Department of Oncology, Hadassah and Hebrew University Medical Centre, Jerusalem, Israel
Department of Surgery and Breast Health Center, Kaplan Medical Centre, Rehovot, Israel.
Anticancer Res. 2020 Nov;40(11):6417-6428. doi: 10.21873/anticanres.14663.
BACKGROUND/AIM: Silencing mediator of retinoid and thyroid receptors (SMRT) is a nuclear corepressor in thyroid and estrogen hormones pathways. The aim was to evaluate SMRT expression in relation to thyroid hormone levels and prognostic markers in breast cancer (BC).
Serum and tumor tissues were obtained from 36 patients with benign breast disease (BBD) and 79 BC patients. SMRT expression was determined by immunohistochemistry. Free-triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were measured in serum.
Higher FT4, lower FT3/FT4 ratio and higher expression of SMRT were found in BC compared to BBD (for all p<0.001). In BC, increased SMRT expression was associated with lower FT3 (p=0.028), higher tumor grade (p=0.031), increased KI67 proliferation index (p=0.015), higher risk of recurrence (p=0.014) and shorter disease-free survival (p=0.006). In multivariate analysis, SMRT overexpression and below-median levels of TSH were independent prognostic factors in BC.
Elevated FT4 and decreased FT3/FT4 in BC patients suggest a role for thyroid hormones in malignant transformation. SMRT tumor overexpression is associated with lower FT3 levels, tumor proliferative activity and an aggressive clinical course.
背景/目的：视黄酸和甲状腺激素受体沉默调节因子（SMRT）是甲状腺激素和雌激素通路中的核核心抑制因子。本研究旨在评估 SMRT 表达与乳腺癌（BC）中甲状腺激素水平和预后标志物的关系。
收集 36 例良性乳腺疾病（BBD）患者和 79 例 BC 患者的血清和肿瘤组织。采用免疫组化法检测 SMRT 表达。检测血清中游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）和促甲状腺激素（TSH）的水平。
与 BBD 相比，BC 患者的 FT4 升高，FT3/FT4 比值降低，SMRT 表达升高（均为 p<0.001）。在 BC 中，SMRT 表达增加与 FT3 降低（p=0.028）、肿瘤分级升高（p=0.031）、Ki67 增殖指数升高（p=0.015）、复发风险增加（p=0.014）和无病生存期缩短（p=0.006）相关。多变量分析显示，SMRT 过表达和 TSH 水平低于中位数是 BC 的独立预后因素。
BC 患者中 FT4 升高和 FT3/FT4 降低提示甲状腺激素在恶性转化中发挥作用。SMRT 肿瘤过表达与 FT3 水平降低、肿瘤增殖活性和侵袭性临床病程相关。
