| Objective To observe the expression of VEGF-C,VEGFR-3 and BMP-9 in the tumor tissues,adjacent normal lung tissues and lymph nodes of non-small cell lung cancer,then combined with clinical and pathological characteristics,the significance of the expression of three in the biological behavior of NSCLC the development of primary lesions and lymph node metastasis was analyzed.Method Tissue specimen of patients with lung cancer who underwent Lobectomy and lymph node dissection and then confirmed by pathology in our hospital were selected as the subjects of the study,and the data of the patients with NSCLC were collected.A total of 51 cases of tumor tissues,51 cases of adjacent normal lung tissues,43 cases of metastatic lymph nodes(8 patients with stage N1:15 cases of stage N1 lymph node;16 patients with stage N2:9 cases of stage N1 lymph node,19 cases of N2 stage lymph node)and 51 cases of non metastatic lymph nodes(10 or 11 groups of affected side)were collected.Immunohistochemical staining was used todetect the expression of VEGF-C,VEGFR-3 and BMP-9 in 51 cases of NSCLC tumor tissues and 51 cases of normal lung tissues,and detect the expression of VEGF-C,VEGFR-3 in 43 metastatic lymph nodes and 51 non-metastatic lymph nodes.The semi quantitative analysis of the results was made by combining the percentage of positive cells and the intensity of staining,and calculated the positive expression rate of three target protein.The positive expression rates of VEGF-C,VEGFR-3 and BMP-9 in different subgroups of gender,age,smoking history,pathological type,T stage,lymph node metastasis,N stage and number of metastatic lymph nodes by statistical methods were obtained,and analysed the statistical relationship among the subgroups and their internal relations of three target protein.Result 1.The positive product of VEGF-C was brown granules,which was mainly expressed in the cytoplasm of tomor cells.The expression rates of VEGF-C in tumor tissues of stage N0,N1 and N2 were significantly higher than that of corresponding normal lung tissues(P<0.05).The expression of VEGF-C in tumor tissues was higher in lymph node metastasis group than in non lymph node metastasis group,the difference was statistically significant(P<0.01).The expression of VEGF-C in normal lung tissues was higher in non lymph node metastasis group than in lymph node metastasis group,the difference was statistically significant(P<0.05).The expression of VEGF-C in tumor tissues in the N2 stage subgroups was higher than that in the N1stage subgroup,and the difference was statistically significant(P<0.05).The expression of VEGF-C in tumor tissues in the N2 stage subgroup was higher than that in the N0 stage subgroup,and the difference was statistically significant(P<0.05).The expression of VEGF-C in tumor tissues in the ?3(LN+)subgroup was higher than that in the 0(LN+)subgroup,and the difference was statistically significant(P<0.01).The expression of VEGF-C in tumor tissues in the ?3(LN+)subgroup was higher than that in the 1~2(LN+)subgroup,and the difference was statistically significant(P<0.05).The expression of VEGF-C in normal lung tissue in the 0(LN+)subgroup was higher than that in the ?3(LN+)subgroup,and the difference was statistically significant(P<0.05).The expression of VEGF-C in normal lung tissue in the 1~2(LN+)subgroup was higher than that in the ?3(LN+)subgroup,and the difference was statistically significant(P<0.05).In the tumor tissues without lymph node metastasis,the expression of VEGF-C was higher in T3-4 stage than that in T2 stage group,and the difference was statistically significant(P<0.05).In the normal lung tissues without lymph node metastasis,the expression of VEGF-C was higher in T3-4 stage than that in T2 stage group,and the difference was statistically significant(P<0.05).2.The positive product of VEGFR-3 was brown yellow granules,which was mainly expressed in the lymphatic endothelial cells and the cytoplasm of some tumor cells.The expression rates of VEGFR-3 in tumor tissues of stageN0,N1 and N2 were significantly higher than that of corresponding normal lung tissues(P<0.05).The expression of VEGFR-3 in tumor tissues was higher in lymph node metastasis group than in non lymph node metastasis group,the difference was statistically significant(P<0.05).The expression of VEGFR-3 in normal lung tissues was higher in lymph node metastasis group than in non lymph node metastasis group,the difference was statistically significant(P<0.05).The expression of VEGFR-3 in tumor tissues in the N2 stage subgroups was higher than that in the N1 stage subgroup,and the difference was statistically significant(P<0.05).The expression of VEGFR-3 in tumor tissues in the N2 stage subgroup was higher than that in the N0 stage subgroup,and the difference was statistically significant(P<0.05).The expression of VEGFR-3 in normal lung tissues in the N2 stage subgroups was higher than that in the N1 stage subgroup,and the difference was statistically significant(P<0.05).The expression of VEGFR-3 in normal lung tissues in the N2 stage subgroup was higher than that in the N0 stage subgroup,and the difference was statistically significant(P<0.05).The expression of