Relationship Between Expression Of Cyclooxygenase-2 And Microvascular, Microloymphatic Density In Human Esophageal Carcinoma Tissue

Background and objectiveEsophageal carcinoma is a common malignant neoplasm, with a high incidence and high mortality in China. The average annual mortality of esophageal carcinoma is 14.59/100 000, which seriously endangers people's health. The carcinogenesis and development of esophageal carcinoma is believed to be a multiple factors,multi-steps,many polygenic variation process, which involves slow growth stage without the blood vessel and rapid proliferation with the blood vessel. The growth of tumor cells mainly relies on the nutrients and oxygen from surrounding cells in the stage without blood vessel. Without angiogenesis, the growth of primary tumor will no more than 1-2mm3.As the tumor increases, the tumor itself or the host organization will establish a new vascular network to supply nutrients. Lymphatic system is an important way for the transfer of esophageal cancer, and lymphatic metastasis plays an important role in clinical treatment and prognosis of esophageal cancer. However, because of the lack of proper lymphatic endothelial-specific markers and right understanding of lymphatic endothelial growth factor, people are used to focus on the relationship between microvascular and tumor proliferation and metastasis. For the presence or absence of lymphatic vessel within the tumor and its relationship with tumor metastasis are in dispute. With the discovery of specific lymphatic endothelial cell markers, many studies have demonstrated the presence of increasing newly formed lymphatic vessel in tumor tissue, which is significantly correlated with the invasion of tumor, lymphatic metastasis and so on. However, the reason, process and molecular mechanism of lymphangiogenesis in neoplasm are still unknown. The new studies report that D2-40 is used to detect newly formed lymphatic vessel in the tissue of gastric cancer and other cancers by reacting selectively with the fixed antigen on lymphatic endothelium. But it is seldom studied in esophageal cancer. Cyclooxygenase (COX) is a rate-limiting enzyme in the metabolism of arachidonate. There are at least two different isoforms of COX, referred to as COX-1 and COX-2. COX-1 is thought to be a housekeeping gene with essentially constant level of expression in most tissues and cells. COX-2, as one of the isoenzymes of COX, differences from COX-1, has been characterized as an immediate-early gene, it can be rapidly induced by various stimuli and involve with many pathological and physiological progresses. Many researches have proved that COX-2 is involved in the occurrence and development of esophageal cancer through promoting the formation of microvascular and microlymphatic vessel. Most of present studies indicate that the expression of COX-2 is elevated in the esophageal carcinoma. The purpose of this study is to use immunohistochemistry to investigate the expression of COX-2 in esophageal carcinoma tissue and assess it s relation to clinicopathological characteristics. The expression of MVD and MLD also are detected by immunohistochemistrical method. The detecting of COX-2 and it's relationship with MVD and MLD may provide a new target point for the treatment of esophageal carcinoma.Materials and methods(1) Esophageal carcinoma tissue samples were obtained from 105 patients who received surgical resection at The Second Affiliated Hospital of Shantou University Medical College from 2005-3～2008-7. Corresponding matched, samples of nonmalignant esophageal squamous epithelium (normal adjacent tissue) was obtained from 10 of the 105 cases of Esophageal carcinoma, which were obtained 5CM away from the margin of the carcinoma and were proved by pathology. As control, all tissue samples were obtained from patients before treatment by radio-therapy or chemotherapy resection. Of the patients,76 were male and 29 were female. The median age was 57.76 years (range,37-75). The patient distribution by stage according to the 2002UICC classification was stageⅠand StageⅡ,68 patients; StageⅢand StageⅣ,37 patients.(2) All cases of esophageal carcinoma were examined by immunohistochemical technique to study the expression of COX-2 in human esophageal carcinoma and it's relations to clinicopathological characteristics. At the same time, CD34 and D2-40 were used to detect the MVD and MLD of esophageal carcinoma, and the relationship between the expression of cox-2 and MVD,MLD was discussed.(3) Statistical analyses were performed using the SPSS 15.0, comparisons with the various prognostic variables were made using the x2 test. The t test was used for the differences of the MVD,MLD at the difference level of the cox-2 expression。Statistical significance was defined as a probability value(P<0.05).Results(1)In the esophageal carcinoma, the positive rate of COX-2 was 96.19% and the high expression rate of COX-2 was 74.3%. The over expression of COX-2 was not related with clinicopathologic parameters, such as tumor size and lymphatic metastasis et al (P<0.05).(2)The average MVD value of all cases is 52.41±22.557, and the MLD is 94.44±37.638. The MVD and MLD of cases with high COX-2 expression groups(59.03±21.816. 99.36±38.818) was significantly higher than those low and without COX-2 expression groups (33.30±10.730,80.22±30.356, P<0.01 and P<0.05)(3) The expression of MVD was not related with clinicopathologic parameters, such as tumor size and lymphatic metastasis et al (P<0.05). But the MLD was related with lymphatic metastasis and the depth of invasion (P<0.05 and P<0.01).ConclusionsThe COX-2 contributing to the tumor neovascularization and lymphatic vessel production, may be helpful in the understanding of intra-tumor angiogenetic and lymphagenetic mechanism in the future. The detecting of COX-2 may provide a new target point for the treatment of esophageal carcinoma. As a specific lymphatic endothelial cells marker, the specificity and sensitivity of D2-40 are better than other lymphatic endothelial cells markers, and The expression of MLD was related with lymphatic metastasis and the depth of invasion.