Mourouzis Iordanis, Tzovaras Alexandros, Armonis Basil, Ardavanis Alexandros, Skondra Maria, Misitzis John, Pectasides Demetrios, Pantos Constantinos
Department of Pharmacology, University of Athens, 75 Mikras Asias Avenue, Goudi, 11527 Athens, Greece.
Second Department of Internal Medicine, Hippokration Hospital, School of Medicine, University of Athens, 11527 Athens, Greece.
Int J Endocrinol. 2015;2015:765406. doi: 10.1155/2015/765406. Epub 2015 Jan 28.
Objective. This study investigated whether thyroid hormone (TH) levels are correlated to cell proliferation (Ki67), in euthyroid breast cancer patients. Design and Methods. 86 newly diagnosed breast cancer patients with estrogen receptor (ER) positive tumors, who referred for surgery, were included in the study. Results. FT3, FT4, and TSH were within normal range. No correlation was seen between Ki67 and FT3 (r = -0.17, P = 0.15), FT4 (r = -0.13, P = 0.25), or TSH (r = -0.10, P = 0.39) in all patients studied. However, subgroup analysis showed that, in HER2(+) patients, a negative correlation existed between FT3 levels and Ki67 (r = -0.60 and P = 0.004) but not between Ki67 and FT4 (r = 0.04 and P = 0.85) or TSH (r = -0.23 and P = 0.30). In HER2(-) patients, there was no significant correlation between Ki67 and FT3 (r = -0.06, P = 0.67), FT4 (r = -0.15, P = 0.26), or TSH (r = -0.09, P = 0.49). Phospho-p44/total p44 ERK levels were found to be increased by 2-fold in HER2(+) versus HER2(-) tumors. No difference was detected in phospho-p42/total p42 ERK levels. Conclusions. TH profile is not altered in patients with newly diagnosed breast cancer. However, FT3 levels, even within normal range, are negatively correlated with cell proliferation in HER2(+) breast cancer tumors. This response may be due to the interaction between ERK and TH signaling.
目的。本研究调查了甲状腺激素（TH）水平与甲状腺功能正常的乳腺癌患者的细胞增殖（Ki67）是否相关。设计与方法。86例新诊断为雌激素受体（ER）阳性肿瘤且前来接受手术的乳腺癌患者纳入本研究。结果。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）均在正常范围内。在所有研究患者中，未发现Ki67与FT3（r = -0.17，P = 0.15）、FT4（r = -0.13，P = 0.25）或TSH（r = -0.10，P = 0.39）之间存在相关性。然而，亚组分析显示，在人表皮生长因子受体2（HER2）阳性患者中，FT3水平与Ki67之间存在负相关（r = -0.60，P = 0.004），但Ki67与FT4（r = 0.04，P = 0.85）或TSH（r = -0.23，P = 0.30）之间无相关性。在HER2阴性患者中，Ki67与FT3（r = -0.06，P = 0.67）、FT4（r = -0.15，P = 0.26）或TSH（r = -0.09，P = 0.49）之间均无显著相关性。发现HER2阳性肿瘤中磷酸化p44/总p44细胞外信号调节激酶（ERK）水平比HER2阴性肿瘤升高了2倍。未检测到磷酸化p42/总p42 ERK水平存在差异。结论。新诊断的乳腺癌患者甲状腺激素谱未改变。然而，即使在正常范围内，FT3水平与HER2阳性乳腺癌肿瘤中的细胞增殖呈负相关。这种反应可能是由于ERK与甲状腺激素信号之间的相互作用。
