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中华乳腺病杂志(电子版)

中华乳腺病杂志(电子版) ›› 2013, Vol. 07 ›› Issue (02) : 80 -85. doi: 10.3877/cma. j. issn.1674-0807.2013.02.002

论著

可手术乳腺癌循环肿瘤细胞与原发肿瘤临床病理特征的关系
崇梅红1, 肇毅2,†(), 王水2, 查小明2, 刘晓安2, 凌立君2   
  1. 1.225000 江苏扬州,江苏省苏北人民医院甲乳外科
    2.210029 南京,南京医科大学第一附属医院乳腺外科
  • 收稿日期:2011-10-19 出版日期:2013-04-01
  • 通信作者: 肇毅
  • 基金资助:
    国家自然科学基金资助项目(81071753)江苏省六大人才高峰项目(2010-ws-079)

Relationship between circulating tumor cells and clinicopathologic characteristics of primary tumor in operable breast cancer patients

Mei-hong CHONG1, Yi ZHAO1,†(), Shui WANG1, Xiao-ming ZHA1, Xiaoan LIU1, Li-jun LING1   

  1. 1.Department of Thyroid and Breast Surgery, Subei People’s Hospital of Jiangsu Province,Yangzhou 225000, China
  • Received:2011-10-19 Published:2013-04-01
  • Corresponding author: Yi ZHAO
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引用本文：

崇梅红, 肇毅, 王水, 查小明, 刘晓安, 凌立君. 可手术乳腺癌循环肿瘤细胞与原发肿瘤临床病理特征的关系[J/OL]. 中华乳腺病杂志(电子版), 2013, 07(02): 80-85.

Mei-hong CHONG, Yi ZHAO, Shui WANG, Xiao-ming ZHA, Xiaoan LIU, Li-jun LING. Relationship between circulating tumor cells and clinicopathologic characteristics of primary tumor in operable breast cancer patients[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2013, 07(02): 80-85.

目的

探讨可手术乳腺癌患者外周血循环肿瘤细胞(CTCs)的阳性率及其与原发肿瘤临床病理特征的关系。

方法

以2010 年9 月至2011 年5 月期间南京医科大学第一附属医院收治的94 例可手术乳腺癌患者为实验组,20 例健康志愿者及20 例乳腺良性疾病患者为对照组,抽取实验组及对照组患者的外周静脉血10 ml,用密度梯度离心法富集分离单个核细胞,以多标志物(CK19、人乳腺珠蛋白、小黏蛋白)联合的实时荧光定量PCR 法检测CTCs。 采用皮尔逊χ2 检验分析可手术乳腺癌组与对照组外周血CTCs 阳性率的差异,以及CTCs 与原发肿瘤临床病理特征的关系。

结果

可手术乳腺癌组外周血CTCs 阳性率显著高于对照组[56%(53/94)比5%(2/40),χ2=30.62,P=0.00]。 可手术乳腺癌患者外周血CTCs 阳性率在不同的年龄、绝经状态、肿块大小、淋巴结转移、TNM 分期、病理分级、病理类型、激素受体状态、HER-2 表达、是否为三阴性乳腺癌、分子分型、P53 表达、Ki67 表达以及增殖细胞核抗原(PCNA)表达分组间差异无统计学意义(P 值均＞0.05)。

结论

可手术乳腺癌患者外周血CTCs 的阳性率较高,但其与原发肿瘤临床病理学特征无关系。

关键词: 乳腺肿瘤, 循环肿瘤细胞, TNM 分期, 激素受体, 人表皮生长因子受体2

Objective

To investigate the positive rate of circulating tumor cells (CTCs) in peripheral blood in patients with operable breast cancer and its relationship with clinicopathologic characteristics of primary tumor.

Methods

From September 2010 to May 2011, ninety-four operable breast cancer patients in the First Affiliated Hospital of Nanjing Medical University were involved as the experiment group, 20 healthy volunteers and 20 patients with benign breast diseases served as control group. Samples of peripheral blood (10 ml) from the experiment group and control group were enriched by density gradient centrifugation for mononuclear cells respectively, and then the cells were detected by a multimarker [CK19, human mammaglobin (hMAM), small breast epithelial mucin (SBEM)] real time quantitative PCR method. Pearson’s Chi-square test was used to analyze the difference on positive rates of CTCs in peripheral blood between the experiment group and control group, and the relationship between the positive rate of CTCs and clinicopathologic characteristics of primary tumors.

