lung cancer is the leading cause of cancer - related death in china , of which 85% are non - small cell lung cancer ( nsclc ) . during the last decades , the treatments for advanced nsclc were confined to platinum - based chemotherapy , with an unsatisfactory response rate of 30% . intensive studies on tumor - related aberrant signaling pathways have led to rapid development in the treatment of lung cancer . medicines targeted at epidermal growth factor receptor ( egfr ) gene mutation or anaplastic lymphoma kinase fusion gene increase the response rate to 6580% , whereas tumor progression is still unavoidable eventually . with a median progression - free survival of about 10 months and a poor overall survival ( os ) , patients with advanced nsclc need new therapeutic targets . fibroblast growth factor receptor 1 ( fgfr1 ) , a transmembrane tyrosine kinase receptor of fibroblast growth factors ( fgfs ) , is encoded by fgfr1 gene ( 8p1112 ) . after combining with fgfs , fgfr ligand - dependent dimerization activates tyrosine kinase domains , resulting in the phosphorylation of intracellular tyrosine residues . phosphorylated tyrosine residues work as docking sites for adaptor proteins , such as grb2 , sos protein , recruiting ras - guanosine diphosphate ( ras - gdp ) , activating mitogen - activated protein kinase , protein kinase c , phosphatidylinositol 3-kinase / akt pathway , and signal transducer and activator of transcription signaling pathways . the overexpression of fgfr1 was found in nsclc and recognized as a novel therapeutic target . although several meta - analyses have been reported , the correlation between the expression status of fgfr1 and clinical pathological features remains controversial [ 810 ] . this study focused on these issues and also studied the promotion of angiogenesis with vegfr2 , which is the main receptor of vegf - a that plays an important role in neoangiogenesis . the expression of vrgfr2 can be detected in a variety of tumor cells , including colorectal cancer , breast cancer , and non - small cell lung cancer . the overexpression of vegfs and vegfr2 is related to tumor invasion and metastasis , mainly because of their effect on angiogenesis . fgf can upregulate the expression of vegf , fgfr , and vegfr in epithelial cells , and vegf can upregulate the expression of fgf . prior studies indicated that neoangiogenesis is essential in developing lung cancer , and microvessel density ( mvd ) is increased even in premalignant lesions and early - stage lung cancer . in this retrospective study , the correlation between fgfr1 and clinical features was explored , including survival analysis and promotion of angiogenesis by fgfr1 and vegfr2 . ninety - two patients pathologically diagnosed with nsclc , who received radical resection ( pneumonectomy + lymph node dissection ) in west china hospital of sichuan university from july 2006 to july 2008 were enrolled in the study . the exclusion criteria were as follows : received neoadjuvant chemotherapy and/or radiotherapy ; received egfr tyrosine kinase inhibitors ; had another kind of carcinoma ; loss to follow - up ; and histopathological specimens unavailable . the study was approved by the hospital ethics committees , and all the patients enrolled gave informed consent . the patients underwent chest computed tomography ( ct ) scan , abdomen ct scan , and brain magnetic resonance imaging , and also bone single - photon emission computed tomography if necessary , during periodic follow - up visit according to the national comprehensive cancer network ( nccn ) guideline . staging was based on the nccn guideline , and histological grading was evaluated according to the world health organization criteria . the clinical features included age , gender , stage , histological type , grade , lymph node status , smoking status , and postoperative adjuvant therapy . the primary endpoint was os , and the secondary endpoint was recurrence - free survival ( rfs ) . formalin - fixed and paraffin - embedded surgical specimens were immunostained according to streptavidin - peroxidase protocol . the paraffin - embedded tissues were sliced up into slices of 4 m . then , after deparaffinization and antigen retrieval , the tissue sections were incubated with fgfr1 antibodies ( monoclonal rabbit anti - human , 1:500 , cell signaling technology co. , ltd , ma , usa ) , vegfr2 antibodies ( polyclonal rabbit anti - human , 1:100 , golden bridge biotechnology co. , ltd . , beijing , china ) , and cd34 antibodies ( monoclonal mouse anti - human , 1:100 , golden bridge biotechnology co. , ltd , beijing , china ) at 37c for 1 h , and then at 4c overnight . the next day the sections were rinsed 3 times with phosphate - buffered saline ( pbs ) before incubating with biotinylated goat anti - rabbit antibodies ( 1:200 , golden bridge biotechnology co. , ltd , beijing , china ) and subsequently with horseradish - labeled streptavidin ( 1:200 , golden bridge biotechnology co. , ltd . , positive controls were provided by reagent companies , and pbs instead of primary antibodies was used as negative control . brownish - black or brown particles displayed in certain places were defined as a specific positive reaction . the weighted score , evaluated in a semi - quantitative way , was calculated by multiplying the quantity score by staining intensity score , representing fgfr1 and vegfr2 expression levels . the quantity scores based on the percentage of stained cells were defined as follows : 0 for < 5% cells stained ; 1 for 525% cells stained ; 2 for 2650% cells stained ; 3 for 5175% cells stained ; and 4 for 76% cells stained . the staining intensity was scored 03 : 0 for no staining ; 1 for pale yellow staining ; 2 for brown staining ; and 3 for brownish - black staining . weighted score 1 , 23 , 46 , or 7 was defined as negative , weak , moderate , or strong , respectively . for statistical analysis , the subgroups were finally dichotomized into high expression ( moderate and strong ) and low expression ( negative and weak ) . the hot spots ( intratumoral areas with a high density of cd34-positive vessels ) were identified under low - power fields , while the cd34-positive vessels in hot spots were quantitated under high - power fields case by case . spss 16.0 software ( spss inc . , il , usa ) was used for statistical analysis . the correlations between the expression of fgfr1and vegfr2 , mvd , and clinicopathological features were tested by chi - square test , t test , and spearman s rank correlation coefficient , respectively . kaplan - meier curve was used to analyze the correlation between the expression of fgfr1 and vegfr2 , mvd , and prognosis . univariate and multivariate analyses were performed by cox regression model . a p value less than 0.05 was considered to be statistically significant ninety - two patients pathologically diagnosed with nsclc , who received radical resection ( pneumonectomy + lymph node dissection ) in west china hospital of sichuan university from july 2006 to july 2008 were enrolled in the study . the exclusion criteria were as follows : received neoadjuvant chemotherapy and/or radiotherapy ; received egfr tyrosine kinase inhibitors ; had another kind of carcinoma ; loss to follow - up ; and histopathological specimens unavailable . the study was approved by the hospital ethics committees , and all the patients enrolled gave informed consent . the patients underwent chest computed tomography ( ct ) scan , abdomen ct scan , and brain magnetic resonance imaging , and also bone single - photon emission computed tomography if necessary , during periodic follow - up visit according to the national comprehensive cancer network ( nccn ) guideline . staging was based on the nccn guideline , and histological grading was evaluated according to the world health organization criteria . the clinical features included age , gender , stage , histological type , grade , lymph node status , smoking status , and postoperative adjuvant therapy . the primary endpoint was os , and the secondary endpoint was recurrence - free survival ( rfs ) . formalin - fixed and paraffin - embedded surgical specimens were immunostained according to streptavidin - peroxidase protocol . then , after deparaffinization and antigen retrieval , the tissue sections were incubated with fgfr1 antibodies ( monoclonal rabbit anti - human , 1:500 , cell signaling technology co. , ltd , ma , usa ) , vegfr2 antibodies ( polyclonal rabbit anti - human , 1:100 , golden bridge biotechnology co. , ltd . , beijing , china ) , and cd34 antibodies ( monoclonal mouse anti - human , 1:100 , golden bridge biotechnology co. , ltd , beijing , china ) at 37c for 1 h , and then at 4c overnight . the next day the sections were rinsed 3 times with phosphate - buffered saline ( pbs ) before incubating with biotinylated goat anti - rabbit antibodies ( 1:200 , golden bridge biotechnology co. , ltd , beijing , china ) and subsequently with horseradish - labeled