ERβ、C-erbB-2、COX-2在乳腺癌组织中的表达及其临床意义的研究
摘要
目的:检测ERα、ERβ、C-erbB-2及COX-2在乳腺浸润性导管癌中的表达,探讨其与乳腺癌临床病理因素,术后生存之间的关系以及ERβ、C-erbB-2与乳腺癌内分泌治疗效果的关系。方法:采用免疫组织化学S-P法检测86例乳腺浸润性导管癌组织中ERα、ERβ、C-erbB-2和COX-2的表达,并结合临床病理指标和预后作分析,采用率的χ2检验、Kaplan-Meier法计算累计生存率、Cox回归进行单因素和多因素分析。结果:(1)ERβ的阳性表达率与临床分期、腋淋巴结转移相关(P<0.05),与年龄、肿瘤大小、组织学分级及月经状况无显著相关性(P>0.05);C-erbB-2的阳性表达率与肿块大小,腋淋巴结转移相关(P<0.05),与年龄、临床分期、组织学分级及月经状况无显著相关性(P>0.05);COX-2的阳性表达率与肿块大小、临床分期、组织学分级相关(P<0.05),与年龄、月经情况及腋淋巴结转移情况无显著相关性(P>0.05)。(2)ERβ阴性患者接受内分泌治疗组5年累计生存率与5年无瘤生存率(分别为87.29%、84.06%)均高于未接受内分泌治疗组(分别为53.87%、53.87%),差异有统计学意义(P<0.05)。ERβ阳性患者接受内分泌治疗组5年的累计生存率与5年无瘤生存率与未接受内分泌治疗组差异无统计学意义(P>0.05)。(3)Cox多因素分析显示ERα,ERβ,C-erbB-2及腋窝淋巴结转移情况是乳腺癌患者术后生存时间的重要影响因素。结论:(1)乳腺浸润性导管癌中ERβ、C-erbB-2、COX-2阳性表达与肿瘤的发生发展密切相关。(2)ERβ阴性的患者内分泌治疗效果明显,C-erbB-2与内分泌治疗耐药有关,联合检测ERα、ERβ及C-erbB-2的表达可作为预测内分泌治疗效果的有用指标。(3)ERα,ERβ,C-erbB-2及腋窝淋巴结转移情况是乳腺癌患者术后生存时间的重要影响因素。
Objective:To investigate the expressions of ERα,ERβ, C-erbB-2 and COX-2 in breast invasive ductal carcinoma and to explore its correlations with the clinicopathological factors and prognosis,and to study the relationship between ERβ、C-erbB-2 and endocrine therapy resistance. Methods:ERα,ERβ,C-erbB-2 and COX-2 were detected by S-P immunohistochemical technique in 86 cases of breast invasive ductal carcinoma.The data was analyzed combining with clinicolpathological character and prognosis usingχ2 test, Kaplan-Meier method and Cox model. Results:(1)The expression of ERβwas significantly correlated with lymph node metastasis,clinical stage(P<0.05),and no significant correlation with age ,tumor size,menopause or not and pathological grading(P>0.05);The expression of C-erbB-2 was significantly correlated with tumor size and lymph node metastasis(P<0.05), and no significant correlation with age , clinical stage,menopause or not and pathological grading(P>0.05);The expression of COX-2 was significantly correlated with tumor size,clinical stage,pathological grading(P<0.05),and no significant correlation with age , lymph node metastasis and menopause or not(P>0.05).(2) For ERβnegative group, the 5-year overrall survival (OS)and disease free survival(DSF) rate in endocrine therapy group were 87.29%,84.06% respectively superior to those in non-endocrine therapy group (53.87%and53.87%) (P<0.05),while for ERβpositive group,the 5-year OS and DFS rate in endocrine therapy group and those in non-endocrine therapy group were no significant difference (P>0.05). (3) ERα, ERβ,C-erbB-2 and lymph node metastasis were important influence factors for the patient survial time in Cox multivariant analysis. Conclusion:(1)The expressions of ERβ、C-erbB-2 and COX-2 may play crucial roles in the carcinogenesis and development of breast invasive ductal carcinoma .(2)Endocrine therapy is effective in ERβnegative breast cancer patients . Detecting the expressions of ERα,ERβand C-erbB-2 is significance in determing the effect of endocrine therapy for breast invasive ductal carcinoma.(3)ERα,ERβ,C-erbB-2 and lymph node metastasis were the relatively factors for breast cancer patient’s postsurgercal survival time.
