Cyclin D1在不同分子亚型乳腺癌中的表达及其对预后的影响
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摘要
目的检测cyclin D1在不同分子亚型乳腺癌中的表达,分析其表达与临床病理特征和预后的关系。方法采用免疫组织化学法检测175例乳腺癌组织标本中cyclin D1的表达情况,应用卡方检验分析cyclin D1在不同分子亚型乳腺癌中的表达,采用Spearman秩相关方法分析cyclin D1表达与临床病理特征的相关性,运用Kaplan-Meier生存曲线分析cyclin D1不同表达对预后的影响。结果①Cyclin D1阳性表达在Luminal A型所占比例最高(P<0.05),而cyclin D1阴性表达在Luminal B型所占比例最高(P<0.05)。②Cyclin D1阳性表达与临床分期、组织学分级及PR无关(P>0.05),与淋巴结转移数目(rs=0.197,P<0.01)、ER呈正相关(rs=0.139,P<0.05);cyclin D1阳性表达与Her-2呈负相关(rs=-0.131,P<0.05)。③Cyclin D1阳性表达越强,无瘤生存时间越长(P<0.05)。结论 Cyclin D1阳性表达与ER、Her-2及淋巴结转移数目有明显相关性,且其阳性表达提示相对良好的预后,可作为乳腺癌预后评估的参考指标。
Objective To detect the expression of cyclin D1 in different kinds of clinical molecular subtypes of breast cancer tissue, and to analyze the relationships of the expression to clinicopathologic characteristics and prognosis. Methods The expression of cyclin D1 was detected in 175 cases of different kinds of clinical molecular subtypes of breast cancer by immunohistochemical method. The expression was compared among different kinds of clinical molecular subtypes of breast cancer by chi-square test. The correlations with clinicopathologic characteristics were analyzed by Spearman rank correlation. The impact of different expression of cyclin D1 on the prognosis was analyzed by the KaplanMeier survival curve. Results ① In the positive expression group of cyclin D1 in the breast cancer, Luminal A type was the highest proportion(P<0.05);but in the negative expression group of cyclin D1 in the breast cancer, Luminal B type was the highest proportion(P<0.05). ② The expression of cyclin D1 had no correlation with clinical stage, histological grade or PR(P>0.05), was positively correlated with number of lymph node metastasis(rs =0.197,P<0.01) or ER(rs =0.139,P<0.05), was negatively correlated with Her-2(rs =-0.131, P<0.05). ③ The positive expression of cyclin D1 was stronger, the tumor free survival time was longer(P< 0.05). Conclusion This study shows that there is a correlation between the positive expression of cyclin D1 and ER, Her-2, or number of lymph node metastasis, and its positive expression prompts a relatively good prognosis, can be used as the prognosis indicator for breast cancer.
Objective To detect the expression of cyclin D1 in different kinds of clinical molecular subtypes of breast cancer tissue, and to analyze the relationships of the expression to clinicopathologic characteristics and prognosis. Methods The expression of cyclin D1 was detected in 175 cases of different kinds of clinical molecular subtypes of breast cancer by immunohistochemical method. The expression was compared among different kinds of clinical molecular subtypes of breast cancer by chi-square test. The correlations with clinicopathologic characteristics were analyzed by Spearman rank correlation. The impact of different expression of cyclin D1 on the prognosis was analyzed by the KaplanMeier survival curve. Results ① In the positive expression group of cyclin D1 in the breast cancer, Luminal A type was the highest proportion(P<0.05);but in the negative expression group of cyclin D1 in the breast cancer, Luminal B type was the highest proportion(P<0.05). ② The expression of cyclin D1 had no correlation with clinical stage, histological grade or PR(P>0.05), was positively correlated with number of lymph node metastasis(rs =0.197,P<0.01) or ER(rs =0.139,P<0.05), was negatively correlated with Her-2(rs =-0.131, P<0.05). ③ The positive expression of cyclin D1 was stronger, the tumor free survival time was longer(P< 0.05). Conclusion This study shows that there is a correlation between the positive expression of cyclin D1 and ER, Her-2, or number of lymph node metastasis, and its positive expression prompts a relatively good prognosis, can be used as the prognosis indicator for breast cancer.
引文
[1]吉爱军,唐金海.乳腺癌术后患者Cyclin A1、A2、D1、E1表达及其临床意义[J].南京医科大学学报:自然科学版,2010,30(9):1290-1294.
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[3]张怡,王娟娟,郭宇,等.microRNA沉默SMYD3基因对乳腺癌细胞Wnt/β-Catenin通路及c-Myc基因影响的研究[J].医学研究杂志,2013,42(6):171-173.
