The Expression And Clinical Significance Of COX-2 And HPV16-E6 In The Process Of Cancerating Of Cervical Epithelium

Objective:. Cervical carcinoma is one of the most common malignant tumour in global women, take the first place of women's reproductive organs malignant tumour. Before occurrence of this malignancy, it underlies a long time of intraepithelial neoplasia, and the prognosis of it is bad to the case of advanced stage, recidivism and metabasis. In recent years, the morbility of cervical intraepithelial neoplasia(CIN) and cervical cancer rises gradually, especially which of young women rising obviously. Generally thinking that HPV oncoprotein plays a main role of the genesis and the development of cervical carcinoma. E6 oncoprotein encoded by the effect of high-risk HPV16 coheres with tumour suppressor protein P53 and devitalize it, which leading to cell multiplication. E7 encoded by the HPV16 induces cell overgrowth. E6 gene enhances the capacity of transformating epithelial of E7 gene. But the studies suggests that infection with HPV alone is not sufficient for the development of CIN or cervical cancer and underscores the importance of other cofactors. Cyclooxygenase-2(COX-2) is the enzyme discovered in 1990s, which is associated with the genesis and development of many types of tumor. COX-2 elective-inhibitor can cut down the morbility of some kinds of tumour. Investigation shows that COX-2 expression ascensus and HPV infection are all nonage event of cervical cancer onset.Methods:All the specimens were recruited from the patients with cervical tissues who were treated first in the gynecology department of the Fourth Affiliated Hospital of Hebei Medical University from June 2004 to June 2006. All the cervical cancer were confirmed by pathologic observation. 45 cervical carcimona, 26 cervical intraepithelial neoplasia, 73 Chronic cervicitis and 21 normal cervical tissues were recruited. Immunohistochemical technique was performed to examine the expression of COX-2 and HPV16E6 protein of the cervical affection tissue. Analyze the relationship between the expression and the clinical pathological characteristics, and the correlation between the expression of COX-2 and HPV16E6 protein in the cervical affection tissue through the statistical analysis with the results above by SAS 8.1 statistic software. Statistical method concludes Chi-square test, Fisher exact probabilitics, partitions ofΧ2 method and Spearman rank correlations.Results: 1 The expression of COX-2 protein in cervical affection tissue: the positive rate of COX-2 protein was 0,36.99%,38.46%,64.44% in cervical cancer, CIN, chronic cervicitis and normal cervical tissues respectively. The comparison of the positive rate of the 4 groups had statistics meaning(Χ2=25.50,P<0.0001). The positive rate of each group was contrasted after partitions ofΧ2 method (α'=0.008333 ).The positive rate in cervical cancer was distinctively higher than chronic cervicitis and normal cervical tissues(Χ2=8.42, P=0.0037;Χ2=24.14, P<0.0001,respectively). The positive rate in CIN and cervicitis was significantly higher than normal cervical tissues(P=0.0044, P=0.001, respectively).2 The expression of HPV16-E6 protein in cervical affection tissue: the positive rate of HPV16-E6 protein was 0.5%,38.35%,46.15%,71.11% in cervical cancer, CIN, chronic cervicitis and normal cervical tissues respectively. The comparison of the positive rate of the 4 groups had statistics meaning(Χ2=27.50, P<0.0001). The positive rate of each group was contrasted after partitions ofΧ2 method (α'=0.008333 ), The positive rate in cervical cancer was distinctively higher than chronic cervicitis and normal cervical tissues(Χ2=11.95, P=0.0005;Χ2=25.21, P<0.0001, respectively). The positive rate in CIN and cervicitis was significantly higher than normal cervical tissues(P=0.0016, P=0.0033, respectively).3 The relationship between the COX-2 expression and clinical pathological features: the positive rate of COX-2 is 57.69% in the patients of cervical cancer whose age is less than 45, by contrast, the positive rate of COX-2 is 73.68% whose age is not less than 45. There is not obvious distinction between them.(Χ2=1.22 , P>0.05) ; The positive rate of COX-2 is respectively 67.65% in the cervical squamous cancer, and 62.5% in the adenocarcinoma of the uterine cervix,and then 33.3% in the other pathological type. There is not obvious distinction among them(Χ2=1.43,P>0.05);COX-2 can be expressed differently with different histological grade. Grade 1 is 75.0%. Grade 2 is 65.0%. Grade 3 is 53.85%. There is not obvious distinction among them(Χ2=1.22,P>0.05);COX-2 can be expressed differently with different FIGO stage. stageⅠis 60.0%. stageⅡis 70.59% . stageⅢis 66.67%. There is not obvious distinction among them(Χ2=0.05,P>0.05);The positive rate of COX-2 is 68.75% in the cervical tumorous focus whose diameter is less than 4cm, by contrast, the positive rate of COX-2 is 53.85% whose diameter is not less than 4cm. There is not obvious distinction between them(Χ2=0.36,P>0.05);The positive rate of COX-2 is 85.0% with lymphatic node metabasis , by contrast, the