Cell cycle regulators show diagnostic and prognostic utility for differentiated thyroid cancer

Cell cycle regulators show diagnostic and prognostic utility for differentiated thyroid cancer
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DOI:
10.1245/s10434-007-9572-8
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发表时间:
2007-12-01
影响因子:
3.7
通讯作者:
Wiseman, Sam M.
Wiseman, Sam M.
中科院分区:
医学2区
文献类型:
--
作者:
Melck, Adrienne;Masoudi, Hamid;Wiseman, Sam M.

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背景:分化型甲状腺癌(DTC)通常具有良好的预后,但一些患者出现局部复发和/或远处转移并最终死于疾病。缺乏准确预测肿瘤行为的分子标记。本研究的目的是确定细胞周期调节因子在预测 DTC 恶性组织学和肿瘤行为中的作用。方法:对由 100 个良性和 105 个恶性甲状腺病变以及 24 个淋巴结样本组成的组织微阵列进行 p16、p21、p27、p53、p57、p63、细胞周期蛋白 D1、细胞周期蛋白 E 和细胞周期蛋白染色。 mdm2。采用统计分析比较良性和 DTC 病变中标志物的表达,并将其表达与临床病理特征相关联。结果:与良性甲状腺病变相比,p16、p21、细胞周期蛋白 D1 和细胞周期蛋白 E 在 DTC 中的表达显着增加 (P < .001) (54.7% vs. 5%、71.7% vs. 38%、87.1%) 分别为 45.7% 和 72.3% 与 37.4%)。其余标志物在良性病变和 DTC 之间的表达没有显着差异。 p16 表达与甲状腺外肿瘤扩展 (P = .02) 和淋巴结中癌症的存在 (P = .03) 显着相关。有淋巴结受累和无淋巴结受累的患者中,分别有 73% 和 45% 的癌症 p16 呈阳性(P = .01)。结论:DTC 和甲状腺良性病变之间 p16、p21、cyclin D1 和 cyclin E 的表达存在统计学差异,并且 p16 表达与临床病理相关。 预测 DTC 不良结果的变量。这些结果表明,甲状腺肿瘤细胞周期紊乱的评估可能成为 DTC 诊断和预后的有用工具。
Background: Differentiated thyroid cancer (DTC) generally has a favorable outcome, but some patients develop local recurrence and/or distant metastases and ultimately die of their disease. Molecular markers that accurately predict tumor behavior are lacking. This study's aim was to ascertain the role of cell cycle regulators in predicting malignant histology and tumor behavior in DTC.Methods: Tissue microarrays consisting of 100 benign and 105 malignant thyroid lesions, plus 24 lymph node samples, were stained for p16, p21, p27, p53, p57, p63, cyclin D1, cyclin E, and mdm2. Statistical analysis was used to compare the expression of the markers in benign versus DTC lesions and correlate their expression with clinicopathologic characteristics.Results: p16, p21, cyclin D1, and cyclin E showed significantly (P < .001) increased expression in DTCs compared with benign thyroid lesions (54.7% vs. 5%, 71.7% vs. 38%, 87.1% vs. 45.7%, and 72.3% vs. 37.4%, respectively). There was no significant difference in expression between benign lesions and DTC for the remaining markers. p16 expression correlated significantly with extrathyroidal tumor extension (P = .02) and the presence of cancer in lymph nodes (P = .03). A total of 73% vs. 45% of the cancers of patients with and without lymph node involvement, respectively, stained positive for p16 (P = .01).Cocnlusions: There is a statistically significant difference in the expression of p16, p21, cyclin D1, and cyclin E between DTCs and benign thyroid lesions, and p16 expression correlates with clinicopathologic variables predicting poor outcomes for DTC. These results suggest that evaluation of cell cycle derangement in thyroid tumors may serve as a useful tool for both DTC diagnosis and prognosis.