The Study Of Expression And Significance Of FGFR1in Breast Carcinoma

Objective：Fibroblast growth factor receptor(FGFR) is comprised oftyrosine kinase receptors。Five FGFRs,FGFR1-FGFR5.Some studys showthat FGFR1is very important to the growth and development of the tumor inrecent years. Although the current studies have shown that over-expression ofFGFR1in some breast cancer cell lines, clinical research of FGFR1expression in breast cancer tissue,is still less. In this study, usingimmunohistochemical staining for the expression of FGFR1in breast cancerpatients in China, combined with clinical and pathological data, investigate therelationship of FGFR1and breast cancer development, prognosis andclinicopathological parameters, explore the role of FGFR1in breast cancerendocrine therapy resistance mechanisms, in order to find reliable molecularmarkers to reveal the clinicopathological features and prognosis, provide auseful prediction of prognosis of breast cancer。Methods：This research collected â… -â…¢ cases of operable breast cancerwhich has clear results of molecular markers(ER,PR,Her-2,GST-Ï€,TOPOⅡα)and clear pathological diagnosis in the HeBei General Hospital firstsurgery(Breast surgery)between January1,2006to December31,2008,excluded the cases of distant metastasis in newly diagnosed,and got60cases of surgical patients'data,at the same time collected20cases ofnormal mammary gland tissue which is control group. The expression ofFGFR1were determined with immunohistochemistry S-P.The FGFR1positivecells defined as when the brown-yellow granules have appared in the cellularmembrane and endochylema,randomly selected10fields,with100tumer cellsper which under the high magnification(×400).The numbers of positive cellsdefined five grades,0score: the number of positive cells<5%;1score: thenumber of positive cells between5%to25%ï¼›2score: the number of positive cells between25%to50%ï¼›3score: the number of positive cells between50%to75%ï¼›4score: the number of positive cell>75%.The strength of stainingdefined four grades,0score:colorless;1score:pale yellow granules haveappared in the cellular membrane and endochylemaï¼›2score: the deepbrown-yellow granulesï¼›3score: the brown-black granules have appared in thecellular membrane and endochylema or the brown-black lumps(The strengthcontrast with background stain).To count scores of per case: the grade ofpositive cells×the score of stain strength,the score less than4is defined asnegative, the score which higher than4is defined as positive. The positivecells of ER and PR defined as when the brown-yellow granules have apparedin nuclei,when the expression rates of ER and PR higher than10%is definedas the positive of ER and PR in the case.The positive cells of GST-Ï€defined as when the brown-yellow granules haveappared in endochylema, and the positive cells of TOPOⅡαdefined as whenthe brown-yellow granules have appared in nuclei,when the expression ratesof GST-Ï€/TOPOⅡα lesser than10%is defined as the negative, and theexpression rates of GST-Ï€/TOPOⅡα higher than10%is defined as thepositive. The human epidermal growth factor receptor2(Her-2) determine thecriterion-referenced 《Breast Cancer Her-2testing Guide》:luminalA subtype[ER(+)and(or)PR(＋),Her-2(-)],LuminalB subtype [ER(+)and(or)PR(＋),Her-2(+)],Her-2subtype [ER(-),PR(-),Her-2(+)]å'ŒBasal-like subtype [ER(-)and(or)PR(-),Her-2(-)]。Carrying on at least1follow-up(telephone follow-up and hospital review)to all cases, which endedby December31,2011or lost,the date of death.Setting the operation time asstarting point,and patient'death,the last follow-up time or lost as terminal pointas the research time.Finally, according to follow-up data analysis therelationship of FGFR1with clinical and pathological features in patients, andfurther analysis of the correlation of expression of FGFR1and endocrineresistance and GST-Ï€/TOPO â…¡ resistance protein。