Skp2、p27和Ki-67在乳腺癌中的表达及意义
|
摘要
目的检测乳腺癌中Skp2、p27和Ki-67的表达情况,探讨三者在乳腺癌中表达的意义及相互关系。方法制作80例乳腺癌肿瘤组织芯片,其中浸润性导管癌,非特殊型42例,浸润性小叶癌12例,特殊类型浸润性癌14例(黏液癌7例,小管癌4例,实性乳头状癌3例),导管原位癌8例,小叶原位癌4例。腋窝淋巴结阳性43例,阴性37例。采用组织芯片技术和免疫组织化学方法检测乳腺癌中Skp2、p27和Ki-67的表达。结果 80例乳腺癌中Skp2、p27的阳性率分别为46.3%、45.0%,Ki-67指数高表达率56.3%(45/80)。p27与Skp2同时阳性表达7例,p27阴性者中Skp2阳性30例(P<0.01)。37例Skp2阳性者中Ki-67高表达29例,43例Skp2阴性者中Ki-67仅16例高表达(P<0.01)。36例p27阳性者中Ki-67高表达仅7例,44例p27阴性者中Ki-67高表达38例(P<0.01)。结论 Skp2高表达、p27失表达和Ki-67指数增高共同参与了乳腺癌的发生和发展过程,并与腋窝淋巴结转移密切相关。乳腺癌组织中Skp2的表达与p27呈负相关,与Ki-67的表达呈正相关,p27与Ki-67的表达呈负相关。
Objective To detect the expression of Skp2, p27 and Ki-67 in breast cancer, and to investigate the significance and relationship between them in breast cancer. Methods 80 cases of tumor tissue microarray in breast cancer were made, including 42 cases of non-special type invasive ductal carcinoma, 12 cases of invasive lobular carcinoma,14 cases of special type invasive carcinoma(7 cases of mucinous carcinoma, 4 cases of small tubular carcinoma, 3 cases of papillary carcinoma), 8 cases of ductal carcinoma in situ, 4 cases of lobular carcinoma in situ. There were 43 positive cases and 37 negative cases in axillary lymph node. The expression of Skp2, p27 and Ki-67 in breast cancer was detected by tissue microarray and immunohistochemistry. Results The positive rates of Skp2 and p27 in 80 cases of breast cancer were 46.3% and 45.0%, respectively. The high expression rate of Ki-67 index was 56.3%(45/80). 7 cases were positive for both p27 and Skp2, 30 cases were positive for Skp2 in p27-negative cases(P<0.01). There were 29 cases of highly expressed Ki-67 in 37 Skp2-positive cases, while there were only 16 cases of highly expressed Ki-67 in 43 Skp2-negative cases(P<0.01). Ki-67 of only 7 cases were highly expressed in 36 p27-positive cases and 38 cases were highly expressed in 44 p27-negative cases(P<0.01). Conclusion High expression of Skp2, loss expression of p27 and Ki-67 index increased are all involved in occurrence and development of breast cancer, and are closely related to axillary lymph node metastasis. The expression of Skp2 in breast cancer tissues was negatively correlated with p27,positively correlated with the expression of Ki-67. p27 is negatively correlated with the expression of Ki-67.
Objective To detect the expression of Skp2, p27 and Ki-67 in breast cancer, and to investigate the significance and relationship between them in breast cancer. Methods 80 cases of tumor tissue microarray in breast cancer were made, including 42 cases of non-special type invasive ductal carcinoma, 12 cases of invasive lobular carcinoma,14 cases of special type invasive carcinoma(7 cases of mucinous carcinoma, 4 cases of small tubular carcinoma, 3 cases of papillary carcinoma), 8 cases of ductal carcinoma in situ, 4 cases of lobular carcinoma in situ. There were 43 positive cases and 37 negative cases in axillary lymph node. The expression of Skp2, p27 and Ki-67 in breast cancer was detected by tissue microarray and immunohistochemistry. Results The positive rates of Skp2 and p27 in 80 cases of breast cancer were 46.3% and 45.0%, respectively. The high expression rate of Ki-67 index was 56.3%(45/80). 7 cases were positive for both p27 and Skp2, 30 cases were positive for Skp2 in p27-negative cases(P<0.01). There were 29 cases of highly expressed Ki-67 in 37 Skp2-positive cases, while there were only 16 cases of highly expressed Ki-67 in 43 Skp2-negative cases(P<0.01). Ki-67 of only 7 cases were highly expressed in 36 p27-positive cases and 38 cases were highly expressed in 44 p27-negative cases(P<0.01). Conclusion High expression of Skp2, loss expression of p27 and Ki-67 index increased are all involved in occurrence and development of breast cancer, and are closely related to axillary lymph node metastasis. The expression of Skp2 in breast cancer tissues was negatively correlated with p27,positively correlated with the expression of Ki-67. p27 is negatively correlated with the expression of Ki-67.
引文
[1]King RW.How proteolysis drives the cell cycle[J].Science,1996,274(5293):1652-1659.
[2]程维刚,李蕾蕾,刘九洲,等.S期激酶相关蛋白2和细胞周期抑制蛋白p27kip1在乳腺癌组织中的表达及其临床意义[J].中华实验外科杂志,2015,32(10):2520-2522.
[3]Kazi A,Carie A,Blaskovich MA,et al.Blockade of protein geranylgerany-lation inhibits Cdk2-dependent p27kip1 phosphorylation on Thr187 and accumulates p27kip1 in the nucleus:Implications for breast cancer therapy[J].Mol Cell Biol,2009,29(8):2254-2263.
[4]Yan L,Yun N,Xiu-Min D,et al.Oncogenic role of Skp2and p27Kip1 in intraductal proliferative lesions of the breast[J].Chin Med Sci J,2012,27(3):162-166.
[5]郭志琴,吕青山,张燕萍,等.乳腺癌SKP2及Thr187磷酸化p27kip1的表达及其预后意义[J].中华病理学杂志,2013,42(3):197-198.
[6]Dmitrenko AP.Lateral differences in Ki-67 in breast cancer[J].Mol Clin Oneol,2016,4(6):1041-1044.
[7]刘庆猛,何平生,谭卫峰,等.应用组织芯片和荧光原位杂交技术检测乳腺癌组织中HER-2/neu基因扩增及其蛋白产物的表达[J].肿瘤,2013,33(8):711-716.
[8]Seki R,Ohshima K,Fujisaki T,et al.Prognostic significance of S-phase kinase-associated protein 2 and p27kipl in patients with diffuse large B-cell lymphoma:Effects of rituximab[J].Ann Oncol,2010,21(4):833-841.
[9]Goldhirseh A,Wood WC,Coates AS,et al.Strategies for subtypes dealing with the diversity of breast cancer:Highlights of the St.Gallen international expert consensus on the primary therapy of early breast cancer 2011[J].Ann Oncol,2011,22(8):1736-1747.
[10]冯爱强,李蕾蕾,张彦武,等.Skp2和p27kip1在乳腺癌组织中的表达及其相关性的研究[J].天津医药,2012,40(5):424-426.
[11]吕艳,牛昀,丁秀敏,等.Skp2和p27Kip1表达异常与乳腺癌发生及临床病理特征的相关性研究[J].诊断病理学杂志,2015,22(7):429-432.
[12]Ravaioli A,Monti F,Regan MM,et al.P27 and SKP2immunoreactivity and its clinical significance with endocrine and chemo-endocrine treatments in node-negative early breast cancer[J].Ann Oncol,2008,19(4):660-668.
[13]徐锦屏,沈卫达,周英姿,等.p16、p27蛋白与乳腺癌临床病理特征的关系及预后价值[J].肿瘤研究与临床,2016,28(5):315-317.
[14]孙立春,隋广杰,于雁,等.Skp2和p27蛋白在乳腺癌中表达及临床意义[J].肿瘤防治研究,2005,32(7):411-413.
