GATA3 Expression In Different Surrogate Molecular Subtypes Of Breast Carcinoma:a Comparison With GCDFP15 And Mammaglobin For Identifying Paired Primary And Metastatic Tumors

Objective: GATA3 has been recognized as the novel marker for identifying primary and metastatic breast carcinomas.Before the availability of GATA3,the cytoplasmic markers gross cystic disease fluid protein 15(GCDFP-15)and membranous marker mammaglobin were the 2 most commonly used IHC markers of breast carcinoma,which show good specificity but lack sensitivity,especially with regard to the triple negative breast cancer.Recent researches have demonstrated that GATA3 was more sensitive than GCDFP15 and Mamaglobin,however,that studies mainly involved histopathology type,sample type,hormonalreceptor status rather than molecular subtypes of breast carcinomas.The goal of our study was to systematically evaluate the sensitivity of the GATA3 for identifying different surrogate molecular subtypes of paired primary and metastatic breast carcinomas,compared with the conventional markers GCDFP15 and MGB,which are provide basis for pathological diagnosis in regard to molecular subtypes of breast carcinomas.Methods: We retrieved 64 cases of matched primary and metastatic breast cancer from the surgical pathology archive at The MeiZhou Affiliated Hospital of SunYat-sen University in march 2013 to march 2016.According to emerging St Gallen2015 Consensus,the molecular subtypes was divided into ER and/or PR(+),HER2(-),abbreviated as A;ER and/or PR(+),HER(+),abbreviated as B;ER and PR(-),HER2(+),abbreviated as C and ER,PR and HER 2(-),abbreviated as D;each types(n=16).Tissue microarrays were created,the sensitivity of monoclonal antibodies to GATA3,GCDFP15 and MGB in different surrogate molecular subtypes of breast carcinoma by using immunohistochemical staining.Staining intensity(0~3+)and extent(0% to 100%)were scored with an H-score calculated(range,0 to 300).The H-Score had been set three cutoffs as any;?50;?150.Results:(1)Compared with GCDFP15 and MGB,GATA3 was more sensitive in primary and metastatic breast carcinomas(regardless of type),the difference was statistically significant(p<0.05).GATA3 was also more sensitive in A and B subtypes of primary and metastatic breast carcinoma,compared with GCDFP15 and MGB,the difference was statistically significant(p<0.05).GATA3 was more sensitive in C subtypes primary and metastatic breast carcinoma,compared with GCDFP15 and MGB,but the difference was not statistically significant(p>0.05).GATA3 was not more sensitive in D subtypes primary and metastatic breast carcinoma,compared with GCDFP15 and MGB,the difference was not statistically significant(p>0.05).(2)GATA3 in conjunction with GCDFP15 and Mammaglobin detection,the sensitivity increase in paired primary and metastatic breast carcinomas of C subtypes,there was significantly more sensitive compared with GATA3 and GCDFP and MGB(p<0.05).However,GATA3 in conjunction with GCDFP15 and MGB detection was not significantly more sensitive than GATA3 and GCDFP and Mammaglobin in paired primary or metastatic of D subtypes(p>0.05).(3)GATA3 staining had significant differences among different subtypes.GATA3 shows diffuse strong staining in A and B subtypes.GATA3 shows patch low,moderate staining in C and D subtypes.GCDFP15 and Mammaglobin staining had no significant differences among different subtypes,GCDFP shows patch low or moderate staining,Mamma shows patch moderate or diffuse strong staining.(4)Comparison of coherence was observed between primary and metastatic breast carcinomas.GATA3 expression [kappa value=0.826>0.75] as compared with the coincidence of GCDFP15 [kappa value=0.492<0.75] and Mammaglobin [kappa value=0.593<0.75](both p<0.05).Conclusions: The matched primary and metastatic tumor expression of GATA3 is good coincidence.GATA3 expression was not the same sensitive as different surrogate molecular subtype of breast cancer.GATA3 expression was superior to GCDFP and MGB in A and B subtypes.GATA3 expression was slight better to GCDFP and MGB in C subtypes.GATA3 expression poorly performed in triple-negative breast cancer.GATA3 expression is positively correlated with ER-positive,PR-positive,and HER2-positive carcinomas.We propose that it is carefully select to GATA3 for identifying the triple-negative breast cancer.