Upload the follow-up dataaccurately to the SPSS13.0statistical package to do the statisticalanalysis,the enumeration data was analyzed by χ2test or Fisher's Exact test,the ranked data was by Non-parametric test,the relationship between was bySpearman rank correlation. Clinical data with the percentage or median oraverage of the statistical description,all tests were performed at the0.05levelof significances。Results：1,The positive rates of expression of FGFR1(37.74%) in breast cancerwas higher than the positive rates of FGFR1in normal tissue(10.00%)(P＜0.05).2,The positive rates of FGFR1in ER positive and ER negative caseswere36.11%,41.18%respectively(P＞0.05); The positive rates of FGFR1inPR positive and PR negative cases were36.36%,40.00%respectively (P＞0.05);The positive rates of FGFR1in Her-2positive and Her-2negative were38.46%,37.50%respectively in the breast cancer (P＞0.05).3,The positive rates of FGFR1in LuminalA subtype,LuminalB subtype,Her-2subtype and Basal-like subtype were38.71%,37.50%,40.00%,33.33%,respectively, there was no significant difference of the FGFR1expression between Her-2subtype and Basal-like subtype, LuminalBsubtype and Basal-like subtype(P＞0.05),but the difference was statisticallysignificant in the other subtypes(P＜0.05).4,The positive rates of FGFR1in GST-Ï€ positive and GST-Ï€ negativecases were63.64%,10.53%respectively(P＜0.05); The positive rates ofFGFR1in TOPOⅡα positive and TOPOⅡα negative cases were48.15%,30.77%respectively (P＞0.05).FGFR1expression was positively withGST-Ï€(r=0.543,P＜0.05)。5,FGFR1expression was positively with ednocrine therapy resistance(r=0.38,P＜0.05)。6, The positive expression rate of FGFR1in lymph nodemetastasis(52.17%) was significantly higher than it in lymph nodenon-metastasis(21.43%)(P＜0.05); The positive rates of FGFR1in maximumsize of tumors≤3cm and maximum size of tumors＞3cm cases were38.23%,36.84%respectively (P＞0.05);The positive rates of FGFR1in the age＜ 50year and the age≥50year cases were34.78%,40.00%respectively (P＞0.05)。7,The positive rates of FGFR1in â… stage,â…¡ stage and â…¢ stage were8.3%(1/12),41.4%(12/30),55.6%(5/9)respectively,the differences werestatistically significant between â…  stage and â…¢ stage,â…¡stage and â…¢stage,â… stage and â…¡stage(Non-parametric test P＜0.05).8,The positive rates of FGFR1in â… grade,â…¡ grade and â…¢ grade of thepathology were3/11,8/22,2/5respectively,the differences were statisticallysignificant between â…  grade and â…¢ grade,â…¡grade and â…¢ grade,â… grade andâ…¡grade(Non-parametric test P＜0.05).9,The positive rates of duct carcinoma,invasive lobular carcinoma,invasive special cancer, medullary carcinoma, mixed carcinoma FGFR1inwere41.94%(13/31),45.94%(5/11),2/3,0/5,0/3respectively(Non-parametric test P＜0.05), there was no significant difference of theFGFR1expression between invasive lobular carcinoma and medullarycarcinoma,invasive special cancer and mixed carcinoma(Non-parametric testP＞0.05), and the positive expression rate of FGFR1were significantlydifference in difference pathotypes (Non-parametric test P＜0.05)。Conclusion：1,The positive rates of FGFR1was related to breast cancer pathologicaltype, histological grade and lymph node metastasis.With increased of thehistological grades,the lager of FGFR1positive rates, FGFR1expression inpoorly differentiated breast cancer was significantly higher than in patientswith well-differentiated; FGFR1expression rate of lymph node-positive washigher than negative。FGFR1over-expression may be closely related to themalignant behavior of breast cancer, may be could predict the poorprognosis of the breast cancer.2,The rates of FGFR1was no related to ER, PR and Her-2, but in thevarious molecular subtypes,the protein of FGFR1is over-expression.3,FGFR1expression was positively correlated with both ednocrinetherapy resistance and GST-Ï€,FGFR1expression was not correlated with TOPO Ⅱα,FGFR1may therapy resistance,FGFR might be involved in breastcancer drug resistance, play a important role in breast cancer resistancemechanisms.