streptavidin ( 1:200 , golden bridge biotechnology co. , ltd . , positive controls were provided by reagent companies , and pbs instead of primary antibodies was used as negative control . brownish - black or brown particles displayed in certain places were defined as a specific positive reaction . the weighted score , evaluated in a semi - quantitative way , was calculated by multiplying the quantity score by staining intensity score , representing fgfr1 and vegfr2 expression levels . the quantity scores based on the percentage of stained cells were defined as follows : 0 for < 5% cells stained ; 1 for 525% cells stained ; 2 for 2650% cells stained ; 3 for 5175% cells stained ; and 4 for 76% cells stained . the staining intensity was scored 03 : 0 for no staining ; 1 for pale yellow staining ; 2 for brown staining ; and 3 for brownish - black staining . weighted score 1 , 23 , 46 , or 7 was defined as negative , weak , moderate , or strong , respectively . for statistical analysis , the subgroups were finally dichotomized into high expression ( moderate and strong ) and low expression ( negative and weak ) . the hot spots ( intratumoral areas with a high density of cd34-positive vessels ) were identified under low - power fields , while the cd34-positive vessels in hot spots were quantitated under high - power fields case by case . spss 16.0 software ( spss inc . , il , usa ) was used for statistical analysis . the correlations between the expression of fgfr1and vegfr2 , mvd , and clinicopathological features were tested by chi - square test , t test , and spearman s rank correlation coefficient , respectively . kaplan - meier curve was used to analyze the correlation between the expression of fgfr1 and vegfr2 , mvd , and prognosis . univariate and multivariate analyses were performed by cox regression model . a p value less than 0.05 was considered to be statistically significant . a total of 92 patients ( 70 males and 22 females ) with a mean age of 58.5 ( range 3879 ) years were enrolled in the study . classified by histological type , 49 patients had squamous lung cancer , 37 had adenocarcinoma , 4 had adenosquamous carcinoma , and 2 had large - cell lung cancer . histologically , 54 samples were poorly differentiated , 36 moderately differentiated , and 2 well differentiated . according to the nccn guideline of 2013 , 25 patients were at stage i , 16 were at stage ii , 42 were at stage iii , and 9 were at stage iv . moreover , 59 of all the patients were continuously smoking ( defined as never quit or quit for less than 1 year ) , and 33 patients were nonsmokers or quit for more than 1 year . both fgfr1 and vegfr2 were mainly expressed in the cytoplasm ( figure 1a , 1b ) . in terms of fgfr1 expression , 25% ( 23/92 ) were negative , 48.9% ( 45/92 ) were weak , 18.5% ( 17/92 ) were moderate , and 7.6% ( 7/92 ) were strong . notably , the high expression rate of fgfr1 was significantly higher in squamous lung cancer than in adenocarcinoma ( table 1 . the high expression of fgfr1 was not correlated with smoking ( 23.7% vs. 30.3% , p=0.491 ) , while in statistical analysis , we found that the expression rate ( patients that had been tested to be positive , including weak , moderate and strong ) of fgfr1 was significantly higher in smoking patients ( 84.7% vs. 60.6% , p=0.009 ) . moreover , 5.4% ( 5/92 ) of samples were vegfr2 negative , 52.2% ( 48/92 ) were weak , 29.3% ( 27/92 ) were moderate , and 13% ( 12/92 ) were strong . patients with lymph node metastasis ( p=0.022 ) and those with tumor size more than 4 cm ( p=0.001 ) had higher expression of vegfr2 . the high expression of fgfr1 and vegfr2 was not correlated with the patients age , gender , smoking status , differentiation , and stage . microvascular endothelial cells could be stained yellow or brownish by cd34 antibody ( figure 1c ) . the number of stained endothelial cells in a certain area was defined as mvd . in this study , patients with lymph node metastasis ( 37.510.7 vs. 31.010.3 , p=0.004 ) and stages iii  iv ( 36.910.7 vs. 31.710.5 , p=0.024 ) presented with a significantly higher mvd in tumor tissues , while no correlation was found between mvd and gender , age , smoking status , histological type , and differentiation . mvd was significantly higher in patients with high expression of vegfr2 than in patients with low expression of vegfr2 ( 40.611.0 vs. 30.18.7 , p<0.001 ) , and a higher mvd was associated with the high expression of fgfr1 as well ( 43.110.1 vs. 