VEGFR-3 in tumor tissues in the ?3(LN+)subgroup was higher than that in the 0(LN+)subgroup,and the difference was statistically significant(P<0.05).The expression of VEGFR-3 in normal lung tissues in the ?3(LN+)subgroup was higher than that in the 0(LN+)subgroup,and the difference was statistically significant(P<0.05).In the normal lung tissues withoutlymph node metastasis,the expression of VEGFR-3 was higher in T3-4 stage than that in T1 stage group,and the difference was statistically significant(P<0.05).In the normal lung tissues without lymph node metastasis,the expression of VEGFR-3 was higher in T3-4 stage than that in T2 stage group,and the difference was statistically significant(P<0.05).3.The positive product of BMP-9 was brown yellow granules,which was mainly expressed in normal lung tissue and some tumor cells and macrophages.The expression of BMP-9 in the normal lung tissues were significantly higher than that of corresponding tumor tissues of stage N0 and stage N2(P<0.05).The expression of BMP-9 in the tumor tissues were significantly higher than that of corresponding normal lung tissues of stage N1(P<0.05).The expression of BMP-9 in tumor tissues was higher in lymph node metastasis group than in non lymph node metastasis group,the difference was statistically significant(P<0.01).The expression of BMP-9 in normal lung tissues was higher in lymph node metastasis group than in non lymph node metastasis group,the difference was statistically significant(P<0.05).The expression of BMP-9 in tumor tissues in the N1 stage subgroups was higher than that in the N0 stage subgroup,and the difference was statistically significant(P<0.01).The expression of BMP-9 in tumor tissues in the N1 stage subgroups was higher than that in the N2 stage subgroup,and the difference was statistically significant(P<0.05).The expression of BMP-9 in normal lung tissues in the N2 stage subgroupswas higher than that in the N1 stage subgroup,and the difference was statistically significant(P<0.05).The expression of BMP-9 in tumor tissues in the N2 stage subgroups was higher than that in the N0 stage subgroup,and the difference was statistically significant(P<0.05).The expression of BMP-9 in normal lung tissues in the N2 stage subgroups was higher than that in the N0 stage subgroup,and the difference was statistically significant(P<0.01).The expression of BMP-9 in tumor tissues in the 1~2(LN+)subgroup was higher than that in the 0(LN+)subgroup,and the difference was statistically significant(P<0.05).The expression of BMP-9 in tumor tissues in the ?3(LN+)subgroup was higher than that in the 0(LN+)subgroup,and the difference was statistically significant(P<0.05).The expression of BMP-9 in normal lung tissues in the ?3(LN+)subgroup was higher than that in the 0(LN+)subgroup,and the difference was statistically significant(P<0.05).In the tomur tissues with lymph node metastasis,the expression of BMP-9 was higher in T3-4 stage than that in T1 and T2 stage group,and the difference was statistically significant(P<0.05).In the normal lung tissues with lymph node metastasis,the expression of BMP-9 was higher in T3-4 stage than that in T1 and T2 stage group,and the difference was statistically significant(P<0.05).In the tomur tissues without lymph node metastasis,the expression of BMP-9 was higher in T3-4 stage than that in T2 stage group,and the difference was statistically significant(P<0.05).4.The expression of VEGF-C,VEGFR-3 and BMP-9 in the tumor tissues and in normal lung tissues were not significantly different from the subgroups of gender,age,smoking history,histological type(P>0.05).5.The expression of VEGF-C in lymph node in the N1 stage subgroup was higher than that in N0 stage group,and the difference was statistically significant(P<0.05).The expression of VEGFR-3 in lymph node in the N1 stage subgroup was higher than that in N0 stage group,and the difference was statistically significant(P<0.01).The expression of VEGF-C in lymph node in the N2 stage subgroup was higher than that in N1 stage group,and the difference was statistically significant(P<0.01).The expression of VEGFR-3 in lymph node in the N2 stage subgroup was higher than that in N1 stage group,and the difference was statistically significant(P<0.05).The expression of VEGF-C in lymph node in the N2 stage subgroup was higher than that in N0 stage group,and the difference was statistically significant(P<0.01),The expression of VEGFR-3 in lymph node in the N2 stage subgroup was higher than that in N0 stage group,and the difference was statistically significant(P<0.01).6.There was a positive correlation between the expression of VEGF-C and VEGFR-3 in 51 cases of NSCLC tumor tissues(r=0.346,P<0.05).There was a positive correlation between the expression of VEGF-C and VEGFR-3 in 24 cases of NSCLC tumor tissues with lymph node metastasis(r=0.755,P<0.01).The expression of VEGF-Cand VEGFR-3 in the 43 cases of metastatic lymph nodes of NSCLC was also positively correlated(r=0.436,P<0.01).The expression of VEGF-C and VEGFR-3 in 23 cases of N1 stage NSCLC lymph node was also positively correlated(r=0.874,P<0.01).The expression of VEGF-C and VEGFR-3 in 44 cases of N2 stage NSCLC lymph node