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实时定量PCR检测乳腺癌患者外周血中CK19和CEA的mRNA表达

[mRNA expression of CK19 and CEA in peripheral blood of patients with breast cancer detected by real-time quantitative PCR].

作者信息

Zheng Hong-yu, Chen Qiang, Ye Yun-bin, Huang Wei-wei

机构信息

Department of Breast Disease, Fujian Provincial Tumor Hospital, Fuzhou 350014, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2008 Aug 19;88(32):2267-70.

PMID:19087676
Abstract

OBJECTIVE

To explore the clinical significance of detection of cytokeratin 19 (CK19) mRNA and carcinoembryonic antigen (CEA) mRNA expression in the diagnosis of micrometastasis in the peripheral blood of patients with breast cancer, and the relationship with other clinicopathological characteristics.

METHODS

Peripheral blood samples were collected from 28 normal female healthy volunteers, 20 patients with benign breast disease, and 108 patients with breast cancer (88 had undergone operation and 20 with metastasis). Real-time quantitative PCR was used to detect the mRNA expression of CK19 and CEA in the peripheral blood.

RESULTS

mRNA expression was negative in the blood samples from the 28 normal volunteers for both CK19 and CEA. None of the 20 patients with benign breast disease was positive for CEA mRNA, but one was positive for CK19 mRNA (5%). Of the 108 patients with breast cancer, 26 (24.1%) were positive for CK19 mRNA, 23 (21.3%) were positive for CEA mRNA, and 15 (13.9%) were positive for both CK19 mRNA and CEA mRNA. The positive rates of CK19 mRNA and/or CEA mRNA of the metastatic breast cancer patients were higher than those of the operable breast cancer patients. Statistically significant differences in tumor size, clinical stage, and expression levels of k(i)67, variant exon 6 containing isoforms of CD44 (CD44v6), and vascular endothelial growth factor (VEGF) were found between the operable breast cancer patients with micrometastasis in peripheral blood and the patients without micrometastasis (all P < 0.05). And there was no statistically significant difference between the two groups in age, tumor location, pathological histological type, nodal metastasis, and expression levels of estrogen receptor (ER), pregnant receptor (PR), CerbB2, and matrix metalloproteinase-9 (MMP9) (all P > 0.05). Multivariate analysis showed that tumor size, clinical stage, expressions of ki67, CD44v6, and VEGF were associated with micrometastasis in peripheral blood.

CONCLUSION

The combined detection of CK19 and CEA mRNA raises the detection rate of micrometastasis in the peripheral blood of breast cancer patients. Tumor size, clinical stage, expressions of ki67, CD44v6, and VEGF are effective predictors of micrometastasis in the peripheral blood of breast cancer patients.

摘要

目的

探讨检测细胞角蛋白19(CK19)mRNA和癌胚抗原(CEA)mRNA表达在乳腺癌患者外周血微转移诊断中的临床意义,以及与其他临床病理特征的关系。

方法

收集28名正常女性健康志愿者、20例乳腺良性疾病患者及108例乳腺癌患者(88例行手术治疗,20例有转移)的外周血样本。采用实时定量PCR检测外周血中CK19和CEA的mRNA表达。

结果

28名正常志愿者血样中CK19和CEA的mRNA表达均为阴性。20例乳腺良性疾病患者中CEA mRNA均为阴性,但1例CK19 mRNA为阳性(5%)。108例乳腺癌患者中,26例(24.1%)CK19 mRNA为阳性,23例(21.3%)CEA mRNA为阳性,15例(13.9%)CK19 mRNA和CEA mRNA均为阳性。转移性乳腺癌患者CK19 mRNA和/或CEA mRNA阳性率高于可手术乳腺癌患者。外周血有微转移的可手术乳腺癌患者与无微转移患者在肿瘤大小、临床分期、增殖细胞核抗原(Ki67)、含6号外显子的CD44变异体(CD44v6)及血管内皮生长因子(VEGF)表达水平上存在统计学差异(均P<0.05)。两组在年龄、肿瘤部位、病理组织学类型、淋巴结转移及雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(CerbB2)和基质金属蛋白酶-9(MMP9)表达水平上无统计学差异(均P>0.05)。多因素分析显示,肿瘤大小、临床分期、Ki67、CD44v6及VEGF表达与外周血微转移有关。

结论

联合检测CK19和CEA mRNA可提高乳腺癌患者外周血微转移的检出率。肿瘤大小、临床分期、Ki67、CD44v6及VEGF表达是乳腺癌患者外周血微转移的有效预测指标。

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