title: Expression of thymidylate synthase, orotate phosphoribosyltransferase and dihydropyrimidine dehydrogenase in thymic epithelial tumors.
abstract: BACKGROUND
  It remains unclear whether thymidylate synthase (TS), orotate phosphoribosyltransferase (OPRT) and dihydropyrimidine dehydrogenase (DPD) expressions are associated with the pathogenesis of thymic epithelial tumors. Therefore, we investigated the expression of TS, OPRT and DPD in thymic epithelial tumors.
  
  
  METHODS
  Fifty-six patients with thymic epithelial tumors were included in this study. Tumors sections were stained by immunohistochemistry for TS, OPRT, DPD, microvessel density (MVD) determined by CD34, and p53. We also conducted in vitro study of TS, OPRT and DPD expression using thymic carcinoma, thymic tumor and thymic fibroblast cell lines.
  
  
  RESULTS
  TS, OPRT and DPD were expressed in 61%, 48% and 41%, respectively. High grade malignancy is significantly associated with higher expression of TS, OPRT and DPD in thymic epithelial tumors. These biomarkers were closely associated with p53 and MVD, and the overexpression of TS and DPD was a prognostic marker for predicting poor outcome in univariate analysis. Our in vitro study showed that marked overexpression of TS and OPRT was observed in thymic carcinoma cells, but not in thymic tumor cells, or thymic fibroblast cells.
  
  
  CONCLUSIONS
  The expression of TS, OPRT and DPD was closely related to the grade of malignancy in thymic epithelial tumors. A positive expression of TS, DPD and OPRT might be an important factor in predicting the effectiveness of 5-FU based chemotherapy in this disease.
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan. kkaira1970@yahoo.co.jp
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Kaira
authors.forename: Masakuni
authors.initials: M
authors.lastname: Serizawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Koh
authors.forename: Satoru
authors.initials: S
authors.lastname: Miura
authors.forename: Rieko
authors.initials: R
authors.lastname: Kaira
authors.forename: Masato
authors.initials: M
authors.lastname: Abe
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Ohde
authors.forename: Takehiro
authors.initials: T
authors.lastname: Okumura
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Murakami
authors.forename: Asuka
authors.initials: A
authors.lastname: Tsuya
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Tateaki
authors.initials: T
authors.lastname: Naito
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: D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000378:metabolism; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D055806:Microvessels / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D060787:Neoplasm Grading; D009389:Neovascularization, Pathologic; D009962:Orotate Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D013940:Thymidylate Synthase / Q000235:genetics / Q000378:metabolism*; D013953:Thymus Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D016159:Tumor Suppressor Protein p53; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase