TOPⅡA在乳腺癌组织中的表达及意义
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摘要
[目的]分析乳腺癌患者肿瘤组织和癌旁正常乳腺组织中拓扑异构酶ⅡA(TOPⅡA)的表达情况以及与患者临床病理参数和预后的相关性。[方法]选取2014年1月至2014年12月期间在我院首次接受乳腺癌切除术治疗的患者116例,采用RT-PCR法和免疫组织化学染色法检测TOPⅡA mRNA和蛋白表达水平。[结果]乳腺癌患者肿瘤组织中TOPⅡAmRNA和蛋白的高表达率分别为68.1%和62.07%,明显高于癌旁组织(P<0.05)。TOPⅡA高表达与与肿瘤体积、淋巴结转移、TNM分期、WHO组织学分级、ER、Her-2、Ki-67表达水平有显著性相关(P<0.05)。截止至2018年1月31日,患者3年无病生存率为75.0%,其中TOPⅡAm RNA高表达和低表达组患者3年无病生存率分别为65.28%和90.91%(P<0.05)。经多因素Cox风险比模型分析,肿瘤体积(HR=2.040,95%CI:1.132～3.675)、淋巴结转移(HR=1.028,95%CI:1.005～1.051)、WHO分级(HR=1.520,95%CI:1.069～2.162)、TNM分期(HR=2.115,95%CI:1.385～3.231)和含蒽环类化疗药物方案(HR=1.985,95%CI:1.094～3.601)是影响TOPⅡAmRNA高表达患者预后的独立因素。[结论]乳腺癌组织TOPⅡA表达与肿瘤分期、组织学分级、分子表型以及预后密切相关,对治疗方案的选择以及预后的评估具有重要的临床指导价值。
[Objective] To analyze the expression of topoisomeraseⅡA(TOPⅡA) in patients with breast carcinoma and its relationship with pathological characteristics. [Methods] The tumor tissues and pericanceropus tissues samples of 116 patients with breast cancer were collected from January 2014 to December 2014 in our hospital. The mRNA and protein expression of TOPⅡA was detected by RT-PCR and IHC,respectively. And the relationship between the TOPⅡA expressions and pathological characteristics was analyzed. [Results] The high expression rate of TOPⅡA proteins and mRNA was 68.1% and 62.07%,which was significantly higher than that of pericancerous tissues(P<0.05). The expression of TOPⅡA mRNA was correlated with the tumor size,lymph node metastasis,TNM stages,WHO classifications and ER,PR,Ki-67 expression statues(P<0.05). The overall 3-year disease free survival rate was 75.0%,while that was 65.28% for patients with high expression of TOPⅡA mRNA and 90.91% for those with low expression(P<0.05). The tumor size(HR=2.040,95%CI:1.132～3.675),lymph node metastasis(HR=1.028; 95%CI:1.005～1.051),WHO grades(HR=1.520; 95%CI:1.069～2.162),TNM staging(HR=2.115; 95%CI:1.385～3.231) and anthracycline-based chemotherapy(HR=1.985; 95%CI:1.094～3.601) were the independent prognostic factors for breast carcinoma patients with TOPⅡA high expression(P<0.05). [Conclusion] The TOPⅡA expression is correlated with stage,pathological classification,molecular typing and prognosis of patients with breast carcinoma,which would be used as a reference indicator for the clinical treatment.
[Objective] To analyze the expression of topoisomeraseⅡA(TOPⅡA) in patients with breast carcinoma and its relationship with pathological characteristics. [Methods] The tumor tissues and pericanceropus tissues samples of 116 patients with breast cancer were collected from January 2014 to December 2014 in our hospital. The mRNA and protein expression of TOPⅡA was detected by RT-PCR and IHC,respectively. And the relationship between the TOPⅡA expressions and pathological characteristics was analyzed. [Results] The high expression rate of TOPⅡA proteins and mRNA was 68.1% and 62.07%,which was significantly higher than that of pericancerous tissues(P<0.05). The expression of TOPⅡA mRNA was correlated with the tumor size,lymph node metastasis,TNM stages,WHO classifications and ER,PR,Ki-67 expression statues(P<0.05). The overall 3-year disease free survival rate was 75.0%,while that was 65.28% for patients with high expression of TOPⅡA mRNA and 90.91% for those with low expression(P<0.05). The tumor size(HR=2.040,95%CI:1.132～3.675),lymph node metastasis(HR=1.028; 95%CI:1.005～1.051),WHO grades(HR=1.520; 95%CI:1.069～2.162),TNM staging(HR=2.115; 95%CI:1.385～3.231) and anthracycline-based chemotherapy(HR=1.985; 95%CI:1.094～3.601) were the independent prognostic factors for breast carcinoma patients with TOPⅡA high expression(P<0.05). [Conclusion] The TOPⅡA expression is correlated with stage,pathological classification,molecular typing and prognosis of patients with breast carcinoma,which would be used as a reference indicator for the clinical treatment.
引文
[1]Sarosiek T.Systemic treatment of early breast cancer-current state of knowledge after the conference St Gallen2017[J].Pol Merkur Lekarski,2017,43(257):232-236.