31.59.6 , p<0.001 ) . the spearman rank correlation analysis ( table 2 ) demonstrated that , to some extent , the expression intensity of vegfr2 ( r=0.224 , p=0.032 ) and fgfr1 ( r=0.265 , p=0.011 ) was positively correlated with mvd . in addition , the expression levels of fgfr1 and vegfr2 were significantly positively correlated ( r=0.619 , p<0.001 ) . with a total follow - up of 80 months , the patients with the high expression of fgfr1 presented with a significantly shorter os ( 23.5 months vs. 39.8 months , p=0.043 ) and rfs ( 15.0 months vs. 28.0 months , p=0.043 ) than those with the low expression of fgfr1 ( figure 2a , 2b ) . the expression level of vegfr2 showed no significant impact on the survival of patients with nsclc . notably , in squamous lung cancer , the os in patients with the high expression of vegfr2 was 32.5 months , which was shorter than that in patients with the low expression ( 51.0 months , p=0.028 ) ( figure 2e ) . however , no significant difference was observed in the survival of patients with adenocarcinoma between high - expression and low - expression groups of vegfr2 ( p = 0.918 ) ( figure 2f ) . the analysis of the impact of mvd on os and rfs is shown in figure 2c and 2d . the rfs of patients with a high and a low value of mvd was 18.1 and 30.4 months ( p=0.010 ) , respectively , while the os in the low - mvd group was significantly longer than the os in the high - mvd group ( 51.0 months vs. 32.5 months , p=0.013 ) . all clinical and pathological features , including gender , age , smoking status , tumor size , differentiation , histological type , lymph node status , stage , adjuvant therapy , fgfr1 expression , vegfr2 expression , and mvd value , were considered in the cox regression model . the univariate analysis showed that tumor stage ( p<0.001 ) , lymph node metastasis ( p=0.003 ) , high expression of fgfr1 ( p=0.043 ) , and high value of mvd ( p=0.013 ) in tumor tissue suggested shorter os , while only stage ( stage iii : hazard ratio [ hr ] 3.451 , 95% confidence interval [ ci ] : 1.6217.345 , p=0.001 ; stage iv : hr 39.207 , 95% ci : 12.201125.986 , p<0.001 ) and high expression of fgfr1 ( hr 2.194,95% ci : 1.2323.908,p=0.008 ) remained independent risk factors of os in multivariate analysis . adjuvant chemotherapy was the protection factor for os ( hr 0.492 , 95% ci : 0.2510.964 , p=0.039 ) ( table 3 ) . considering that stage is universally thought to be the most important prognostic factor , stratified analysis based on stages was done ( figure 3 ) . the os was not significantly different between low- and high - expression of fgfr1 in stage i , ii , iii and iv , respectively , while when the patients with stage i and ii were all taken into account , the os was significantly longer in those with low fgfr1 expression than high fgfr1 expression ( p=0.044 ) . no significant difference was observed in the survival of patients with low and high fgfr1 expression in stage iii a total of 92 patients ( 70 males and 22 females ) with a mean age of 58.5 ( range 3879 ) years were enrolled in the study . classified by histological type , 49 patients had squamous lung cancer , 37 had adenocarcinoma , 4 had adenosquamous carcinoma , and 2 had large - cell lung cancer . histologically , 54 samples were poorly differentiated , 36 moderately differentiated , and 2 well differentiated . according to the nccn guideline of 2013 , 25 patients were at stage i , 16 were at stage ii , 42 were at stage iii , and 9 were at stage iv . moreover , 59 of all the patients were continuously smoking ( defined as never quit or quit for less than 1 year ) , and 33 patients were nonsmokers or quit for more than 1 year . both fgfr1 and vegfr2 were mainly expressed in the cytoplasm ( figure 1a , 1b ) . in terms of fgfr1 expression , 25% ( 23/92 ) were negative , 48.9% ( 45/92 ) were weak , 18.5% ( 17/92 ) were moderate , and 7.6% ( 7/92 ) were strong . notably , the high expression rate of fgfr1 was significantly higher in squamous lung cancer than in adenocarcinoma ( table 1 . the high expression of fgfr1 was not correlated with smoking ( 23.7% vs. 30.3% , p=0.491 ) , while in statistical analysis , we found that the expression rate ( patients that had been tested to be positive , including weak , moderate and strong ) of fgfr1 was significantly higher in smoking patients ( 84.7% vs. 60.6% , p=0.009 ) . moreover , 5.4% ( 5/92 ) of samples were vegfr2 negative , 52.2% ( 48/92 ) were weak , 29.3% ( 27/92 ) were moderate , and 