Expression of wild-type ret, ret/PTC and ret/PTC variants in papillary thyroid carcinoma in Germany

Langenbecks Arch Surg. 1999 Feb;384(1):54-9. doi: 10.1007/s004230050174.

Abstract

Introduction: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Papillary / epidemiology
  • Carcinoma, Papillary / genetics*
  • Genetic Variation
  • Germany / epidemiology
  • Humans
  • Immunohistochemistry
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogenes*
  • Thyroid Neoplasms / epidemiology
  • Thyroid Neoplasms / genetics*

Substances

  • Proto-Oncogene Proteins