胃癌组织Maspin,uPA,MMP-7表达的意义

目的:观察胃癌及正常胃黏膜Maspin,uPA, MMP-7表达的意义．方法:应用免疫组化SP法检测胃管状腺癌30 例,胃印戒细胞癌30例,正常胃黏膜组织20例中Maspin,uPA,MMP-7的表达情况．结果:在胃管状腺癌中Maspin,uPA,MMP-7 阳性表达率分别为50％,70％和80％;胃印戒细胞癌中阳性表达率分别为46．7％,76．7％和 90％;正常胃黏膜组织中阳性表达率分别为 90％,35％和30％．Maspin的表达与浸润深度、淋巴结转移相关,而与肿块的大小和TNM分期无关．uPA和MMP-7的表达与浸润深度、淋巴结转移、TNM分期相关,而与肿块的大小无关．Maspin的表达与uPA和MMP-7的表达呈负相关(P=0．012,r=-0．322;P=0．008,r= -0．341);uPA的表达与MMP-7的表达呈正相关 (P=0．034,r=0．274)．结论:Maspin在胃癌中表达下调,uPA和 MMP-7在胃癌中过表达,他们在胃癌的浸润转移中起重要作用,可作为反应胃癌病理生物学行为的有效指标．     

环氧合酶-2、基质金属蛋白酶-9和核增殖抗原在胃癌组织中的表达及临床意义

目的 探讨环氧合酶-2(COX-2)、基质金属蛋白酶-9(MMP-9)及核增殖抗原(Ki67)在胃癌中的表达与胃癌发生、浸润和转移的关系.方法 选择2003年1月至2005年12月手术切除、病理证实的胃癌存档蜡块标本58例,其中男37例,女21例.年龄31～76岁,中位年龄58.2岁.另取上述胃癌根治术患者距肿瘤5～6 cm的癌旁组织作对照.采用免疫组化法检测胃癌组织中COX2、MMP-9、Ki67的表达.结果 COX-2、MMP-9在胃癌组织中的表达率分别为82.76%和68.9%,均高于对照组(37.93%和24.14%,P＜0.01).COX-2、MMP-9的表达与胃癌患者性别、年龄、部位及大小无相关性(P＞0.05),与胃癌浸润深度、淋巴结转移及TNM分期有关(P＜0.05),MMP-9还与胃癌分化程度相关(P＜0.05).COX-2与MMP-9在胃癌组织中的表达有相关性(P＜0.05,C=0.359).MMP-9、COX-2表达阳性者Ki67表达水平高于阴性者,两者间差异有统计学意义(P＜0.01).结论 COX-2、MMP-9、Ki67在胃癌浸润、转移过程中起重要作用,共同促进肿瘤的发生、发展.     

Correlation of integrin β3 mRNA and vascular endothelial growth factor protein expression profiles with the clinicopathological features and prognosis of gastric carcinoma

