The Diagnosis And Prognosis Significance Of FOXA1 And P-cadherin In Molecular Subtype Of Breast Carcinomas

ObjectivesTo investigate the expressions of FOXA1 and P-cadherin in breast invasive ductal carcinomas and the relevances with the clinicopathological parameters.Further to observe the FOXA1 and P-cadherin expressions in all molecular subtypes of breast invasive ductal carcinomas and its hints at the meaning of diagnosis and prognosis.MethodsRandomly selected 213 breast invasive ductal carcinoma cases with more than 5 years follow-up data.The expressions of FOXA1 and Ki67 in the tissues from 213 invasive ductal carcinomas were detected by using immunohistochemistry staining. The 213 cases were divided into Luminal A,Luminal B,HER2 overexpression subtype,normal breast-like and basal-like subtype according to the standard of molecular breast cancer subtypes.The expressions of CK5/6,CK14 were detected in order to distinguish between the normal breast-like subtype and the basal-like subtype.Results213 invasive breast carcinomas were grouped into Luminal A subtype 72cases,Luminal B subtype 27cases,HER2 overexpression subtype 35cases,basal-like subtype 36 cases,normal-like subtype 43cases.FOXA1 expression(score greater than 3) was seen in 150 cases of 213 breast invasive ductal carcinomas.The positive rate is 70.4%.P-cadherin expression was seen in 91 cases of 213 breast invasive ductal carcinomas.The positive rate is 42.7%.FOXA1 correlated positively with ER(_x2=11.532,P=0.001),PR(_x2=10.785,P= 0.001);negatively with histological grade(_x2=11.102,P=0.004),Nottingham prognostic index(_x2=9.927,P=0.007),p53(_X2=5.864,P=0.015),Ki67(_x2=6.485, P=0.011).There were no significance found between FOXA1 expression and age,size,clinical stage,lymph node metastases,HER2,recurrence and distant metastase,invasion of vascular and soft tissues.FOXA1 expression had difference between the Luminal subtype and the non-Luminal subtypes(_x2=9.578,P=0.002).In Luminal subtype,FOXA1 expression was associated with histological grade(_x2=8.674,P=0.013),PR(_x2=4.557,P=0.033),NPI(_x2=7.963,P=0.019) and Ki67(_x2=4.22I,P=0.040).In prognosis FOXA1 expression indicated a long disease-free survival and overall survival.In Luminal subtype and Luminal A subtype FOXA1 expression was associated with better overall survival.Univariate analysis showed tumor grade,tumor size,clinical stage,lymph node metastasis,ER,PR, HER2,Ki67,NPI,FOXA1 as significant predictors of overall survival.However, multivariate analysis showed that only tumor grade,ER and clinical stage were significant predictors of overall survival.P-cadherin correlated negatively with ER(_x2=11.660,P=0.001),PR(_x2=10.997, P=0.001) and FOXAI(_x2=6.020,P=0.014);positively with histological grade(_x2=11.698,P=0.003),Nottingham prognostic index(x₂=10.457,P=0.005), p53(_x2=4.326,P=0.038),Ki67(_x2=5.229,P =0.022).P-cadherin expression showed a strong correlation with recurrence and distant metastasis(_x2=6.888,P=0.009), invasion of vascular and soft tissues(_x2=8.232,P=0.004).P-cadherin expression has difference among the five subtypes(_x2=25.945,P=0.000).The difference also existed between the basal-like subtype and non basal-like subtypes(_x2= 12.641,P=0.000).In prognosis P-cadherin expression was associated with decreased patient disease-free survival and overall survival.Univariate analysis showed tumor grade,tumor size, clinical stage,lymph node metastasis,ER,PR,HER2,Ki67,NPI and P-cadherin as significant predictors of overall survival.Furthermore,multivariate analysis showed that tumor grade,ER and clinical stage as well as P-cadherin were significant predictors of overall survival.ConclusionBased on the FOXA1 expression and the association with markers of good prognosis and Luminal subtype,we can include FOXA1 expression is associated with good prognosis.Tumors expressing FOXA1 have significantly optimal DFS and OS and are most likely to be Luminal A tumours.FOXA1 is a promising candidate for identification of Luminal A subtype in the clinic.Prognostic ability of FOXA1 in these low risk of breast cancers may prove to be useful in clinical treatment decision making.However,P-cadherin expression is associated with poor prognosis.P-cadherin may be used to distinguish the basal-like subtype because its expression is associated with basal-like subtype.P-cadherin may be used to predict the outcome in view of the relationship with DFS and OS.Furthermore,P-cadherin expression may be useful in treatmeat decision because it is a independent predictor.