Oncogene profile of papillary thyroid carcinoma

Background. Our purpose was to study the expression of multiple oncogenes i n papillary thyroid cancer for possible interactions and prognostic signifi cance. Methods. Twenty papillary thyroid carcinomas were studied for expression/mu tation 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 conforma tion polymorphism and sequencing. The thyroid oncogene ret/PTC was identifi ed by reverse transcription (RT)-PCR Gene amplification of erbB-2/neu was a nalyzed by differential PCR. The transmembrane domain of erbB-2/neu was seq uenced for activating mutations. Quantitation of erbB-2/neu mRNA was evalua ted by competitive RT-PCR, and protein expression was determined by immunoh istochemistry. Results. Among 20 tumors, 3 had insular/anaplastic dedifferentiation, 13 we re intrathyroidal, and 7 were metastatic to cervical lymph nodes (6) or lun g (I). An W-ras 13 mutation was found in I metastatic tumor and an N-ras 61 mutation in I intrathyroidal tumor ret/PTC was identified in 3 intrathyroi dal and 5 metastatic tumors. No erbB-2/neu DNA amplification or mutations w ere identified, although 4 tumors had elevated erbB-2/neu mRNA levels. Thre e of 20 patients had abnormalities detected in multiple oncogenes; 2 had el evated erbB-2/neu mRNA and ret/PTC rearrangements, and I of these had pulmo nary 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 mut ations are rare (10%). erbB-2/neu gene amplification and activating mutatio ns are not detected although elevated mRNA levels were found in 20% of papi llary 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.