[15]帅萍.乳腺癌组织中Skp2和p27Kip1表达与临床病理因素的关系[J].中国普通外科杂志,2015,24(11):1583-1586.
[16]Niikura N,Masuda S,Kumaki N,et al.Prognostic significance of the Ki-67 scoring categories in breast cancer subgroups[J].Clin Breast Cancer,2014,14(5):323-329.
[17]郭志琴,吕青山,袁琳娜,等.Thr187磷酸化p27kip1与人乳腺癌MCF-7细胞化疗敏感性的关系[J].浙江医学,2017,39(1):24-27.
[18]徐玲,刘荫华,叶京明,等.乳腺癌组织中Ki-67表达与蒽环类联合紫杉类新辅助化疗效果的相关性[J].中华外科杂志,2010,48(6):450-453.
[19]Kim DK,Kim DW,Kim SW,et al.Ki-67 antigen as a predictive factor for prognosis of sinonasal mucosal melanoma[J].Clin Exp Otorhinolaryngol,2008,1(4):206-210.
[20]陈青,吴克瑾.Ki-67乳腺癌临床应用价值及其临界值界定的研究进展[J].中华外科杂志,2015,53(8):634-637.
[21]张彦收,唐甜甜,周涛,等.Ki-67表达水平检测在乳腺癌新辅助化疗疗效评估中的价值[J].现代肿瘤医学,2017,25(14):2256-2259.
[22]Kononen J,Bubendorf L,Kallioniemi A,et al.Tissue microarrays for high-throughput molecular profiling of tumour specimens[J].Nat Med,1998,4(7):844-847.
[23]楼立新,林恒军,王荣飞.金华地区Ki-67在乳腺癌中的表达及意义[J].中国现代医生,2016,54(31):9-13.
[24]张书卿,张绪良,黄丹青.Ki-67和p53在乳腺癌中的表达及临床意义[J].医学综述,2015,22(18):3400-3402.
[25]王锋刚,樊利妮,王天昶,等.三阴性乳腺癌中Ki-67的表达及意义[J].疑难病杂志,2015,(12):1269-1272.
[26]李军扩,杨海军,张静芳.Ki-67和p53在三阴乳腺癌中的表达及意义[J].中国医学创新,2016,13(2):12-14.
[27]左云海.Ki-67、P53在乳腺癌腋窝淋巴结转移中的表达与意义[J].现代诊断与治疗,2014,25(24):5548-5549.
[2]程维刚,李蕾蕾,刘九洲,等.S期激酶相关蛋白2和细胞周期抑制蛋白p27kip1在乳腺癌组织中的表达及其临床意义[J].中华实验外科杂志,2015,32(10):2520-2522.
[3]Kazi A,Carie A,Blaskovich MA,et al.Blockade of protein geranylgerany-lation inhibits Cdk2-dependent p27kip1 phosphorylation on Thr187 and accumulates p27kip1 in the nucleus:Implications for breast cancer therapy[J].Mol Cell Biol,2009,29(8):2254-2263.
[4]Yan L,Yun N,Xiu-Min D,et al.Oncogenic role of Skp2and p27Kip1 in intraductal proliferative lesions of the breast[J].Chin Med Sci J,2012,27(3):162-166.
[5]郭志琴,吕青山,张燕萍,等.乳腺癌SKP2及Thr187磷酸化p27kip1的表达及其预后意义[J].中华病理学杂志,2013,42(3):197-198.
[6]Dmitrenko AP.Lateral differences in Ki-67 in breast cancer[J].Mol Clin Oneol,2016,4(6):1041-1044.
[7]刘庆猛,何平生,谭卫峰,等.应用组织芯片和荧光原位杂交技术检测乳腺癌组织中HER-2/neu基因扩增及其蛋白产物的表达[J].肿瘤,2013,33(8):711-716.
