Study Of Correlation Among P53,MDM2 And Cervical Carcinoma In Uigur Women In Xinjiang

Objective: To investigate the status of HPV infection and the expression of P53 and MDM2, and to explore their interaction in the carcinogenesis in Uigur cervical carcinoma, we detected HPV 16 DNA, expression of P53 and MDM2 gene and p53 codon 72 polymorphism.Methods: HPV16 DNA, P53 and MDM2 protein of 79 cases of cervical carcinoma and 40 cases of normal cervical tissue were detected by semi-nested PCR and immunohistochemistry, respectively. MDM2 mRNA of 58 cases of carcinoma and 29 cases of normal tissue was detected by using RT-PCR. Furthermore. PCR-RFLP was employed to determine the distribution and frequency of p53 codon72 genotypes in all cases.Results: (1) HPV16 DNA was found in 64 of 79(81.0%) in cervical carcinoma and in 3 of 40 (7.5%) in normal group. The positive rate of HPV16 was significantly higher in cervical carcinoma than that in normal group (x~2=58.328, p=0.000). (2) The expression of P53 protein detected in 54 of 79 (68.4%) in cervical carcinoma was higher than in 5 of 40 (12.5%) in normal group (x~2=33.140. p=0.000). Significant association was observed between P53 immunophenotype and differentiation status of carcinomas, the expression of P53 protein in moderate or poorly-differentiated carcinomas was significantly higher than that in carcinoma in situ. (3) The expression of MDM2 protein was detected in 31 of 79 (39.2%) in cervical carcinoma, and was significantly higher than that in normal group (x~2=10.936. p=0.001). The overexpression of MDM2 mRNA was determined in cervical carcinoma by semiquantitive analysis. The average ratio of MDM2 mRNA/β-actin mRNA in cervical carcinoma was significantly higher than that in normal group(0.9379±0.2830). There was a significant correlation between MDM2 mRNA and MDM2 protein expression in cervical carcinoma (x~2=6.801, p=0.009). (4) No significant association between the expression of P53 and MDM2 protein and p53 codon 72 genotypes.Conclusion: (1) Degradation and inactivation of P53 protein by High-risk HPV E6 may be a major mechanism in uigur cervical carcinoma. But this mechanism would not be invoked to explain the phenomenon in which P53 protein was accumulated in some HPV infective cases. This phenomenon suggests that the carcinogenesis of Uigur cervical carcinoma may involve in other events of multiple genetic abnormalities and multiple steps. (2) The overexpression of MDM2 mRNA and MDM2 protein suggests that MDM2 may play an important role in carcinogengsis of Uigur cervical carcinoma. (3) The association between HPV infection and the expression of P53 and MDM2 reveals that their interaction is important in development of HPV-positive cervical carcinoma. With regard to the carcinogengsis of HPV-negtive cervical carcinoma, MDM2 may play a role through p53-dependent or p53-independent pathway. In addition, HPV, P53 and MDM2 may be independently associated with carcinogengsis of Uigur cervical carcinoma, respectively. (4) No correlation between expression of P53 and MDM2 protein and p53 codon 72 polymorphism suggests that further research may be nessesary to explore the carcinogenesis involved in the p53 codon 72 polymorphism.