positive rate of COX-2 is 48.0% without lymphatic node metabasis. There is obvious distinction between them(Χ2=6.63,P<0.05);The positive rate of COX-2 is 78.95% with infiltration of latero-uterus or haemal tube , by contrast, the positive rate of COX-2 is 53.85% without infiltration of latero-uterus or haemal tube. There is obvious distinction between them(Χ2=4.60,P<0.05); The positive rate of COX-2 is 50.0% in shallow- muscular laye infiltration,by contrast, the positive rate of COX-2 is 84.21% in deep- muscular laye infiltration. There is obvious distinction between them(Χ2=5.60,P<0.05).4 The relationship between the HPV16-E6 expression and clinical pathological features: HPV16-E6 can be expressed differently with different histological grade. Grade 1 is 83.33%. Grade 2 is 70.0%. Grade 3 is 61.54%. There is not obvious distinction among them(Χ2=1.46,P>0.05);HPV16-E6 can be expressed differently with different FIGO stage. stageⅠis 68.0%. stageⅡis 76.47% . stageⅢis 66.67%. There is not obvious distinction among them(Χ2=0.39,P>0.05);The positive rate of HPV16-E6 is 65.0% with lymphatic node metabasis , by contrast, the positive rate of HPV16-E6 is 76.0% without lymphatic node metabasis. There is not obvious distinction between them(Χ2=0.65,P>0.05).The positive rate of HPV16-E6 is 78.13% in the cervical tumorous focus whose diameter is less than 4cm, by contrast, the positive rate of HPV16-E6 is 53.85% whose diameter is not less than 4cm. There is not obvious distinction between them;(Χ2=1.60,P>0.05);The positive rate of HPV16-E6 is 69.23% in shallow- muscular laye infiltration,by contrast, the positive rate of HPV16-E6 is 73.68% in deep- muscular laye infiltration. There is not obvious distinction between them(Χ2=0.11,P>0.05). The positive rate of HPV16-E6 is 57.65% in the patients of cervical cancer whose age is less than 45, by contrast, the positive rate of HPV16-E6 is 89.47% whose age is not less than 45. There is obvious distinction between them(Χ2=5.39,P<0.05); The positive rate of HPV16-E6 is 88.24% in the squamous cancer, by contrast, the positive rate of HPV16-E6 is 18.18% non-squamous cancer. There is obvious distinction between them(Χ2=16.59,P<0.05); The positive rate of HPV16-E6 is 89.47% with infiltration of latero-uterus or haemal tube , by contrast, the positive rate of HPV16-E6 is 57.69% without infiltration of latero-uterus or haemal tube. There is obvious distinction between them(Χ2=5.40,P<0.05).5 The correlation between COX-2 and HPV16E6 protein in cervical affection tissue: the relationship between COX-2 and HPV16-E6 protein was positive correlation in cervicitis and cervical cancer (rs=0.7794, P<0.01),(rs=0.6014, P<0.01).Conclusions: 1 The positive rate of cervical cancer was significantly higher than cervisitis and normal cervical tissue, which suggests that COX-2 and HPV16-E6 proteis were closely associated with genesis, development and malignant biological behavior.The positive rate of CIN and cervisitis was distinctively higher than normal cervical tissue, which shows that expression of COX-2 and HPV16-E6 protein is acending in the initial stage of cervical canceration, and suggests that the up-regulation of COX-2 and HPV16-E6 protein is an initial circumstance in the genesis of cervical cancer. Detecting the expression of COX-2 and HPV16-E6 protein in cervical tissues conduces to early diagnosis micro invasive cervical carcinoma and CIN.2 The relationship between expression of COX-2 and HPV16-E6 protein and clinical pathology feature in cervical cancer: the expression of COX-2 is not associated with onset age, pathological type,degree of histodifferentiation, FIGO stage, tumour diameter, while it is associated with lymphatic node metabasis, infiltration of latero-uterus or haemal tube and infiltrative depth. The expression of HPV16-E6 is associated with onset age, pathological type, infiltration of latero-uterus or haemal tube, while it is not associated with degree of histodifferentiation, FIGO stage, lymphatic gland metabasis, tumour diameter, infiltrative depth. This suggests that COX-2 persistently produces a marked effect in the whole procedure of the genesis, development and deadexis. Expression level of COX-2 could be taken as prognostic indicator to reflect malignant extent and the invasive, metastatic capacity in cervical cancer. Cervical carcinoma induced by the High-risk type HPV16 betide mostly elder women (not less than 45). HPV16 is more intimate with cervical squamous cancer than other pathological type. HPV16 possibly produces a marked effect to invasion and metabasis in cervical cancer.3 Analyze the correlation beween COX-2 and HPV16-E6 protein in cervical affection tissues, and then draw a conclusion that the expression of COX-2 and HPV16-E6 protein is positive correlation in cervical cervisitis and cervical carcinoma. This suggests COX-2 and HPV16-E6 produce a marked effect each other, facilitate cell malignant transformation in the incipience of CIN, the above factors to induce cervical canceration. COX-2 and HPV16-E6 possibly produce a synergistic effect to the invasion and metabasis of tumour in cervical carcinoma.