Department of Molecular Oncology and Immunology, Federal State Budgetary Scientific Institution "Tomsk Cancer Research Institute", 5 Kooperativny Street, Tomsk, Russian Federation, 634050.
Department of Translational Cellular and Molecular Biomedicine, National Research Tomsk State University, Tomsk, Russian Federation, 634050.
Clin Exp Med. 2017 Aug;17(3):383-393. doi: 10.1007/s10238-016-0428-z. Epub 2016 May 25.
Identification of additional biomarkers associated with ER genomic and nongenomic pathways could be very useful to distinguish patients who will benefit from tamoxifen treatment. The aim of this study was to analyze the prognostic significance of the distribution pattern of ERα expression, ESR1 gene single-nucleotide polymorphisms and expression levels of growth factor receptors in Russian hormone receptor-positive breast cancer patients treated with adjuvant tamoxifen. Formalin-fixed paraffin-embedded tumor tissue samples from 97 patients were examined for the distribution pattern of ERα expression, as well as for EGFR and TGF-βR1 expression by immunohistochemistry. Genotypes for ESR1 +30T>C (rs2077647) and ESR1 2014G>A (rs2228480) were analyzed using a TaqMan assay. Progression-free survival (PFS) was used as an endpoint for the survival analyses. We found that patients with the heterogeneous distribution of ERα expression had poor prognosis on tamoxifen treatment (P = 0.021). We identified a high EGFR expression in patients who developed distant metastasis or recurrence during tamoxifen treatment (a tamoxifen-resistant group-TR) in contrast to the distant metastasis-free patients (a tamoxifen-sensitive group-TS) (80.0 vs. 41.9 %, respectively, P = 0.009). Carriers of the ESR12014A mutant allele were more prevalent among the TR patients compared to the TS patients (26.3 vs. 8.0 %, respectively, P = 0.009). EGFR expression and the distribution pattern of ERα expression were associated with the response to tamoxifen by both univariate and multivariate logistic regression analyses. The presence of these markers either alone or in combination was correlated with the worse PFS for all patients. Analysis of the distribution pattern of ERα expression and the EGFR status in tumor tissue may be valuable for patient selection for tamoxifen adjuvant therapy.
鉴定与 ER 基因组和非基因组通路相关的其他生物标志物，可能对于区分将从他莫昔芬治疗中获益的患者非常有用。本研究的目的是分析 ERα 表达、ESR1 基因单核苷酸多态性和生长因子受体表达水平的分布模式在接受辅助他莫昔芬治疗的俄罗斯激素受体阳性乳腺癌患者中的预后意义。通过免疫组织化学法检测 97 例患者福尔马林固定石蜡包埋肿瘤组织样本中 ERα 表达、EGFR 和 TGF-βR1 的表达情况。使用 TaqMan 检测分析 ESR1 +30T>C（rs2077647）和 ESR1 2014G>A（rs2228480）的基因型。使用无进展生存期（PFS）作为生存分析的终点。我们发现，ERα 表达异质性分布的患者在他莫昔芬治疗中预后不良（P=0.021）。我们发现，与无远处转移的患者（他莫昔芬敏感组，TS）相比，在接受他莫昔芬治疗时发生远处转移或复发的患者（他莫昔芬耐药组，TR）中 EGFR 表达较高（分别为 80.0%和 41.9%，P=0.009）。与 TS 患者相比，TR 患者中 ESR12014A 突变等位基因的携带者更为常见（分别为 26.3%和 8.0%，P=0.009）。单变量和多变量逻辑回归分析显示，EGFR 表达和 ERα 表达的分布模式与他莫昔芬的反应相关。这些标志物单独或联合存在与所有患者的 PFS 更差相关。分析肿瘤组织中 ERα 表达和 EGFR 状态的分布模式可能对他莫昔芬辅助治疗的患者选择有价值。
