Imbalance between expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in invasiveness and metastasis of human gastric carcinoma

AIM: The expressive balance between matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor of metalloproteinase-1 (TIMP-1) plays a critical role in maintaining the degradation and synthesis of extracellular matrix. Loss of such balance is associated with invasion and metastasis of tumors. This study aimed to determine the expression of MMP-9 and TIMP-1 in gastric carcinoma, and the association of the expressive imbalance between MMP9 and TIMP-1 with the invasion and metastasis and prognosis of gastric carcinoma.METHODS: We used immunohistochemistry to determine the expressions of MMP-9, TTMP-1 and proliferating cell nuclear antigen Ki-67 in the gastric specimens taken from 256 patients with primary gastric carcinoma. The patients were followed-up for up to 96 months.RESULTS: No association between the expression of MMP9 and TIMP-1 and patients' sex and age, tumor size and location of gastric carcinoma was observed. The incidence of the positive expression of MMP-9 in cases with tumors invasion to muscularis propria and visceral peritoneum (70.13% and 69.09%, respectively) was significantly higher than that in cases with tumor invasion only to lamina propria or submucosa (42.50 %, P=0.0162). The positive correlation between MMP-9 expression and the depth of tumor invasion was observed (Pearson correlation coefficient=0.2129,P=0.016). Along with the increase of the metastatic station of lymph nodes, the incidence of the MMP-9 expression was increased by degrees; a positive correlation between them was observed (Pearson correlation coefficient=0.2910,P=0.0001). There was also a significant correlation between MMP-9 expression and the TNM stage in gastric carcinoma (Pearson correlation coefficient=0.3027, P＜0.0001). The incidence of MMP-9 expression in stage Ⅱ and Ⅲ/Ⅳ (75.00%and 76.15%, respectively) was significantly higher than those in stage Ⅰ (46.15 %, P＜0.0001). A negative correlation between TIMP-1 immunoreactivity and the depth of invasion,status of lymph node metastasis and TNM stage was observed (Pearson correlation coefficient =-0.1688, -0.3556and -0.3004, P=0.023, ＜0.0001 and ＜0.0001, respectively).Four types of co-expression of MMP-9 and TIMP-1 were observed; i.e. MMP-9 positive but T IMP-1 negative (n=115),both positive (n=52), both negative (n=62) and MMP-9negative but TIMP-1 positive (n=27). The frequency of serosal invasiveness was significant higher in patients with MMP-9 but without TIMP-1 expression than those with other types of the co-expression (P=0.0303). The incidence of lymph node metastasis was highest in patients with MMP-9but without TIMP-1 expression, and lowest in those with TIMP-1 but without MMP-9 expression (P＜0.0001). The survival rate in patients with MMP-9 but without TIMP-1expression was lower than that in those with TIMP-1 but without MMP-9 expression (P=0.0014).CONCLUSION: Our results in gastric carcinoma demonstrated a significant positive association of MMP-9 over-expression with proliferation of tumor cells, the depth of invasiveness,lymph node metastasis and TNM stage, suggesting MMP-9can serve as a molecular marker of tumor invasion and metastasis. We also demonstrate a significant negative relationship of TIMP-1 expression with the depth of invasiveness and lymph node metastasis, which provide a new idea in the tumor biological and genetic treatment.The interaction between MMP-9 and TIMP-1 in the processes of tumor invasion and metastasis is that MMP-9 mainly promotes tumor invasion and metastasis and TIMP-1 inhibits functions of MMP-9. The imbalance between MMP-9 and TIMP-1 expression may suggest the occurrence of tumor invasion and metastasis, predict poor prognosis. For patients with imbalanced MMP-9 and TIMP-1 expression, the optimal treatment scheme needs to be selected.     

