Prognostic value of the molecular detection of circulating tumor cells using a multimarker reverse transcription-PCR assay for cytokeratin 19, mammaglobin A, and HER2 in early breast cancer
Prognostic value of the molecular detection of circulating tumor cells using a multimarker reverse transcription-PCR assay for cytokeratin 19, mammaglobin A, and HER2 in early breast cancer
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DOI：
10.1158/1078-0432.ccr-07-4758
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发表时间：
2008-05-01
影响因子：
11.5
通讯作者：
Mavroudis, Dimitris
中科院分区：
文献类型：
--
作者：
Ignatiadis, Michail;Kallergi, Galatea;Mavroudis, Dimitris
目的：探讨使用三种标志物[细胞角蛋白19（CK19）、乳房珠蛋白A（MGB1）和HER2]对循环肿瘤细胞（CTC）进行分子检测对早期乳腺癌的预后价值。实验设计：使用实时（CK19）和巢式（MGB1和HER2）逆转录PCR检测外周血中的CK19mRNA+、MGB1mRNA+和HER2mRNA+细胞研究人员对 175 名在开始辅助化疗前患有 I 至 III 期乳腺癌的女性进行了研究。 CTC 的检测与临床结果相关。对10例患者进行免疫荧光染色实验，检测CTC中细胞角蛋白、MGB1和HER2的共表达情况。结果：175例患者中，CK19mRNA+、MGB1mRNA+和HER2mRNA+细胞分别检出41.1%、8%和28.6%。患者具有以下分子特征之一：CK19mRNA+/MGB1m RNA+/HER2m RNA+ (n = 8)、CK19mRNA+/MGB1mRNA+/HER2mRNA- (n = 1)、CK19mRNA+/MGB1mRNA-/HER2m RNA+ (n = 42)、CK19mRNA+/MGB1mRNA-/HER2mRNA- (n = 21)、 CK19mRNA-/MGB1m RNA+/HER2m RNA- (n = 5) 和 CK19mRNA-/MGB1mRNA-/HER2mRNA- (n = 98)。双免疫荧光实验证实了以下 CTC 表型：CK+/MGB1+、CK+/MGB1-、CK-/MGB1+、CK+/HER2+、CK+/HER2-、MGB1+/HER2- 和 MGB1+/HER2+。在单变量分析中，CK19mRNA+、MGB1mRNA+和HER2mRNA+细胞的检测与较短的无病生存期相关（DFS；分别为P<0.001、P=0.001和P<0.001），而CK19mRNA+和MGB1mRNA+细胞的检测与较差的总生存期相关（分别为P=0.044和0.034）。在多变量分析中，雌激素受体阴性肿瘤以及CK19mRNA+和MGB1mRNA+细胞的检测与较差的DFS独立相关。结论：辅助化疗前外周血CK19mRNA+和MGB1mRNA+细胞的检测预测早期乳腺癌女性的DFS较差。
Purpose: To investigate the prognostic value of the molecular detection of circulating tumor cells (CTCs) using three markers [cytokeratin 19 (CK19), mammaglobin A (MGB1), and HER2] in early breast cancer.Experimental Design: CK19mRNA+, MGBlmRNA+, and HER2mRNA+ cells were detected using real-time (CK19) and nested (MGB1 and HER2) reverse transcription-PCR in the peripheral blood of 175 women with stage I to III breast cancer before the initiation of adjuvant chemotherapy. The detection of CTCs was correlated with clinical outcome. In 10 patients, immunofluorescence staining experiments were done to investigate the coexpression of cytokeratin, MGB1 and HER2 in CTCs.Results: CK19mRNA+, MGBlmRNA+, and HER2mRNA+ cells were detected in 41.1%, 8%, and 28.6% of the 175 patients, respectively. Patients had one of the following molecular profiles: CK19mRNA+/MGB1m RNA+/HER2m RNA+ (n = 8), CK19mRNA+/MGB1mRNA+/HER2mRNA- (n = 1), CK19mRNA+/MGB1mRNA-/HER2m RNA+ (n = 42), CK19mRNA+/MGB1mRNA-/HER2mRNA- (n = 21), CK19mRNA-/MGB1m RNA+/HER2m RNA- (n = 5), and CK19mRNA-/MGB1mRNA-/HER2mRNA- (n = 98). Double-immunofluorescence experiments confirmed the following CTC phenotypes: CK+/MGB1+, CK+/MGB1-, CK-/MGB1+, CK+/ HER2+, CK+/HER2-, MGB1+/HER2-, and MGB1+/HER2+. In univariate analysis, the detection of CK19mRNA+, MGB1mRNA+, and HER2mRNA+ cells was associated with shorter disease-free survival (DFS; P < 0.001, P = 0.001, and P < 0.001, respectively), whereas the detection of CK19mRNA+ and MGBlmRNA+ cells was associated with worse overall survival (P = 0.044 and 0.034, respectively). In multivariate analysis, estrogen receptor - negative tumors and the detection of CK19mRNA+ and MGB1mRNA+ cells were independently associated with worse DFS.Conclusion: The detection of peripheral blood CK19mRNA+ and MGB1mRNA+ cells before adjuvant chemotherapy predicts poor DFS in women with early breast cancer.