Results

The positive rate of CTCs in peripheral blood in the experiment group (56%, 53/94) was significantly higher than that in control group (5%,2/40) (χ2=30.62,P=0.00). The positive rates of CTCs in operable breast cancer patients showed no significant difference among the different subgroups with regards to age, menopausal status, tumor size, lymph node metastasis, TNM stage, histological grade, histological type,hormone receptor status, human epithelial growth factor receptor 2 (HER-2) expression, triple negative status,molecular type, P53 expression, Ki67 expression, and proliferating cell nuclear antigen(PCNA) expression(P ＞0.05).

Conclusion

The patients with operable breast cancer show a high positive rate of CTCs in peripheral blood, but no significant correlation is found between the presence of CTCs and the clinicopathologic characteristics of primary tumor.

Key words: breast neoplasms, circulating tumor cell, TNM stage, hormone receptor, human epithelial growth factor receptor 2
表1 引物
名称 序列
CK19-F 5′-TCCGAACCAAGTTTGAGACG-3′
CK19-R 5′-CCCTCAGCGTACTGATTTCCT-3′
hMAM-F 5′-ATGAAGTTGCTGATGGTCCTCAT-3′
hMAM-R 5′-GTCTTAGACACTTGTGGATTGATTGTCT-3′
SBEM-F 5′-GTATCCAGCTACTGGTCCTGCT-3′
SBEM-R 5′-CAATTGCAGAAGACTCAAGCTG-3′
β-actin-F 5′-GCTGTGCTATCCCTGTACGC-3′
β-actin-R 5′-TGCCTCAGGGCAGCGGAACC-3′
表2 对照组与可手术乳腺癌组外周血循环肿瘤细胞阳性率比较
组别 例数 循环肿瘤细胞[例(%)] χ 2值 P值
阳性 阴性
对照组 40 2(5%) 38(95%) 30.62 0.00
可手术乳腺癌组 94 53(56%) 41(44%)
表3 94 例可手术乳腺癌患者外周血循环肿瘤细胞与临床病理因素的关系
临床病理因素 例数 循环肿瘤细胞 χ 2值 P值 临床病理因素 例数 循环肿瘤细胞 χ 2值 P值
阳性(例) 阴性(例) 阳性(例) 阴性(例)
年龄 0.77 0.38 HER-2状态 1.87 0.17
≤45岁 20 13 7 阴性 69 36 33
＞45岁 74 40 34 阳性 25 17 8
绝经状态 0.06 0.81 三阴性乳腺癌b 0.37 0.54
绝经前 38 22 16 是 18 9 9
绝经后 56 31 25 否 76 44 32
原发肿瘤分期a 3.26 0.19 分子分型c 4.28 0.37
T1 28 14 14 Luminal A 51 27 24
T2 62 35 27 Luminal B 15 12 3
T3 4 4 0 Basal-like 8 4 4
淋巴结病理分期a 2.41 0.49 Normal-like 10 5 5
pN0 49 25 24 HER-2过表达 10 5 5
pN1 20 12 8 P53 4.17 0.23
pN2 13 7 6 阴性 26 11 15
pN3 12 9 3 弱阳性 16 8 8
TNM分期a 1.18 0.55 阳性 48 31 17
Ⅰ期 17 9 8 未知d 4
Ⅱ期 51 27 24 Ki67 4.91 0.43
Ⅲ期 26 17 9 阴性 2 0 2
组织学分级 3.18 0.20 ＜10%阳性 15 9 6
1级 26 14 12 10%～30%阳性 24 12 12
2级 41 20 21 ＞30%～60%阳性 17 10 7
3级 27 19 8 ＞60%阳性 23 13 10
病理类型 2.92 0.19 未知d 13
导管原位癌 2 0 2 PCNA 2.02 0.62
浸润性导管癌 91 52 39 阴性 2 1 1
浸润性小叶癌 1 1 0 弱阳性 7 4 3
激素受体状态 0.66 0.42 阳性 68 36 32
阴性 28 14 14 未知d 17
阳性 66 39 27
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