The expression of matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs) and angiogenesis in relation to the depth of tumor invasion and lymph node metastasis in submucosally invasive colorectal carcinoma]

BACKGROUND/AIMS: Lymph node (LN) metastasis occurs in approximately 10% of patients with submucosally invasive colorectal carcinoma. This study was performed to determine the role of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) production and microvessel formation on the LN metastasis in submucosally invasive colorectal carcinoma. METHODS: A total of forty-one subjects with surgically resected submucosally invasive colorectal carcinoma were included in this study. Immunohistochemical staining of MMP-2, MMP-9, TIMP-1, TIMP-2, and urokinase-type plasminogen activator were performed. Angiogenesis was evaluated by counting the number of microvessels in each pathologic specimen as identified by CD34 immunohistochemical staining. RESULTS: The depth of submucosal invasion was not significantly correlated with the expression of MMP-2, MMP-9, TIMP-1, TIMP-2, or urokinase-type plasminogen activator, but the microvessel count was significantly correlated with the absolute depth of invasion (r=0.312, p<0.05). Upregulation of TIMP-2 was positively correlated with adjacent lymphatic invasion (p<0.05) and increased TIMP-2 expression was correlated with LN metastasis in submucosally invasive colorectal carcinoma (p=0.088). CONCLUSIONS: These results suggest that the expression of TIMP-2 and the microvessel count may be useful parameters for considering additional surgery after endoscopic treatment of submucosally invasive colorectal carcinoma.     

胃癌组织中KISS-1和MMP-9的表达及其意义

目的探讨肿瘤转移抑制基因K ISS-1及基质金属蛋白酶9（MMP-9）与胃癌侵袭、转移的关系,为研究胃癌的转移机制及治疗提供理论基础。方法采用逆转录聚合酶链反应（RT-PCR）检测36例胃癌组织及36例正常胃组织中K ISS-1 mRNA及MMP-9 mRNA的表达情况,分析其与胃癌患者各临床病理指标的关系及二者的相关性。结果 K ISS-1 mRNA在胃癌组织中的阳性表达率及表达水平均低于正常胃组织（P均〈0.01）,并且其低表达与淋巴结转移密切相关（P〈0.05）;MMP-9 mRNA在胃癌组织中的阳性表达率及表达水平均高于正常胃组织（P均〈0.05）,MMP-9 mRNA的高表达与癌的浸润深度和淋巴结转移密切相关（P均〈0.05）;K ISS-1与MMP-9表达呈负相关（P〈0.05）。结论 K ISS-1表达缺失和MMP-9过表达可能与胃癌的侵袭相关。     

基质金属蛋白酶-9和组织金属蛋白酶抑制剂-1在食管鳞癌中的表达

目的探讨基质金属蛋白酶-9（MMP-9）和组织金属蛋白酶抑制剂-1（TIMP-1）在食管鳞癌中的表达及其临床意义。方法用免疫组化和Western blot法分别检测41例食管鳞癌患者的癌及相应正常组织中MMP-9和TIMP-1的表达变化。结果食管鳞癌组织中MMP-9阳性表达率与食管癌淋巴结及静脉转移有关；MMP-9的阳性表达率与表达量均显著高于TIMP-1；MMP-9和TIMP-1的表达呈负相关。结论MMP-9与食管鳞癌的侵袭转移有关，其机制可能与食管鳞癌组织中的MMP-9／TIMP-1平衡失调有关；MMP-9与TIMP-1联合检测有助于食管鳞癌生物学行为的判断。     

胃癌组织中MTA1,PTEN,E-cadherin的表达及其相互关系

目的:观察MTA1,PTEN,E-cadherin蛋白在胃癌和正常胃黏膜组织中的表达,探讨其与胃癌浸润、转移和生物学行为的关系.方法:应用免疫组织化学方法检测54例胃癌手术切除标本和15例正常胃黏膜组织中MTA1,PTEN,E-cadherin的表达.各指标之间相关因素的差异性比较采用χ2检验,相关性研究采用Spearman相关分析:结果:与正常胃组织相比,MTA1蛋白在胃癌组织中高表达(46.3% vs 6.7%,P＜0.01),PTEN和E-cadherin蛋白在胃癌组织中表达下调或缺失(51.9% vs 100%,42.6% vs 100%,均P＜0.01).MTA1和PTEN的阳性表达率与肿瘤浸润深度(P=0.003,P=0.001)、病理分期(P=0.004,P=0.008)、淋巴转移(P=0.000,P=0.001)、远隔转移(P=0.004,P=0.006)、临床分期有关(P=0.001,P=0.000);E-cadherin的正常表达率与肿瘤浸润深度(P=0.027)、病理分化程度(P=0.006)、淋巴转移(P=0.044)、临床分期有关(P=0.000).Spearman相关分析显MTA1与PTEN蛋白、MTA1与E-cadherin蛋白的表达呈负相关(r=-0.518,r=-0.424,均p＜0.05).PTEN蛋白与E-cadherin蛋白的表达呈正相关(r=0.53,P＜0.05).结论:MTA1蛋白水平高表达和PTEN,E-cadherin蛋白水平低表达可能与胃癌浸润和转移有关,且联合检测可以用于判断胃癌的生物学行为.     