AIM: To investigate integrin 133 mRNA and vascular endothelial growth factor (VEGF) protein expression in gastric carcinoma, and its correlation with microvascular density, growth-pattern, invasion, metastasis and prognosis. METHODS: In situ hybridization(ISH) of integrin β3 mRNA and immunohistochemistry of VEGF and CD34 protein were performed on samples from 118 patients with gastric cancer. RESULTS: The positive rate of integrin 133 mRNA in non- tumor gastric mucosa (20%) was significantly lower than that of the gastric cancer tissue (52.5%, x2 = 10.20, P ＜ 0.01). In patients of infiltrating type, stage T3-T4, vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the positive expression rates of integrin β3 mRNA were significantly higher than those in patients of expanding type (P ＜ 0.01), stage T1-T2 (P ＜ 0.01), non-vessel invasion (P ＜ 0.01), without lymphatic metastasis (P ＜ 0.01), without hepatic and peritoneal metastasis (P ＜ 0.01), respectively. In patients of infiltrating type, stage T3-T4, vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the positive expression rates of VEGF protein were significantly higher than those in patients of expanding type (P ＜ 0.01), stage T1-T2 (P ＜ 0.01), non-vessel invasion (P ＜ 0.01), without lymphatic metastasis (P ＜ 0.01), without hepatic and peritoneal metastasis (P ＜ 0.01), respectively. In patients of infiltrating type, stage T3-T4, vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the mean MVD were significantly higher than those in patients of expanding type (P ＜ 0.01), stage T1-T2 (P ＜ 0.01), non-vessel invasion (P ＜ 0.01), without lymphatic metastasis (P ＜ 0.01), without hepatic and peritoneal metastasis (P ＜ 0.01), respectively. It was found that the positive expression rate of integrin β3 mRNA was positively related to that of VEGF protein (P ＜ 0.01) and MVD (P ＜ 0.05), meanwhile the positive expression rate of VEGF protein was positively related to NVD (P ＜ 0.05). The mean survival period in patients with positive expression of integrin β3 mRNA and VEGF, and MVD ≥ 54.9/mm2 was significantly shorter than that in patients with negative expression of integrin β3 mRNA (P ＜ 0.05) and VEGF (P ＜ 0.01), and MVD ＜ 54.9/mm2 (P ＜ 0.01). Five-year survival rate in patients with positive expression of integrin β3 mRNA and VEGF, and MVD ≥ 54.9/mm2 was significantly lower than those with negative expression of integrin β3 mRNA (P ＜ 0.05), VEGF (P ＜ 0.05), and NVD ＜ 54.9/mm2 (P ＜ 0.01). CONCLUSION: Integrin β3 and VEGF expression can synergistically enhance tumor angiogenesis, and may play a crucial role in invasion and metastasis of gastric carcinoma. Therefore, they may be prognostic biomarkers and novel molecular therapeutic targets.     

Expression and significance of CD44s, CD44v6, and nm23 mRNA in human cancer

AIM: To investigate the relationship between the expression levels of nm23 mRNA, CD44s, and CD44v6,and oncogenesis, development and metastasis of human gastric adenocarcinoma, colorectal adenocarcinoma,intraductal carcinoma of breast, and lung cancer.METHODS: Using tissue microarray by immuhistochemical (IHC) staining and in situ hybri-dization (ISH), we examined the expression levels of nm23mRNA, CD44s, and CD44v6 in 62 specimens of human gastric adenocarcinoma and 62 specimens of colorectal adenocarcinoma; the expression of CD44s and CD44v6in 120 specimens of intraductal carcinoma of breast and 20 specimens of normal breast tissue; the expression of nm23 mRNA in 72 specimens of human lung cancer and 23 specimens of normal tissue adjacent to cancer.RESULTS: The expression of nm23 mRNA in the tissues of gastric and colorectal adenocarcinoma was not significantly different from that in the normal tissues adjacent to cancer (P＞0.05), and was not associated with the invasion of tumor and the pathology grade of adenocarcinoma (P＞0.05). However, the expression of nm23 mRNA was correlated negatively to the lymph node metastasis of gastric and colorectal adenocarcinoma (r = -0.49, P＜0.01; r = -4.93, P＜0.01). The expression of CD44s in the tissues of gastric and colorectal adenocarcinoma was significantly different from that in the normal tissues adjacent to cancer (P＜0.05;P＜0.01). CD44v6 was expressed in the tissues of gastric and colorectal adenocarcinoma only, the expression of CD44v6 was significantly associated with the lymph node metastasis, invasion and pathological grade of the tumor (r = 0.47, P＜0.01; r = 5.04, P＜0.01). CD44sand CD44v6 were expressed in intraductal carcinoma of breast, the expression of CD44s and CD44v6 was significantly associated with lymph node metastases and invasion (P＜0.01). However, neither of them was expressed in the normal breast tissue. In addition, the expression of CD44v6 was closely related to the degree of cell differentiation of intraductal carcinoma of breast (x2= 5.68, P＜0.05). The expressional level of nm23mRNA was closely related to the degree of cell differentiation (P＜0.05) and lymph node metastasis (P＜0.01), but the expression of nm23 gene was not related to sex, age, and type of histological classification (P＞0.05).CONCLUSION: Patients with overexpression of CD44s and CD44v6 and low expression of nm23 mRNA have a higher lymph node metastatic rate and invasion. In addition, overexpression of CD44v6 is closely related to the degree of cell differentiation. Detection of the three genes is able to provide a reliable index to evaluate the invasion and metastasis of tumor cells.     

