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中华乳腺病杂志(电子版)

中华乳腺病杂志(电子版) ›› 2012, Vol. 06 ›› Issue (04) : 394 -401. doi: 10.3877/cma. j. issn.1674-0807.2012.04.006

论著

新辅助化疗前后乳腺癌患者外周血细胞角蛋白19表达变化及其临床意义
毛莹1, 邹天宁1,†(), 杨庄青1, 张季1   
  1. 1.650118 昆明,云南省肿瘤医院乳腺病科,云南省乳腺癌临床研究中心
  • 收稿日期:2012-03-15 出版日期:2012-08-01
  • 通信作者: 邹天宁
  • 基金资助:
    云南省应用基础研究自筹经费项目(2010zc132)

Change of CK19 expression in peripheral blood of breast cancer patients before and after neoadjuvant chemotherapy and its clinical significance

Ying MAO1, Tianning ZOU†,1(), Zhuang-qing YANG1, Ji ZHANG1   

  1. 1.Department of Breast Diseases, Tumor Hospital of Yunnan Province, Kunming 650118, China
  • Received:2012-03-15 Published:2012-08-01
  • Corresponding author: Tianning ZOU
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毛莹, 邹天宁, 杨庄青, 张季. 新辅助化疗前后乳腺癌患者外周血细胞角蛋白19表达变化及其临床意义[J/OL]. 中华乳腺病杂志(电子版), 2012, 06(04): 394-401.

Ying MAO, Tianning ZOU, Zhuang-qing YANG, Ji ZHANG. Change of CK19 expression in peripheral blood of breast cancer patients before and after neoadjuvant chemotherapy and its clinical significance[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2012, 06(04): 394-401.

目的

探讨细胞角蛋白(CK)19 在乳腺癌新辅助化疗前后表达的变化及其临床意义。

方法

采用实时定量RT-PCR 技术检测86 例乳腺癌患者新辅助化疗前后外周血CK19 mRNA 的表达变化,将30 例乳腺良性疾病患者和20 例健康体检志愿者作为对照。 对非正态分布或方差不齐的数据采用Wilcoxon 非参数秩和检验,用中位数±百分位数之差[M(QR)] 表示,计数资料组间采用χ2 检验。

结果

新辅助化疗前乳腺癌患者外周血中CK19 mRNA 阳性表达率为32.56% (28/86),与腋窝淋巴结转移、临床分期有关(分别P<0.001);而新辅助化疗后阳性表达率为13.95% (12/86),化疗前后CK19 mRNA 表达差异具有统计学意义(P=0.004);新辅助化疗后CK19 mRNA 阳性表达的患者中,57.14%(16/28)获得临床完全缓解成部分缓解,低于CK19 mRNA 阴性患者的93.10%(54/58),差异有统计学意义(P<0.001),这提示CK19 mNRA 表达水平变化可能与新辅助化疗疗效有关。

结论

CK19 可作为新辅助化疗疗效判定的早期预测指标之一。

关键词: 乳腺肿瘤, 新辅助化疗, 细胞角蛋白19, 实时定量RT-PCR

Objective

To investigate the expression change of CK19 in breast cancer patients after neoadjuvant chemotherapy and its clinical significance.

Methods

Using real-time quantitative RT-PCR (qRT-PCR), CK19 mRNA expression in peripheral blood of 86 patients with breast cancer were detected before and after neoadjuvant chemotherapy, with 20 healthy individuals and 24 patients with benign breast lesions as controls. The data with non-normal distribution or heterogeneity of variance were processed using Wilcoxon nonparametric rank sum test, expressed as M(QR).χ2 test was performed for numeration data.

Results

The positive rate of CK19 mRNA in peripheral blood before neoadjuvant chemotherapy was 32.56%(28/86), which showed a correlation with lymphatic metastasis and clinical stages(P<0.001). But it decreased to 13.95% (12/86) after neoadjuvant chemotherapy, which was significantly lower than that before neoadjuvant chemotherapy (P=0.004). After neoadjuvant chemotherapy, 57.14%of the patients(16/28)with CK19 mRNA positive expression showed complete or partial remission, significantly lower than 93.10% (54/58)in the patients with CK19 mRNA negative expression(P<0.001), which suggested that the change of CK19 mRNA expression may correlate with neoadjuvant chemotherapy response.

Conclusion

CK19 can be used as an early predictor of neoadjuvant chemotherapy efficacy.