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[4]Zhao Y,Zheng X.Biological subtype of breast cancer and treatment as well as prognosis[J].Chinese J of Pratical Surgery,2015,35(7):704-708.[赵毅,郑鑫.乳腺癌分子分型与治疗策略[J].中国实用外科杂志,2015,35(7):704-708.]
[5]Hall SR,Toulany J,Bennett LG,et al.Jadomycins inhibit typeⅡtopoisomerases and promote DNA damage and apoptosis in multidrug-resistant triple-negative breast cancer cells[J].J Pharmacol Exp Ther,2017,363(2):196-210.
[6]De Grandis RA,de Camargo MS,da Silva MM,et al.Human topoisomerase inhibition and DNA/BSA binding of Ru(II)-SCAR complexes as potential anticancer candidates for oral application[J].Biometals,2017,30(3):321-334.
[7]Rao N,Qiu J,Wu J,et al.Significance of tumor-infiltrating lymphocytes and the expression of topoisomeraseⅡαin the prediction of the clinical outcome of patients with triple negative breast cancer after taxane-anthracyclinebased neoadjuvant chemotherapy[J].Chemotherapy,2017,62(4):246-255.
[8]Long WG,Li XQ,Wang HY,et al.Association of TOP2Awith the efficacy of adjuvant chemotherapy and epirubicin in gastric cancer[J].Chinese Clinical Oncology,2017,22(11):984-989.[龙卫国,李小琴,王宏宇,等.TOP2A与胃癌术后辅助化疗及表柔比星疗效的关系[J].临床肿瘤学杂志,2017,22(11):984-989.]
[9]Jin J,Zheng D,Liu Y.Correlation between the expression of TopoⅡαand Ki67 in breast cancer and its clinical pathological characteristics[J].Pak J Med Sci,2017,33(4):844-848.
[10]Fountzilas G,Valavanis C,Kotoula V,et al.HER2 and TOP2A in high-risk early breast cancer patients treated with adjuvant epirubicin baseddose dense sequential chemotherapy[J].J Buon,2012,10:1-21.
[11]Personeni N,Baretti M,Bozzarelli S,et al.Assessment of HER2 status in patients with gastroesophageal adenocarcinoma treated with epirubicin-based chemotherapy:heterogeneity-related issues and prognostic implications[J].Gastric Cancer,2017,20(3):428-437.
[2]Neama RAA,Habib MA,Ali SA,et al.Assessment of topoisomeraseⅡ-alpha gene status by dual color chromogenic hybridization in a set of Iraqi patients with invasive breast carcinoma[J].Indian J Pathol Microbiol,2017,60(4):475-480.
[3]Zhou B,Liu SW,Gao GX,et al.Updates and interpretations of the national comprehensive cancer network guidelines for breast cancer(Version 1,2016)[J].Chinese Jof Pratical Surgery,2016,36(10):1066-1072.[周斌,刘世伟,高国璇,等.2016年NCCN乳腺癌临床实践指南(第1版)更新与解读[J].中国实用外科杂志,2016,36(10):1066-1072.]
[4]Zhao Y,Zheng X.Biological subtype of breast cancer and treatment as well as prognosis[J].Chinese J of Pratical Surgery,2015,35(7):704-708.[赵毅,郑鑫.乳腺癌分子分型与治疗策略[J].中国实用外科杂志,2015,35(7):704-708.]
[5]Hall SR,Toulany J,Bennett LG,et al.Jadomycins inhibit typeⅡtopoisomerases and promote DNA damage and apoptosis in multidrug-resistant triple-negative breast cancer cells[J].J Pharmacol Exp Ther,2017,363(2):196-210.
[6]De Grandis RA,de Camargo MS,da Silva MM,et al.Human topoisomerase inhibition and DNA/BSA binding of Ru(II)-SCAR complexes as potential anticancer candidates for oral application[J].Biometals,2017,30(3):321-334.
[7]Rao N,Qiu J,Wu J,et al.Significance of tumor-infiltrating lymphocytes and the expression of topoisomeraseⅡαin the prediction of the clinical outcome of patients with triple negative breast cancer after taxane-anthracyclinebased neoadjuvant chemotherapy[J].Chemotherapy,2017,62(4):246-255.
[8]Long WG,Li XQ,Wang HY,et al.Association of TOP2Awith the efficacy of adjuvant chemotherapy and epirubicin in gastric cancer[J].Chinese Clinical Oncology,2017,22(11):984-989.[龙卫国,李小琴,王宏宇,等.TOP2A与胃癌术后辅助化疗及表柔比星疗效的关系[J].临床肿瘤学杂志,2017,22(11):984-989.]
[9]Jin J,Zheng D,Liu Y.Correlation between the expression of TopoⅡαand Ki67 in breast cancer and its clinical pathological characteristics[J].Pak J Med Sci,2017,33(4):844-848.
[10]Fountzilas G,Valavanis C,Kotoula V,et al.HER2 and TOP2A in high-risk early breast cancer patients treated with adjuvant epirubicin baseddose dense sequential chemotherapy[J].J Buon,2012,10:1-21.
[11]Personeni N,Baretti M,Bozzarelli S,et al.Assessment of HER2 status in patients with gastroesophageal adenocarcinoma treated with epirubicin-based chemotherapy:heterogeneity-related issues and prognostic implications[J].Gastric Cancer,2017,20(3):428-437.