胃癌中胸苷磷酸化酶和基质金属蛋白酶2的表达及意义

目的探讨胃癌中胸苷磷酸化酶（TP）和基质金属蛋白酶2（MMP-2）表达的意义及其与肿瘤浸润转移的关系。方法免疫组化SP法检测69例不同胃黏膜组织（正常胃黏膜组10例、慢性胃炎组10例、胃癌组39例、胃癌转移的淋巴结组10例）中TP和MMP-2的表达情况。结果胃癌组织及淋巴结胃癌转移灶中TP与MMP-2的表达较正常组及慢性胃炎组显著增高（P〈0．05）。TP与MMP-2表达与胃癌患者的性别、年龄及肿瘤的分化程度无关。肿瘤≥5cm组及T3-4组TP阳性率湿著高于〈5cm组及T1-2组,有远处转移的胃癌组TP阳性率高于无远处转移组,差具有显著性（P〈0．05）;临床Ⅰ-Ⅱ期和Ⅲ-Ⅳ期之间TP阳性率的差异也具有显著性（P〈0．001）。MMP-2在T1-2组与T3-4组的阳性率分别为60．87％和93．75％,有显著性差异（P〈0．05）。在有淋巴结转移的胃癌组MMP-2阳性率显著高于无淋巴结转移组（P〈0．05）;临床Ⅰ-Ⅱ期阳性表达59．09％,Ⅲ-Ⅳ期阳性表达为94．12％,两组有显著性差异（P〈0．05）。而MMP-2表达却与肿瘤大小及远处转移无关。TP表达阳性的胃癌中MMP-2阳性率88．00％高于TP阴性组的50．00％。结论胃癌中TP与MMP-2表达增高与肿瘤进展的病理临床参数有关;TP的表达与MMP-2的表达有关,提示TP在影响肿瘤进展的过程中可能通过MMP-2促进肿瘤浸润转移。     

Correlative studies on uPA mRNA and uPAR mRNA expression with vascular endothelial growth factor, microvessel density, progression and survival time of patients with gastric cancer

