| Background and objective The morbidity and mortality of gastric carcinoma are much high in China ,especially in Anhui province.The current staging system for gastric cancer is inadequate for predicting the outcome of reatment.Patients with gastric carcinoma of the same pathology and clinical stage often show different prognosis and some will relapse and become metastatic quickly.These suggest there may be unknown different molecular makers which are useful for classifying tumors and formulating a prognosis for patients with gastric cance.This study is to investigate whether expression of COX-2,MMP-2 and MMP-9 in gastric carcinoma are higher than paracancerous normal tissues,and to correlate these expressions with clinicopathological parameters.This is first reported in China.Clinical materials Archival formalin fixed,paraffin embedded specimens from 96 patients who had undergone radical surgery for primary gastric carcinoma between April 2004 and February 2006 in Anhui provincial hospital were investigated in this study.Cancer tissue was excised from each surgical specimen and adjacent normal tissue (at least 5 cm from the tumor) was compared. There were 69 male and 27 female with a median age of 60 years(range 32~85).According to the TNM staging system of the AJCC 2003,the number of patients with stages I,II,III, and IV was 18,23,38 and 17 respectively.Methed COX-2,MMP-2 and MMP-9 protein expression were detected in gastric carcinoma tissue and adjacent normal tissue by streptavidin-peroxidase immunohistochemistry.Statistical anaysis was performed using SPSS statistical software package(11.0).Results 1.The COX-2 expression rates in gastric carcinoma tissue was 74.0%(71/96),in which,positive+,++,+++ were 8.3%(8/96),35.4%(34/96) and 30.2% (29/96),respectively,with significant differences compared to those in the normal tissue (32.3%,31/96)(P<0.001).The level of COX-2 expression had significant correlations with site(P=0.002),depth invaded(P=0.005),TNM stage(P=0.000) and lymphnode metastasis (P=0.000) of gastric carcinoma.There was no Correlation between COX-2 expression and age,sex,size and histological differentiation of gastric carcinoma (all P>0.05).2.The positive expression rates of MMP-2 in gastric carcinoma tissue was 72.9%(70/96),including 13.5%(13/96) of positive +,35.4%(34/96)of positive ++,24.0%(23/96)of positive +++ ,while that in the normal tissue was 30.2%(29/96)( P<0.001).The expression of MMP-2 was significantly correlated with site(P= 0.002), depth invaded(P= 0.001),TNM stage(P= 0.000) and lymphnode metastasis (P= 0.029) of gastric carcinoma,and no significant correlation was found between MMP-2 expression and age,sex,size,histological differentiation of gastric carcinoma(all P>0.05).3.The MMP-9 expression rates in gastric carcinoma tissue was 66.7%(64/96),in which,there were 25.0%(24/96) of positive +,28.1%(27/96) of positive++,13.5% (13/96) positive +++,and that in the normal tissue was 31.3%(29/96)( P<0.001).The level of MMP-9 expression was significantly related to site(P=0.002),depth invaded(P=0.024),TNM stage(P=0.029) and lymphnode metastasis (P=0.036) of gastric carcinoma,but not to age,sex,tumor size,histological differentiation of gastric carcinoma(all P>0.05). 4.The Spearman rank correlation test showed that COX-2 expression was closely associated with MMP-2(R=0.648,P<0.001) and MMP-9(R=0.626,P<0.001) expression.Conclusions 1.there are over-expressions of COX-2,MMP-2,MMP-9 protein in gastric carcinoma,and all are significantly higher than those in the normal tissue. 2.There is positive correlation between COX-2 expression and MMP-2 ,MMP-9 expression,which shows that one of the pathways COX-2 facilitates tumor invasion and metastasis through up-regulation of MMP-2 and MMP-9 activation.3.Expression of COX-2,MMP-2 and MMP-9 protein in gastric carcinoma are all significantly correlated with site,depth invaded,TNM stage and lymphnode metastasis of gastric carcinoma,which indicated poor prognosis in those patients who have positive expression of COX-2,MMP-2 and MMP-9 protein in gastric carcinoma. |
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