[8]Seki R,Ohshima K,Fujisaki T,et al.Prognostic significance of S-phase kinase-associated protein 2 and p27kipl in patients with diffuse large B-cell lymphoma:Effects of rituximab[J].Ann Oncol,2010,21(4):833-841.
[9]Goldhirseh A,Wood WC,Coates AS,et al.Strategies for subtypes dealing with the diversity of breast cancer:Highlights of the St.Gallen international expert consensus on the primary therapy of early breast cancer 2011[J].Ann Oncol,2011,22(8):1736-1747.
[10]冯爱强,李蕾蕾,张彦武,等.Skp2和p27kip1在乳腺癌组织中的表达及其相关性的研究[J].天津医药,2012,40(5):424-426.
[11]吕艳,牛昀,丁秀敏,等.Skp2和p27Kip1表达异常与乳腺癌发生及临床病理特征的相关性研究[J].诊断病理学杂志,2015,22(7):429-432.
[12]Ravaioli A,Monti F,Regan MM,et al.P27 and SKP2immunoreactivity and its clinical significance with endocrine and chemo-endocrine treatments in node-negative early breast cancer[J].Ann Oncol,2008,19(4):660-668.
[13]徐锦屏,沈卫达,周英姿,等.p16、p27蛋白与乳腺癌临床病理特征的关系及预后价值[J].肿瘤研究与临床,2016,28(5):315-317.
[14]孙立春,隋广杰,于雁,等.Skp2和p27蛋白在乳腺癌中表达及临床意义[J].肿瘤防治研究,2005,32(7):411-413.
[15]帅萍.乳腺癌组织中Skp2和p27Kip1表达与临床病理因素的关系[J].中国普通外科杂志,2015,24(11):1583-1586.
[16]Niikura N,Masuda S,Kumaki N,et al.Prognostic significance of the Ki-67 scoring categories in breast cancer subgroups[J].Clin Breast Cancer,2014,14(5):323-329.
[17]郭志琴,吕青山,袁琳娜,等.Thr187磷酸化p27kip1与人乳腺癌MCF-7细胞化疗敏感性的关系[J].浙江医学,2017,39(1):24-27.
[18]徐玲,刘荫华,叶京明,等.乳腺癌组织中Ki-67表达与蒽环类联合紫杉类新辅助化疗效果的相关性[J].中华外科杂志,2010,48(6):450-453.
[19]Kim DK,Kim DW,Kim SW,et al.Ki-67 antigen as a predictive factor for prognosis of sinonasal mucosal melanoma[J].Clin Exp Otorhinolaryngol,2008,1(4):206-210.
[20]陈青,吴克瑾.Ki-67乳腺癌临床应用价值及其临界值界定的研究进展[J].中华外科杂志,2015,53(8):634-637.
[21]张彦收,唐甜甜,周涛,等.Ki-67表达水平检测在乳腺癌新辅助化疗疗效评估中的价值[J].现代肿瘤医学,2017,25(14):2256-2259.
[22]Kononen J,Bubendorf L,Kallioniemi A,et al.Tissue microarrays for high-throughput molecular profiling of tumour specimens[J].Nat Med,1998,4(7):844-847.
[23]楼立新,林恒军,王荣飞.金华地区Ki-67在乳腺癌中的表达及意义[J].中国现代医生,2016,54(31):9-13.
[24]张书卿,张绪良,黄丹青.Ki-67和p53在乳腺癌中的表达及临床意义[J].医学综述,2015,22(18):3400-3402.
[25]王锋刚,樊利妮,王天昶,等.三阴性乳腺癌中Ki-67的表达及意义[J].疑难病杂志,2015,(12):1269-1272.
[26]李军扩,杨海军,张静芳.Ki-67和p53在三阴乳腺癌中的表达及意义[J].中国医学创新,2016,13(2):12-14.
[27]左云海.Ki-67、P53在乳腺癌腋窝淋巴结转移中的表达与意义[J].现代诊断与治疗,2014,25(24):5548-5549.