13% ( 12/92 ) were strong . patients with lymph node metastasis ( p=0.022 ) and those with tumor size more than 4 cm ( p=0.001 ) had higher expression of vegfr2 . the high expression of fgfr1 and vegfr2 was not correlated with the patients age , gender , smoking status , differentiation , and stage . microvascular endothelial cells could be stained yellow or brownish by cd34 antibody ( figure 1c ) . the number of stained endothelial cells in a certain area was defined as mvd . in this study , patients with lymph node metastasis ( 37.510.7 vs. 31.010.3 , p=0.004 ) and stages iii  iv ( 36.910.7 vs. 31.710.5 , p=0.024 ) presented with a significantly higher mvd in tumor tissues , while no correlation was found between mvd and gender , age , smoking status , histological type , and differentiation . mvd was significantly higher in patients with high expression of vegfr2 than in patients with low expression of vegfr2 ( 40.611.0 vs. 30.18.7 , p<0.001 ) , and a higher mvd was associated with the high expression of fgfr1 as well ( 43.110.1 vs. 31.59.6 , p<0.001 ) . the spearman rank correlation analysis ( table 2 ) demonstrated that , to some extent , the expression intensity of vegfr2 ( r=0.224 , p=0.032 ) and fgfr1 ( r=0.265 , p=0.011 ) was positively correlated with mvd . in addition , the expression levels of fgfr1 and vegfr2 were significantly positively correlated ( r=0.619 , p<0.001 ) . with a total follow - up of 80 months , the patients with the high expression of fgfr1 presented with a significantly shorter os ( 23.5 months vs. 39.8 months , p=0.043 ) and rfs ( 15.0 months vs. 28.0 months , p=0.043 ) than those with the low expression of fgfr1 ( figure 2a , 2b ) . the expression level of vegfr2 showed no significant impact on the survival of patients with nsclc . notably , in squamous lung cancer , the os in patients with the high expression of vegfr2 was 32.5 months , which was shorter than that in patients with the low expression ( 51.0 months , p=0.028 ) ( figure 2e ) . however , no significant difference was observed in the survival of patients with adenocarcinoma between high - expression and low - expression groups of vegfr2 ( p = 0.918 ) ( figure 2f ) . the analysis of the impact of mvd on os and rfs is shown in figure 2c and 2d . the rfs of patients with a high and a low value of mvd was 18.1 and 30.4 months ( p=0.010 ) , respectively , while the os in the low - mvd group was significantly longer than the os in the high - mvd group ( 51.0 months vs. 32.5 months , p=0.013 ) . all clinical and pathological features , including gender , age , smoking status , tumor size , differentiation , histological type , lymph node status , stage , adjuvant therapy , fgfr1 expression , vegfr2 expression , and mvd value , were considered in the cox regression model . the univariate analysis showed that tumor stage ( p<0.001 ) , lymph node metastasis ( p=0.003 ) , high expression of fgfr1 ( p=0.043 ) , and high value of mvd ( p=0.013 ) in tumor tissue suggested shorter os , while only stage ( stage iii : hazard ratio [ hr ] 3.451 , 95% confidence interval [ ci ] : 1.6217.345 , p=0.001 ; stage iv : hr 39.207 , 95% ci : 12.201125.986 , p<0.001 ) and high expression of fgfr1 ( hr 2.194,95% ci : 1.2323.908,p=0.008 ) remained independent risk factors of os in multivariate analysis . adjuvant chemotherapy was the protection factor for os ( hr 0.492 , 95% ci : 0.2510.964 , p=0.039 ) ( table 3 ) . considering that stage is universally thought to be the most important prognostic factor , stratified analysis based on stages was done ( figure 3 ) . the os was not significantly different between low- and high - expression of fgfr1 in stage i , ii , iii and iv , respectively , while when the patients with stage i and ii were all taken into account , the os was significantly longer in those with low fgfr1 expression than high fgfr1 expression ( p=0.044 ) . no significant difference was observed in the survival of patients with low and high fgfr1 expression in stage iii the malfunction of fgfr signaling pathway , mainly caused by the overexpression and/or mutation of receptor genes , was found in a variety of epithelial tumors [ 2528 ] , such as breast cancer , prostatic cancer , oral carcinoma , and gastric cancer . both in vitro and in vivo experiments showed that the fgfr signal pathway played an important role in growth , survival , and migration of lung cancer cells , which could be blocked by fgfr tyrosine kinase inhibitor . previous studies compared