Expression Of YAP1 And CyclinE1 In Breast Ductal Carcinoma And Its Clinical Significance

Objective: To study the expression of YAP1 and Cyclin E1 in breast normal tissue,atypical ductal epithelial hyperplasia,ductal carcinoma of breast,breast infiltrating carcinoma and invasive breast cancer,and to explore the clinical significance of expression of YAP1 and Cyclin E1 in breast cancer.Method: A total of 202 cases of breast ductal carcinoma(46 cases of low grade ductal carcinoma,70 cases of middle grade ductal carcinoma and 86 cases of high grade ductal carcinoma)were collected from January 2004 to December 2011 in the Fourth Hospital of Hebei Medical University.41 cases of normal breast tissue were selected,53 cases of atypical hyperplasia of breast ductal epithelium,60 cases of breast infiltrating carcinoma and 52 cases of invasive breast cancer.totaling 408 cases.All specimens were fixed with10% neutral formalin,paraffin embedded,continuous sections,confirmed by pathology.And the expression of YAP1 and Cyclin E1 protein was detected by immunohistochemical SP method.The experimental data were processed by SPSS21.0 statistical software,and the counting data were chi-square test.Correlation study using Spearman correlation analysis,survival analysis using Kaplan-Meier method to ? = 0.05 for the test,P <0.05 means that the difference was statistically significant.Result: 1 Breast ductal cancer patients in general: patients aged 22-81 years,median age 50 years,mean age 51.79 years old.Breast ductal cancer tumor diameter of 0.40cm-5.40 cm.Average diameter of 3.05 cm,the median value of 3.00 cm.94 cases with tumor diameter<2cm,102 cases with tumor diameter > 2cm and ? 5cm,6 cases with tumor diameter > 5cm.Premenopausal 108 cases,postmenopausal 94 cases.There were 46 cases of Luminal A type,84 cases of Luminal B type,28 cases of HER2 overexpression type and 44 cases of Basal-like type.There were 2 cases of recurrence and metastasis in 202 cases of ductal carcinoma of the breast,2cases of death,survival time of 39 months to 157 months,the median survival time of 120 months,the average survival time of 120.49 months.2 YAP1 protein expressionThe positive expression rate of YAP1 in normal breast tissue was 92.68%(38/41).The positive expression rate of YAP1 was 86.79%(46/53)in breast ductal epithelium and the positive expression rate in low grade ductal carcinoma The positive expression rate was 47.43%(22/46)in the mid-grade ductal carcinoma and 31.43%(22/70)in the intravascular carcinoma.The positive expression rate was 24.42%(21/86)in the high-grade ductal carcinoma.The positive expression rate in invasive carcinoma was 18.33%(11/60).The positive expression rate in invasive carcinoma was 13.46%(7/52).The expression of YAP1 in normal breast tissue,breast ductal epithelial dysplasia,breast ductal carcinoma,breast microinflammatory carcinoma and breast invasive carcinoma was statistically significant(P = 0.000).There was no significant difference in the expression of YAP1 in the age of breast ductal carcinoma(P = 0.310).There was no significant difference in the expression of tumor size(P = 0.996)There was no significant difference between the two groups before and after menopause(P = 0.082).There was no significant difference in Luminal typing(P = 0.110).There was no significant correlation between YAP1 and ER expression in breast ductal carcinoma(P = 0.692).There was no significant correlation between YAP1 and PR expression in breast ductal carcinoma(P = 0.070).There was no significant correlation between YAP1 and HER2 expression in ductal carcinoma(P = 0.594).3 Cyclin E1 protein expressionThe positive expression rate of Cyclin E1 in normal breast tissue was7.32%(3/41).The positive expression rate of Cyclin E1 in normal breast tissue was 13.21%(7/53)in breast ductal epithelium,and positive expression in low-grade ductal carcinoma The positive expression rate was 43.48%(20/46).The positive expression rate was 61.43%(43/70)in the intraductal carcinoma and 65.12%(56/86)in the high grade ductal carcinoma.The positiveexpression rate was 76.67%(46/60)in breast infiltrating carcinoma and82.69%(43/52)in breast invasive carcinoma.The expression of Cyclin E1 in normal breast tissue,breast ductal epithelial dysplasia,ductal carcinoma of breast,breast infiltrating carcinoma and breast invasive carcinoma was statistically significant(P = 0.000).The expression of Cyclin E1 in the age of breast ductal carcinoma was not statistically significant(P = 0.759).There was no significant difference in the expression of Cyclin E1 in tumor size(P =0.086).There was no significant difference between the two groups before and after menopause(P = 0.123).There was no significant difference in Luminal typing(P = 0.968).There was a significant negative correlation between the expression of Cyclin E1 and ER(P = 0.000).There was no significant correlation between Cyclin E1 and PR expression(P = 0.530).There was no significant correlation between Cyclin E1 and HER2 expression(P = 0.732).4 There was a significant negative correlation between YAP1 and Cyclin E1 protein expression in DCIS.(r =-0.327,P =0.000).5 Kaplan-Meier survival analysisFollow-up data showed that the 5-year survival rate was 92.5% in 202 patients with ductal carcinoma of the breast and the 10-year survival rate was99.01%.The relationship between YAP1 expression and recurrence-free survival of DCIS was statistically significant(P = 0.000).The relationship between the expression of YAP1 and the overall survival rate of DCIS was statistically significant(P = 0.000).The relationship between the expression of Cyclin E1 and the recurrence-free survival rate of DCIS was statistically significant(P = 0.000).The relationship between the expression of Cyclin E1 and the overall survival rate of DCIS was statistically significant(P = 0.000).Conclusion:1 The expression intensity and range of YAP1 in normal breast tissue,breast ductal epithelial dysplasia,breast ductal carcinoma,breast infiltrating carcinoma and breast invasive carcinoma were significantly decreasing,suggesting that YAP1 protein deletion may be involved in the occurrence and development of DCIS.2 The expression intensity and range of Cyclin E1 in normal breast tissue,breast ductal epithelial dysplasia,breast ductal carcinoma,breast infiltrating carcinoma and breast invasive carcinoma were significantly increased,suggesting that overexpression of Cyclin E1 protein may be involved in the occurrence and development of DCIS.3 The survival time of patients with breast ductal carcinoma was significantly different from that of YAP1 and Cyclin E1.The higher the expression of YAP1 protein,the longer the survival time of breast cancer patients.In contrast,the lower the expression of Cyclin E1,the longer the survival of breast cancer patients.