细胞周期调控基因对局部晚期乳腺癌新辅助化疗疗效的影响  

Effects of cell cycle regulatory genes on breast cancer neo-adjuvant chemotherapy by M-FISH

作　　者：李春艳[1] 苏薇[1] 张晟[1] 胡蕴慧[1] 刘晶晶[1] 张瑾[1] 

机构地区：[1]天津医科大学肿瘤医院乳腺肿瘤三科国家肿瘤临床医学研究中心天津市“肿瘤防治”重点实验室天津市恶性肿瘤临床医学研究中心乳腺癌防治教育部重点实验室,300060

出　　处：《中华医学杂志》2017年第34期2682-2686,共5页National Medical Journal of China

摘　　要：目的 探讨局部晚期乳腺癌患者G1/S期检测点调控基因的拷贝数改变与新辅助化疗临床疗效间的相关性,以期发现可以预测新辅助化疗疗效的指标并为临床治疗提供指导.方法 收集天津医科大学肿瘤医院接受紫杉类/蒽环类/环磷酰胺方案新辅助化疗的局部晚期乳腺癌患者95例.运用多基因荧光原位杂交（M-FISH）技术对化疗前组织标本进行细胞周期调控基因（c-Myc、Mdm2、CCND1、CHEK2、Rb1、p53、p16、p21）的拷贝数检测,并分析其与新辅助化疗疗效间的相关性.结果 有效组中,c-Myc扩增18例,未扩增52例;CCND1扩增11例,未扩增59例;p53缺失12例,未缺失58例;p16缺失11例,未缺失59例.无效组中c-Myc扩增12例,未扩增13例;CCND1扩增9例,未扩增16例;p53缺失10例,未缺失15例;p16缺失10例,未缺失15例.以上4个基因的拷贝数改变在两组间具有统计学差异,发生c-Myc扩增（P =0.040）、CCND1扩增（P =0.033）、p53缺失（P=0.020）、p16缺失（P=0.012）的患者化疗疗效较差.其中,发生2个及2个以上基因的拷贝数改变的患者较发生单个或未发生基因拷贝数改变的患者疗效差（P=0.000）.此外,CCND1（P=0.049）、c-Myc（P=0.049）、p16（P=0.008）基因拷贝数的改变分别与Luminal型、Her-2过表达型、三阴性乳腺癌患者化疗疗效较差显著相关.结论 c-Myc、CCND1、p53、p16基因拷贝数改变与较差的新辅助化疗疗效具有相关性.Objective The dysregulation of cell cycle could influence cell proliferation,differentiation and response to medicine.The purpose of this study is to explore the correlation between cell cycle regulatory genes and breast cancer neo-adjuvant chemotherapy （NAC） in patients with local advancedbreast cancer,and thus to find some predictors of NAC to provide guidance for clinical treatment.Methods Ninety five cases of local advanced breast cancer were collected,which were treated with NAC of TAC （Taxanes/Anthracycline/Cyclophosphamide） regimen.Multi-gene fluorescence in situ hybridization （M-FISH） was used to study the correlation between copy number variations of cell cycle regulatory genes （cmyc,Mdm2,CCND1,CHEK2,Rb1,p53,p16,p21） and clinical effect of NAC.Results In the effective group,there were 18 cases of c-Myc amplification and 52 cases of no amplification.There were 11 cases of CCND1 amplification and 59 cases of no amplification;12 cases of p53 deletion and 58 cases without deletion;11 cases of p16 deletion and 59 cases without deletion.In the ineffective group,there were 12 cases of c-Myc amplification and 13 cases of no amplification;CCND1 amplification in 9 cases,no amplification in 16 cases;p53 deletion in 10 cases,no deletion in 15 cases;p16 deletion in 10 cases and no deletion in 15 cases.The copy number of the above four genes was statistically different between the two groups.C-Myc gene amplification （P =0.040）,CCND1 gene amplification （P =0.033）,p53 gene deletion （P=0.020） and p16 gene deletion （P=0.012） were significant correlation with poor effect of NAC.Among them,the effect of NAC in patients with two or more genes copy number variations of c-Myc,CCND1,p53,p16 were poorer than that in patients with one or not gene copy number variations （P =0.000）.In addition,the copy number variations of CCND1 （P =0.049）,c-Myc （P =0.049）,and p16 （P =0.008） were correlated with neo-adjuvant chemotherapeutic effect respectively in Luminal breast cancer,Her-2 positive

关 键 词：乳腺肿瘤 新辅助化疗 细胞周期 

分 类 号：R737.9[医药卫生—肿瘤]