胃癌组织中MMP-9和TIMP-1的表达及其临床意义

背景：有关胃癌组织中基质金属蛋白酶（MMPs）和金属蛋白酶组织抑制剂（TIMPs）表达的研究不多且结果不一。目的：探讨胃癌组织中MMP-9和TIMP-1的表达及其临床意义。方法：收集临床病理资料完整的98例胃癌患者。应用免疫组化法检测组织中MMP-9和TIMP-1表达．并分析其与临床病理特征的关系以及各参数对胃癌患者预后的影响。结果：胃癌组织中MMP-9高表达与浸润深度、淋巴结转移和TNM分期显著相关（P〈0．01）。单因素分析显示胃癌患者预后与MMP-9高表达（P=0．014）、浸润深度（P〈0．001）、淋巴结转移（P〈0．0001）和TNM分期（P〈0．0001）相关。TIMP-1表达与胃癌患者临床病理特征和预后无关。结论：MMP-9高表达与胃癌的发生、进展有关,可作为胃癌患者预后指标之一。     

Relationship between cell adhesion molecules expression and the biological behavior of gastric carcinoma

AIM： To evaluate the relationship between the expression of cell adhesion molecules （CAMs） and the biological behavior of gastric carcinoma. METHODS： Expression of syndecan-1, E-cadherin and integrin β3 were evaluated by immunohistochemical study in a total of 118 gastric carcinomas and 20 nontumor gastric mucosas. RESULTS： The expressions of syndecan-1 and E-cadherin were significantly lower in gastric carcinoma compared to non-tumor gastric mucosa, and the low expression rates were positively correlated to the tumor invasion depth, vessel invasion, lymph node metastasis and distant metastasis （P 〈 0.01 in all cases）. However, the expression of integrin β3 was significantly higher in gastric carcinoma compared to non-tumor gastric mucosa, and the high expression rates were positively correlated to the tumor invasion depth, vessel invasion, lymph node metastasis and distant metastasis （P 〈 0.01 in all cases）. In addition, the three protein expressions were correlated to the tumor growth pattern （P 〈 0.01, P 〈 0.01, and P 〈 0.05 respectively）, but not correlated to tumor differentiation （P 〉 0.05, P 〉 0.05 and P 〉 0.05 respectively）. Positive correlation was observed between the expressions of syndecan-1 and E-cadherin, but they which were negatively correlated to the expression of integrin β3 （P 〈 0.01 in all cases）. Univariate analysis demonstrated that the mean survival time and 5-year survival rate were lower in the cases with low expressions of syndecan-1 and E-cadherin and high expression of integrin β3 （P 〈 0.01, in all cases）. COX multivariate analysis showed that the expression level of syndecan-1 could be an independent prognostic index of gastric carcinoma （P 〈 0.01）, whereas E-cadherin and integrin β3 could not be independent indexes （P 〉 0.05, P 〉 0.05 respectively）.CONCLUSION： The low expression of syndecan-1 and E-cadherin and the high expression of integrin β3 are significantly correlated with the invasion and metastasis o     

Usefulness of MMP-9/TIMP-1 in Predicting Tumor Recurrence in Patients Undergoing Curative Surgical Resection for Gastric Carcinoma

Degradation of the extracellular matrix is an essential step in tumor invasion and metastasis. It involves the actions of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). We evaluated the expression of MMP-9 and TIMP-1 in gastric carcinomas and the relationship between this expression and tumor recurrence. Eighty patients who had undergone curative surgical resection for gastric carcinoma were included. Resected gastric tissue samples were stained immunohistochemically to evaluate the expression of MMP-9 and TIMP-1. TIMP-1 expression was related to the depth of tumor invasion and lymph node metastasis. The proportion of tumors larger than 5 cm, or displaying muscle layer invasion, and the cumulative incidence of tumor recurrence were significantly elevated in patients with tumors expressing TIMP-1. Furthermore, these measures were lowest in patients with no TIMP-1 expression and highest in patients who only expressed TIMP-1. In conclusion, TIMP-1 expression and the balance between expression of MMP-9 and expression of TIMP-1 may be important indicators of tumor progression and predictors of tumor recurrence.     

