p57~(KIP2)、cyclin D1、cyclin E在男性乳腺癌组织中的表达及其临床意义
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摘要
目的:探讨p57~(KIP2)、cyclin D1、cyclin E在男性乳腺癌(male breast cancer,MBC)组织中的表达及其临床意义。方法:收集2000年1月至2016年12月60例温州医科大学附属第一医院MBC患者的组织标本,分为乳腺浸润性导管癌组(infiltrating ductal carcinoma,IDC)40例、乳腺导管原位癌组(ductal carcinoma in situ,DCIS)20例,选取20例男性乳腺发育症(gynecomastia,GYM)作为对照组。应用RT-PCR、免疫组织化学法分别检测IDC、DCIS、GYM组织中的p57~(KIP2)、cyclin D1、cyclin E m RNA及蛋白的表达情况。结果:IDC的p57~(KIP2)mRNA表达水平为0.18±0.07,低于DCIS的0.42±0.05、GYM的0.75±0.04;IDC的p57~(KIP2)蛋白阳性率为25%(10/40),低于DCIS的60%(12/20)、GYM的90%(18/20);p57~(KIP2)mRNA及蛋白表达三组间两两比较,差异均具有统计学意义(P<0.05)。IDC的cyclin D1、cyclin E mRNA表达水平分别为0.92±0.12、0.96±0.08,高于DCIS的0.72±0.06、0.64±0.01及GYM的0.38±0.03、0.21±0.02;IDC的cyclin D1、cyclin E蛋白阳性率分别为90%(36/40)、88%(35/40),高于DCIS的80%(16/20)、85%(17/20)及GYM的25%(5/20)、20%(4/20),差异均具有统计学意义(P<0.05)。在IDC组织中p57~(KIP2)、cyclin D1、cyclin E表达均与临床分期、组织学分级相关(P<0.05),p57~(KIP2)蛋白的表达与淋巴结转移相关(P<0.05);p57~(KIP2)与cyclin D1、p57~(KIP2)与cyclin E呈负相关(P<0.05),cyclin D1与cyclin E呈正相关(P<0.05)。结论:p57~(KIP2)、cyclin D1、cyclin E可能参与了MBC的发生发展过程,联合检测p57~(KIP2)、cyclin D1、cyclin E可为进一步发现MBC的发病机制及治疗提供重要参考。
Objective: To explore the relationship between the expression of p57~(KIP2), cyclin D1, and cyclin E receptors in male breast cancer(MBC) and its clinical significance. Methods: Data of MBC cases diagnosed in The First Affiliated Hospital of Wenzhou Medical University between January 2000 and December 2016 were reviewed. Forty cases of infiltrating ductal carcinoma(IDC) and 20 cases of male ductal carcinoma in situ(DCIS) were selected, and 20 cases of gynecomastia(GYM) were selected as controls. The expression of p57~(KIP2), cyclin D1, and cyclin E mRNA and protein in the tissue samples obtained from IDC, DCIS, and GYM cases were measured by reverse transcription polymerase chain reaction and immunohistochemistry, respectively. Results: The expression of p57~(KIP2) mRNA in IDC was 0.18±0.07, which was lower than that in DCIS(0.42±0.05) and GYM(0.75±0.04). The rate of p57~(KIP2) positivity in IDC was 25%(10/40), which was lower than that in DCIS 60%(12/20) and GYM 90%(18/20). There were significant differences in the expression of p57~(KIP2) mRNA and protein among the three groups(P<0.05). The expression of cyclin D1 and cyclin E m RNA in IDC was 0.92±0.12 and0.96±0.08, which was higher than that in DCIS(0.72±0.06, 0.64±0.01) and GYM(0.38±0.03, 0.21±0.02), respectively. Cyclin D1 and cyclin E protein positive rates in IDC were 90%(36/40) and 88%(35/40), which were higher than those in DCIS [80%(16/20), 85%(17/20)], and GYM [25%(5/20), 20%(4/20)]. In IDC tissues, the expression of p57~(KIP2), cyclin D1, and cyclin E proteins was associated with the clinical stage and histological grade(P<0.05), and the expression of p57~(KIP2) protein was correlated with axillary node metastasis(P<0.05). There was a negative correlation between the expression of p57~(KIP2) and cyclin D1 and between p57~(KIP2) and cyclin E. However, the correlation between cyclin D1 and cyclin E expression was positive(P<0.05). Conclusions: p57~(KIP2), cyclin D1, and cyclin E may play an important role in the development and progression of MBC. Combined clinicopathological detection of p57~(KIP2), cyclin D1, and cyclin E can aid future research on MBC.