Objective:To investigate the expressions of ERα,ERβ, C-erbB-2 and COX-2 in breast invasive ductal carcinoma and to explore its correlations with the clinicopathological factors and prognosis,and to study the relationship between ERβ、C-erbB-2 and endocrine therapy resistance. Methods:ERα,ERβ,C-erbB-2 and COX-2 were detected by S-P immunohistochemical technique in 86 cases of breast invasive ductal carcinoma.The data was analyzed combining with clinicolpathological character and prognosis usingχ2 test, Kaplan-Meier method and Cox model. Results:(1)The expression of ERβwas significantly correlated with lymph node metastasis,clinical stage(P<0.05),and no significant correlation with age ,tumor size,menopause or not and pathological grading(P>0.05);The expression of C-erbB-2 was significantly correlated with tumor size and lymph node metastasis(P<0.05), and no significant correlation with age , clinical stage,menopause or not and pathological grading(P>0.05);The expression of COX-2 was significantly correlated with tumor size,clinical stage,pathological grading(P<0.05),and no significant correlation with age , lymph node metastasis and menopause or not(P>0.05).(2) For ERβnegative group, the 5-year overrall survival (OS)and disease free survival(DSF) rate in endocrine therapy group were 87.29%,84.06% respectively superior to those in non-endocrine therapy group (53.87%and53.87%) (P<0.05),while for ERβpositive group,the 5-year OS and DFS rate in endocrine therapy group and those in non-endocrine therapy group were no significant difference (P>0.05). (3) ERα, ERβ,C-erbB-2 and lymph node metastasis were important influence factors for the patient survial time in Cox multivariant analysis. Conclusion:(1)The expressions of ERβ、C-erbB-2 and COX-2 may play crucial roles in the carcinogenesis and development of breast invasive ductal carcinoma .(2)Endocrine therapy is effective in ERβnegative breast cancer patients . Detecting the expressions of ERα,ERβand C-erbB-2 is significance in determing the effect of endocrine therapy for breast invasive ductal carcinoma.(3)ERα,ERβ,C-erbB-2 and lymph node metastasis were the relatively factors for breast cancer patient’s postsurgercal survival time.
引文
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[21] Hynes NE.The biology of c-erbB2/nue/HER-2 and its role in cancer.Acta Biochim Biophys,1994,1198:165-168
[22] Dowset,M. Overexpression of HER-2 as a resistance mechanism to hormonal therapy for breast cancer.Endocr Relat Cancer, 2001,8:191-192
[23] Lai LC. Role of steroid liomones and growth factors in Breast cancer.Clin Chem Lab Med,2002,40:969-974
[24] Myers E,Fleming FJ,Crotty TB,et al,Inverse relationship between ER-beta and SRC-I predicts outcome in endocrine-resistant breast cancer [J].Br J Cancer,2004,91(9):1687
[25] Nakopoulou L,Lazaris AC,Panayotopoulou EG,et al.The Favorable prognostic value of estrogen receptor beta immunohistochemical expression in breast cancer[J].Clin Pathol,2004,57(5):523-528
[26]赵峰,李迅,李景英ERα、ERβ及C-erbB-2在乳腺癌中的表达及临床意义[J].中华现代临床医学杂志,2005,3(18),1885-1887
[27]王维娜,张文清,冯秀洁等.乳腺癌中ERα及ERβ的表达与C-erbB-2表达关系的研究[J].肿瘤研究与临床,2006,18(1)19-20
[28] Benz C C,Scott G K,Sarup J C,et a1.Estrogen-dependent,tamoxifen-resistant tumorigenic growth of MCF-7 cells transfected with Her2/neu[J].Breast Cancer Res Treat,1993,24(1):85-95
[29] Lai LC. Role of steroid liomones and growth factors in Breast cancer[J].Clin Chem Lab Med,2002,40:969-974