基质金属蛋白酶及其组织抑制剂与食管癌浸润转移的关系

目的:研究基质金属蛋白酶-9(MMP-9)及其相应的组织金属蛋白酶抑制剂-1(TIMP-1)在食管癌组织上的表达及其在细胞浸润转移过程中所起的重要作用。方法:采用免疫组织化学链霉素抗生物素蛋白-过氧化物酶(SP)法检测的50例食管癌组织中MMP-9及TIMP-1的表达。结果:MMP-9在食管癌组织的阳性表达率为76％,其表达与淋巴结转移呈正相关(Pearson列联系数0.343,P<0.05)。TIMP-1在食管癌组织表达的阳性率为30％,其表达与淋巴转移呈负棚关(Pearson列联系数为O.333,P<0.05)。结论:MMP-9阳性表达与食管癌浸润转移呈正相关,TIMP-1阳性表达与食管癌浸润转移呈负相关,二者在食管癌浸润转移中的关系表现为MMP-9促进肿瘤转移,TIMP-1对食管癌有独立的抑制作用。通过检测食管癌组织中的MMP-9及TIMP-1的表达,对预后的评价有一定价值。     

Significance of lymphatic invasion and cancer invasion-related proteins on lymph node metastasis in gastric cancer

Background and Aims:  Cancer invasion and metastasis are critical events for patient prognosis; however, the most important step in the whole process of lymph node (LN) metastasis in gastric cancer remains obscure. In this study, the significance of cancer cell behaviors, such as cell detachment, stromal invasion and lymphatic invasion on regional LN metastasis in gastric cancer was investigated by comprehensive immunohistochemistry.
Methods:  A total of 210 cases with gastric cancer were selected. These consisted of 105 cases with regional LN metastasis (LN[+] group) and 105 cases without LN metastasis (LN[–] group). Both groups exhibited the same depth of invasion. Cancer tissues were subjected to immunohistochemistry with antibodies against claudin-3, claudin-4, β-catenin, matrix metalloproteinase (MMP)-1, and MMP-2, as well as endothelial markers of lymphatic vessel endothelial hyaluronan receptor-1 and von Willebrand factor for the objective discrimination between lymphatics and blood vessels. The expression of each protein as well as the histopathological parameters were compared between LN(+) and LN(−) groups.
Results:  Along with lymphatic invasion by cancer cells and gross tumor size, MMP-1 expression in cancer cells at the invasive front of the primary tumor was a significant, independent predictor of LN metastasis. The expression of claudins and β-catenin was associated with the histopathological type of cancer, but not with LN status.
Conclusion:  Among the cancer invasion-related proteins examined, MMP-1 plays a vital role in LN metastasis of gastric cancer. Tumor size, lymphatic invasion and MMP-1 expression level at the invasive front were the predictive factors of LN metastasis of gastric cancer.     

Matrix metalloproteinase-2 and tissue inhibitor of metallo-proteinase-2 in colorectal carcinoma invasion and metastasis

AIM: To explore the relationship between matrix metallopr- oteinase-2 (MMP-2) and tissue inhibitor of metallopr- oteinase-2 (TIMP-2) in the development of colorectal carcinoma and to provide a valuable marker for clinical diagnosis. METHODS: Twenty-five patients with colorectal carcinoma underwent surgical resection. Samples were taken from tumor sites and normal tissues. MMP-2 activity was determined by gelatin zymography. Western blot and ABC immunohist-ochemical staining were used to detect the expression levels of MMP-2 and TIMP-2 in normal and colorectal carcinoma tissues. Statistical analyses were performed using the Student's t test and one-way ANOVA. P<0.05 was considered statistically .significant. All the statistical analyses were performed using SPSS 10.0 software. RESULTS: MMP-2 activity could be detected in both normal and colorectal carcinoma tissues. MMP-2 activity in colorectal carcinoma tissues was much higher than that in normal tissues (P<0.05, t=3.916,4.227). MMP-2 activity was positively related to the colorectal carcinoma invasion depth, lymph node metastasis and Duke's stage. Western blot and ABC immunohistochemical staining demonstrated that the expression level of MMP-2 in colorectal carcinoma tissues was much higher than that in normal tissues (P<0.05, t = 9.429), but the expression level of TIMP-2 in colorectal carcinoma tissues was much lower than that in normal tissues (P<0.05, t = 7.329). The MMP-2/TIMP-2 ratio of colorectal carcinoma was much higher than that of normal tissues. With the progression of invasion depth, lymph node metastasis and tumor Duke's stage, the activity and expression level of MMP-2 and TIMP-2 gradually increased, but the MMP-2/TIMP-2 ratio gradually decreased. CONCLUSION: The balance between MMP-2 and TIMP-2 plays a crucial role in the process of colorectal carcinoma invasion and metastasis.     