was also positively correlated(r=0.702,P<0.01).Conclusion 1.The expression of VEGF-C and VEGFR-3 in tumor tissues of NSCLC with different N stage was significantly higher than that in adjacent tissues.The expression of VEGF-C and VEGFR-3 in tumor tissues of NSCLC was both significantly correlated with lymph node metastasis.The expression of VEGF-C and VEGFR-3 in normal lung tissues of NSCLC was both significantly correlated with lymph node metastasis.The expression of VEGF-C and VEGFR-3 in tumor tissues of NSCLC in stage N2 stage subgroup was both significantly higher than that in stage N1 stage subgroup,N0 stage subgroup.The expression of VEGFR-3 in tumor tissues of NSCLC in stage N2 stage subgroup was both significantly higher than that in stage N1 stage subgroup,N0 stage subgroup.The expression of VEGF-C and VEGFR-3 in tumor tissues of NSCLC in ?3(LN+)subgroups was both significantly higher than that in 0(LN+)subgroup.The expression of VEGF-C and VEGFR-3 in normal lung tissues of NSCLC in ?3(LN+)subgroups was both significantly higher than thatin 0(LN+)subgroup.The expression of VEGF-C in tumor tissues of NSCLC in ?3(LN+)subgroups was significantly higher than that in 1~2(LN+)subgroup.The expression of VEGF-C in normai lung tissues of NSCLC in ?3(LN+)subgroups was significantly higher than that in 1~2(LN+)subgroup.In the tumor tissues and normal lung tissues without lymph node metastasis,the expression of VEGF-C in the T3-4 stage was significantly higher than that in the T2 stage group.In the normal lung tissues of NSCLC without lymph node metastasis,the expression of VEGFR-3 in T3-4 stage group was higher than that in T1 and T2 stage group.The expression of VEGF-C and VEGFR-3 in tumor tissues of NSCLC with lymph node metastasis was significantly positively correlated,and the expression of the two in metastatic lymph nodes was also positively correlated.The expression of VEGF-C and VEGFR-3 in lymph nodes was significantly correlated with N stage.We observed that the elevated expression of VEGF-C and VEGFR-3 in tumor tissues,normai lung tissues and lymph node of NSCLC,which was similar to that reported in other literatures.VEGF-C and VEGFR-3 may be involved in local invasion of primary carcinoma,lymphangiogenesis and lymph node metastasis of NSCLC.2.The expression of BMP-9 in the tumor tissues of N0 and N2 stage of NSCLC was significantly lower than that in normal lung tissues,and expression of BMP-9 in the tumor tissues of N1 stage of NSCLC wassignificantly higher than that in normal lung tissues.The expression of BMP-9 in tumor tissues and in normal lung tissues was both significantly correlated with lymph node metastasis.The expression of BMP-9 in tumor tissues in stage N1 subgroup was significantly higher than that in stage N0,N2 subgroup,and the expression of BMP-9 in tumor tissues in stage N2 subgroup was significantly higher than that in stage N0 subgroup.The expression of BMP-9 in tumor tissues of NSCLC in ?3(LN+)subgroups was significantly higher than that in 0(LN+)subgroup,and the expression of BMP-9 in tumor tissues of NSCLC in 1~2(LN+)subgroups was significantly higher than that in 0(LN+)subgroup.The expression of BMP-9 in normal lung tissues of NSCLC in stage N2 subgroup was significantly higher than that in stage N1,N0 subgroup.The expression of BMP-9 in normal lung tissues of NSCLC in ?3(LN+)subgroups was significantly higher than that in 0(LN+)subgroup.In the tumor tissues with lymph node metastasis,the expression of BMP-9 in the T3-4 stage subgroup was significantly higher than that in the T2 and T1 stage group.In the normal lung tissues with lymph node metastasis,the expression of BMP-9 in the T3-4 stage was significantly higher than that in the T2 and T1 stage group.In the tumor tissues without lymph node metastasis,the expression of BMP-9 in the T3-4 stage was significantly higher than that in the T2 group.We observed that the relative decline in the expression of BMP-9 in tumor tissues of NSCLC without lymph node metastasis,and that relativeincrease in the expression of BMP-9 in tumor tissues of NSCLC and the normal lung tissues with lymph node metastasis,which was similar to that reported in other literatures.BMP-9 may inhibit the lymphangiogenesis and lymph node metastasis of NSCLC to some extent,and may promote local invasion of NSCLC primary carcinoma.3.The expression of VEGF-C,VEGFR-3,BMP-9 in tumor tissue and in normal lung tissue were not significantly different from those of patients with gender,age,smoking history and pathological type.4.The expression of VEGF-C and VEGFR-3 in NSCLC tumor tissues,adjacent normal lung tissues and lymph nodes was positively correlated with NSCLC lymphangiogenesis and lymph node metastasis,but expression of BMP-9 in tumor tissues and adjacent tissues of NSCLC had a negative correlation with NSCLC lymphangiogenesis and lymph node metastasis,and expression of VEGF-C,VEGFR-3 and BMP-9 in tumor tissues and adjacent tissues showed a positive correlation with the progression of primary tumor invasion,which is beneficial to further study the positive and negative targeting therapy of NSCLC metastasis. |
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