摘要
目的 探讨胃癌组织中抑癌基因PTEN/MMAC1/TEP1(以下简称PTEN)蛋白与血管内皮生长因子(VEGF)的表达关系及其在胃癌生物学行为和血管生成的作用。方法 应用免疫组织化学SP法检测35例胃癌及8例慢性胃炎组织中PTEN和VEGF蛋白的表达水平及CD_(34)标记的微血管密度(MVD)。结果 (1)与慢性胃炎组比较,胃癌组PTEN蛋白表达呈显著下降(t=2.45,P<0.05)而VEGF与MVD表达均显著增强(t=2.21,2.30,P<0.05);进展期胃癌PTEN蛋白表达显著下调(t=1.85,P<0.05),而VEGF表达呈明显上调(t=1.46,P>0.05),但差异无显著性;(2)PTEN蛋白表达下调主要与胃癌淋巴结转移(t=2.92,P<0.05)、浸润深度(t=1.85,P<0.05)、年龄(t=2.26,P<0.05)、TNM分期(t=1.77,P<0.10)有较密切的关系;PTEN蛋白阴性表达者MVD较阳性者显著增加(t=2.60,P<0.05),且两者呈显著负相关(γ=-0.363,P<0.05)。(3)VEGF表达与胃癌浆膜浸润、淋巴结转移及TNM分期均显著正相关(t=4.38、2.28、2.27,P<0.01、0.05、0.05),VEGF阳性表达者MVD显著增加(t=3.35,P=0.02),且两者呈显著正相关(γ=0.512,P<0.05);(4)胃癌PTEN蛋白阴性表达者VEGF表达较阳性者显著上调(t=-1.99,P=0.055),两者呈显著负相关(γ=-0.403,P<0.05)。结论 胃癌PTEN基因编码蛋白失表达可能通过上调VEGF表达途径。
Objective To investigate the correlation between tumor suppressor gene PTEN/MMAC1/TEP1-encoding protein and vascular endothelial growth factor (VEGF) expression, and their roles in biologic behavior and angiogenesis in gastric cancer (GC). Methods The expression of PTEN-encoding protein, VEGF and CD_(34)-labeled microvessel density (MVD) were measured on the paraffinembedded sections by immunohistochemical staining (SP) in 35 cases of primary gastric carcinoma (GC) and 8 cases of chronic superficial gastritis (CSG). Results The PTEN expression was significantly down-regulated ( t=2.45, P<0.05), while the VEGF expression was up-regulated and MVD increased in GC group as compared with those in CSG group. In advance GC, there was a significant down-regulation of PTEN expression (t=1.85, P<0.05) and a considerable up-regulation of VEGF expression (t=1.46, P>0.05), but there was no significant difference in comparison to those in early-stage GC; The down-regulation of PTEN expression in GC was significantly associated with lymph node metastasis (t=2.92, P<0.01), invasion depth (t=1.85, P<0.05), TNM stage (t=1.77, P<0.10) and age (t=2.26, P<0.05 ). MVD in PTEN-negative GC group was much more higher than that in the PTEN-positive GC (t=2.60, P<0.05) and there was a significantly inverse correlation between the PTEN expression and MVD (γ=-0.363, P<0.05). The VEGF expression was significantly associated with serosa invasion ( t=4.38, P<0.01 ), lymph node metastasis ( t=2.28, P<0.05) and TNM stage ( t=2.27, P<0.05). MVD in the VEGF-positive GC is much more higher than that in the VEGF-negative GC ( t=3.35, P=0.02 ) and there was a significantly positive correlation between the VEGF ex- pression and MVD (γ=0.512, P<0.05). The VEGF expression in the PTEN-negative GC was significantly up-regulated as compared with that in PTEN-positive GC (t=-1.99, P=0.055) and there was a significant inverse correlation between the PTEN and VEGF expression (γ=-0.403, P<0.05). Conclusion Loss expression of PTEN-encoding protein in GC might be responsible for the enhanced activity in tumor-induced neovascularization, invasion and metastasis via a putative pathway of up-regulating VEGF expression; PTEN might be a viable target of gene therapy for gastric cancer.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2004年第8期954-956,共3页
Chinese Journal of Experimental Surgery