AIM: TO investigate the correlations between the expression of urokinase-type plasminogen activator (uPA) mRNA, uPA receptor (uPAR) mRNA and vascular endothelial growth factor (VEGF) protein and clinicopathologic features, microvessel density (MVD) and survival time. METHODS: In situ hybridization and immuno-histochemistry techniques were used to study the expressions of uPA mRNA, uPAR mRNA, VEGF and CD34 protein in 105 gastric carcinoma specimens. RESULTS: Expressions of uPA mRNA, uPAR mRNA and VEGF protein were observed in 61 (58.1%) cases, 70 (66.7%) cases and 67 (63.8%) cases, respectively. The uPA mRNA and uPAR mRNA positive expression rates in infiltrating-type cases (73.7%, 75.4%), stageⅢ-Ⅳ(72.1%, 75.4%), vessel invasion (63.2%, 69.9%), lymphatic metastasis (67.1%, 74.4%) and distant metastasis (88.1%, 85.7%) were significantly higher than those of the expanding-type (X2= 15.57, P= 0.001; X2=6.91, P=0.046), stageⅠ-Ⅱ(X2 = 19.22, P = 0.001; X2= 16.75, P= 0.001), non-vessel invasion (X2 = 11.92, P = 0.006; X2 = 14.15, P = 0.002), non-lymphatic metastasis (X2 = 28.41, P = 0.001; X2= 22.5, P=0.005) and non-distant metastasis (X2 = 12.32, P= 0.004; X2= 17.42, P = 0.002; X2 = 11.25, P = 0.012; X2 = 18.12, P = 0.002).The VEGF positive expression rates in infiltrating-type cases (75.4%), stageⅢ-Ⅳ(88.5%), vessel invasion (82.9%), lymphatic metastasis (84.3%) and distant metastasis (95.2%) were significantly higher than those of the expanding-type (X2 = 9.61, P = 0.021), stage I-II (X2=16.66, P = 0.001), non-vessel invasion (X2= 29.38, P = 0.001), non-lymphatic metastasis (X2 = 18.68, P = 0.005), and non-distant metastasis (X2= 22.72, P = 0.007; X2 = 21.62, P = 0.004). The mean MVD in the specimens positive for the uPA mRNA, uPAR mRNA and VEGF protein was markedly higher than those with negative expression groups. Moreover, a positive relation between MVD and uPA mRNA (rs = 0.199, P = 0.042), uPAR mRNA (rs = 0.278, P = 0.035), and VEGF (rs = 0.398, P = 0.048) expressions was observed. The mean survival time in cases with positive uPA mRNA, uPAR mRNA and VEGF protein expression or MVD value≥54.9 was significantly shorter than those in cases with negative expression or MVD value < 54.9. CONCLUSION: uPA and uPAR expressions are correlated with enhanced VEGF-induced tumor angiogenesis and may play a role in invasion and nodal metastasis of gastric carcinoma, thereby serving as prognostic markers of gastric cancer.     

胃癌组织FAT10与突变型p53表达及其相互关系

目的 检测FAT10与突变型p53在胃癌组织中的表达情况及相互间关系.方法 采用免疫组化和逆转录-聚合酶链反应(RT-PCR)方法检测FAT10和突变型p53在62例胃癌患者的胃癌组织、癌旁组织(距癌边缘2～5 cm)及正常胃组织(距癌边缘>5 cm)中的表达水平,统计分析两者表达间的关联性及FAT10与胃癌预后之间的关系.结果 FAT10蛋白和突变型p53蛋白在胃癌组织中的表达阳性率分别为51.61%(32/62)和45.16%(28/62),显著高于癌旁组织[12.90%(8/62)和14.51%(9/62),χ2值分别=21.26和20.69,P值均<0.01]及正常胃组织[6.45%(4/62)和9.68%(6/62),χ2值分别=13.91和19.61,P值均<0.01].胃癌FAT10蛋白及mRNA的表达上升主要与胃癌的淋巴转移及TNM分期密切相关(P值均<0.05).胃癌组织中FAT10表达在蛋白及基因水平均与突变型p53表达呈正相关性(r值分别=0.865和0.761,P值分别<0.05和0.01).FAT10蛋白阳性表达或mRNA表达水平高者,其累计生存时间显著低于FAT10阴性者(P值均<0.05).结论 FAT10与突变型p53在胃癌组织中表达上调且呈正相关性,两者可能共同参与胃癌的形成与发展,FAT10对评价胃癌的预后可能有较好的价值.     

Effect of a nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester on invasion of human colorectal cancer cell line SL-174T

