title: Oncogene profile of papillary thyroid carcinoma.
abstract: BACKGROUND
  Our purpose was to study the expression of multiple oncogenes in papillary thyroid cancer for possible interactions and prognostic significance.
  
  
  METHODS
  Twenty papillary thyroid carcinomas were studied for expression/mutation of 3 oncogenes: ras, ret/PTC, and erbB-2/neu. H, N, and K ras codons were examined by polymerase chain reaction (PCR), single-stranded conformation polymorphism, and sequencing. The thyroid oncogene ret/PTC was identified by reverse transcription (RT)-PCR. Gene amplification of erbB-2/neu was analyzed by differential PCR. The transmembrane domain of erbB-2/neu was sequenced for activating mutations. Quantitation of erbB-2/neu mRNA was evaluated by competitive RT-PCR, and protein expression was determined by immunohistochemistry.
  
  
  RESULTS
  Among 20 tumors, 3 had insular/anaplastic dedifferentiation, 13 were intrathyroidal, and 7 were metastatic to cervical lymph nodes (6) or lung (1). An H-ras 13 mutation was found in 1 metastatic tumor and an N-ras 61 mutation in 1 intrathyroidal tumor. ret/PTC was identified in 3 intrathyroidal and 5 metastatic tumors. No erbB-2/neu DNA amplification or mutations were identified, although 4 tumors had elevated erbB-2/neu mRNA levels. Three of 20 patients had abnormalities detected in multiple oncogenes; 2 had elevated erbB-2/neu mRNA and ret/PTC rearrangements, and 1 of these had pulmonary metastasis. An intrathyroidal papillary cancer had an N61 ras mutation and a ret/PTC gene rearrangement.
  
  
  CONCLUSIONS
  ret/PTC rearrangements are present in 40% of papillary thyroid carcinomas and may play a role in metastatic behavior. In contrast, ras mutations are rare (10%). erbB-2/neu gene amplification and activating mutations are not detected, although elevated mRNA levels were found in 20% of papillary carcinomas. The lack of correlation among the 3 oncogenes in 17 of 20 (85%) papillary thyroid carcinomas suggests that they were not cumulative factors in the pathogenesis of these tumors.
authors.affiliation: Department of Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: S L
authors.initials: SL
authors.lastname: Sugg
authors.forename: S
authors.initials: S
authors.lastname: Ezzat
authors.forename: L
authors.initials: L
authors.lastname: Zheng
authors.forename: J L
authors.initials: JL
authors.lastname: Freeman
authors.forename: I B
authors.initials: IB
authors.lastname: Rosen
authors.forename: S L
authors.initials: SL
authors.lastname: Asa
mesh_terms: D000328:Adult; D000368:Aged; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008297:Male; D008875:Middle Aged; D009857:Oncogenes; D016133:Polymerase Chain Reaction / Q000379:methods; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery
chemical_list: D004273:DNA, Neoplasm; D012333:RNA, Messenger; D012334:RNA, Neoplasm