Lacka Katarzyna, Maciejewski Adam, Tyburski Piotr, Manuszewska-Jopek Ewa, Majewski Przemysław, Więckowska Barbara
Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznan, Poland.
Student Scientific Society, Poznan University of Medical Sciences, 60-806 Poznan, Poland.
Int J Mol Sci. 2025 Jan 25;26(3):1035. doi: 10.3390/ijms26031035.
The p53 protein is a tumor-suppressing transcription factor that is critical in tumorigenesis. While mutations are rare in differentiated thyroid cancer (DTC), they are significantly more common in anaplastic thyroid cancer (ATC). This study presents original results and a meta-analysis reevaluating the prognostic value of mutations in thyroid cancer, including surrogate markers such as immunohistochemical p53 expression and serum p53-Abs levels. mutations were analyzed using SSSP and direct sequencing in a DTC group (15 patients), an ATC group (3 patients), and a control group (25 patients). The immunohistochemical p53 expression was assessed in tissue samples. A meta-analysis of 14 eligible studies identified through the PubMed, Scopus, Google Scholar, and Cochrane databases was conducted. Our results showed mutations in all ATC cases, 6.67% of DTC cases (1 out of 15), and none in the control group. Immunohistochemical p53 overexpression was observed in 4 out of 15 DTC (26.67%) and all ATC cases but absent in controls. A meta-analysis confirmed that mutations are significantly more frequent in ATC than controls (OR 8.95; 95% CI: 1.36-58.70; = 0.02) but not in DTC vs. controls (OR 1.87; 95% CI: 0.53-6.58; = 0.33). p53 overexpression was significantly higher in both DTC and ATC vs. controls (OR 7.99; 95% CI: 5.11-12.51; < 0.01 and OR 64.37; 95% CI: 27.28-151.89; < 0.01, respectively). The serum p53-Abs positivity was also elevated in patients with PTC vs. controls (OR 2.07; 95% CI: 1.24-3.47; < 0.01). mutations are frequent events in the pathogenesis of ATC. In DTC, further prospective studies are needed to determine the prognostic value of mutations and related surrogate markers (immunohistochemical p53 expression, p53-Abs positivity).
p53蛋白是一种肿瘤抑制转录因子，在肿瘤发生过程中至关重要。虽然p53突变在分化型甲状腺癌（DTC）中很少见，但在未分化型甲状腺癌（ATC）中则更为常见。本研究展示了原始结果并进行了一项荟萃分析，重新评估p53突变在甲状腺癌中的预后价值，包括免疫组化p53表达和血清p53抗体水平等替代标志物。在一个DTC组（15例患者）、一个ATC组（3例患者）和一个对照组（25例患者）中，使用单链特异性引物PCR（SSSP）和直接测序法分析p53突变。对组织样本进行免疫组化p53表达评估。通过PubMed、Scopus、谷歌学术和Cochrane数据库确定了14项符合条件的研究并进行荟萃分析。我们的结果显示，所有ATC病例均存在p53突变，DTC病例中有6.67%（15例中的1例）存在突变，而对照组中无一例突变。在15例DTC中有4例（26.67%）以及所有ATC病例中观察到免疫组化p53过表达，而对照组中未出现。荟萃分析证实，ATC中p53突变显著多于对照组（优势比8.95；95%置信区间：1.36 - 58.70；P = 0.02），但DTC与对照组相比则无显著差异（优势比1.87；95%置信区间：0.53 - 6.58；P = 0.33）。DTC和ATC中p53过表达均显著高于对照组（优势比分别为7.99；95%置信区间：5.11 - 12.51；P < 0.01和优势比64.37；95%置信区间：27.28 - 151.89；P < 0.01）。与对照组相比，甲状腺乳头状癌（PTC）患者血清p53抗体阳性率也升高（优势比2.07；95%置信区间：1.24 - 3.47；P < 0.01）。p53突变是ATC发病机制中的常见事件。在DTC中，需要进一步的前瞻性研究来确定p53突变及相关替代标志物（免疫组化p53表达、p53抗体阳性）的预后价值。