AIM: To investigate the effect and mechanism of action of the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on invasion and metastasis of human colorectal cancer cell line SL-174T.METHODS: Human colorectal cancer cell line SL-174T was cultured and treated separately with four different dosages of L-NAME for 72 h. Nitric oxide (NO) production was measured with Griess reagent. The effect of L-NAME on invasion and migration of SL-174T cells were evaluated by using Transwell chambers attached with polycarbonate filters and reconstituted basement membrane (Matrigel).RT-PCR was performed to determine the mRNA levels of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor metalloproteinase-2 (TIMP-2).RESULTS: L-NAME could significantly inhibit NO production of SL-174T in a dose-dependent manner. After being treated for 72 h with 0.2, 0.4, 0.8, and 1.0 mmol/L LNAME, respectively, the ability of the L-NAME treated SL174T cells to invade the reconstituted basement membrane decreased significantly (t = 8.056, P＜0.05;t= 14.467, P＜0.01;t= 27.785, P＜0.01;and t= 29.405,P＜0.01, respectively) and the inhibition rates were 10.29%,19.62%, 34.08%, and 42.23%, respectively. Moreover,L-NAME could inhibit migration of SL-174T cells, and the inhibition rates were 20.76%, 24.95%, 39.43%, and 46.85% for L-NAME at 0.2, 0.4, 0.8, and 1.0 mmol/L,respectively (t = 15.116, P＜0.01). In addition, after treatment with L-NAME, expression of MMP-2 mRNA was significantly decreased (t = 71.238, P＜0.01) and that of TIMP-2 mRNA was markedly increased (t = -13.020,P＜O.01).CONCLUSION: L-NAME exerts anti-invasive and antimetastatic effects on SL-174T cell line via downregulating MMP-2 mRNA expression and upregulating TIMP-2 mRNA expression.     

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.     

microRNA-101和环氧合酶-2在胃癌中的表达及其临床意义

背景：microRNAs是一类对靶基因表达具有转录后调控作用的非编码小RNA。microRNA-101（miR-101）在多种恶性肿瘤中呈低表达,而过表达外源性miR-101可发挥肿瘤抑制作用。前期体内、外实验发现外源性miR-101可抑制胃癌细胞增殖和环氧合酶-2（COX-2）表达。目的：检测胃癌组织中的miR-101、COX-2表达并探讨其临床意义。方法：收集手术切除胃癌组织和配对癌旁非癌组织标本30例,以实时荧光定量RT—PCR检测miR-101、COX-2mRNA表达,分析两者间以及两者与胃癌主要临床病理特征的关系。结果：绝大多数胃癌组织中miR-101表达低下,COX-2mRNA则呈过表达。胃癌组织与癌旁非癌组织间miR-101、COX-2mRNA表达量差异显著（P〈0．01）,且两者表达在癌组织和癌旁组织中均呈负相关（癌组织：r=-0．767,P=0．000;癌旁组织：r=-0．718,P=0．000）。TNMⅢ、IV期胃癌和伴淋巴结转移的胃癌中,miR-101表达分别显著低于TNMI、Ⅱ期病例和无淋巴结转移病例（P〈0．05）,COX-2mRNA表达分别显著高于TNMI、Ⅱ期病例和无淋巴结转移病例（P〈0．05）。结论：miR-101与COX-2之间的负相关性可能有助于胃癌的临床诊断;miR-101表达低下伴COX-2过表达与胃癌临床进展和转移有关,对预后判断有一定参考价值。     

Relationship between preoperative staging by endoscopic ultrasonography and MMP-9 expression in gastric carcinoma

AIM： To investigate the relationship between the staging by endoscopic ultrasonography （EUS） and the expression of carcinoma metastasis associated gene in the patients with gastric carcinoma.
METHODS： Sixty-three patients with gastric cancer were diagnosed by electric gastroscopy and EUS. The preoperative staging of gastric cancer was measured by EUS and compared with pathologic staging and MMP-9 expression. Peripheral serum level of MMP-9 was measured with enzyme-linked immunosorbent assay （ELISA）, while the expression of MMP-9 protein was tested with immunohistochemistry and hybridization in situ in the gastric carcinoma tissues.
RESULTS： The total accuracy of EUS in estimating invasive depth of gastric cancer was 80.95%, while that in estimating lymphatic metastasis was 73.02%.Serum MMP-9 levels were consistent with the expression of MMP-9 protein and MMP-9 mRNA in tissue, a result closely correlated with invasive degree, staging with EUS and lymphatic metastasis in gastric cancer （P 〈 0.05）.The total accuracy of estimating invasive depth in gastric cancer was 95.22% using both EUS and MMP-9.
CONCLUSION： The MMP-9 level of preoperative serum presents the reference value for preoperative staging by EUS in the patients with gastric cancer. When serum MMP-9 level in gastric cancer is significantly high,physicians should pay closer attention to the metastasis which reaches the serosa or beyond. Combining EUS and MMP-9 improves the accuracy in deciding the invasion and metastasis in the patients with gastric carcinoma.     

