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RET Expression in Papillary Thyroid Cancer from Patients Irradiated in Childhood for Benign Conditions

Section of Endocrinology (B.J.C., A.B.S., E.S.-F.), University of Illinois at Chicago, Chicago, Illinois 60612; Istituto Nazionale dei Tumori di Napoli (G.C.), Fondazione Senatore Pascale, 80131 Naples, Italy; Michael Reese Hospital (B.J.C., A.B.S., L.F., T.G., E.S.-F., G.J.), Chicago, Illinois 60616; and the Centro di Endocrinologia ed Oncologia Sperimentale del CNR (A.F., M.S., F.P.), Dipartimento di Biologia e Patologia Cellulare e Moleculare, Università di Napoli "Federico II," 80131 Naples, Italy

Address all correspondence and requests for reprints to: Barbara J. Collins, Ph.D., University of Illinois at Chicago, Section of Endocrinology and Metabolism (MC 640), 1819 West Polk Street, Chicago, Illinois 60612. E-mail: . bcollins{at}uic.edu

Abstract

Both external and internal exposure to radiation have been linked to the development of papillary thyroid cancer. Rearrangement of the gene for RET tyrosine kinase and subsequent expression of this protein has also been found to occur in many papillary thyroid cancers, and with increased frequency in radiation-related cancers following the Chernobyl accident. However, little has been reported on the frequency of RET rearrangements in cancers after exposure to external radiation. We here report on RET protein immunoreactivity in paraffin-embedded thyroid samples from 30 patients with papillary thyroid cancer who received radiation treatment during childhood for benign conditions at Michael Reese Hospital in Chicago, and in 34 patients identified from the tumor registry as having papillary thyroid cancer with no history of therapeutic radiation. The subjects were characterized by sex, age at surgery, and the following attributes of tumor pathology: size, number of lobes involved, number of foci, lymph node metastases, and soft tissue invasion. Representative tissue samples were reacted with an antibody against the RET tyrosine kinase domain whose expression has been shown to correlate highly with RET/PTC rearrangements. A greater percentage of cancers positive for RET immunoreactivity was found in the radiation-exposed group (86.7% vs. 52.9%, P = 0.006). Although the mean age at surgery of the exposed group was lower than the control group, there was no correlation of positive RET immunoreactivity with the age at surgery. No characteristics of the tumors were associated with positive RET immunoreactivity. In summary, the greater incidence of RET-immunopositives in the irradiated group indicates that the expression of RET immunoreactivity is strongly associated with radiation exposure, but the prognostic significance of this is not yet clear.

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