title: Thymidylate synthase expression is closely associated with outcome in patients with pulmonary adenocarcinoma.
abstract: The aim of this study is to elucidate the prognostic significance of thymidylate synthase (TS), orotate phosphoribosyltransferase (OPRT) and dihydropyrimidine dehydrogenase (DPD) in completely resected non-small cell lung cancer (NSCLC). One hundred and sixty patients with NSCLC were included in this study. Tumor sections were stained by immunohistochemistry for TS, OPRT, DPD, glucose transporter 1 (Glut1), hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), microvessel density (MVD) determinated by CD34, epidermal growth factor receptor (EGFR), phosph-Akt, phosph-mammalian target of rapamycin (mTOR) and p53. TS, OPRT and DPD were positively expressed in 46, 71 and 54%, respectively. The expression of TS and OPRT was significantly higher in patients with non-adenocarcinoma (non-AC) (n = 53) than adenocarcinoma (AC) (n = 107), and DPD expression was higher in adenocarcinoma as compared with non-adenocarcinoma. A positive TS expression was an independent prognostic factor for predicting a poor outcome in patients with AC, but not in those with non-AC. In AC patients, TS expression was significantly associated with advanced stage, lymph node metastases, vascular invasion, Glut1, HIF-1α, angiogenesis, EGFR signaling pathway and p53. In patients with non-AC, TS expression was not closely correlated with outcome and these biomarkers. A positive TS expression was a powerful prognostic factor to predict a poor outcome in completely resected AC patients.
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan. kkaira1970@yahoo.co.jp
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Kaira
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Ohde
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Takehiro
authors.initials: T
authors.lastname: Okumura
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Murakami
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kondo
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakajima
authors.forename: Masahiro
authors.initials: M
authors.lastname: Endo
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000032:analysis / Q000096:biosynthesis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009962:Orotate Phosphoribosyltransferase / Q000032:analysis / Q000096:biosynthesis; D011379:Prognosis; D016016:Proportional Hazards Models; D013940:Thymidylate Synthase / Q000032:analysis / Q000096:biosynthesis*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase