| Objective: The gastric carcinoma is one of the most common malignant tumors in our country. The mortality is the highest in all kinds of the malignant tumors. The gastric carcinoma threatens greatly human healthy. Soakage, transfusion and recrudescence are not only the important reason of death but also the main factor in the effect of clinic therapy and prognostic. Above all, many cell factors have important effects. It shows that nuclear factor-кB (NF-кB), as an important nuclear factor, regulates the expression of many genes. It influences on the gastric carcinoma biological behavior. Cyclooxygenase-2 (COX-2) is a inducible enzyme, which is strongly expressed when it suffer from different stimulus, such as inflammatory cytokine, growth factors, endotoxin, carcinogenic promoting agent. COX-2 and NF-кB are strongly correlated to the progression and aggressiveness of carcinomas, because there are binding site of NF-кB in COX-2. However in recent years, the correlation research between the two mostly is done on the level of phlogosis, and few on tumors, even fewer on the gastric carcinoma. Presently, there is no report on the expression of the gastric carcinoma tissues, regional lymph nodes tissues NF-кB, COX-2 or their correlation research. Therefore, in this study we detected the expressions of COX-2 and NF-кB in gastric carcinoma tissues, the first station regional lymph node tissues and normal gastric mucosa by S-P immunohistochemical technique, analyzed the relationship between the expressions and the ability of invasion and metastasis of tumor cells and the expressions and the biological behavior of gastric carcinoma. This study aims at the relation between the expression of NF-кB, COX-2 and the related factors of the gastric carcinoma, and the influence on the gastric carcinoma biological behavior. The purpose is that we can provide the theoretical foundation for prophylaxis and therapy of gastric carcinoma, and provide a new target to treat carcinoma and we are likely to open up a new way for cure carcinoma.Methods: In this study, we select 73 samples of gastric carcinoma. All patients had gastrectomy in the 4th hospital of HeBei Medical University from August 2005 to October 2006. We gather gastric carcinoma, normal gastric mucosa(around gastric carcinoma >5cm) and first station of lymph node of every patients. All these samples have been without chemotherapy or radiotherapy before surgery, which have been proved adenocarcinoma by pathology. In this study, we use S-P immunohistochemical technique to detect the expressions of protein NF-кBp65 and COX-2 in gastric carcinoma tissues, first station of lymph node and normal gastric mucosa. The relationship between the expressions of NF-кB and COX-2 and the biological behavior of gastric carcinoma were analyzed, including patients'sex, age, tumor location, size, Gross types, differentiation degree, infiltration depth, lymph nodes metastasis and TNM stage etc. Among the 73 cases of gastric carcinoma we selected 44 cases with lymph nodes metastases and comparison the expression of NF-кBp65 and COX-2 in primary foci of gastric carcinoma and their lymph node metastatic foci. All statistical analyses were carried out with SPSS 12.0, and p<0.05 was considered significant.Results: 1 The positive staining of NF-кBp65 was mainly located in cytoplasm and/or nucleus. There was partly in some inflammatory cells and smooth muscle cells. The positive rates of NF-кBp65 were 67.12% in tissues of gastric carcinoma, which were significantly higher than the rates of 20.55% in normal gastric mucosa(p<0.01).78.43% of NF-кB in gastric carcinoma tissue existed in the tumor bigger than 5cm, and the percentage was higher than 40.91 % in the tumor smaller than 5cm. The comparison of the two shows significant difference (P<0.01);As to the differentiate extent, the moderately and poorly differentiated positive expression rate was 79.49%, which was higher than 52.94%, the well and moderately differentiated rate. The comparison of the two showed significant difference (P<0.05); As to the infiltration depth, the positive expression rate of T3+T4 was 73.44%, which was higher than 22.22%, the expression rate of T1+T2. The comparison of the two showed significant difference (P<0.01); The positive expression rate of tumors with lymphoid nodes metastasis was 79.55%, which was higher than 48.28%, the expression rate of tumors without lymphoid nodes metastasis. The comparison of the two showed significant difference (P<0.01);The positive expression rate in clinical stages III-IV was 78.26%, which was higher than 48.15%, the expression rate in clinical stages I-II. The comparison of the two showed significant difference(P<0.01). NF-кBp65 protein expression in gastric carcinoma tissues had no significant relevance to sex, age, tumor location or Gross types (p>0.05).2 The positive staining of COX-2 was mainly located in cytoplasm. COX-2 protein positive expression rate in gastric carcinoma tissue was 60.27%, which was higher than 17.81%, the expression rate in normal gastric mucosa. The comparison of the two shows significant difference (P<0.01). 70.59% of COX-2 in gastric carcinoma tissue existed in the tumor bigger than 5cm, and the percentage was higher than 36.36 % in the tumor smaller than 5cm. The comparison of the two shows significant difference (P<0.01). As to the differentiate extent, the moderately and poorly differentiated positive expression rate was 71.79%, which was higher than 47.06%, the well and moderately differentiated positive expression rate. The comparison of the two shows significant difference (P<0.05). As to the infiltration depth, the positive expression rate of T3+T4 was 65.63%, which was higher than 22.22%, the expression rate of T1+T2. The comparison of the two shows significant difference (P<0.05). The positive expression rate of tumors with lymphoid nodes metastasis was 72.73%, which was higher than 41.38%, the expression rate of tumors without lymphoid nodes metastasis. The comparison of the two shows significant difference (P<0.01). The positive expression rate in clinical stages III-IV was 73.91%, which was higher than 37.04%, the expression rate in clinical stages I-II. The comparison of the two shows significant difference (P<0.01). COX-2 protein expression in gastric carcinoma tissues has no significant relevance to sex, age, tumor location or Gross types (p>0.05).3 In lymph nodes metastatic foci, the positive rates of protein NF-кBp65 and COX-2(95.45% and 81.82%) were significantly higher than in their primary foci of gastric carcinoma(the positive rates were 88.64% and 70.45%)(P<0.05).4 The expressions of protein NF-кBp65 and COX-2 have direct correlation in gastric carcinoma tissues (rs=0.539, P<0.01). Conclusions: 1 Expressions of protein NF-кBp65 and COX-2 in gastric carcinoma tissues were significantly higher than that normal gastric mucosa. It shows that the two were in administrative relation and cooperate in the process of gastric carcinoma development. To detect NF-кBp65 and COX-2 would be useful molecular marker for gastric diagnosis.2 The protein positive expression rate of NF-кBp65 and COX-2 in gastric carcinoma tissues was obviously higher than that around gastric carcinoma mucosa tissues. There were significant correlation between protein NF-кBp65 positive expression in gastric carcinoma tissues and differentiation degree to lower, the increasing of gross tumor volume, the depth of invasion to deeper, lymph nodes metastasis, TNM stage,and was related to the infiltration depth of gastric carcinoma and lymph nodes metathesis. This shows that they both can be the important index of judging gastric carcinoma prognosis.3 In lymph nodes metastatic foci, the expressions of protein NF-кBp65 and COX-2 were significantly higher than in their primary foci of gastric carcinoma. It's likely that there is difference between primary foci of gastric carcinoma and lymph nodes metastatic foci on molecular level. COX-2 and NF-кB are likely to be related factors for gastric carcinoma metastasis, and play a certain role in the formation of lymph nodes metastatic foci.4 The protein positive expressions of NF-кBp65 and COX-2 had positive correlation, which shows that the two were in administrative relation and cooperate in the process of gastric carcinoma development,invasion and metathesis.In conclusion, the protein expression maladjustment of NF-кBp65 and COX-2 in gastric carcinoma tissues plays an important part in gastric carcinoma invasion and metathesis and other biological behaviors. It shows expressions of protein NF-кBp65 and COX-2 in gastric regional lymph nodes tissues unusually were correlated with lymph nodes metastasis and have an effect on the patient prognosis. The combined detection of protein expressions of NF-кBp65 and COX-2 in gastric carcinoma tissues and regional lymph nodes tissues could be useful in gastric carcinoma diagnosis, prediction of recurrence, metastasis and prognosis reasonable dissection of lymph nodes in operation and selection of treatment after operation. The inhibitor specially designed for the two is very likely to become the new way to treat tumors. |
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