflecting the biologic behaviors of tumor and viabletargets in therapeutic approaches to inhibit angiogenesis ofgastric cancers. Zhou YJ, Xiong YX, Wu XT, Shi D, Fan W, Zhou T, Li YC, Huang X.Inactivation of PTEN is associated with increased angiogenesis and VEGF overexpression in gastric cancer. World J Gastroenterol 2004; 10 (21): 3225-3229 http: //www.wjgnet.com/1007-9327/10/ 3225.asp