结肠癌中P15,P16与MMP-9的表达及相关性

目的:研究P15,P16和MMP-9在结肠癌及正常组织中的表达,并探讨其与临床病理学特征的关系.方法:采用免疫组化法检测50例结肠癌组织、癌旁3cm组织及切缘正常组织中P15、P16和MMP-9表达的差异.结果:肿瘤、癌旁3cm与切缘正常组织中,P15的阳性表达率分别为84%,94%和100%,P16的阳性表达率分别为76%、90%和100%,MMP-9的阳性表达率分别为82%、44%和0,均有显著性差异(P<0.05).P15,P16和MMP-9的表达与结肠癌的分化程度、Dukes分期和淋巴结转移均有显著相关.结肠癌组织中MMP-9与P15、P16呈负相关性(r=-0.834,P<0.05;r=-0.752,P<0.05).结论:P15,P16表达的下调和MMP-9表达上调将促进结肠癌浸润和转移,二者在癌组织中表达的高低是结肠癌细胞重要的恶性生物学特征,有助于对结肠癌转移及患者预后的判断.     

Cyr61在胃癌中的表达和意义

背景：Cyr61为CCN家族成员之一,又名CCN1,是一种分泌性蛋白。研究发现Cyr61过表达在多种人类恶性肿瘤的发生、侵袭、转移、复发中发挥重要作用。近年来,Cyr61与胃癌的关系日益受到关注。目的：检测Cyr61在胃癌组织和配对癌旁非癌胃黏膜中的表达并探讨其意义。方法：以RT—PCR检测43例胃癌、40例癌旁非癌胃黏膜标本的Cyr61mRNA表达．以免疫组化方法检测82例胃癌、80例癌旁非癌胃黏膜石蜡包埋组织的Cyr61蛋白表达,分析Cvr61在癌旁非癌胃黏膜和不同浸润深度胃癌组织中的表达差异。结果：胃癌组织Cyr61mRNA相对表达量和Cyr61蛋白高表达率均显著高于癌旁非癌胃黏膜（Cvr61mRNA：0．5286＋0．2139对0．3450＋0．1862,P=0．000;Cyr61蛋白：61．0％对32．5％,P〈0．05）。T。期胃癌组织Cyr61蛋白高表达率显著高于T。。期胃癌组织和癌旁非癌胃黏膜（72．2％对39．3％和32．5％,P〈0．05）,T1-2期胃癌组织与癌旁非癌胃黏膜之间则无明显差异（P〉0．05）。结论：Cyr61在胃癌组织中呈过表达．其表达与胃癌浸润深度相关．提示Cyr61可促进胃癌侵袭,并有望成为预测胃癌预后的分子标记物。     

胃癌组织中VEGF-C、VEGF-D、MMP-9的表达变化及意义

目的观察血管内皮生长因子（VEGF）C、D和基质金属蛋白酶MMP-9在胃癌组织中的表达及其意义。方法采用免疫组织化学染色检测108例胃癌手术切除标本中VEGF-C、D及MMP-9的表达情况,并以正常胃黏膜组织作为对照。结果VEGF-C、VEGF-D及MMP-9在胃癌组织中的阳性表达率分别为55．7％、77．8％、75．0％,而在正常胃黏膜的阳性表达率分别为15．0％、20．0％、10．0％,三者的表达率在两组问均有明显差异（P均〈0．05）。伴淋巴结转移的胃癌病例其VEGF-D及MMP-9阳性表达率（87．0％,83．3％）高于无淋巴结转移者（31．5％,33．3％）,P均〈0．05;而VEGF-C在两组的阳性表达率相近,P〉0．05。结论VEGF-D及MMP-9的表达与胃癌分期、淋巴结转移关系密切,有望成为胃癌治疗的新靶点。     

