| Background and Objective:Condyloma acuminate, also called genital warts, is one of the most common sexually transmitted diseases. The incidence of the disease increases these years. Human papilloma virus (HPV) is etiologically associated with the development of genital warts. Over 100 subtypes of HPV are identified recently. Genital warts typically are caused by HPV subtypes 6, 11, 16 and 18. The HPV 16 and HPV 18 are also correlated with cervix carcinoma. Clinically the genital warts are found to grow fast and easily bleed when used physical and chemical therapy. The hyperproliferation of keratinocyte and the high lever of microvessel density with dilation of vessel lumen in derma are also confirmed by routine pathological methods. It is suggested that some factors promote cell proliferation and angiogenesis in condyloma acuminate. Our previous experiments demonstrate that VEGF, TGFβ1 are over expressed in CA. Protease-activated receptor 1 (PAR-1) is one of G Protein-coupled receptors. Its physiology functions are related to cell proliferation, angiogenesis, expressions of VEGF mRNA and so on.β-catenin is the key downstream factor of Wnt/β-catenin pathway. Wnt/β-catenin signaling transduction is a important pathway for the differentiation and development of embryonic tissues and cell proliferation. Over expression of wnt-1 protein was confirmed in our previous study, which suggested wnt-1 signaling pathway affect cell growth in CA.To reveal the possible pathogenesis of CA, this study is to investigate the expression of PAR-1 andβ-catenin, and to determine HPV6/11, 16/18 subtypes in CA and normal tissues.Methods:Immunohistochemical study was used to detect PAR-1 andβ-catenin expression in 28 cases of CA tissues and 17 specimens of normal foreskin. Human papilloma virus type 6, 11, 16, 18 (HPV 6/11, 16/18) were identified by PCR, and the expression of PAR-1 mRNA were assessed by RT-PCR method, meanwhile the blood vessel density is quantified in the same specimens.Results:The blood vessel density in CA tissues (20.81±9.09) was significantly higher than that in normal human foreskin tissues (11.36±2.45, t=5.192, P<0.001). The expression of PAR mRNA in CA(1.541±0.1280)was higher than that in the normal foreskin tissue (0.728±0.214,t=7.55,P<0.001). The expression of PAR-1 protein in CA specimens was significantly higher than that in normal foreskin tissues (X2=16.218,P< 0.001). The distribution of PAR-1 in healthy controls was only in basal cell layer, whereas, in CA was throughout the epidermis except the stratum corneum, and the positive intensity of staining in CA was also significantly higher than that in normal foreskin tissues.There was a striking correlation between the expression of PAR-1 protein and the blood vessel density(r=0.832,P<0.001).β-catenin was normally expressed in the entire normal foreskin. The aberrant expression rate ofβ-catenin (21.4%) in CA lesions was higher than that in the normal tissue (X2=4.203, P<0.05). In CA, PAR-1 was positively correlated with the aberrant expression ofβ-catenin(P<0.05,r=0.101).HPV were found in all the cases with CA,including 82.1%(23/28)were detectable for HPV 6/11, and 17.9%(5/28)were positive for HPV16/18. HPV16/18 infection had positive correlation with aberrant expression ofβ-catenin(P<0.001, r = 0.893).Conclusion:The over expression of PAR-1 and correlation with blood vessel density might be associated with angiogenesis of CA. Both the overexpression of PAR-1 and the aberrant expression ofβ-catenin might be associated with the proliferation of keratinocyte and angiogenesis in CA. The HPV6/11 subtype is the mainly malgenic virus in CA.
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