[4]张荣君,章佳新,扶德元,等.SOX7、β-catenin和cyclin D1蛋白在浸润性乳腺癌组织中的表达及临床意义[J].国际外科学杂志,2013,40(9):599-604.
[5]吴珏堃.β-catenin与cyclin D1在乳腺癌中的表达及与其他临床病理指标的相关性分析[J].实用医学杂志,2011,27(9):1613-1616.
[6]师杰,梁智勇,刘彤华.Cyclin D1在乳腺浸润性小叶癌的表达及其意义[J].协和医学杂志,2012,3(1):8-12.
[7]疏楠,李连宏,孙志刚,等.P16、CDK4、cyclinD1在乳腺癌中的表达及临床意义[J].大连医科大学学报,2009,31(4):255-259.
[8]罗洁,陈俞霖,许辉.β-catenin,cyclin D1和ERα在乳腺癌组织中的表达[J].实用预防医学,2010,17(8):1502-1504.
[9]Zwijsen RM,Wientjens E,Klompmaker R,et al.CDK-independent activation of estrogen receptor by cyclin D1[J].Cell,1997,88(3):405-415.
[10]Umekita Y,Ohi Y,Sagara Y,et al.Overexpression of cyclinD1predicts for poor prognosis in estrogen receptor-negative breast cancer patients[J].Int J Cancer,2002,98(3):415-418.
[11]赵俊玲,杨金巧,赖毅.Cyclin D1基因扩增及其蛋白表达在乳腺癌中的意义[J].中国普外基础与临床杂志,2000,7(3):147-149.
[12]Sutherland RL,Prall OW,Alle KM,et al.Cyclin dependent kinases as downstream targets of oestrogen action:potential prognostic indicators and therapeutic targets[J].Endorine Related Cancer,1997,4:357-370.
[13]Khalil S,Tan GA,Giri DD,et al.Activation status of Wnt/?-catenin signaling in normal and neoplastic breast tissues:relationship to HER2/neu expression in human and mouse[J].PLoS One,2012,7(3):e33421.
[14]Geyer FC,Lacroix-Triki M,Savage K,et al.β-Catenin pathway activation in breast cancer is associated with triple-negative phenotype but not with CTNNB1 mutation[J].Mod Pathol,2011,24(2):209-231.
[15]夏红强,何建蓉.Ki-67、EGFR、HER-2和p53在乳腺癌中的表达及其相关性[J].临床肿瘤学杂志,2011,16(2):139-143.
[16]何艳蛟,乔超,刘朝霞,等.乳腺癌中β-catenin,cyclinD1,c-myc表达及意义[J].首都医科大学学报,2011,32(4):549-552.
[17]Carey LA,Perou CM,Livasy CA,et al.Race,breast cancer subtypes,and survival in the Carolina Breast Cancer Study[J].JAMA,2006,295(21):2492-2502.
[18]张英军,吴君心,侯如蓉.乳腺癌的分子分型[J].实用癌症杂志,2012,27(1):98-100.
[19]Su YH,Zheng Y,Zheng W,et al.Distinct distribution and prognostic significance of molecular subtypes of breast cancer in Chinese women:a population-based cohort study[J].BMC Cancer,2011,11:292.
[20]董晓,房新志,柴敏秀,等.β-Catenin和CyclinD1在乳腺癌中的表达及意义[J].新疆医科大学学报,2008,31(5):541-547.
[21]高鹏,周庚寅,刘文君,等.乳腺癌中细胞周期素D1基因改变和转录异常对其蛋白表达的影响[J].中国现代普通外科进展,2004,7(1):31-34.
[22]Hwang TS,Han HS,Hong YC,et al.Prognostic value of combined analysis of cyclin D1 and estrogen receptor status in breast cancer patients[J].Pathol Int,2003,53(2):74-80.
[23]陈晓曦,陈吉彩,程骏,等.cyclinD1在乳腺癌中的表达及意义[J].山东医药,2006,46(34):64-65.
[24]Gillett C,Smith P,Gregory W,et al.Cyclin D1 and prognosis in human breast cancer[J].Int J Cancer,1996,69(2):92-99.
[25]Pelosio P,Barbareschi M,Bonoldi E,et al.Clinical signifi cance of cyclin D1 expression in patients with node-positive breast carcinoma treated with adjuvant therapy[J].Ann Oncol,1996,7(7):695-703.
[26]张云伟,贾宗良.乳腺癌改良根治术后复发和转移因素分析[J].中国普外基础与临床杂志,2012,19(9):988-990.
[2]Kohlberger PD,Breitenecker F,Kaider A,et al.Modifi ed truecolor computer-assisted image analysis versus subjective scoring of estrogen receptor expression in breast cancer:a comparison[J].Anticancer Res,1999,19(3B):2189-2193.
[3]张怡,王娟娟,郭宇,等.microRNA沉默SMYD3基因对乳腺癌细胞Wnt/β-Catenin通路及c-Myc基因影响的研究[J].医学研究杂志,2013,42(6):171-173.
[4]张荣君,章佳新,扶德元,等.SOX7、β-catenin和cyclin D1蛋白在浸润性乳腺癌组织中的表达及临床意义[J].国际外科学杂志,2013,40(9):599-604.
[5]吴珏堃.β-catenin与cyclin D1在乳腺癌中的表达及与其他临床病理指标的相关性分析[J].实用医学杂志,2011,27(9):1613-1616.
[6]师杰,梁智勇,刘彤华.Cyclin D1在乳腺浸润性小叶癌的表达及其意义[J].协和医学杂志,2012,3(1):8-12.
[7]疏楠,李连宏,孙志刚,等.P16、CDK4、cyclinD1在乳腺癌中的表达及临床意义[J].大连医科大学学报,2009,31(4):255-259.
[8]罗洁,陈俞霖,许辉.β-catenin,cyclin D1和ERα在乳腺癌组织中的表达[J].实用预防医学,2010,17(8):1502-1504.
[9]Zwijsen RM,Wientjens E,Klompmaker R,et al.CDK-independent activation of estrogen receptor by cyclin D1[J].Cell,1997,88(3):405-415.
[10]Umekita Y,Ohi Y,Sagara Y,et al.Overexpression of cyclinD1predicts for poor prognosis in estrogen receptor-negative breast cancer patients[J].Int J Cancer,2002,98(3):415-418.
[11]赵俊玲,杨金巧,赖毅.Cyclin D1基因扩增及其蛋白表达在乳腺癌中的意义[J].中国普外基础与临床杂志,2000,7(3):147-149.
[12]Sutherland RL,Prall OW,Alle KM,et al.Cyclin dependent kinases as downstream targets of oestrogen action:potential prognostic indicators and therapeutic targets[J].Endorine Related Cancer,1997,4:357-370.
[13]Khalil S,Tan GA,Giri DD,et al.Activation status of Wnt/?-catenin signaling in normal and neoplastic breast tissues:relationship to HER2/neu expression in human and mouse[J].PLoS One,2012,7(3):e33421.
[14]Geyer FC,Lacroix-Triki M,Savage K,et al.β-Catenin pathway activation in breast cancer is associated with triple-negative phenotype but not with CTNNB1 mutation[J].Mod Pathol,2011,24(2):209-231.
[15]夏红强,何建蓉.Ki-67、EGFR、HER-2和p53在乳腺癌中的表达及其相关性[J].临床肿瘤学杂志,2011,16(2):139-143.
[16]何艳蛟,乔超,刘朝霞,等.乳腺癌中β-catenin,cyclinD1,c-myc表达及意义[J].首都医科大学学报,2011,32(4):549-552.
[17]Carey LA,Perou CM,Livasy CA,et al.Race,breast cancer subtypes,and survival in the Carolina Breast Cancer Study[J].JAMA,2006,295(21):2492-2502.
[18]张英军,吴君心,侯如蓉.乳腺癌的分子分型[J].实用癌症杂志,2012,27(1):98-100.
[19]Su YH,Zheng Y,Zheng W,et al.Distinct distribution and prognostic significance of molecular subtypes of breast cancer in Chinese women:a population-based cohort study[J].BMC Cancer,2011,11:292.
[20]董晓,房新志,柴敏秀,等.β-Catenin和CyclinD1在乳腺癌中的表达及意义[J].新疆医科大学学报,2008,31(5):541-547.
[21]高鹏,周庚寅,刘文君,等.乳腺癌中细胞周期素D1基因改变和转录异常对其蛋白表达的影响[J].中国现代普通外科进展,2004,7(1):31-34.
[22]Hwang TS,Han HS,Hong YC,et al.Prognostic value of combined analysis of cyclin D1 and estrogen receptor status in breast cancer patients[J].Pathol Int,2003,53(2):74-80.
[23]陈晓曦,陈吉彩,程骏,等.cyclinD1在乳腺癌中的表达及意义[J].山东医药,2006,46(34):64-65.
[24]Gillett C,Smith P,Gregory W,et al.Cyclin D1 and prognosis in human breast cancer[J].Int J Cancer,1996,69(2):92-99.
[25]Pelosio P,Barbareschi M,Bonoldi E,et al.Clinical signifi cance of cyclin D1 expression in patients with node-positive breast carcinoma treated with adjuvant therapy[J].Ann Oncol,1996,7(7):695-703.
[26]张云伟,贾宗良.乳腺癌改良根治术后复发和转移因素分析[J].中国普外基础与临床杂志,2012,19(9):988-990.