the results between fluorescence in situ hybridization and immunohistochemistry ( ihc ) in detecting the overexpression of fgfr1 , where no significant difference was detected between the 2 methods . in this study , the expression of fgfr1 by ihc , and its correlation with vegfr2 and mvd , was analyzed to evaluate its correlation with clinical features and the impact on prognosis . according to previous reports , gene amplification of fgfr1 was about 1620% in squamous lung cancer and 5% in adenocarcinoma . inconsistently , researches from weiss   and schildhaus   showed no fgfr1 gene amplification in adenocarcinoma . several common histological types , such as squamous lung cancer , adenocarcinoma , large - cell lung cancer , and adenosquamous carcinoma , were included in this study . the present study showed that 2 patients with large - cell lung cancer and 4 with adenosquamous carcinoma had fgfr1 negative or weak expression . fgfr1 expression was significantly higher in squamous lung cancer than in adenocarcinoma ( 36.7% vs. 16.2% , p=0.036 ) , which was consistent with most previous reports . the similarity between these results implicated no significant ethnic diversity in the fgfr1 status while large - scale researches are still in need . the expression rate of fgfr1 was slightly higher in this study than in previous reports , which might be due to different detection methods . for example , a newly published research using reverse transcription - polymerase chain reaction showed an extremely higher amplification rate of fgfr1 ( 41.5% in squamous lung cancer and 14.3% in nonsquamous lung cancer ) than in any other researches . ihc is a widely used method in detecting the expression of specific proteins , which could test the expression of fgfr1 . zhang s research showed that fgfr1 inhibitor induced tumor stasis or regression in the fgfr1-amplified nsclc model . this study demonstrated that fgfr1 was overexpressed in some nsclcs , especially in squamous lung cancer in the chinese population , suggesting that fgfr1 might be a potential target for targeted therapy and its inhibitor might be applied for the treatment of squamous lung cancer and a small part of adenocarcinoma harboring the high expression of fgfr1 . some studies suggested that smoking was also positively correlated with fgfr1 amplification , while some did not . this study showed some differences , as the high expression of fgfr1 was not correlated with smoking ( 23.7% vs. 30.3% , p=0.491 ) , while the expression rate of fgfr1 was significantly higher in smoking patients ( 84.7% vs. 60.6% , p=0.009 ) . in conclusion , no correlation was found between high expression of fgfr1 and clinical characteristics such as age , gender , stage , grade , smoking status , and lymph node metastasis , suggesting no special predictive potential of these clinical characteristics for fgfr1 status in patients with nsclc . inconsistent pathological types and different egfr - tki treatment status in analysis might explain the differing results . in this study , patients who had taken egfr - tki after relapse were excluded , and multivariate analysis was used to identify the correlation between fgfr1 expression and clinical features . it showed that the high expression of fgfr1 was related to poor prognosis , which was consistent with the findings of weiss s research . however , in weiss s study , clinical pathological characteristics ( e.g. , stage , smoking status , and adjuvant chemotherapy ) were not taken into consideration . the present study , using multivariate analysis ( including gender , age , smoking status , tumor size , degree of differentiation , lymph node metastasis , stage , and adjuvant chemotherapy ) , demonstrated that patients with high expression of fgfr1 had shorter rfs and os , suggesting that the high expression of fgfr1 was the independent prognostic indicator of nsclc . although we found no significant difference in survival between low and high fgfr1 expression in stage i , ii , iii , and iv , when we combined the patients with stage i and ii , the os was significantly longer in those with low fgfr1 expression than high fgfr1 expression ( p=0.044 ) . no significant difference was observed in the survival of patients with low- and high - fgfr1 expression in stage iii iv ( p=0.253 ) , indicating that the prognostic value could be more important in early stage of lung cancer . the small sample size may be why we did not get statistical significance in stage i and