Expression Of Mtp53, PTEN In Hepatocellular Carcinoma And Their Impact On Overall Survival Of Patients

Objective:The generation and development of HCC (hepatocellular carcinoma) with high morbidity and poor prognosis is a multi-factor, multi-step and multi-stage process. And the overall5-year survival rate of HCC patients is less than5%. The mutation and deletion of tumor suppressor genes associated with survival time are closely related to the pathogenesis of HCC. This study analyzed the expression of Mtp53, PTEN in patients with HCC and their impact on overall survival, which provides the basis not only for improving the prognosis of HCC, but also for further study at the molecular biology level and subsequent experiments.Methods:The subject investigated were the clinical data and paraffin blocks of surgical resection specimens of90patients (69males and21females) who were collected from September2001to December2009at the Department of Pathology in the First Affiliated Hospital of Dalian Medical University. These patients were diagnosed as hepatocellular carcinoma refering to "primary liver cancer diagnosis and treatment practices (2011)." And the histopathological types of these patients were hepatocellular carcinoma.The overall survival time of patients entering the research were inquired by the Center for Disease Control and hospital medical records room. And some patients were inquired by telephone,etc. Using immunohistochemical Max Vision method to detect the expression of Mpt53and PTEN. MedCalc11.4.2.0software was used for statistical analysis. Results:1. Among the90cases of HCC, the number of negative expression of Mtp53was56while the number of positive expression of Mtp53was34. The positive rate was37.78%. The cases of negative expression of PTEN were70while the cases of positive expression of PTEN were20. And the positive rate was22.22%.The positive rate of Mtp53protein in Ⅰ, Ⅱ,Ⅲ/Ⅳ stage (ⅢA,ⅢB,ⅢC,ⅣA,ⅣB stage)(AJCC(2010) TNM staging criteria) of HCC was34.48%(10/29),35.14%(13/37),45.83%(11/24) respectively. However,the relationship between these positive rate and TNM stage of HCC (P>0.05) was not statistically significant. The positive rate of PTEN protein in Ⅰ,Ⅱ, Ⅲ/Ⅳ stage (ⅢA、ⅢB、ⅢC、ⅥA、ⅣB stage) of HCC was7.24%(5/29),29.73%(11/37),16.67%(4/24) respectively. Still there was no statistically significant relationship between these positive rate and TNM stage of HCC(P>0.05).2. Among the90cases of HCC, the cases of simultaneous negative and positive expression of Mtp53and PTEN protein were43and7respectively. The cases of negative expression of Mtp53while positive expression of PTEN were13. The cases of positive expression of Mtp53while negative expression of PTEN were27. But the statistical analysis showed no obvious correlation between Mtp53and PTEN protein (P>0.05, r=-0.0306).3. The median survival of negative expression groups of Mtp53was65.0months. The median survival of positive expression groups of Mtp53was58.0months. And the analysis showed statistically significant difference between negative and positive expression of Mtp53in overall survival by Kaplan-Meier analysis (P=0.0256). The overall survival of positive group was apparently lower than the negative group.4. The median survival of negative expression groups of PTEN was62.0months. The median survival of positive expression groups of PTEN was87.0months. And the analysis showed statistically obvious difference between negative and positive expression of PTEN in overall survival by Kaplan-Meier analysis (P=0.0346). The overall survival of positive group was significantly higher than the negative group.5. The clinical data of90cases of HCC affecting their overall survival was analyzed via univariate analysis of Kaplan-Meier method. And the result showed that overall survival of patients with AFP<20IU/ml compared with AFP>20IU/ml was significantly increased (P=0.0194). This suggested that the patients with AFP>20IU/ml had shortened survival and were in poor prognosis. However, other clinical data, such as virus infection status, HBsAg positive or not, the number of tumors and TNM stage, could not predict the length of overall survival of patients with HCC(P>0.05).6. The expression of Mtp53, PTEN protein and clinical data of HCC affecting their overall survival were analyzed via multivariate analysis of COX proportional hazard model. And the result showed that t the positive expression of Mtp53protein, negative expression of PTEN protein and AFP>20IU/ml were the main independent predictors for shortening overall survival.(P were0.0292,0.0411and0.0421respectively). While age,gender,virus infection status,HBsAg-positive or not, the number of tumors and TNM stage impacting on overall survival were not independent predictors(P>0.05).Conclusions1. The univariate analysis showed that patients with positive expression of Mtp53, negative expression of PTEN and AFP<20IU/ml shortened the overall survival and were in poor prognosis.2. The multivariate analysis showed that the positive expression of Mtp53protein, negative expression of PTEN protein and AFP>20IU/ml were the main independent predictors for shortening overall survival.