Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
Oncol Rep. 2014 Jan;31(1):209-15. doi: 10.3892/or.2013.2816. Epub 2013 Oct 24.
The aim of this study was to investigate the relationship between the expression levels of thymidylate synthase (TS) and 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (¹⁸F-FDG) uptake on positron emission tomography (PET) in various thoracic neoplasms. In total, 392 patients [non-small cell lung cancer (NSCLC) (n=140), malignant pleural mesothelioma (MPM) (n=21), pulmonary metastatic tumors (PMT) (n=148), thymic epithelial tumors (n=49) and pulmonary neuroendocrine (NE) tumor (n=34)] who underwent ¹⁸F-FDG PET before treatment were included in this study. Tumor sections were stained using immunohistochemistry for determination of TS, orotate phosphoribosyltransferase (OPRT), dihydropyrimidine dehydrogenase (DPD), vascular endothelial growth factor (VEGF), microvessel density (MVD), CD34 and p53. The expression of TS in thoracic neoplasms had a positivity of 58% (230/392), and the positive rates of TS expression in NSCLC, PMT, thymic epithelial tumor, NE tumor and MPM samples were 56, 57, 57, 85 and 47%, respectively. The positivity of TS expression was significantly higher in NE tumors compared to that in other thoracic tumors. A statistically significant correlation between TS expression and ¹⁸F-FDG uptake was observed in thoracic neoplasms, in particular primary lung adenocarcinomas, high-grade NE tumors, thymomas and MPMs. Moreover, TS expression was closely associated with angiogenesis, DPD, OPRT and p53. Our results indicated that SUV(max) by ¹⁸F-FDG uptake may be an alternative biomarker for predicting TS expression in patients with primary lung adenocarcinoma, high-grade NE tumor, thymoma and MPM.
本研究旨在探讨胸内肿瘤中胸苷酸合成酶(TS)表达水平与正电子发射断层扫描(PET)上 2-[¹⁸F]-氟-2-脱氧-D-葡萄糖(¹⁸F-FDG)摄取之间的关系。本研究共纳入 392 例患者(非小细胞肺癌(NSCLC)(n=140)、恶性胸膜间皮瘤(MPM)(n=21)、肺转移瘤(PMT)(n=148)、胸内上皮性肿瘤(n=49)和肺神经内分泌(NE)肿瘤(n=34)),这些患者在治疗前均接受了¹⁸F-FDG PET 检查。使用免疫组织化学法对肿瘤切片进行 TS、乳清酸磷酸核糖基转移酶(OPRT)、二氢嘧啶脱氢酶(DPD)、血管内皮生长因子(VEGF)、微血管密度(MVD)、CD34 和 p53 的检测。胸内肿瘤中 TS 的阳性表达率为 58%(230/392),NSCLC、PMT、胸内上皮性肿瘤、NE 肿瘤和 MPM 样本中 TS 表达阳性率分别为 56%、57%、57%、85%和 47%。与其他胸内肿瘤相比,NE 肿瘤中 TS 的阳性表达率显著更高。在胸内肿瘤中,尤其是原发性肺腺癌、高级别 NE 肿瘤、胸腺瘤和 MPM 中,TS 表达与¹⁸F-FDG 摄取之间存在显著的相关性。此外,TS 表达与血管生成、DPD、OPRT 和 p53 密切相关。我们的研究结果表明,¹⁸F-FDG 摄取的 SUV(max) 可能是预测原发性肺腺癌、高级别 NE 肿瘤、胸腺瘤和 MPM 患者 TS 表达的替代生物标志物。