Expression And Significance Of HMLH1/hMSH2 And COX-1/COX-2 Protein In Gastric Cancer

Objective: Gastric cancer(GC) is the most common malignant tumor in digestive tract, and its death rate is at the first place in all kinds of cancer. Recently, people have investigated gastric cancer by many ways, but there is no any index that can indicate its true pathogenesis. It is common believed that the development of GC is multipath. Many investigation found that deficiency of any mismatch repair enzyme(MRE) is the direct reason of microsatellite instability(MSI),which leads to tumor's occurrence. At the same time, many research works involving Cyclooxygenase(COX) have been done. They reported the most important function of COX-1 protein was to maintain the normal function of cells. And may be COX-2 protein took part in many kinds of pathophysiological procedure, especially in the occurrence and development of cancer. Yamamoto reported MSI(-) when the expression of COX-2 protein was positive in GC; by immunohistochemistry staining, Karnes found that the expression of COX-2 protein reduced in colon cancer with MSI(+). These results indicated that deficiency of MRE and positive expression of COX-2 protein might be two pathways of GC occurrence. But the relationship between MRE and COX-2 protein have been no clear. By SP method, we detected the expression of hMLH1/hMSH2 and COX-1/COX-2 protein in GC, and discussed their relationship, the biological behavior and corresponding genesis pathway. These data may provide experimental basis for early diagnosis, therapy and prognosis of GC. Methods: A total of 48 patients with GC were investigated. There was 30 males, 18 females, ranging in age from 36 to 84 years old, and the mean age was 57.21. Among 48 patients, there was 18 with high and middle differentiation gland cancer, 13 with mucus gland cancer, 4 with signet ring cell, and 13 with low or no differentiation cancer. All samples were divided into the high or middle differentiation group(18) and the low or no differentiation group(30). No patient underwent any anti- tumor treatment before operation.48 normal gastric tissues were used as control group. All of samples were fixed in neutrality formalin solutions, embedded by paraffin, and sliced into 4 μm continuous sections. HE and SP staining were done in every section. According to the count of stained cell judge the staining result: the amount of stained cell >25% means positive expression. On the basis of the intensity and the number of the staining cells, four different staining levels were defined,-,+,++,+++. Chi-Square and Spearman test were used as the method of statistical analysis by SAS 6.12. P<0.05 were considered as statistically significant.Result: Expression of hMLH1/hMSH2 and COX-1/COX-2 protein 1.1 In all of 48 cases, 9(18.75%) and 6(12.50%) were negative expression of hMLH1 and hMSH2 protein respectively, and 1(2.09%) was both of them. No significant difference was found between hMLH1 and hMSH2 protein expression(P>0.05).The negative rate of hMLH1 and hMSH2 protein was all 0% in the normal gastric tissues. The negative expression rate of hMLH1 and hMSH2 protein between cancerous and normal gastric tissues showed significant difference(P<0.05).1.2 COX-1 protein showed different levels of expression in cancerous and normal gastric tissues, but the difference of two groups was no significance (P>0.05).1.3 The rate of COX-2 protein positive expression was 72.92% (35/48) in cancerous tissues and 4.17%(2/48) in normal tissues respectively. The difference of two groups was significant (P<0.05).1.4 The group of COX-2 protein positive expression almost have normal expression of hMLH1/hMSH2 protein, while the group of COX-2 protein negative expression often have abnormal expression of hMLH1/hMSH2 protein. The difference of two groups was significant (P<0.05).2 The correlation between the expression of hMLH1/hMSH2 and COX-1/COX-2 protein and the clinicpathological character 2.1 No significant correlation between the expression of hMLH1/hMSH2 protein and gender, age, differentiation, size of tumor, meta...