title: Messenger RNA and protein expression of thymidylate synthase and DNA repair genes in thymic tumors.
abstract: BACKGROUND
  Thymic epithelial tumors include several entities with different biologic behavior. Chemotherapy is indicated in advanced disease, but limited data exist on gene expression correlation with the response to chemotherapeutic agents.
  
  
  METHODS
  A series of 69 thymic neoplasms (7 A-, 6 AB-, 6 B1-, 10 B2-, 14 B3-thymomas, 22 carcinomas and 4 combined tumors) was collected to assess gene expression of thymidylate synthase (TS), excision repair cross complementing-1 (ERCC1), ribonucleotide reductase subunit 1 (RRM1), topoisomerase 2α (TOP2A) and mTOR.
  
  
  RESULTS
  A strong linear correlation between TS gene and protein expression was observed (P<0.0001, R=0.40). TS expression was significantly lower in pure A-thymomas and thymic carcinomas (P<0.0001) and progressively decreasing from B1-type to thymic carcinomas (B1>B2>B3>C; P<0.0001). RRM1 and TOP2A mRNA expression levels were significantly correlated with TS levels (both P=0.03) with a similar trend of expression among histotypes. RRM1 and TOP2A high levels were significantly correlated with high TS (P=0.03) and low tumor stages (I-II) (P<0.0001 and P<0.01, respectively). No relevant changes of ERCC1 and mTOR were detected.
  
  
  CONCLUSIONS
  Low TS and, to a minor extent, RRM1 and TOP2A expression were detected in aggressive thymic tumors. These findings should be prospectively considered in selecting the most appropriate chemotherapy.
authors.affiliation: Division of Pathology, Department of Clinical & Biological Sciences, University of Torino at St Luigi Hospital, Turin, Italy. valentina.monica@unito.it
authors.forename: Valentina
authors.initials: V
authors.lastname: Monica
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Familiari
authors.forename: Luigi
authors.initials: L
authors.lastname: Chiusa
authors.forename: Giulio
authors.initials: G
authors.lastname: Rossi
authors.forename: Domenico
authors.initials: D
authors.lastname: Novero
authors.forename: Simone
authors.initials: S
authors.lastname: Busso
authors.forename: Enrico
authors.initials: E
authors.lastname: Ruffini
authors.forename: Francesco
authors.initials: F
authors.lastname: Ardissone
authors.forename: Giorgio V
authors.initials: GV
authors.lastname: Scagliotti
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D004260:DNA Repair / Q000235:genetics*; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D000075223:Poly-ADP-Ribose Binding Proteins; D012333:RNA, Messenger / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D013940:Thymidylate Synthase / Q000235:genetics / Q000378:metabolism*; D013945:Thymoma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D013953:Thymus Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D055815:Young Adult; D020726:ral Guanine Nucleotide Exchange Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D012333:RNA, Messenger; C521670:Rgl3 protein, human; D020726:ral Guanine Nucleotide Exchange Factor; D013940:Thymidylate Synthase; D058570:TOR Serine-Threonine Kinases; C071447:ERCC1 protein, human; D004720:Endonucleases; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human