Key words: breast neoplasms, neoadjuvant chemotherapy, cytokeratin 19, qRTPCR
图1 CK19 熔解曲线
图2 CK19 扩增曲线荧光定量PCR 反应的荧光阈值
图3 内参基因β-actin 扩增曲线荧光定量PCR 反应的荧光阈值
图4 内参基因β-actin 熔解曲线
图5 CK19 标准曲线
图6 内参基因β-actin 标准曲线
表1 CK19 mRNA 表达与乳腺癌临床病理特征之间的关系
临床参数 例数 CK19mRNA 阳性率(%) χ2值 P值
(-) (+)
年龄
＞50岁 28 16 12 42.86 1.162 0.281
≤50岁 58 42 16 27.59
绝经
是 24 18 6 25.00 0.866 0.352
否 62 40 22 35.48
肿瘤直径
≤5cm 56 38 18 32.14 0.013 0.911
>5cm 30 20 10 33.33
淋巴结转移
有 38 16 22 57.89 19.904 ＜0.001
无 48 42 6 12.50
TNM分期
Ⅱ期 48 40 8 16.67 12.494 ＜0.001
Ⅲ期 38 18 20 57.63
ER
阳性 52 36 16 30.77 0.192 0.662
阴性 34 22 12 35.29
PR
阳性 40 28 12 30.00 0.223 0.637
阴性 46 30 16 34.78
表2 新辅助化疗前与2 个化疗周期后CK19 mRNA 阳性例数的变化
化疗前后 CK19mRNA χ2值 P值
+ -
化疗前 28 58 8.339 0.004
化疗2个周期后 12 74
表3 新辅助化疗前与2 个周期化疗后CK19 mRNA 表达水平的变化
化疗前后 例数 CK19[(M(QR),×10-3] Z值 P值a
化疗前 86 0.29(1.35)
化疗2个周期后 86 0.24(0.11) -3.997 ＜0.001
表4 CK19 mRNA 的表达与临床疗效关系
临床疗效 CK19mRNA P值
+ -
CR+PR 16 54 ＜0. 001
SD 12 4
[1]
Iakovlev VV, Goswami RS, Vecchiarelli J, et al. Quantitative detection of circulating epithelial cells by Q-RT-PCR[J].Breast Cancer Res Treat,2008,107(1):145-154.
[2]
Ignatiadis M, Georgoulias V, Mavroudis D. Circulating tumor cells in breast cancer [J]. Curr Opin Obstet Gynecol,2008,20(1):55-60.
[3]
Stathopoulou A, Ntoulia M, Perraki M, et al. A highly specific real-time RT-PCR method for the quantitative determination of CK-19 mRNA positive cells in peripheral blood of patients with operable breast cancer [J]. Int J Cancer,2006,119(7):1654-1659.
[4]
Reinholz MM,Kitzmann KA,Tenner K,et al. Cytokeratin-19 and mammaglobin gene expression in circulating tumor cells from metastatic breast cancer patients enrolled in North Central Cancer Treatment Group trials[J]. Clin Cancer Res,2011,15;17(22):7183-7193.
[5]
Sanislo L, Vertakova-Krakovska B, Kuliffay P, et al. Detection of circulating tumor cells in metastatic breast cancer patients [J]. Endocr Regul,2011,45 (3):113-124.
[6]
Xenidis N, Ignatiadis M, Apostolaki S, et al. Cytokeratin-19 mRNA-positive circulating tumor cells after adjuvant chemotherapy in patients with early breast cancer [J]. Clin Oncol,2009,27(13):2177-2184.
[7]
Stathopoulou A, Vlachonikolis I, Mavroudis D, et al. Molecular detection of cytokeratin-19-positive cells in the peripheral blood of patients with operable breast cancer:evaluation of their prognostic significance [J]. Clin Oncol,2002,20 (16):3404-3412.
[8]
Pantel K, Brakenhoff RH, Brandt B. Detection, clinical relevance and specific biological properties of disseminating tumour cells [J]. Nat Rev Cancer,2008,8(5):329-340.
[9]
Yuan CC, Wang PH, Ng HT, et al. Detecting cytokeratin 19 mRNA in the peripheral blood cells of cervical cancer patients and its clinical-pathological correlation[J]. Gynecol Oncol,2002,85(1):148-153.
[10]
Muller V, Riethdorf S, Loibl S, et al. Prospective monitoring of circulating tumor cells in breast cancer patients treated with primary systemic therapy-a translational project of the German Breast Group study GeparQuattro [J]. Clin Oncol,2007,25(18S):21085.
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