Relationship Of Expression Of Tiam1, HIF-1α And Tumour Angiogenesis In Non-small Cell Lung Cancer

Background and Objective:Lung cancer is one of the most common malignancies that every country in the world encounters nowadays.While NSCLC approximately takes up nearly 80%～85%of primary lung cancer,so understanding of all the biological behavior of NSCLC is of great importance to the clinical therapy,judgement and prognosis.The formation,growth, invasion and metastasis all depend on the formation of blood vessels,the main cause of NSCLC patients'death is that tumors'spread or metastasis through blood vessels and lymphatic vessel,with the growth of research on Tiaml and HIF-1αin tumor,their relationship with the formation and growth of tumor begins to be emphasized,but the relationship between Tiam1,HIF-1αand NSCLC is still not clear,and this experiment adopts immunohistochemical method and western blotting to detect the expression of Tiam1 and HIF-1αin NSCLC of human's cancer tissue and benign lung diseased tissue to do a preliminary study and investigation of relationship between expression of Tiaml and HIF-1αand all clinical pathologic parameters and the formation of tumor blood vessels.Selection of Cases:select the filed paraffin block of patients in The First Hospital of Baoding,Beijing Union Eedical College Hospital and The Third Hospital of Baoding,dating from Feb.2004 to Jan.2005,among which 71 are samples of NSCLC confirmed by pathology,including 43 males and 20 females,aging from 35 to 79(55.66±9.52),and the cases include 34 lung adenocarcinoma,37 lung squamous carcinoma,52 cases of well and moderately differentiated,19 cases of poorly differentiated,32 cases of periodsⅠandⅡ,and 39 cases of periodsⅢandⅣ,28 with lymphatic metastasis,43 cases without lymphaden metastasis,18 have metastatic encephaloma,53 without metastatic encephaloma.All the patients never received chemo-treatment,radiation treatment and other kinds of treatments.A comparison was made to the 34 the filed paraffin block of samples of benign lung lesion.A collection of 42 fresh samples from The Fourth Hospital of Hebei Medical University which were pathologically confirmed to be NSCLC, including 23 males and 19 females,aging from 31 to 77(52.42±8.19),23 cases are lung adenocarcinoma,19 cases have lung squamous carcinoma,27 are well and moderately differentiated and 15 are poorly differentiated,20 are of periodsⅠandⅡ,22 are of the periodsⅢandⅣ,18 are with metastatic lymphonode and 24 are without that.A comparison was made to the 15 fresh samples of benign lung lesion.Methods:Using immunohistochemical method and western blotting to detect the expression of Tiam1 and HIF-1αin NSCLC,and CD34 monoclonal antibody to mark the MVD.Results:The positive expression rate of Tiam1 and HIF-1αin NSCLC tissue is higher than that in the benign lung diseased tissues(P＜0.01);the expression of HIF-1αis unrelated to the histology types of NSCLC(P＞0.05); the positive expression rate of Tiam1 and HIF-1αin positive team of lymphatic metastasis is obviously higher than that of the negative team(P＜0.01);and the positive expression inⅢ,Ⅳperiod is obviously higher than that of theⅠ,Ⅱperiod(P＜0.05);the expression of Tiam1 and HIF-1αdemonstrate positive correlation(P＜0.01);the average MVD in non-small cell lung cancer tissues is apparently higher than benign lung diseased tissues(P＜0.01);the average MVD is unrelated to histology types of NSCLC, degree of differentiation,whether there is lymphatic metastasis and metastatic encephaloma(P＞0.05);the average MVD inⅢandⅣis higher than that of theⅠ,Ⅱperiod(P＜0.05);the expression of Tiaml has positive correlation with MVD(P＜0.01),and the expression of HIF-1αalso has positive correlation with MVD(P＜0.01).Conclusion:(1) Tiam1 and HIF-1αare highly expressed in NSCLC tissues and have apparent positive correlation with CD34,and Tiaml and HIF-1αhave close relation with the formation of tumor blood vessel,and may accelerate the formation and growth of tumor vessel.(2)The pathology has proved that expression of Tiaml and HIF-1αin lymphatic metastasis NSCLC is higher than that of the cases in non-metastatic tumors,and the positive expression rate in periodⅢandⅣis apparently higher than that of the periodⅠandⅡ,demonstrating that there exists a close correlation between the expression of Tiaml and HIF-1αand the infection and metastasis ability of NSCLC,so the higher the expression rate is,the higher degree of lung cancer invasiveness and metastasis,and the two indexes can be marker of the biological behavior of NSCLC.(3)Expression level of Tiaml and HIF-1αin NSCLC is unrelated to the age,sex and clinical typing.(4) Expression between Tiam1 and HIF-1αhas positive correlation in NSCLC tissues,demonstrating that there may be regulation and mechanism and both of them act in synergy with each other during the process of the formation,growth,invasion and metastasis of NSCLC.