Clinical significance of changes in tumor markers, extracellular matrix, MMP-9 and VEGF in patients with gastric carcinoma

BACKGROUND/AIMS: The aim of this study was to evaluate the prognostic significance of some serum tumor marker level, extracellular matrix (ECM), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF) in patients with gastric cancer. METHODOLOGY: The serum tumor markers included CEA, CA50 and CA19-9, ECM included laminin (LN), hyaluronic acid (HA), and collagen type III and IV were measured in 40 patients with gastric carcinoma and 20 matched healthy controls by radioimmunoassay. MMP-9, VEGF and MVD were measured with immunohistochemical methods and the computer image analyzer. Microvascular density (MVD) in tissues of patients with gastric carcinoma was detected. RESULTS: The levels of CEA, CA50, CA19-9, HA, LN and collagen type IV in the patients with metastasis were significantly higher than those in the patients without metastasis (p < 0.05). The expression of MMP-9 and collage type IV in the patients with metastasis and poorly differentiated carcinomas were significantly higher than those in the patients without metastasis whose tumors were well/moderately differentiated (p < 0.05). CONCLUSIONS: CEA, CA50, CA19-9, HA, LN and collagen type IV levels can be used as a signal of metastasis and disease progression in patients with gastric carcinoma. When a gastric carcinoma expresses a high level of MMP-9 and VEGF with high MVD, the power of infiltration and metastasis of the gastric carcinoma is enhanced.     

Pathobiological significance of vascular endothelial growth factor and Maspin expressions in human gastric carcinoma

AIM: To investigate the correlation between expression of vascular endothelial growth factor (VEGF) and cell differentiation, invasion, metastasis and Maspin expression in gastric carcinoma.METHODS: Formalin-fixed paraffin-embedded tissue specimens from 73 cases of gastric carcinoma were studied with SP immunohistochemistry, using anti-VEGF monoclonal antibody, and thirty-nine of them were studied using antiMaspin monoclonal antibody. VEGF expression was compared with the clinical stage, lymph node metastasis, and Borrmann‘s and WHO‘s classification of gastric carcinoma.RESULTS: The positive rate of VEGF expression was significantly higher in adjacent non-carcinoma epithelia (ANCE) than in non-metaplastic, non-carcinoma gastric epithelia (NMNCE), which were at least 4 cm distant from the primary tumor (P = 0.000, x^2= 73.03). The positive rate of VEGF expression was significantly higher in advanced gastric carcinoma (AGC) than in early gastric carcinoma (EGC) (P = 0.032, x^2 = 4.62). The positive rate of VEGF expression in gastric carcinomas with lymph node metastases was significantly higher than that in those without metastasis (P = 0.006, x^2 = 7.47). Maspin was weakly expressed in 16 out of 39 cases of NMNCE, and the positive immunoreaction was limited to gland cells of the stomach body. There was no significant correlation between the expression of VEGF and histological or gross classifications, and correlation between the expressions of VEGF and Maspin in gastric carcinoma (P = 0.648, x^2 = 0.21).CONCLUSION: Expression of VEGF is significantly correlated to the malignant biological behaviors of gastric carcinoma,but there is no significant correlation between the expression of VEGF and Maspin.     

