Expression Of Angiopoietin-1,2 In Gastric Carcinomas And Its Relationship With Characteristic Of Clinic And Pathology

ObjectiveTumor blood vessel is a passage by which oxide and nutrition are delivered totumor cell. Besides, tumor blood vessel is also a very important passage for tumortransfer. Ang is a kind of blood vessel growth adjustment factor that correlatesintimately with blood vessel neogenesis.Four members of the growth adjustment factorare found: Ang-1, 2, 3, and 4. Ang-2 and Ang-1 are combined by Tie-2 in a samelocation. Ang-2 decreases stability of blood vessel by refraining Biological function ofAng-1, which results in serous instability, vimmaturity. There exists a possibility thatexpression imbalance of Ang-2 and Ang-1 plays a critical role in blood vesselformation of tumor.Now the express of Ang-2 and Ang-1 are found in various tumor tissues. In thisexperiment, the status of express of gastric cancer and normal gastric tissues is tested byimmunohistochemical technique, and the result is analyzed. The goal of thisexperiment is to discuss the role of Ang-2 and Ang-1 in development of gastriccancer.Materials1.Patients and specimen: 54 cases of gastric adenocarcinoma specimens wereselected from paraffin wax embodied specimens.with full clinicopathological data, andwere grouped by factors of clinic and pathology. Another 15 cases of normal gastricmucous specimens were selected to be the control group. All specimens were takenbefore operation without chemotherapy andradiotherapy, and confirmed to beadenocarcinoma. 2.Primary agems and instruments: The monoclonal antibodies againstAng-1 and Ang-2were used, The immunohistochemistry SP kits and DAB kits. Andthose routine agents and instruments used in immunohistochemistry.MethodsParaffin wax block slices are stained with hematomylin-eosin for histologicaldiagnosis and differentiation. SP immunohistochemistry is used to measure theexpression of Ang-1 and Ang-2 in gastric cancer and normal gastric tissues. Thepositive stain is obvious yellow to brown granules located in cytoplasm. The stainedresults are measured by the percent of positive stain in all congeneric cells, stainintensity. The data is statistical analyzed by X~2 test. The level of significancer is set atP＜0.05.Results1. The expression of Ang-1 and Ang-2 in gastric cancer and normal gastric tissues.The positive response signal of Ang-1 and Ang-2 shows yellow to brown granuleslocated in the cancer cells o The positive rate of expression of Ang-2 in gastric canceris72.2%(39/54), and that in normal gastric tissues is 33.3% (5/15). The result indicatesthat express of Ang-2 in gastric cancer is higher than that in normal gastric tissues, andthe difference is obvious (P＜0.01). The positive rate of expression of Ang-1 in gastriccancer is 29.6% (16/54), that in normal gastric tissues is 73.3%(11/15). The resultindicates that express of Ang-1 in normal gastric tissues is higher than that in gastriccancer, and the difference is obvious (P＜0.01).2.the relationship between express of Ang-2 and clinical characteristic of gastriccancer.The express level of Ang-2 has nothing to do with patient's gender, age, and thevolume of cancer, occurring of lymphatic, invasive depth(P＞0.05), but is correlatedwith long distance metastasis,reduced histological differentiation and clinical stages.The express of Ang-2 of well-differentiated adenocarcinoma is critically lowerthan that in poorly differentiated adenocarcinoma adenocarcinoma (P＜0.05), and the express in stageⅣis higher than that in stageⅠobviously (P＜0.01).DiscussionGastric cancer is one of the most popular malignant tumors, whose death rate is25.53%, which accounts for 23.93% in malignant tumors.Tumor's infiltration andtransfer are main reasons. Its invasion and metastasis are a multiplicity processincluding many steps, many processes and many factors, which become major factorsof prognosis with gastric cancer patient.Angiopoietin is found recently to include both receptor agonist and receptordepressor. Now there are four members: Ang-1,Ang-2,Ang-3,Ang-4. All of them canidentify Tie-2, but mechanism is different. Ang-1 and Ang-2 are located in 8q22.3-q23and 8p23.1 of human chromosome, whose coding outcomes are glucoprotein. Theirmolecular weights are about 75ku. Their autoploidy gets to 60%.The present research thinks that express of Ang-1 has no close relationship withtumor blood vessel formation. Ang-1 promotes animation and chemotaxis by activatingTie-2, and stabilizes blood vessels, prevents leakage. Aug-2 is a kind ofsecretingtypeglucoprotein. Ang-2 participates remodeling of blood vessels and unstabilizationof endomembrane by restraining activation of Tie-2. The combination of Aug-2 withcceptor would result in dephosphorization of acceptor, and would break the linkbetweenendotheliocyte and perithelial cell of blood vessels, therefore would result ininstability of blood vessel structure. Now the farther research shows express of Aug-1and Ang-2 in gastric cancer, especially that of Ang-2, is critically higher than that innormal gastric tissues, participates in the formation and continuation of new bloodvessel of tumor, and influences growth and transfer of tumor. The present researchthinks that express of Ang-1 has little correlation with tumor blood vessel formation.However, the express of Ang-2 has high correlation with the number of tumor bloodvessel, clinical stages and prognosis..Now the express of Ang-2 is found in varioustumor tissues. We apply for immunohistochemical technique to test the status ofexpress of Ang-1 and Ang-2 in gastric cancer and normal gastric tissues of 54 cases.The result shows the express of Ang-2 in gastric cancer has obvious differencecompared with that in normal gastric tissues (P＜0.01), which hints Ang-2 could play an important role in development of gastric cancer。The express of Ang-1 in normalgastric tissues is higher than that in gastric cancer. There exists obvious differencebetween gastric cancer and normal gastric tissues (P＜0.01), which farther proves thatexpress of Ang-1 has little correlation with tumor blood vessel formation, andcompetitive combination of Ang-2 and Ang-1 with Tie-2 of endodermis cell inducesfission and aversion endodermis cell, promotes nonpullulate growth of new bloodvessel。Lobov IB etal report, the level of Ang-2 and Ang-1 is similar in the early stageof tumor. With the increase of cancer volume, the concentration of Ang-2 is higher thanthat orang-1。In tumor tissue, two formats exist for competitive combination of Ang-2and Ang-1 with Tie-2:①Ang-2 combines Tie-2 of endodermis cell to block Ang-1to induce Phosphorylation of Tie-2;②over-express of Ang-2 and under express ofAng-1 in tumortissues, which breaks the balance of growth adjustment factor of bloodvessel. The two formats participate in tumor blood vessel formation. The level ofexpress of Ang-2 of blood route metastasis is higher than that of no hematogenousmetastasis (P＜0.05), The level of express of Ang-2 is correlated with stages. It ishigher in stageⅣthan in stageⅠ(P＜0.01), which shows the over-express orang-2 canpromote carcinoma tissue blood route metastasis, and influence development andprognosis, of gastric cancer。Besides, the higher of the level of express of Ang-2, thelower of level of carcinoma histodifferentiation (P＜0.01), which hints that Ang-2 mayincrease reproductive activity of cancer cells。Therefore, the level of express ofAng-2, is possible to be a indicator of malignant extent of gastric cancer and patient'sprognosis.In conclusion, the correlation between Ang-2 and infiltration,growth transfer,metastasis of gastric cancer by, is helpful for us to study the transfer mechanism ofgastric cancer. By gene engineering, analog of Ang-1 and Ang-2 can be made. Theanalog is able to induce imbalance of express of Ang-1 or Ang-2, consequentlyinterfere effective formation of new blood vessel of tumor, and refrain growth of tumor.This can be a new path to treat tumor.Conclusion1. Ang-2 expressed higher in gastric cancers. Ang-1 expressed higher in normalgastric tissues but lower in gastric cancers. This indicates Ang-2participates in formation and continuation of tumor new blood vessel, influences growth andtransfer of tumor.2. The expression of Ang-2 in gastric cancer tissues were of consanguineouscorrelation with tumor long distance metastasis and clinical stages, which suggestedthat Ang-2 could play an important role in infiltration, process and transfer of gastriccancer.