title: ¹⁸F-FDG uptake on PET is a predictive marker of thymidylate synthase expression in patients with thoracic neoplasms.
abstract: 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.
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Kaira
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Endo
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Kenmotsu
authors.forename: Tateaki
authors.initials: T
authors.lastname: Naito
authors.forename: Akira
authors.initials: A
authors.lastname: Ono
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Murakami
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Ohde
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakajima
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology; D000077192:Adenocarcinoma of Lung; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000201:enzymology; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000096:biosynthesis; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000201:enzymology; D008297:Male; D008654:Mesothelioma / Q000000981:diagnostic imaging / Q000201:enzymology; D000086002:Mesothelioma, Malignant; D055806:Microvessels / Q000502:physiology; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging / Q000201:enzymology; D009962:Orotate Phosphoribosyltransferase / Q000096:biosynthesis; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013899:Thoracic Neoplasms / Q000000981:diagnostic imaging / Q000201:enzymology*; D013940:Thymidylate Synthase / Q000096:biosynthesis*; D013953:Thymus Neoplasms / Q000000981:diagnostic imaging / Q000201:enzymology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D019275:Radiopharmaceuticals; D016159:Tumor Suppressor Protein p53; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019788:Fluorodeoxyglucose F18; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase