PTEN在食管癌中的表达及其与微血管密度和临床病理特征的关系

目的:探讨抑癌基因PTEN在食管癌及癌旁正常组织中的表达, 及其与微血管密度(MVD)和临床病理特征的关系.方法:选用食管鳞癌手术切除病理标本48例,手术远端正常食管组织标本40例. 采用免疫组织化学SP法检测PTEN编码蛋白的表达水平,CD31抗体进行血管内皮染色、计算微血管密度, 分析PTEN在不同组织中的表达与MVD和食管癌组织分化程度、浸润深度、淋巴结转移的关系.结果:食管鳞癌组织中PTEN编码蛋白阳性表达率低于癌旁正常食管黏膜组织(52.08%vs 92.50%, P<0.01), 而其MVD值显著高于癌旁正常组织(41.72±8.67 vs 21.01±3.85, P<0.01); Ⅰ、Ⅱ、Ⅲ级鳞癌PTEN阳性表达率有显著差异(75.0% vs 55.0% vs 33.33%, 均P<0.05), MVD值差异无统计学意义; 癌组织侵及浅肌层以上与深肌层PTEN与MVD值的表达有显著差异(77.27% vs 42.31%; 35.49±5.89vs 46.01±6.27, 均P<0.01); 淋巴结转移组与非转移组PTEN阳性表达率无显著差异, MVD值差异则有统计学意义(46.71±7.89 vs 35.92±2.54, P<0.01).结论:抑癌基因PTEN、MVD在食管癌中表达的高低, 与肿瘤的生长、浸润和转移相关.PTEN基因表达的突变或缺失能促进肿瘤血管的形成, 可作为临床治疗和判断预后的依据.     

胃癌组织碱性成纤维细胞生长因子表达及对血管新生和肿瘤进展的影响

目的　探讨碱性成纤维细胞生长因子 (bFGF)在胃癌组织中表达及其对血管新生和肿瘤生物学行为的影响。方法　应用免疫组化SP法检测 74例胃癌 ,17例癌旁组织bFGF表达及间质微血管密度 (MVD)。结果　胃癌组织中肿瘤细胞、间质新生血管高度表达bFGF。癌组织bFGF表达(77.0 3% )明显高于癌旁组织 (2 9.4 1% ,P <0 .0 1)。癌旁胃黏膜及伴有肠上皮化生的胃黏膜表达bFGF较弱。bFGF高表达组的平均MVD值 (79.3± 11.2 )明显高于bFGF低表达组 (71.2± 11.9,P <0 .0 5 )。此外bFGF表达程度与胃癌淋巴结转移和癌浸润深度密切相关。结论　bFGF可促进肿瘤间质微血管生成 ,加速肿瘤浸润和转移。     

抑癌基因PTEN在食管癌中的表达及其临床意义

目的　研究食管癌中第 10号染色体丢失的张力蛋白同源的磷酸脂酶基因 (PTEN基因 )的表达及其临床意义。方法　用免疫组化方法检测 68例食管癌和癌旁正常组织中PTEN蛋白的表达水平。结果　食管癌中PTEN蛋白表达率为 70 .6% ,而癌旁正常组织为 10 0 % ,PTEN蛋白表达与肿瘤分化程度、浸润深度、淋巴结转移及TNM分期相关 (P <0 .0 5 )。PTEN蛋白在高中低分化组的阳性表达率分别为 90 .17%、66.67%和 5 0 %。单变量分析PTEN蛋白阳性表达组 3、5年生存率分别为 70 .3 %和 5 4.6% ,高于阴性表达组的 40 .2 5 %和 16.1%。经long rank时序检验差异有显著性(P =0 .0 2 5 8) ,Cox回归模型多变量分析显示 ,PTEN是一个独立预后指标 (P =0 .0 12 )。结论　从蛋白水平证明PTEN基因表达缺失或降低与食管癌的发生发展有关 ,PTEN蛋白表达的检测可能成为判断食管癌细胞生物学行为及部分患者预后的参考指标之一     

Eph-B4受体及其配体Ephrin-B2在胃癌组织中的表达及其病理学意义

目的 :探讨Eph B4受体与其配体Ephrin B2在胃癌组织中的表达及其对血管生成和肿瘤生物学行为的影响。方法 :应用免疫组化SABC法检测 93例胃癌和 30例癌旁组织中Enp B4受体与其配体Ephrin B2的表达及间质微血管密度 (MVD)。结果 :胃癌组织中肿瘤细胞、间质新生血管的Eph B4与Ephrin B2高度表达 ,癌组织中Eph B4与Ephrin B2的阳性表达 (分别为 49.46 %和 50 .54 % )明显高于癌旁组织 (分别为 2 0 .0 %和 2 3 .3 % ,P <0 .0 1 )。Enp B4与Ephrin B2阳性表达组的平均MVD值 (分别为 56 .2 1± 1 5 .3和 62 .41± 1 6 .9)明显高于Enp B4与Ephrin B2阴性表达组 (分别为 32 .2 2± 1 2 .9和 34 .1 2± 1 4 .7,P <0 .0 5和P <0 .0 1 )。此外 ,Enp B4与Ephrin B2表达程度还与胃癌的转移和癌浸润程度密切相关。结论 :Enp B4与Ephrin B2可以促进肿瘤间质的血管生成 ,加速肿瘤浸润和转移     

PTTG、ERK蛋白在结肠腺癌中的表达及其与MVD的关系

应用免疫组化SP法检测垂体瘤转化基因(PTTG)和细胞外信号调节蛋白激酶(ERK)蛋白在结肠腺癌、中重度结肠不典型增生和癌旁肠组织中的表达情况,CD34标记血管内皮细胞并计数微血管密度(MVD).结果 PTTG、ERK蛋白在癌旁肠组织中均无表达,明显低于结肠不典型增生和结肠腺癌组(P均＜0.05);PTTG、ERK蛋白表达与肿瘤组织分化程度、浸润深度、淋巴结转移及分期有关(P＜0.05);PTTG、ERK蛋白在结肠癌组织中的表达呈显著正相关(P＜0.05);MVD在PTTG蛋白阳性表达组的均值明显高于其阴性表达组(P＜0.05).认为PTTG、ERK蛋白可能在结肠癌的演进中起着协同作用并参与肿瘤微血管的生成.     

微血管密度与肝癌脉管侵袭关系的研究

探讨肿瘤新生微血管密度 (microvesseldensity,MVD)与原发性肝细胞癌 (hepatocellularcarcinoma ,HCC)脉管侵袭和转移的关系。采用免疫组化法 (streptavidinperoxidase ,S -P链霉素抗生物素蛋白 -过氧化酶 )对手术切除的 5 8例原发性肝细胞癌和 5 8例癌旁组织的石蜡包埋组织标本中的MVD进行了检测。在 4 0 0倍视野下选择 5个最密集区 ,记算MVD数量 ,取其均数。 (1)MVD在HCC组织中比癌旁组织明显增高 (P <0 0 1) ;(2 )HCC中有转移者及包膜不完整者 ,MVD明显高于无转移者及包膜完整者 ,(P <0 0 1) ;(3)HCC中脉管侵袭阳性组 ,MVD明显高于脉管侵袭阴性组 (P <0 0 1)。原发性肝细胞癌组织中的MVD与肿瘤的脉管侵袭和转移行为密切相关 ,可作为判定HCC转移及预后的指标     

PTEN、survivin蛋白在食管癌中的表达及其相关性

应用免疫组织化学sP法检测60例食管癌组织及20例癌旁正常黏膜的survivin和PTEN的表达水平。结果：survivin在食管癌组织的阳性表达率为70．0％,癌旁正常黏膜为40．0％（P〈0．05）;低、高分化癌的阳性表达率差异显著（P〈0．05）;有、无淋巴结转移者的阳性表达率分别为88．9％、61．9％（P〈0、05）;其表达与肿瘤的浸润深度显著相关（P〈0．05）,与患者的性别、年龄无关（P〉0．05）。PTEN在癌旁正常黏膜阳性表达率为90．0％。食管癌组织为36．7％（P〈0．05）。低、高分化癌的阳性表达率差异显著（P〈0．05）;有、无淋巴结转移者的阳性表达率分别为16．7％、45．2％（P〈0．05）;与患者的性别、年龄及浸润深度无关（P〉0．05）。survivin和PTEN在食管癌中的表达呈负相关。认为PTEN低表达及survivin的过表达与食管癌的发生及其生物学行为密切相关,可作为食管癌早期诊断及评估预后的客观指标。     

Survivin在原发性肝细胞癌中的表达及意义

目的　Survivin是凋亡抑制蛋白中的一种 ,选择性地表达于恶性肿瘤组织。该文研究Sur vivin基因在原发性肝细胞癌中的表达及生物学意义。方法　收集 2株肝细胞癌细胞株 ,4 0例原发性肝癌组织标本及相应的癌旁组织 ,以Westernblotting法检测Survivin蛋白表达 ;半定量RT PCR法检测SurvivinmRNA表达 ;肝癌细胞凋亡指数采用原位末端标记法检测。结果　 2株肝癌细胞株和 85 % (34例 )的肝癌组织表达Survivin蛋白和mRNA ,而癌旁组织内无一例阳性表达。Survivin蛋白表达的阳性率在肝内转移组为 93.5 % ,显著高于肝内无转移组 (5 5 .6 % ,P <0 .0 5 ) ;在门静脉癌栓浸润组为 92 .8% ,显著高于无门静脉癌栓浸润组 (6 6 .7% ,P <0 .0 5 )。RT PCR显示 ,2株肝癌细胞株和 85 .0 % (34例 )的肝癌组织表达SurvivinmRNA ,与Westernblotting的结果一致 ,SurvivinmRNA的表达水平在肝内转移组 (1.10 5± 0 .396 )和门静脉癌栓浸润组 (1.137± 0 .4 0 4 )中 ,显著高于肝内无转移组 (0 .5 72± 0 .0 82 )和无门静脉癌栓浸润组 (0 .6 2 7± 0 .12 2 ,P <0 .0 5 )。所有肝癌组织标本中均可检测到凋亡细胞 ,但Survivin表达阳性组的凋亡指数 (1.15 2 %± 0 .32 6 % )显著低于Survivin表达阴性组 (4.5 0 2 %± 0 .830 % ,P <0 .0 5     

血管内皮细胞生长因子的表达及微血管密度与胆囊癌浸润、转移及预后的相关研究

探讨血管内皮细胞生长因子 (vascularendothelialgrowthfactor,VEGF)及微血管密度 (Microvesseldensity ,MVD)在胆囊癌发生发展中的作用及与胆囊癌浸润、转移及预后的关系。应用S -P免疫组化技术对 3 1例经手术切除的原发性胆囊癌及 10例经手术切除的慢性胆囊炎标本进行VEGF蛋白和微血管密度检测。 3 1例胆囊癌组织中癌旁VEGF表达及MVD值均明显高于癌中央及正常组织 ,三者差异具有显著性 (P <0 0 1) ;VEGF表达与MVD具有相关性 ,VEGF阳性者MVD值显著高于阴性者 (P <0 0 1) ;VEGF表达和MVD与胆囊癌分化程度、浸润转移、Nevin分期密切相关 (P <0 0 1) ;VEGF阳性者及高MVD者预后较阴性者差 ;Cox比例危险模型多因素分析表明 :VEGF对胆囊癌是一个独立的预后因子。VEGF的表达及MVD在胆囊癌的发生和浸润转移过程中发挥重要的作用 ,VEGF和MVD可作为反映胆囊癌生物学行为的指标     

结肠癌血管内皮生长因子与微血管密度和p53的关系

目的探讨血管内皮生长因子(VEGF)在结肠癌中的表达及其与微血管密度(MVD)和p53之间的关系.方法用免疫组化SABC法检测68例结肠癌组织不同区域VEGF、MVD和p53的阳性表达.结果结肠癌区VEGF、MVD和p53的表达明显高于癌旁区和正常区.结肠癌组织VEGF及p53的表达与肿瘤浸润深度、淋巴结转移、远处转移、血管侵犯及Dukes分期密切相关,而与组织学分型无关.p53(+)或VEGF(+)组MVD(34.6±12.2;31.2±12.6)均显著高于p53(-)或VEGF(-)组(15.0±7.9;12.7±6.3,P＜0.01);VEGF和p53均为阳性时,MVD值最大(36.5±11.9,P＜0.01).MVD记数与VEGF表达明显相关(P＜0.01),p3表达与VEGF表达和MVD记数均显著相关(P＜0.01).结论在结肠癌血管生成过程中,可能存在p53-VEGF调节旁路,p53基因在调控肿瘤血管形成方面起重要作用.     

Coexpression of vascular endothelial growth factor and p53 protein in squamous cell carcinoma of the esophagus

OBJECTIVE: p53 plays a role in tumor angiogenesis, and vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis. The aim of the present study was to clarify how expression of p53 protein participates in angiogenesis, and whether the coexpression of VEGF and p53 protein has a significance for angiogenesis and the clinicopathological features in esophageal squamous cell carcinoma (SCC). METHODS: Tissues samples were taken from 60 patients with esophageal SCC after surgery. The expression of VEGF and p53 protein in these SCC was examined immunohistochemically. Microvessel density (MVD) was determined by counting microvessels in tumor sections stained for Factor VIII-related antigen. Ki-67 labeling index (LI) was calculated, based on Ki-67 antigen immunostaining, as a proliferative marker. Apoptotic index (AI) was calculated, based on the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling, to evaluate apoptosis. RESULTS: VEGF expression was observed in 58.3%, and p53 protein expression was observed in 61.7% of the 60 patients. VEGF and p53 protein were significantly coexpressed in 26 (43.4%). Histological venous invasion (p < 0.01) and distant metastasis (p < 0.05) were significantly correlated with p53 protein expression. The two parameters were more frequently observed in the SCC with VEGF/p53 coexpression than in those without the coexpression. The MVD and Ki-67 LI were significantly higher (p < 0.01 and p < 0.001), and the AI was significantly lower (p < 0.001) in the SCC with p53 protein expression than in the SCC without it. The MVD and Ki-67 LI were higher, and the AI was lower in the SCC with VEGF/p53 coexpression than in those without the coexpression. The 5-yr survival rate in patients with the coexpression was poorer than in the other patients. CONCLUSION: These results suggest that mutant p53 expression is associated with angiogenesis and distant metastasis in esophageal SCC, and that the coexpression of p53 and VEGF may play an important role in angiogenesis, and have important clinical significance.     

Tnactivation of PTEN is associated with increased angiogenesis and VEGF overexpression in gastric cancer

AIM: To investigate the expression of PTEN/MMAC1/TEP1and 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 microvascular density (MVD) on paraffin-embedded sections in 70 patients with primary gastric cancer and 24 patients with chronic superficial 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) whereas both VEGF expression and MVD significant increased (t = 4.29 and 4.41, respectively, both P＜0.01)in gastric cancer group compared with CSG group. PTEN expression was significantly down-regulated (t = 1.95,P＜0.05) whereas VEGF expression (t = 2.37, P＜0.05) and MVD (t = 3.28, P＜0.01) was significantly up-regulated in advanced gastric cancer compared with early-stage gastric cancer. PTEN expression in gastric cancer showed a negative association 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 significantly higher 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). VEGF expression was positively associated with invasion depth (especially with serosa invasion, t = 4.69, P＜0.01), lymph node metastasis (t= 2.31, P＜0.05) and TNM stage (t= 3.04,P＜0.01). MVD in VEGF-positive gastric cancer was significantly higher 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 (γ = 0.512, P＜0.05). VEGF expression in PTEN-negative gastric cancer was significantly stronger than that in PTEN-positive gastric cancer (t = 2.61,P＜0.05), and there was a significantly negative correlation between the expression of VEGF and PTEN (γ = -0.403,P＜0.05).CONCLUSION: Our results imply that inactivation of PTEN gene and over-expression of VEGF contribute to the neovascularization and progression of gastric cancer. PTENrelated 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 viable targets in therapeutic approaches to inhibit angiogenesis of gastric cancers.     

Significance of macrophage chemoattractant protein-1 expression and macrophage infiltration in squamous cell carcinoma of the esophagus

OBJECTIVES: Macrophage chemoattractant protein-1 (MCP-1) is a chemokine-inducing infiltration of macrophages, which can play several roles in tumor growth and metastasis. We have attempted to clarify the relationship between MCP-1 expression and macrophage infiltration in esophageal squamous cell carcinoma (SCC). METHODS: Paraffin-embedded sections of tissue samples taken from 56 patients with esophageal SCC after curative surgery were immunohistochemically stained for MCP-1, CC chemokine receptor 2 (CCR-2), and thymidine phosphorylase (TP). Macrophage recruitment in SCC was evaluated by monocytic count based on CD68 immunostaining. Microvessels immunostained for Factor VIII-related antigen were counted in SCC, and microvessel density (MVD) was determined. Ki-67 labeling index was calculated based on Ki-67 immunostaining, and an apoptotic index was calculated based on the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling. RESULTS: MCP-1 was expressed in cancer cells of 31 SCC (55.4%) and in stromal cells mainly identified as macrophages of 16 SCC (28.6%). CCR-2 was expressed in stromal cells of all SCC and in vascular endothelial cells of 15 SCC (26.8%). There was a significant correlation between the expression of MCP-1 in cancer cells and of CCR-2 in stromal cells. TP was expressed in stromal cells in 76.7% of the SCC. Monocytic count, MVD, and Ki-67 LI in SCC with MCP-1 expression in cancer cells were higher than that without, and apoptotic index in SCC with MCP-1 expression in cancer cells were lower than that without. Furthermore, the monocytic count was positively correlated with MVD, while it was inversely correlated with apoptotic index. Clinicopathologically, MCP-1 expression in cancer cells was correlated with venous invasion, distant metastasis, and lymph node metastasis. Monocytic count in SCC with venous invasion, distant metastasis, or lymph node metastasis was higher than that without them. Five-year survival rate in the patients with high monocytic count or MCP-1 expression was worse than that with a low monocytic count or without MCP-1 expression. CONCLUSIONS: These results suggest that MCP-1 expression and macrophage infiltration is associated with angiogenic promotion in esophageal SCC. MCP-1 expression may be interactively associated with macrophage infiltration in esophageal SCC; MCP-1 may play an important role in tumor angiogenesis through production of angiogenic factors, such as TP, by recruited macrophages in esophageal SCC. Furthermore, CCR-2 expression in vascular endothelial cells may participate partially in angiogenesis. Clinicopathologically, esophageal SCC patients with MCP-1 expression have no favorable prognosis.     

大肠癌PTEN蛋白的表达及与血管形成的关系

目的探讨PTEN基因在大肠癌中的表达规律以及在血管形成中的作用。方法采用免疫组化SP法检测72例大肠癌PTEN的蛋白表达以及微血管密度(MVD)。结果大肠癌组织PTEN的表达率明显低于正常结肠黏膜组织(P<0.01)。低分化大肠癌PTEN的表达率显著低于中分化和高分化大肠癌(P<0.01)。PTEN的表达与肿瘤大小、有无淋巴结和肝转移、浸润深度以及Dukes分期无明显关系(P>0.05)。此外,PTEN阳性表达组大肠癌的MVD数量明显低于阴性组(P<0.01)。结论大肠癌中存在PTEN基因的失活,PTEN的表达和大肠癌的分化程度密切相关,并且在肿瘤的血管形成中起一定作用。     

Histochemical study of angiogenesis in basaloid squamous carcinoma of the esophagus

Angiogenesis of esophageal basaloid squamous carcinoma (BSC) was studied immunohistochemically and compared with that of squamous cell carcinoma (SCC). In tissues taken from six patients with esophageal BSC and 35 with esophageal SCC, angiogenesis was evaluated by measuring microvessel density (MVD), defined as the microvessel count determined using factor VIII-related antigen immunostaining, and by measuring immunoreactivity of vascular endothelial growth factor (VEGF) and thymidine phosphorylase (dThdPase). Three of the six patients with BSC had distant metastases. There was no difference of MVD between BSC and SCC (22.0 +/- 4.6 vs. 27.6 +/- 9.4). VEGF expression tended to be more frequently observed in BSC than in SCC (100% vs. 60.0%; p = 0.066). Strong expression of VEGF was detected in three BSC with distant metastases; however, there was no difference in the rate of strong VEGF expression between BSC and SCC. The MVD in the cases of BSC with strong VEGF expression, i.e. in the cases with distant metastases, was higher than that in the cases of BSC with weak VEGF expression (p=0.049). There was no difference in dThdPase expression of the cancer cells between BSC and SCC (50.0% vs. 54.3%), whereas the infiltrating stromal cells of all the BSC expressed dThdPase. Strong dThdPase expression in the cancer cells or in the infiltrating stromal cells was observed in two and three BSC, respectively. However, there were no differences in the rate of cancer cells or stromal cells with strong dThdPase expression between BSC and SCC. In one BSC with high MVD and distant metastases, VEGF and dThdPase were both strongly expressed. The vascularity of esophageal BSC was not different from that of SCC. VEGF may participate in angiogenesis of esophageal BSC and may influence the rate of metastasis in esophageal BSC patients. dThdPase may play a partial rule in angiogenesis and metastasis in some cases of BSC.     

Expression of PTEN and its correlation with angiogenesis in gastric carcinoma]

BACKGROUND/AIMS: Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a recently clarified tumor suppressor gene located in 10q23.3. Alterations of this gene are associated with tumor progression and unfavorable outcome in various human cancers. Recently, PTEN has a possible role in angiogenesis by modulating angiogenic factor including vascular endothelial growth factor (VEGF). The aim of this study was to investigate the roles of PTEN and VEGF status for angiogenesis in human gastric cancer. METHODS: We conducted an immunohistochemical investigation of PTEN and VEGF expression in 90 cases of paraffin section obtained from gastric cancer patients undergone surgical treatment. RESULTS: Negative expression of PTEN and positive expression of VEGF in gastric cancer tissues, were demonstrated in 40.0% and 77.8% of cases, respectively. However, no significant correlation was found between PTEN, VEGF expression and various clinicopathological parameters. PTEN expression did not correlate significantly with VEGF expression (p=0.301). High microvessel density (MVD) was significantly associated with lymph node metastasis and poor survival (p=0.014, 0.011, respectively). The mean MVD value of PTEN negative tumors was 90.4+/-43.0 and significantly higher than that of PTEN positive tumors (p=0.028). The mean MVD value of VEGF positive tumors was 86.4+/-6.7 and significantly higher than that of VEGF negative tumors (p=0.002). The mean MVD value of PTEN negative and VEGF positive tumors was 98.0+/-42.2, and significantly higher than those of the others. CONCLUSIONS: These results suggest that loss of PTEN expression may play a critical role in tumor progression and metastasis by stimulating tumor angiogenesis in human gastric cancer.     

血管内皮生长因子和血管生成与大肠癌发展的关系

目的：探讨血管内皮细胞生长因子（VEGF）和血管生成与大肠癌发展的关系。方法：应用免疫组化法,检测102例大肠癌组织VEGF蛋白表达和微血管密度（MVD）,分析VEGF和MVD及其与大肠癌组织学分级、浸润深度、Dukes分期、淋巴结转移、肝转移和预后的关系。结果：VEGF阳性者MVD值显著高于阴性者（P＜0．01）,VEGF表达和MVD与大肠癌Dukds分期、淋巴结转移和肝转移密切相关（P均＜0．01）,VEGF表达阳性或高MVD的大肠癌患者5年生存率较低（P＜0．01）。结论：VEGF与大肠癌的血管生成密切相关,对大肠癌的生长和浸润转移有促进作用,VEGF和MVD可作为反映大肠癌生物学行为的客观指标。     

Inactivation of PTEN is associated with increased angiogenesis and VEGF overexpression in gastric cancer

AIM: To investigate the expression of PTEN/MMAC1/TEP1 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 microvascular density (MVD) on paraffin-embedded sections in 70 patients with primary gastric cancer and 24 patients with chronic superficial 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&lt;0.01) whereas both VEGF expression and MVD significant increased (t = 4.29 and 4.41, respectively, both P&lt;0.01) in gastric cancer group compared with CSG group. PTEN expression was significantly down-regulated (t=1.95, P&lt;0.05) whereas VEGF expression (t = 2.37, P&lt;0.05) and MVD (t= 3.28, P&lt;0.01) was significantly up-regulated in advanced gastric cancer compared with early-stage gastric cancer. PTEN expression in gastric cancer showed a negative association with lymph node metastasis (t= 3.91, P&lt;0.01), invasion depth (t= 1.95, P&lt;0.05) and age (t= 4.69, P&lt;0.01). MVD in PTEN-negative gastric cancer was significantly higher than that in PTEN-positive gastric cancer (t=3.69, P&lt;0.01), and there was a negative correlation betweenPTEN expression and MVD (γ=-0.363, P&lt;0.05). VEGF expression was positively associated with invasion depth (especially with serosa invasion, t = 4.69, P&lt;0.01), lymph node metastasis (t= 2.31, P&lt;0.05) and TNM stage (t= 3.04, P&lt;0.01). MVD in VEGF-positive gaslyic cancer was significantly higher than that in VEGF-negative gastric cancer (t=4.62, P&lt;0.01), and there was a positive correlation between VEGF expression of and MVD (y = 0.512, P&lt;0.05). VEGF expression in PTEN-negative gaslyic cancer was significantly stronger than that in PTEN-positive gastric cancer (t=2.61, P&lt;0.05), and there was a significantly negative correlation between the expression of VEGF and PTEN (γ=-0.403, P&lt;0.05).CONCLUSION: Our results imply that inactivation of PTEN gene 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 viable targets in therapeutic approaches to inhibit angiogenesis of gastric cancers.