ii separately . vegfr2 expression , mainly located in the cytoplasm , was found in most tumor tissues ( 94.6% ) in this study , which was consistent with decaussin s report . the expression of vegfr2 was not influenced by age , gender , smoking status , stage , or grade , but it was significantly higher in patients with lymph node metastasis ( p=0.022 ) and/or tumor size more than 4 cm ( p=0.001 ) . seto s study , involving 60 postsurgery patients with stage i lung cancer , indicated that patients with vegfr2 expression in tumor cells presented with poorer survival , while some other studies showed no correlation between vegfr2 expression and prognosis . a recent meta - analysis found no statistically significant effect of vegfr2 expression on survival , but vegfa / vegfr2 co - expression had an influence on survival ( 40 ) . the differences might be caused by the diversity in stage , histological type , period of follow - up , and sample size between different studies . the present study showed no correlation between the expression statuses of vegfr2 and rfs and os in patients with nsclc after surgery . the subgroup analysis , however , showed that in a subgroup of squamous lung cancer , patients with the high expression of vegfr2 had shorter rfs and os compared with the low - expression group ( p=0.028 ; p=0.033 ) , while this correlation was not found in adenocarcinoma . according to the literature the expression status of vegfr2 might play different roles in the prognosis of different histological types . in the meantime , it reflected indirectly that carcinomas with different histological types present with different biological characteristics , so that personalized treatment should be emphasized during treatment . the proangiogenic effect of vegf and bfgf is mediated through the vegf receptor 2 and fgf receptor 1 , respectively . previous researches also showed crosstalk between them in vitro and in vivo . in this study , mvd , which reflected the number of vessels , was significantly higher in tumors with the high expression of vegfr2 than in tumors with the low expression of vegfr2 . the present study , using human tumor tissues , verified in terms of histopathology that the expression of fgfr1 and vegfr2 was significantly correlated ( r=0.619 ) , and both of them had more or less positive correlation with mvd ( r=0.224 ; r=0.265 ) . although the sample size was small , this study found and verified some important findings in china . the role of fgfr1 in squamous lung cancer and its crosstalk with vegfr2 in tumor development need to be explored further . it is hoped that fgfr1 would serve as one of the treatment targets in nsclc , especially in squamous lung cancer . the high expression of fgfr1 existed in part of nsclc ( including squamous lung cancer and adenocarcinoma ) and was the independent prognostic factor associated with poor prognosis , especially in early stages . the expression of fgfr1 and vegfr2 was positively correlated , and both of them were associated with angiogenesis .
backgroundthis study aimed to explore the correlation between fgfr1 and clinical features , including survival analysis and the promotion of angiogenesis by fibroblast growth factor receptor 1 ( fgfr1 ) and vascular endothelial growth factor receptor 2 ( vegfr2 ) . 
 fgfr1 gene amplification has been found in non - small cell lung cancer ( nsclc ) . 
 however , the prognostic value of fgfr1 and the correlation between fgfr1 and clinical features are still controversial.material/methodsa total of 92 patients with nsclc who underwent r0 resection between july 2006 and july 2008 were enrolled in the study . 
 the expression of fgfr1 , vegfr2 , and cd34 was detected by immunohistochemistry . 
 the correlations between the aforementioned markers and the patients clinical features were analyzed by the chi - square test . 
 the impact factors of prognosis were evaluated by cox regression analyses.resultsthe expression ratios of fgfr1 and vegfr2 were 26.1% and 43.4% , respectively . 
 the intensity of fgfr1 expression was related to vegfr2 and histopathology . to some extent , 
 the average microvessel density ( mvd ) had correlation to the expression of fgfr1 and vgefr2 . 
 the pathological stages iii  iv and high expression of fgfr1 were found to be independent prognostic factors.conclusionsthe expression intensity of fgfr1 and vegfr2 was associated with mvd , and the expression of fgfr1 is one of the independent prognostic indicators for nsclc .