Objective: To explore the relationship between the expression of p57~(KIP2), cyclin D1, and cyclin E receptors in male breast cancer(MBC) and its clinical significance. Methods: Data of MBC cases diagnosed in The First Affiliated Hospital of Wenzhou Medical University between January 2000 and December 2016 were reviewed. Forty cases of infiltrating ductal carcinoma(IDC) and 20 cases of male ductal carcinoma in situ(DCIS) were selected, and 20 cases of gynecomastia(GYM) were selected as controls. The expression of p57~(KIP2), cyclin D1, and cyclin E mRNA and protein in the tissue samples obtained from IDC, DCIS, and GYM cases were measured by reverse transcription polymerase chain reaction and immunohistochemistry, respectively. Results: The expression of p57~(KIP2) mRNA in IDC was 0.18±0.07, which was lower than that in DCIS(0.42±0.05) and GYM(0.75±0.04). The rate of p57~(KIP2) positivity in IDC was 25%(10/40), which was lower than that in DCIS 60%(12/20) and GYM 90%(18/20). There were significant differences in the expression of p57~(KIP2) mRNA and protein among the three groups(P<0.05). The expression of cyclin D1 and cyclin E m RNA in IDC was 0.92±0.12 and0.96±0.08, which was higher than that in DCIS(0.72±0.06, 0.64±0.01) and GYM(0.38±0.03, 0.21±0.02), respectively. Cyclin D1 and cyclin E protein positive rates in IDC were 90%(36/40) and 88%(35/40), which were higher than those in DCIS [80%(16/20), 85%(17/20)], and GYM [25%(5/20), 20%(4/20)]. In IDC tissues, the expression of p57~(KIP2), cyclin D1, and cyclin E proteins was associated with the clinical stage and histological grade(P<0.05), and the expression of p57~(KIP2) protein was correlated with axillary node metastasis(P<0.05). There was a negative correlation between the expression of p57~(KIP2) and cyclin D1 and between p57~(KIP2) and cyclin E. However, the correlation between cyclin D1 and cyclin E expression was positive(P<0.05). Conclusions: p57~(KIP2), cyclin D1, and cyclin E may play an important role in the development and progression of MBC. Combined clinicopathological detection of p57~(KIP2), cyclin D1, and cyclin E can aid future research on MBC.
引文
[1]Patten DK,Sharifi LK,Fazel M.New approaches in the management of male breast cancer[J].Clin Breast Cancer,2013,13(5):309-314.
[2]Rossi MN,Antonangeli F.Cellular response upon stress:p57 contribution to the final outcome[J].Mediators Inflamm,2015,2015:259325.
[3]Edge SB,Byrd DR,Compton CC,et al.AJCC Cancer staging manual[M].7th ed.New York:Springer,2010.
[4]郭娜娜,葛霞,承泽农.MCM4、p53在子宫颈上皮内瘤变和子宫颈癌中的表达及其临床意义[J].临床与实验病理学杂志,2010,26(5):572-575.
[5]Matsuoka S,Edwards MC,Bai C,et al.p57 Kip2,a structurally distinct member of the p21CIP1 Cdk inhibitor family,is a candidate tumor suppressor gene[J].Genes Dev,1995,9(6):650-662.
[6]Kavanagh E,Joseph B.The hallmarks of CDKN1C(p57,KIP2)in cancer[J].Biochim Biophys Acta,2011,1816(1):50-56.
