Study Of The Relationship Between The Expression Of GATA3, Bcl-2and Clinicopathological Features And Prognosis In Breast Cancer

ObjectivesTo investigate the expression of GATA3and Bcl-2in breast invasive carcinomasand the relevance with the clinicopathological parameters, and investigate the GATA3andBcl-2expression in different molecular subtypes of breast invasive ductalcarcinomas.Further to hints at the meaning of diagnosis and prognosis.MethodsCollected124cases breast cancer surgery samples and their clinical data fromeFebruary2008to February2012in the First Affiliate Hospital of Jinan University inGuang Zhou.The follow up data is from12to60month,the median follow up time is43months and the mean follow up tine is41.7months. All the breast cancer surgery sampleswere diagnosised bye two Pathologists and all cases have complete follow-up data. The124cases breast cancer sample were divided into Luminal A, Luminal B, Her-2overexpression subtype by the result of immunohistochemistry of ER、PR、Her-2、Ki-67.Using EnVision two-step method detected four group of samples in two biologicalindicators as GATA3and Bcl-2. Correlation analysis was done between the findings andclinicopathologic parameters of the patients such as status of menstrustion, tumor size,clinical stage, histological grading, status of lymph nodes, vascular tumor embolus, ER、PR、Her-2、Ki-67status，recurrence risk and disease-free survival.Study the prognosisof GATA3and Bcl-2in breast cancer by univariate and multivariate COX analysis.Results124invasive breast carcinomas were grouped into luminal A subtype36cases(29.0%),Luminal B subtypes50cases（40.3%）,triple-nagative subtypes27cases(21.8%),Her-2overexpression subtypes11cases(8.9%). In all breast carcinomas,GATA3positiveexpression rate is56.5%(70/124),and in Luminal A subtype is69.4%（25/36）,in LuminalB subtype is74%（37/50）,in Her-2over expression subtype is36.4%（4/11）and intriple-negative breast cancer is14.8%（4/27）。In all breast carcinomas, Bcl-2positiveexpression rate is60.5%（75/124），the poor positive rate is16.1%（20/124）,the middlepositive rate is16.1%（20/124）and the high positive expression rate is36.3% (45/124);Bcl-2positive expression rate in Luminal subtype breast cancer is67.4%(58/86), the poor positive rate is11.6%(10/86),the middle positive rate is7.0%(6/86)and the high positive expression rate is48.8%(42/86); Bcl-2positive expression rate inNon-Luminal subtype breast cancer is44.7%(17/38), the poor positive rate is26.3%(10/38),the middle positive rate is10.5%(4/38)and the high positive expression rate is7.9%(3/38).GATA3correlated positively with ER(χ~2=20.18，P=0.000)，PR(χ~2=12.73，P=0.000),negatively with clinical stage(χ~2=7.31，P=0.026)，P53(χ~2=9.60，P=0.002)，Ki-67(t=3.38, P=0.002)lymphovascular(χ~2=5.01，P=0.025),histological grade(χ~2=7.46，P=0.024), status of menstrustion(χ~2=6.80，P=0.011)，recurrence risk(χ~2=83.79，P=0.000)and disease-free survival (χ~2=5.84，P=0.019).There were nosignificance found between GATA3expression and tumor size,lymph nodemetastases,Her-2expression(P＞0.05).GATA3expression had difference between theLuminal subtype and the non-Luminal subtype(sP≤0.05),and in Luminal subtype,GATA3expression was association with disease-free surviva(lLog Rank=4.76, P=0.029)，also inall breast cancer,GATA3positive expression have longer disease-free survival comparewith GATA3negative expression(χ~2k=4.42, P=0.038).Bcl-2correlated positively with ER(χ~2=32.85，P=0.000)，PR(χ~2=19.66，P=0.000),negatively with P53(χ~2=19.48， P=0.000)， Ki-67(t=2.75P=0.007),lymphovascula(r2=19.68，P=0.000), histological grade(χ~2=13.06，P=0.042),tumor size(2=11.98，P=0.007), status of menstrustion(χ~2=10.09，P=0.018)，recurrencerisk(χ~2=12.18，P=0.007).There were no significance found between Bcl-2expressionand lymph node metastases,Her-2expression(P＞0.05).GATA3expression had differencebetween the Luminal subtype and the non-Luminal subtypes(P≤0.05). In all breastcancer,Bcl-2positive expression have longer disease-free survival compare with Bcl-2negative expression(χ~2=36.65, P=0.000).In order to further assess the value GATA3and Bcl-2in prognosis, we find thatunivariate analysis showed GATA3、Bcl-2、ER、PR、Her-2、tumor size、P53、limphnode metastasis、 histological grade、 lymphovascular、 clinical stage as significant predictors of overall survival. Furthermore,multivariate analysis showed that ER、tumorsize and limph node metastasis were significant predictors of overall survival.GATA3and Bcl-2correlated strong positively with ER、PR. Furthermore we findthat there was a positive correlation between the expression of GATA3and Bcl-2(χ~2=5.51，P=0.031, Kappa=0.204).ConclusionBased one the GATA3expression and the negative association with poor prognosisfactors such as histological grade、lymphovascular、clinical stage、P53gene mutation, wecan indirect include that GATA3expression is associated with good prognosis factor.andunivariate analysis showed GATA3have significant predictor of overall survival.GATA3protein is high expressed in Luminal subtypes and it showed significantly optimal DFS inLuminal subtype.Bcl-2expression is negative associate with poor prognosis factors such as tumorsize、histological grade、clinical stage、lymphovascular、P53gene mutation.Bcl-2proteinexpression group showed better DFS than negative expression group, and univariateanalysis showed Bcl-2as significant predictors of overall survival. so we can detect Bcl-2protein expression in clinical to evaluate patients prognosis and guide choose appropriatetreatment program.We can clearer understanding of heterogeneity of breast cancer and understandbiological characteristics of different subtypes of breast cancer by detect the expression ofGATA3and Bcl-2. It’s useful to guiding individualized treatment of patients, and evaluatetheir prognosis.