title: ret/PTC-1, -2, and -3 oncogene rearrangements in human thyroid carcinomas: implications for metastatic potential?
abstract: The ret/PTC oncogene is unique to papillary thyroid cancer. Three forms of this oncogene, formed by translocation of three different genes to the tyrosine kinase domain of the ret protooncogene, result in constitutive kinase activation. Correlation with clinical outcome is controversial; ret/PTC-1 has been suggested to predict aggressive behavior. There is no morphological description of ret/PTC-positive tumors. We analyzed 60 thyroid carcinomas for ret/PTC expression to determine correlation with clinical history, disease stage, or tumor morphology. Ribonucleic acid extracted from frozen tissue was reverse transcribed; PCR was performed to amplify ret/PTC-1, 2, and -3. The TPC-1 cell line was the positive control for ret/PTC-1. All tumors were characterized morphologically. Clinical data were collected. The 57 papillary and 3 follicular carcinomas were resected from 44 female patients and 15 males. The average age at diagnosis was 46.2 yr (range. 24-83 yr). Three patients had a history of neck irradiation. At diagnosis, 11 patients had extrathyroidal tumor extension, 20 had lymph node metastases, and 1 had lung metastasis. Thirteen patients had tall cell papillary carcinomas; 3 tumors had focal insular or anaplastic dedifferentiation. The average follow-up was 13.4 months, during which 4 patients had recurrent disease. No deaths occurred. One papillary carcinoma (1.7%) was positive for ret/PTC-1, none was positive for ret/PTC-2, and 2(3.4%) were positive for ret/PTC-3. Although all 3 patients who had tumors containing ret/PTC rearrangements were under the age of 45 yr (range, 26-44 yr) and had small tumors (< 1.2 cm), 2 of these 3 patients presented with lymph node metastases, and the third had lymphatic invasion. ret/PTC oncogene expression did not correlate with radiation history. In summary, ret/PTC oncogene rearrangements were found in 3 of 60 (5%) thyroid carcinomas and were not present in tumors with aggressive morphological features. However, we found ret/PTC rearrangements in young patients (< 45 yr of age) with small thyroid carcinomas showing a predisposition for lymphatic involvement, suggesting a possible role in the development of this subgroup of tumors.
authors.affiliation: Department of Surgery, University of Toronto, Ontario, Canada.
authors.forename: S L
authors.initials: SL
authors.lastname: Sugg
authors.forename: L
authors.initials: L
authors.lastname: Zheng
authors.forename: I B
authors.initials: IB
authors.lastname: Rosen
authors.forename: J L
authors.initials: JL
authors.lastname: Freeman
authors.forename: S
authors.initials: S
authors.lastname: Ezzat
authors.forename: S L
authors.initials: SL
authors.lastname: Asa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D029721:Drosophila Proteins; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion; D009857:Oncogenes / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D012194:RNA-Directed DNA Polymerase; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D017421:Sequence Analysis; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C093573:ret-PTC fusion oncoproteins, human; D012194:RNA-Directed DNA Polymerase