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Involvement of the PAX8/Peroxisome Proliferator-Activated Receptor Rearrangement in Follicular Thyroid Tumors

Endocrine Tumor Unit (T.D., S.R.T., T.Fo., W.O.L., T.Fr., C.L.), Department of Molecular Medicine, Karolinska Hospital CMM L8:01, Stockholm, SE-171 76 Sweden; Centre for Metabolism and Endocrinology (T.D., T.Fo., T.Fr., J.Z.), Department of Surgery, Karolinska Institutet at Huddinge University Hospital, Stockholm, SE-141 86 Sweden; Department of Surgery (T.Fo., G.W., T.Fr.), Karolinska Hospital P9:03, Stockholm, SE-171 76 Sweden; and Department of Oncology and Pathology (A.H.), Karolinska Hospital P1:02, Stockholm, SE-171 76 Sweden

Address all correspondence and requests for reprints to: Trisha Dwight, Ph.D., or Catharina Larsson, Department of Molecular Medicine Endocrine Tumor Unit, CMM L8:01 Karolinska Hospital, SE-171 76, Stockholm, Sweden. E-mail: Trisha.Dwight{at}cmm.ki.se or Catharina.Larsson{at}cmm.ki.se.

Recently, a translocation t(2; 3)(q13;p25), involving the fusion of PAX8 and peroxisome proliferator-activated receptor (PPAR) was suggested to arise only in follicular thyroid carcinomas. In this study, a group of 87 thyroid tumors were analyzed to determine the involvement of the PAX8/PPAR fusion gene in these tumors, and also to determine whether this rearrangement can be used as a diagnostic marker for the differentiation between follicular thyroid carcinoma and adenoma. The PAX8/PPAR rearrangement was detected by RT-PCR, fluorescence in situ hybridization, and/or Western analysis in 10 of 34 (29%) follicular thyroid carcinomas and in one of 20 (5%) atypical follicular thyroid adenomas, but not in any of the 20 follicular thyroid adenomas or 13 anaplastic thyroid carcinomas studied. In addition, seven of the 87 thyroid tumors exhibited involvement of PPAR alone. Our findings suggest that PAX8/PPAR occurs frequently in follicular thyroid carcinomas, and the presence of this rearrangement is likely to prove highly suggestive of a malignant tumor. Lack of the PAX8/PPAR rearrangement in the anaplastic thyroid carcinoma group suggests that the tumorigenic pathway in these tumors is likely to be independent of this fusion. Furthermore, the results suggest that other rearrangements, involving PPAR and other unidentified genes, may be involved in follicular thyroid tumorigenesis.

This work was supported by the Swedish Cancer Foundation, the Gustav V Jubilee Foundation, the Milton Foundation, the Cancer Society in Stockholm, the Emil and Vera Cornell Foundation, the Wenner-Gren Foundation, and the Torsten and Ragnar Söderberg Foundations.

Abbreviations: AFTA, Atypical FTA; ATC, anaplastic thyroid carcinomas; FISH, fluorescence in situ hybridization; FTA, follicular thyroid adenoma; FTC, follicular thyroid carcinoma; PPAR, peroxisome proliferator-activated receptor .

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