The Expression And Significance Of Vegf, Vegfr-1 And Vegfr-2 In Condyloma Acuminatum

Condyloma acuminatum(CA) is a common sexually transmitted disease which caused by human papilloma virus(HPV) and occurs in sexually active young and middle-aged.The incidence of it is increasing gradually in recent years.The mainly clinical manifestation of it is cauliflower or papilloma neoplasm in external genital organs.CA is a kind of benign disease.But some has oncogenic potential and a few cases can rather too thick hyperplasy to shape giant condyloma acuminatum (Buschke-loewenstein tumor).CA has some characteristics of strong infectivity,rapid growth and high recurrence rate.So it is harm to not only physical and mental health of patients with CA but also the stabilization of society and family.More and more people are playing close attention to it and it is designated as a kind of emphasis detected sexually transmitted disease by national venerism control center.Angiogenesis has a close correlation with tumor and the development of tumor depends on angiogenesis.CA is a mucocutaneous proliferative lesion caused by HPV infection and it possibly related to neovascularization and blood supply in CA organizations.So it is important to study the role of angiogenesis in CA.Vascular endothelial growth factor(VEGF) is currently the most potent,highest-specific angiogenesis factor by acting on the VEGF receptor of vascular endothelial cells to regulate endothelial cell proliferation and angiogenesis.VEGFR-1(fms-like tyrosine kinase,Flt),which are activated can regulate interactions not only endothelial cells but also between endothelial cell and basement membrane and promote the formation of the lumen.VEGFR-2(Kinase insert domain containing receptor,KDR),also known as fetal liver kinase-1(FLK-1),can mediate the endothelial cell proliferation, migration,and promote the formation of neovascularization.Recently there are scarce reports about the expressions of VEGFR-1 and VEGFR-2,and the relationships between the above factors are few investigated in CA.In order to explore the expressions of VEGF,VEGFR-1 and VEGFR-2 in CA, the relationships between the above factors and the possible roles they play in angiogenesis of CA,the expressions of VEGF,VEGFR-1 and VEGFR-2 in CA were respectively detected by the immunohistochemistry and with a view to provide a new train of thought to the clinical treatment of CA.Materials and Methods1.Materials:Specimens of CA were obtained from 40 outpatients in the department of dermatology and venereology of the first affiliated hospital,Zheng Zhou University from August,2007 to February,2008.In the group of CA there were 24 males and 16 females,ages from 18 years old to 58 years old(mean 29.75 years). The course ranges from 21 days to 110 days and mean 58.9 days.All cases of the clinical and laboratory diagnosis were made by typical clinic manifestation, confirmed by histopathology examination,and evidence of HPV infection.All patients didn't accept any immunotherapy before histopathology examination and had no other disease.The specimens of control group derived from the normal foreskin tissues of 20 adult males who underwent surgery.2.Methods:SP immunohistochemistry method was used to measure the expressions of VEGF,VEGFR-1 and VEGFR-2 in 40 cases of CA and 20 normal skin controls.We will get half quantitation ranking scores according to stain intensity (negative:0 point,buff:1 point,yellow:2 points,ocher yellow:3 points) and the percentage of positive cells(≤10%:0 point,11%～25%:1 point,26%～50%:2 points, 51%～75%:3 points,≥76%:4 points).According to the above score's respective multiplications,the final scores of the expressions of VEGF,VEGFR-1 and VEGFR-2 in CA were divided into four ranks:(negative(-):0 point,weak positive(+):1～4 points,positive(++):6～8 points,strong positive(+++):9～12 points).3.Statistical analysis:Statistical analysis was executed by SPSS11.0 statistical package.The data analyzed by Wilcoxon Signed Ranks Test and Spearman Rank Correlation Analysis.P value of less than 0.05 was considered significant.Results1.The expression of VEGF protein in CA tissues and normal foreskin tissues.Both of the positive rates of VEGF in CA tissues and control group were 100% (40/40,20/20).There was no significant difference between two groups(P＞0.05). The positive cells mainly located in cell kytoplasm.The distribution of VEGF in CA was throughout the epidermis expect the stratum corneum.The intensity of VEGF expression in CA was significant higher(++～+++) than that in normal control(+～++)(u=3.139,P＜0.05).2.The expression of VEGFR-1 protein in CA tissues and normal foreskin tissues.The positive rates of VEGFR-1 in CA tissues and normal controls were both 100%(40/40,20/20).There was no significant difference between two groups(P＞0.05).The distribution of VEGFR-1 in CA was throughout the epidermis and gradually decreased from the basal layer,the prickle cell layer to the stratum granulosum.The intensity of VEGFR-1 expression in CA was significant higher (++～+++) than that in normal control(+～++)(u=4.071,P＜0.05).3.The expression of VEGFR-2 protein in CA tissues and normal foreskin tissues.The positive rate of VEGFR-2 in the 40 cases of CA tissues was 100% (40/40).The positive cells mainly located in cell kytoplasm,some in membrane and stained cells were dyed from yellow to clay brown.The positive rate of VEGFR-2 in normal control was also 100%(20/20),and there was no significant difference comparing with CA group.While the intensity of VEGFR-2 expression in CA was significant higher(++～+++) than that in normal control(+～++)(u=4.286,P＜0.05).4.The correlation analyse of expression of VEGF,VEGFR-1 and VEGFR-2 in the CA tissues.The positive correlation was observed between the expression of VEGF and VEGFR-1,the expression of VEGF and VEGFR-2,and the expression of VEGFR-1 and VEGFR-2 in CA tissues,respectively(r=0.415,0.397,0.343,P＜0.05).Conclusions1.The levels of VEGF,VEGFR-1 and VEGFR-2 expression are significantly higher in CA tissues than that in the control group,which suggests that VEGF, VEGFR-1 and VEGFR-2 take part in the formation mechanism of CA and also may play an important role in it.2.The positive correlations between VEGF and VEGFR-1 expression,VEGF and VEGFR-2 expression in CA tissues show that VEGF and VEGFR-1 or VEGFR-2 may interact to co-promote the growth and angiogenesis in CA tissues.3.There is a positive correlation between VEGFR-1 and VEGFR-2 expression. It indicates that VEGFR-1 and VEGFR-2 may promote angiogenesis and lead to the growth of CA through interactions with VEGF.