胃癌中MMP-9和VEGF的表达及其临床意义

目的探讨基质金属蛋白酶-9(matrix metalloproteinases-9,MMP-9)基因和血管内皮生长因子(VEGF)在胃癌中的表达及其与临床病理因素之间的关系。方法采用免疫组化SP法检测97例胃癌组织中MMP-9和VEGF的表达情况。结果97例胃癌组织中MMP-9和VEGF阳性率分别为82.47%(80/97)、86.59%(84/97),两者表达存在相关性(P<0.05)。结论MMP-9和VEGF蛋白在胃癌中过量表达与胃癌的发生发展相关,可以作为判断预后的指标之一。     

Clinicopathological significance of B-cell-specific Moloney murine leukemia virus insertion site 1 expression in gastric carcinoma and its precancerous lesion

AIM： To explore the relation between B-cell-specific Moloney murine leukemia virus insertion site 1 （Bmi-1） expression and the clinicopathological features of gastric carcinoma （GC）.METHODS： Immunohistochemistry was used to detect the expression of Bmi-1 and ki-67. Doublelabeling staining was used to display the distribution of Bcl-2^＋/ki-67 cells in 162 cases of GC and its matched normal mucosa and precancerous lesion.RESULTS： The positive rate of Bmi-1 expression in GC（52.5%） was significantly higher than that in normal gastric mucosa （21.6%, X^2 = 33.088, P 〈 0.05）. The Bmi-1 expression in GC was closely related with the Lauren＇s and Borrmann＇s classification and clinicalstage （X^2 = 4.400, 6.122 and 11.190, respectively, P〈 0.05）. The expression of ki-67 was related to the Borrmann＇s classification （X^2 = 13.380, P 〈 0.05）.Bcl-2 expression was correlated with the Lauren＇s classification （Z2 = 4.725, P 〈 0.05）, and the Bmi-1 expression both in GC （rk = 0.157, P 〈 0.05） and inintestinal metaplasia （rk = 0.270, P 〈 0.05）.CONCLUSION： Abnormal Bmi-1 expression in GCmay be involved in cell proliferation, apoptosis andcancerization. This marker can objectively indicate theclinicopathological characteristics of GC.     

Expression of MMP—2,TIMP—2 protein and the ratio of MMP—2／TIMP—2 in gallbladder carcinoma and their significance

AIM: To study the correlation between expression of MMP-2, TIMP-2 protein and the ratio of MMP-2/TIMP-2 and clinicalpathological parameters of patients with gallbladder carcinoma.METHODS: Carcinomas (n=45) and polypoid lesions (n=15) of the gallbladder were studied for the expression of MMP-2 and TIMP-2 protein by immunohistochemical avidin-biotin-complex method and image analysis. Clinicalpathological data of patients with gallbladder carcinoma such as histological type, grade of differentiation, level of infiltration, liver invasion and lymph node involvement, etc, were recorded.RESULTS: There was significant difference between the average level (1.123±0.108 VS 1.030±0.054, P=0.002) of MMP-2, the ratio (1.050±0.013 VS0.937±0.078, P=0.003) of MMP-2/TIMP-2 in gallbladder carcinomas and in polypoid lesions of the gallbladder. Significant difference was found between the expression of MMP-2 in early stage and advanced tumors, but there was no correlation between MMP-2 protein expression and histological type, differentiation degree, infiltration level, lymph node involvement or liver invasion. Although no difference was observed between TIMP-2 expression and histological type or differentiation degree, signific ant difference was found between TIMP-2 expression and different Nevin stage, infiltration level, local lymph node involvement or liver invasion (1.168±0.067 VS1.048±0.075, 1.170±0.062 vs 1.039±0.06g, 1.039±0.076 VS1.147±0.083, 1.048±0.074 vs 1.103±0.095, P＜0.05). MMP-2/TIMP-2 ratio did not correlate with histological type, grade of differentiation and liver invasion, but significant differences were found between MMP-2/TIMP-2 ratio and different Nevin stage, infiltration level and lymph node involvement in patients with carcinoma of gallbladder.CONCLUSION: TIMP-2 and MMP-2/TIMP-2 ratio could reflect more accurately biological characteristic of gallbladder carcinoma and MMP-2/TIMP-2 ratio might be a new significant marker in early diagnosis, in the judgment of invasion or metastasis and the estimate of prognosis in patients with gallbladder carcinomas.     

