title: Expression of wild-type ret, ret/PTC and ret/PTC variants in papillary thyroid carcinoma in Germany.
abstract: BACKGROUND
  Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. Although the clinical course is usually rather benign, a subset of tumors is more aggressive. The ret/PTC oncogene was found only in PTC, with varying frequencies of up to 30%. Recently, two new variants of ret/PTC could be identified in post-Chernobyl PTCs, which raised the possibility that the prevalence of ret/PTC in non-radiation-induced PTCs might be higher than previously described. Normal thyroid cells do not express wild-type ret, but there is evidence that ret activation from any cause, including wild-type ret, occurs in more than a half of papillary tumors.
  
  
  METHODS
  We used reverse transcription polymerase chain reaction and sequencing to examine wild-type ret and all five forms of ret/PTC known today in 99 PTCs from Hannover, Dusseldorf, Halle and Regensburg. Our method could also detect other variants within the known breakpoint regions. The presence of the ret tyrosine-kinase domain was examined by immunohistochemistry.
  
  
  RESULTS
  Seven PTC1-positive tumors and one PTC3-positive tumor (8%), but none with the new variants or other variants of PTC1, 2 or 3 could be detected. Of 43 tumors examined, 20 showed expression of wild-type ret mRNA and staining of ret protein located predominantly to the cell membrane.
  
  
  CONCLUSIONS
  Variants of ret/PTC do not substantially contribute to non-radiation-related ret/PTC-positive tumors, and the prevalence of ret/PTC in Germany is low in contrast to the high rate of wild-type ret expression. Thus, expression of wild-type ret should be examined for pathogenic, prognostic and possible therapeutic implications.
authors.affiliation: Abteilung Klinische Endokrinologie, Medizinische Hochschule Hannover, Germany. Mayr.Bernhard@MH-Hannover.de
authors.forename: B
authors.initials: B
authors.lastname: Mayr
authors.forename: E
authors.initials: E
authors.lastname: Pötter
authors.forename: P
authors.initials: P
authors.lastname: Goretzki
authors.forename: J
authors.initials: J
authors.lastname: Rüschoff
authors.forename: W
authors.initials: W
authors.lastname: Dietmaier
authors.forename: C
authors.initials: C
authors.lastname: Hoang-Vu
authors.forename: H
authors.initials: H
authors.lastname: Dralle
authors.forename: G
authors.initials: G
authors.lastname: Brabant
mesh_terms: D002291:Carcinoma, Papillary / Q000453:epidemiology / Q000235:genetics*; D014644:Genetic Variation; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007150:Immunohistochemistry; D011518:Proto-Oncogene Proteins / Q000032:analysis; D011519:Proto-Oncogenes; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000235:genetics*
chemical_list: D011518:Proto-Oncogene Proteins