| With the survey and treatment of cervical cancer, at present there is a decline o the incidence of cervical cancer worldwide. While young patients get more and more,still the cervical cancer remains a worldwide concern and research focus. Some people pay attention to embryonic development and cancer long before, they are similar in rapid growth. Signaling pathways plays an important role in the regulation of embryo development, also was introduced into the tumor genetics, such as TGF, Wnt, Notch and Hedgehog signaling pathways. So many researches show that any link of one signaling pathway is abnormal, such as the ligand over-expression or mutation of other downstream molecules may lead to out of control throughout the signal pathway which can lead to tumors, first found in the skin basal cell carcinoma. The p53 gene mutation exists in almost 50% of human tumors.Objective:To detect the expression of Hedgehog(Hh), smoothened(Smo) and p53 in cervical carcinomas and explore the relationship between them and clinical significance,also study the relationship with its development and metastasis of cervical cancer.Mehtods:Using immunohistochemistry to detecte the expression of Hh, Smo and tumor suppressor gene p53 in 52 cases of cervical squamous cell carcinoma,14 cases of cervical intraepithelial lesions (CIN-II, CINIII) and 14 cases of normal cervicix; and situ hybridization to detected the expression of SHh and p53mRNA with Dig labeled RNA Probe in 44 specimens (25 cases of cervical cancer, CINⅡ-Ⅲ10 cases,9 cases of normal cervix).Results:(1) the staining of Hh and Smo protein located in both epithelium and stroma of normal cervix, CIN and cervical cancer. The expression of Hh and smo protein was higher in cervical cancer than its precancerous lesions and normal cervical tissue, with statistical significance(p<0.05); and higher in precancerous lesions than in the normal cervical tissue, without statistical significance(p>0.05); Hh and Smo proteins in CSCC were higher with clinical stage, pelvic Lymph node metastasis and upper histological grade((p<0.05)), while no difference between the groups of patients'age(p>0.05). The correlation between Hh and Smo were:epithelium (Hh and Smo):r= 0.3427, p<0.05; interstitial (Hh and Smo):r=0.3427,p＜0.05; Hh (epithelial and mesenchymal): r=1,p<0.05; Smo (epithelial and mesenchymal):r=1,p<0.05). SHh mRNA in situ expression was high degree of consistency with Hh protein expression rate (kappa> 0.80).(2)The over-expression of p53 protein in normal cervix and CINII-III epithelium gradually increased and had a significant difference (p<0.05); the over expression in CINII-III epithelium was significantly higher than that in cervical cancer, with a significant difference (p<0.05); p53 in well over-expression in cervical epithelium were significantly higher than those in poorly differentiated groups((p <0.05)). Overexpression of p53 mRNA in situ rate and rate of p53 protein over expression was positively correlated (r= 0.8999, p<0.05), and overexpressed in cervical cancer was significantly higher than the expression of p53 protein.(3) Hh, Smo protein and p53 protein overexpression in cervical epithelium showed a negative correlation (p53 and Hh:r=-0.4298, p<0.05; p53 and Smo:r=-0.5255, p<0.05)Conclusions:(1) The over expression of Hh-Smo signaling pathway was gradual sustained, suggesting that Hh-Smo signaling pathway was abnormal activated in the development and existence of cervical cancer.(2) The over expression of p53 in the process of cervical cancer development may play a negative regulatory role; lower expression of p53 protein in cervical cancer (compared with CINII-III), while the overexpression rate of p53mRNA increased,may show that p53 protein is inactivated and with poor prognosis.(3) Hh-Smo signaling pathway and the p53 tumor suppressor gene in cervical cancer may play an antagonistic effect.(4) Smo may be a new drug target for treatment or gene therapy of cervical cancer... |