COX-2与MMP-2蛋白在胃癌组织中的表达及意义

目的　探讨COX 2和MMP 2蛋白在胃癌组织中的表达、相互关系及意义。方法　应用免疫组化S P法检测 45例胃癌及 2 0例正常胃组织MMP 2、COX 2蛋白的表达情况。结果　 45例胃癌组织COX 2的表达阳性率为 60 % ( 2 7/ 45 ) ,2 0例正常胃组织COX 2的表达阳性率为 15 %O( 3 / 2 0 ) ,COX 2在胃癌组织中的表达阳性率显著高于正常胃组织中的表达阳性率 (P <0 0 1) ;45例胃癌组织中MMP 2的表达阳性率为 64 4% ( 2 9/ 45 ) ,2 0例正常胃组织MMP 2表达阳性率为 2 5 % ( 5 / 2 0 ) ,MMP 2在胃癌组织中的表达阳性率显著高于在正常胃组织中的表达阳性率 (P <0 0 1) ;在胃癌组织中MMP 2、COX 2蛋白的表达之间存在显著正相关 (rs=0 5 69,P <0 0 1)。结论　胃癌组织中存在COX 2、MMP 2的高表达 ,且两者之间的表达强度具有等级相关性。COX 2蛋白可通过诱导MMP 2蛋白的表达上调 ,增加胃癌细胞的侵袭力 ,从而成为其促进胃癌浸润、转移的途径之一     

VEGF、uPA及uPAR与胃癌侵袭和转移的相关性

目的探讨血管内皮生长因子(VEGF)、尿激酶型纤溶酶原激活物(uPA)及其受体(uPAR)与胃癌侵袭、转移的关系及其相关性。方法采用免疫组化SP方法检测198份胃癌组织标本(胃癌组)、60份正常胃黏膜组织标本(对照组)VEGF、uPA、uPAR表达。结果与对照组比较,胃癌组VEGF呈高表达,并与浸润深度、淋巴结转移和临床分期呈正相关,与肿瘤的分化程度呈负相关,P均<0.05;胃癌组uPA和uPAR呈高表达,与病理分级、浸润深度、淋巴转移、临床分期有关,P均<0.05。胃癌组VEGF与uPA表达呈正相关,P<0.01;uPA与uPAR表达呈正相关,P<0.01。结论 VEGF、uPA、uPAR在胃癌发生、发展、侵袭和转移中起促进作用;三者相互促进,相互协调,关系密切。三者均可作为胃癌诊断和预后估计的指标及胃癌治疗的新靶点。     

Relationship between matrix metalloproteinase-2 mRNA expression and clinicopathological and urokinase-type plasminogen activator system parameters and prognosis in human gastric cancer

AIM: To investigate the relationship between matrix metalloproteinase-2 (MMP-2) mRNA expression and clinicopathologic and urokinase-type plasminogen activator (uPA) system parameter and prognosis in human gastric cancer. METHODS: Expression of MMP-2 mRNA, uPA, and uPA-R mRNA in tumor tissues and ≥5 cm adjacent normal tissues from 67 cases of gastric cancer was studied using RT-PCR and Northern blot respectively.Survival analyses were done using the Kaplan-Meier method. RESULTS: The expression rates of MMP-2 mRNA,uPA and uPA-R mRNA in tumor tissues (31%,41%,and 51%, respectively) were significantly higher than those in ≥5 cm adjacent tissues (19%, 11%, and 9%; X2=4.59,43.58, and 53.24 respectively, P<0.05,0.0001,and 0.0001, respectively). Expression of MMP-2 mRNA was significantly correlated with lymph node metastasis (metastasis: 61.9%, no metastasis: 39.1%, X2= 7.61, P<0.05),Lauren's classification of diffuse/mixed types:54.2%,intestinal type: 26.3%,X2 = 4.25, P<0.05, expression of uPA and uPA-R mRNA (uPA+: 55.1%, uPA-: 22.2% and uPA-R+: 54.9%, uPA-R-: 18.8%, X2=5.72 and 6.40 respectively, P<0.05).Kaplan-Meier survival analysis of MMP-2 mRNA expression did not show significant difference in all 67 cases, but revealed an association of the expression of MMP-2 mRNA, uPA, and uPA-R mRNA with worse prognosis (P= 0.0083, 0.0160, and 0.0094, respectively). CONCLUSION: MMP-2 may play an important role in the development of invasion and metastasis of gastric cancer.