Enwere Emeka K, Dean Michelle L, Li Haocheng, D'Silva Adrijana, Bebb D Gwyn
Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Translational Laboratories, Tom Baker Cancer Center, Calgary, Alberta, Canada.
Transl Lung Cancer Res. 2020 Jun;9(3):496-506. doi: 10.21037/tlcr.2020.03.34.
Estrogen receptor beta (ERβ) is the predominant estrogen receptor (ER) expressed in non-small cell lung cancer (NSCLC); however, due to methodological disparities among prior studies, the prognostic value of ERβ expression in NSCLC remains unclear. Our objective was to apply improved detection and analysis techniques to assess the prognostic value of ERβ expression in NSCLC.
A tissue microarray (TMA) was used which contained resected and biopsy specimens from 299 patients diagnosed at a single center with stages I-IV NSCLC. Sections of this array were stained using high-sensitivity fluorescence immunohistochemistry, with the well-validated PPG5/10 monoclonal antibody. Digital images of the stained array slides were analyzed using software-based image analysis, which reported ERβ expression as a continuous variable in different subcellular domains.
There were no differences in ERβ expression between male and female patients. High expression of ERβ was not a prognostic factor, but was significantly associated with stage IV disease in both tumor and stroma (P<0.001). In multivariable analysis, a high nuclear/cytoplasmic (N/C) ratio of ERβ expression was significantly associated with shorter overall survival, based on expression in the tumor [hazard ratio (HR): 1.65; 95% confidence interval (CI): 1.25-2.19; P<0.001] and in the stroma (HR: 1.57; 95% CI: 1.16-2.12; P=0.003).
These results suggest that subcellular localization of ERβ, but not absolute expression, is a prognostic factor in NSCLC.
雌激素受体β（ERβ）是在非小细胞肺癌（NSCLC）中表达的主要雌激素受体（ER）；然而，由于先前研究方法上的差异，ERβ表达在NSCLC中的预后价值仍不清楚。我们的目的是应用改进的检测和分析技术来评估ERβ表达在NSCLC中的预后价值。
使用组织微阵列（TMA），其包含来自在单一中心诊断为I-IV期NSCLC的299例患者的切除标本和活检标本。使用高灵敏度荧光免疫组织化学对该阵列的切片进行染色，采用经过充分验证的PPG5/10单克隆抗体。使用基于软件的图像分析对染色的阵列玻片的数字图像进行分析，该分析将ERβ表达报告为不同亚细胞结构域中的连续变量。
男性和女性患者之间的ERβ表达没有差异。ERβ的高表达不是一个预后因素，但在肿瘤和基质中均与IV期疾病显著相关（P<0.001）。在多变量分析中，基于肿瘤中的表达[风险比（HR）：1.65；95%置信区间（CI）：1.25-2.19；P<0.001]和基质中的表达（HR：1.57；95%CI：1.16-2.12；P=0.003），ERβ表达的高核/质（N/C）比与较短的总生存期显著相关。
这些结果表明，ERβ的亚细胞定位而非绝对表达量是NSCLC的一个预后因素。