Significance of vascular endothelial growth factor expression and its correlation with inducible nitric oxide synthase in gastric cancer

AIM:To investigate the clinical significance of theexpression of VEGF_(165)mRNA and the correlation withvascular endothelial growth factor (VEGF) protein andinducible nitric oxide synthase (iNO) in human gastriccancer.METHODS:We tested VEGF_(165)mRNA expression in 31 casesof resected gastric cancer specimens and normal pairedgastric mucosae by RT-PCR.Total RNA was extracted withTRIzol reagents,transcribed into cDNA with oligo (dT_(15))priming,inner controlled with β-actin expression andagarose gel isolated after PCR.VEGF expression wasquantitated with IS1000 imaging system.Meanwhile wealso examined expression levels of VEGF protein and iNOSin 85 cases of gastric cancer.All paraffin-embeddedsamples were immunohistochemically stained by streptavidin-peroxidase method (SP).RESULTS:The mean expression of VEGF_(165)mRNA ingastric cancer was 1.125±0.356,significantly higher thanthat of normal paired mucosae,which was 0.7604±0.278.The data indicated that the expression level ofVEGF_(165)mRNA was well related to lymph node metastasisand TNM stages of UICC.The expression levels in patientswith lymph node metastasis and without lymph nodemetastasis were 1.219±0.377 and 0.927±0.205 respectively(P<0.05).The expression in stages Ⅰ,Ⅱ,Ⅲ,Ⅳ was0.934±0.194,1.262±0.386 respectively (P<0.01).Furtheranalysis showed the lymph node metastasis rate in thegroup with over-expression of VEGF was higher than thatin the group with low expression of VEGF (83.3% vs 46.2%),and the ratio of stage Ⅲ Ⅳ in the group with over-expression of VEGF was also higher than that in the groupwith low expression with VEGF (77.8% vs 33.8%) (P<0.05).The positive rates of expression of VEGF protein and iNOSin 85 cases of gastric cancer were 75.4% and 58.8%respectively,and 50.1% of the patients showed positivestaining both for iNOS and VEGF,the correlation with thetwo factors was significant (P=0.018).But more intensive analysis showed the immunoreactive grades of VEGF werenot associated with that of iNOS.CONCLUSIONS:The expression of VEGF_(165)mRNA is wellrelated with lymph node metastasis and TNM stages of UlCCin gastric cancer,and is concerned with the invasivenessand metastasis of gastric cancer.The relationship can beobserved between the expression of VEGF and iNOS in gastriccancer.     

CD147和基质金属蛋白酶-2在大肠癌组织中的表达及其临床意义

目的 研究细胞外基质金属蛋白酶诱导因子(CD147)和基质金属蛋白酶-2(MMP-2)在大肠癌组织中的表达及其与大肠癌临床病理因素间的关系,探讨其与大肠癌侵袭和转移的相关性及二者间的相互联系.方法 应用免疫组织化学方法检测44例大肠癌患者癌组织、癌旁组织和正常对照组织中CD147和MMP-2的表达,以图象分析软件进行半定量分析.结果 大肠癌组织、癌旁组织和正常对照组织中CD147和MMP-2表达阳性率呈递减改变.CD147和MMP-2的表达部位和染色强度相似,半定量分析显示两者呈正相关(r=0.777,P＜0.05).两者的表达与大肠癌患者年龄、肿瘤分型、肿瘤分化程度未见相关性(P＜0.05),而在大肠癌患者伴转移组显著高于无转移组(P＜0.05).结论 CD147在大肠癌患者组织中的表达增高与大肠癌侵袭转移密切相关,其促MMP-2的激活和表达增高的作用可能是其中一个重要因素.