[30] Kurokawa H,Arteaga C L.Inhibition of erbB receptor(HER)tyrosine kinases as a strategy to abrogate antiestrogen resistance in human breast cancer[J].Clin Cancer Res,2001,7(supp1):4436-4442
[31] Dannenberg AJ,Altorki NK,Boyle JO,et al.cyclooxygenase-2:aph-armacological target for the prevention of cancer[J].Lancet Oncol,2001,2(9):544-551
[32] Half E,Tang XM.Gwyn K.et al.(yclooxygenase-2 expression in human breast cancers and adjacent dductal carcinoma in situ[J].Cancer R es,2002.62(6): 1676-1681
[33]罗伟仁,陈小毅.环氧化酶-2与肿瘤的关系[J],肿瘤防治研究,2006,33(1):62-64
[34] Brodie A M, Lu Q B, Long J,et al. Aromatase and COX-2 expressionin human breast cancers[J].J Steroid B iochem Mol Bio1,2001,79(1-5):41-47
[35] Subbaramaiah Kotha.Norton Larrv,Gerald William,et a l.Cyclooxygenase-2 is overexpressed in her2/neu-positive breast cancer. Evidence for involvement of AP-1 and PEA3[J]. J Biol Chem,2002,277(21):18649-18657
[36] Denkert C,Winzer KJ,Muller BM,et al.Elevated expression of cyclooxygenase-2 is a negative prognostic factor for disease free survival and overall survival in patients with breast carcinoma.Cancer,2003,97 (12):2978-2987
[37] Harris RE,Alshafie GA,Abou-Issa H,et al.Chemoprevention of breast cancer in rats by celecoxib,a cyclooxygenase 2 inhibitor.Cancer Res,2000,60(8):2101-2103
[38] Kundu N,Smyth MJ,Samsel L,et al.cyclooxygenase inhibitors block cell growth, increase ceramide and inhibit cell cycle.Breast Cancer Res Treat ,2002, 76(1): 57-64
[39] Canney PA,Machin MA,Curto J, A feasibility study of the efficacy and tolerability of the combination of Exemestance with the COX-2 inhibitor Celecoxib in post-menopausal patients with advanced breast cancer.Eur J Cancer,2006,42(16): 2751-2756
[2] Lazennec G, Bresson D, Lucas A, et a1.ERβinhibits proliferation and invasion of breast cancer cells [J].Endocrinology, 2001, 142(9):4120-4130
[3] Omoto Y, Eguchi H, Yamamoto Yamaguchi Y, et al. Estrogen receptor(ER)beta and ERbetacx/beta2 inhibit ERalpha function differently in breast cancer cell line MCF7. Oncogene,2003,22(32):5011-5020
[4] Strom A, Hartman J, Foster JS, et al. Estrogen receptor beta inhibits 17beta-estradiol-stimulated proliferation of the breast cancer cell line T47D. Proc Natl Acad Sci USA,2004,101(6):1566-1571
[5] Kurebayashi J. Endocrine-resistant breast cancer: underlying mechanisms and strategies for overcoming resistance[J]. Breast Cancer,2003,10(2):112-119
[6] Hynes NE.The biology of c-erbB2/nue/HER-2 and its role in cancer. Acta Biochim Biophys,1994,1198:165-168
[7] Dowset,M. Overexpression of HER-2 as a resistance mechanism to hormonalt herapy for breast cancer.Endocr Relat Cancer, 2001,8:191-192
[8] Lai LC. Role of steroid homones and growth factors in breast cancer. Clin Chem Lab Mad,2002,40:969-974
[9] Myers E,Fleming FJ,Crotty TB,et al,Inverse relationship between ER-beta and SRC-1 predicts outcome in endocrine-resistant breast cancer [J].Br J Cancer,2004, 91(9):1687
[10] Nakopoulou L,Lazaris AC,Panayotopoulou EG,et al.The favourable prognostic value of estrogen receptor beta immunohistochemical expression in breast cancer[J].J Clin Pathol,2004,57(5):523-528
[11]赵峰,李迅,李景英. ERα、ERβ及C-erbB-2在乳腺癌中的表达及临床意义[J].中华现代临床医学杂志,2005,3(18):1885-1887
[12]王维娜,张文清,冯秀洁等.乳腺癌中ERα及ERβ的表达与C-erbB-2表达关系的研究[J].肿瘤研究与临床,2006,18(1):19-20
[13]李云涛,李海平,范忠林.乳腺癌组织中雌激素受体亚型ERβ的表达及其与临床病理指标的关系[J].肿瘤防治研究,2007,34(10):767-769
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