Expression of wild-type ret, ret/PTC and ret/PTC variants in papillary thyroid carcinoma in Germany.
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.
Mayr
B
B
Abteilung Klinische Endokrinologie, Medizinische Hochschule Hannover, Germany. Mayr.Bernhard@MH-Hannover.de
Pötter
E
E
Goretzki
P
P
Rüschoff
J
J
Dietmaier
W
W
Hoang-Vu
C
C
Dralle
H
H
Brabant
G
G
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*
D011518:Proto-Oncogene Proteins