Expression Of FGFR1, AIB1and Their Correlation In Invasive Ductal Carcinoma Of Breast

Objective:Breast cancer is one of the most common malignant in women.At present,over one million women were diagnosed as the breast cancer in theglobal every year,which accounts for about25%of the women’s cancer. At thesame time,the incidence of the breast cancer is of an upward trend year by year.However,to improve the life quality and prognosis of patients with breastcancer is the primary task. Invasive ductal carcinoma of breast（IDC）is themost common histological type. ER, PR and HER-2are proved to be the mostimportant molecular markers to guide the treatment of breast cancer andinfluence the prognosis.Because of high malignant degree and strongheterogeneity in breast cancer,it is very important to research biologicalmarkers associated with breast cancer. Fibroblast growth factorreceptor1(FGFR1),plays an important role in the process ofapoptosis,proliferation,angiogenesis and endocrine therapy resistance.Amplified in breast cancer1(AIB1),a member of the nuclear coactivator(NCoA-3) and p160steroid receptor co-activator (SRC) family,which play animportant part in the biological processes of cell growth,proliferation,differentiation, and so on.The current studies about the expression andcorrelation of FGFR1and AIB1in IDC is not thorough.The purpose of thepresent study was to investigate the expression of FGFR1protein and AIB1protein in IDC,and to analyze the relationship between FGFR1、AIB1and theclinical-pathological features and the association between them；Understandthe expression of FGFR1and AIB1in different moleculesubtypes;Furthermore,to analyze the expression of them in the group ofendocrine resistance and effective group and the correlation between FGFR1and AIB1in endocrine resistance,which in order to find some reliablemolecular markers to the clinical features and prognosis and provide the basis for judging prognosis and setting individualized treatment strategies.Methods:S-P immunohistochemical techniques was adopted to detectthe expression of FGFR1、AIB1in100cases of IDC whom had beenconfirmed by histopathology,and with the complete clinical data in HebeiGeneral Hospital Department of Pathology from January2006to June2011.Carrying on at least1follow-up(telephone follow-up and hospital review)toall cases,which ended by June30,2012or lost,the date of death.Setting theoperation time as starting point,and patients’death,the last follow-up time orlost as terminal point as the research time.Finally,according to follow-updata analysis the relationship of FGFR1,AIB1with endocrine therapy inpatients,and further analysis of the correlation of expression of FGFR1andAIB1in endocrine resistance.SPSS17.0statistical software was used forstatistical analysis.The enumeration data was analyzed by χ2test or Fisher’sExact test. the relationship between the two variables using the Spearman rankcorrelation.Logistic regression analysis was applied for the analysis of positiveexpression-related factors of FGFR1and AIB1.Clinical data with thepercentage or median or average for the statistical description，All tests wereperformed at the0.05level of significances.Results:1. In the100cases tissue of invasive ductal carcinoma of breast,thepositive rates of expression of FGFR1and AIB1was31.00%(31/100) and75.00%(75/100),respectively.2. In IDC,the expression of FGFR1and AIB1were not related with ageand tumor size(P>0.05).However,both of them were significant difference inlymph node metastasis and lymph node non-metastasis(P<0.05).At the sametime,there was a statistically difference in the positive rates of FGFR1andAIB1expression inⅠgrade、Ⅱ grade and Ⅲ grade of the pathology andⅠstage、Ⅱstage and Ⅲ-Ⅳstage of TNM stage(P<0.05),and increased alongwith the histologic grading and TNM stage,the positive expression rate ofFGFR1and AIB1increased gradually.3. The main factor which influences the expression of FGFR1and AIB1in IDC is histopathological grade (WaldX2=13.488,P=0.003;WaldX2=7.958，P=0.001).4. In all100cases,the positive expression of FGFR1and AIB1were28cases,the common negative were22cases.Furthermore,to analyze thecharacteristics of distribution about the expression of FGFR1and AIB1bothpositive and negative cases,which shows that the proportion of positive bothtwo is significantly more than both negative in the group of lymph nodemetastasis,with statistically significant(P<0.05).At the same time,theproportion of positive both two is significantly more than both negative in Ⅲgrade of the pathology,with statistically significant(P<0.05).The Spearmanrank correlation shows that there was a significant positive correlationbetween the positive expression of FGFR1and AIB1(r=0.237,P=0.017).5. The expression of FGFR1in Luminal B and Her-2(+) of IDC is higherthan the other two molecular subtypes, but it has no significant difference indifferent molecule subtypes（P>0.05）.However，the expression of AIB1indifferent molecular subtypes of IDC has significant difference（P<0.05）,ofwhich the expression of AIB1in Luminal A is much lower than the others.6. Follow-up the60cases with ER positive and tamoxifen treated，33caseswere effective,and27cases appeared endocrine resistance.the positiveexpression rates of FGFR1、AIB1in the group of endocrine resistancesignificantly higher than the effective group,there were statisticaldifference(P<0.001;P=0.036).7. In the cases of endocrine resistance,both positive of FGFR1and AIB1were14cases,the common negative were5cases.The Spearman rankcorrelation shows that there was a significant positive correlation between theexpression of FGFR1and AIB1in endocrine resistance(r=0.418,P=0.030).Conclusion:1. The expression of FGFR1and AIB1was not related with age and tumorsize. They had close correlation with lymph node metastasis、histologicalgrade and TNM stage.Furthermore,to analyze the relationship of FGFR1andAIB1,there were positive correlation between them,which presents that both proteins were closely related to the malignant behavior of IDC.2. The expression of FGFR1in Luminal B and Her-2(+) of IDC washigher than the other two molecular subtypes,but it had no significantdifference in different molecule subtypes.However,the expression of AIB1indifferent molecular subtypes of IDC had significant difference,of which theexpression of AIB1in Luminal A is much lower than the others.3. The expression rates of FGFR1and AIB1in the group of endocrineresistance were significantly higher than the effective group,there werestatistical difference.The Spearman rank correlation show that there was asignificant positive correlation between the expression of FGFR1and AIB1inendocrine resistance,which suggests that FGFR1、AIB1may had synergy inendocrine resistance of IDC.