The Expression Of P63, CK14 And CK8 In Cervical Lesions And Their Correlations

Background: Cervical cancer is the second most frequently occurred tumor in female reproductive system worldwide and its incidence rate is rapidly increasing among young women. About 20 million women die of cervical cancer every year, so it is threat to health can not be ignored, it is essential to find a new effective drug target for clinical treatment as soon as possible,Because there is a long time for precancerous lesions to cervical cancer, and it will last nearly ten years time form CINⅠto cervical cancer, it offers a good chance for early detection and early treatment. The 5-year survival rate of the early stage cervical cancer is nearly 90%. So the early diagnosis of cervical cancer has been concerned. P63 is a recently found member of P53 family, playing an important role in the development, differentiation and morphogenesis of various epithelial tissues. Due to the different promoters and the different modes of cutting 3'terminal, the gene P63 may code many different isomers with different function. One type is TA isomer, which has the same character with P53 of inducing the stasis of cell cycle and apoptosis, and the other type isΔN isomer, promoting the growth of transformed cells by inhibiting the function of P53. P63 usually promotes but not inhibits cancers'development.Cytokeratin (CK) is one kind of intermediate filament proteins. Up to now 54 genotypes have been found in human cells, in which 20 early found types have been understood clearly. Different CKs are expressed in different stage of cell differentiation and in different kind of epithelial cells. As the important member of the family of intermediate filament proteins, CK8 is expressed widely in epithelial tissues and many epithelial-developed tumors. Correlated with various characteristic of tumors, such as susceptibility to drugs, CKs usually are used as tumor markers.Objective:To determine the expression of P63, CK14 and CK8, the three important representative of p63 signaling pathway, in various cervical lesions, to investigate their relationship with cervical tumorigenesis and progression, and to approach the specificity of CK8 and CK14 as new treatment targets. Forming a complete signaling pathway of P63, we approach the clinicopathological significance and the possible molecular mechanism in cervical tumorigenesis and progression. It is valuable in the study of pathogenesis, early diagnosis and prevention of cervical cancer.Mathods:1. Cervical specimens were collected, containing 15 normal tissues, 12 cervical intraepithelial neoplasia (CIN) I, 12 CIN II, 21 CIN III lesions and 17 cervical cancer (SCC).2. The expression of P63, CK14 and CK8 in all tissues was examined by S-P method of immunohistochemistry.3. Data was analyzed using SPSS11.5. Significance was defined at p<0.05.Results:1. The expression of P63 in various cervical lesions P63 was expressed in 13.3% of normal cervical tissues, and in 58.3%,75.0%,85.7% and 94.1% of CINI,CINII,CINIII and cervical cancer tissues, respectively. The expression of P63 was gradually raised up, showing significant difference between normal cervical tissue and various cervical lesions (p<0.01).2. The positive expression rate of CK14 was 20.0%,58.3%,66.7%,90.5% and 100% in normal cervical tissue,CINI,CINII,CINIII and cervical cancer, respectively. Likewise, the expression of CK14 was gradually raised up, significantly different between normal cervical tissue and various cervical lesions (p<0.01).3. The expression of CK8 in various cervical lesions CK8 was expressed in 13.3% of normal cervical tissues. The positive expression rate of CK8 was 50.0%,75.0%,95.2% and 100% in CINI,CINII,CINIII and cervical cancer, respectively. The data showed significant difference between normal cervical tissue and various cervical lesions (p<0.01).4. The correlation between the expression of P63, CK14 and CK18 and cervical lesions (CIN and cervical cancer)The expression of P63, CK14 and CK18 had a positive correlation with cervical cancer (p<0.05).Conclusion:1. The expression of P63 was gradually higher in CIN I, CINII, CINIII and cervical cancer than in normal cervical tissue, indicating that P63 signaling pathway is activated in and has intimate correlation with cervical tumorigenesis and progression. 2. The expression of CK8 and CK14 gradually raised up in normal cervical tissue, CIN I, CINII, CINIII and cervical cancer. As the markers of reserve cells, CK8 and CK14 are useful for early diagnosis when combined examined.