[7]Sun CC,Li SJ,Li G,et al.Long intergenic noncoding RNA 00511 acts as an oncogene in non-small-cell lung cancer by binding to EZH2and suppressing p57[J].Mol Ther Nucleic Acids,2016,5(11):e385.
[8]Guo H,Li Y,Tian T,et al.The role of cytoplasmic p57 in invasion of hepatocellular carcinoma[J].BMC Gastroenterol,2015,15:104.
[9]Yang C,Nan H,Ma J,et al.High Skp2/Low p57(Kip2)expression is associated with poor prognosis in human breast carcinoma[J].Breast Cancer(Auckl),2015,9(Suppl 1):13-21.
[10]Xu XY,Wang WQ,Zhang L,et al.Clinical implications of p57KIP2 expression in breast cancer[J].Asian Pac J Cancer Prev,2012,13(10):5033-5036.
[11]Ahlin C,Lundgren C,Embretsén-Varro EE,et al.High expression of cyclin D1 is associated to high proliferation rate and increased risk of mortality in women with ER-positive but not in ER-negative breast cancers[J].Breast Cancer Res Treat,2017,164(3):667-678.
[12]Lucenay KS,Doostan I,Karakas C,et al.Cyclin E associates with the lipogenic enzyme ATP-citrate lyase to enable malignant growth of breast cancer cells[J].Cancer Res,2016,76(8):2406-2418.
[13]Abreu MH,Afonso N,Abreu PH,et al.Male breast cancer:Looking for better prognostic subgroups[J].Breast,2016,26:18-24.
[2]Rossi MN,Antonangeli F.Cellular response upon stress:p57 contribution to the final outcome[J].Mediators Inflamm,2015,2015:259325.
[3]Edge SB,Byrd DR,Compton CC,et al.AJCC Cancer staging manual[M].7th ed.New York:Springer,2010.
[4]郭娜娜,葛霞,承泽农.MCM4、p53在子宫颈上皮内瘤变和子宫颈癌中的表达及其临床意义[J].临床与实验病理学杂志,2010,26(5):572-575.
[5]Matsuoka S,Edwards MC,Bai C,et al.p57 Kip2,a structurally distinct member of the p21CIP1 Cdk inhibitor family,is a candidate tumor suppressor gene[J].Genes Dev,1995,9(6):650-662.
[6]Kavanagh E,Joseph B.The hallmarks of CDKN1C(p57,KIP2)in cancer[J].Biochim Biophys Acta,2011,1816(1):50-56.
[7]Sun CC,Li SJ,Li G,et al.Long intergenic noncoding RNA 00511 acts as an oncogene in non-small-cell lung cancer by binding to EZH2and suppressing p57[J].Mol Ther Nucleic Acids,2016,5(11):e385.
[8]Guo H,Li Y,Tian T,et al.The role of cytoplasmic p57 in invasion of hepatocellular carcinoma[J].BMC Gastroenterol,2015,15:104.
[9]Yang C,Nan H,Ma J,et al.High Skp2/Low p57(Kip2)expression is associated with poor prognosis in human breast carcinoma[J].Breast Cancer(Auckl),2015,9(Suppl 1):13-21.
[10]Xu XY,Wang WQ,Zhang L,et al.Clinical implications of p57KIP2 expression in breast cancer[J].Asian Pac J Cancer Prev,2012,13(10):5033-5036.
[11]Ahlin C,Lundgren C,Embretsén-Varro EE,et al.High expression of cyclin D1 is associated to high proliferation rate and increased risk of mortality in women with ER-positive but not in ER-negative breast cancers[J].Breast Cancer Res Treat,2017,164(3):667-678.
[12]Lucenay KS,Doostan I,Karakas C,et al.Cyclin E associates with the lipogenic enzyme ATP-citrate lyase to enable malignant growth of breast cancer cells[J].Cancer Res,2016,76(8):2406-2418.
[13]Abreu MH,Afonso N,Abreu PH,et al.Male breast cancer:Looking for better prognostic subgroups[J].Breast,2016,26:18-24.