Kuniyoshi Renata K, Gehrke Flávia de Sousa, Alves Beatriz C A, Vilas-Bôas Viviane, Coló Anna E, Sousa Naiara, Nunes João, Fonseca Fernando L A, Del Giglio Auro
Oncology and Hematology Department, ABC Medical School, Av. Príncipe de Gales, 821, CEP 09060-650, Santo André, SP, Brazil.
Fundação Pio XII-Hospital de Câncer de Barretos, R. Antenor Duarte Vilela, 1331, Barretos, SP, Brazil.
Tumour Biol. 2015 Sep;36(10):8075-83. doi: 10.1007/s13277-015-3529-5. Epub 2015 May 16.
The gene profile of primary tumors, as well as the identification of circulating tumor cells (CTCs), can provide important prognostic and predictive information. In this study, our objective was to perform tumor gene profiling (TGP) in combination with CTC characterization in women with nonmetastatic breast cancer. Biological samples (from peripheral blood and tumors) from 167 patients diagnosed with stage I, II, and III mammary carcinoma, who were also referred for adjuvant/neoadjuvant chemotherapy, were assessed for the following parameters: (a) the presence of CTCs identified by the expression of CK-19 and c-erbB-2 in the peripheral blood mononuclear cell (PBMC) fraction by quantitative reverse transcription PCR (RT-PCR) and (b) the TGP, which was determined by analyzing the expression of 21 genes in paraffin-embedded tissue samples by quantitative multiplex RT-PCR with the Plexor® system. We observed a statistically significant correlation between the progression-free interval (PFI) and the clinical stage (p = 0.000701), the TGP score (p = 0.006538), and the presence of hormone receptors in the tumor (p = 0.0432). We observed no correlation between the PFI and the presence or absence of CK-19 or HER2 expression in the PBMC fraction prior to the start of treatment or in the two following readouts. Multivariate analysis revealed that only the TGP score significantly correlated with the PFI (p = 0.029247). The TGP is an important prognostic variable for patients with locoregional breast cancer. The presence of CTCs adds no prognostic value to the information already provided by the TGP.
原发性肿瘤的基因图谱以及循环肿瘤细胞(CTC)的鉴定,可以提供重要的预后和预测信息。在本研究中,我们的目的是对非转移性乳腺癌女性患者进行肿瘤基因谱分析(TGP)并结合CTC特征分析。对167例诊断为I、II和III期乳腺癌且接受辅助/新辅助化疗的患者的生物样本(外周血和肿瘤样本)进行了以下参数评估:(a)通过定量逆转录聚合酶链反应(RT-PCR)检测外周血单个核细胞(PBMC)组分中CK-19和c-erbB-2表达来鉴定CTC的存在;(b)TGP,通过使用Plexor®系统的定量多重RT-PCR分析石蜡包埋组织样本中21个基因的表达来确定。我们观察到无进展生存期(PFI)与临床分期(p = 0.000701)、TGP评分(p = 0.006538)以及肿瘤中激素受体的存在(p = 0.0432)之间存在统计学显著相关性。我们未观察到PFI与治疗开始前或接下来两次检测中PBMC组分中CK-19或HER2表达的有无之间存在相关性。多变量分析显示,只有TGP评分与PFI显著相关(p = 0.029247)。TGP是局部区域乳腺癌患者的一个重要预后变量。CTC的存在并未为TGP已提供的信息增加预后价值。