title: Human telomerase reverse transcriptase (hTERT) gene expression in thyroid neoplasms.
abstract: Ten percent of fine-needle aspirations (FNAs) of the thyroid are deemed "indeterminate" or "suspicious" for malignancy by the cytopathologist, but most of these lesions are benign. Therefore, additional markers of malignancy may prove to be a useful adjunct. The catalytic component of telomerase, human telomerase reverse transcriptase (hTERT), has been found to be reactivated in immortalized cell lines. Reverse transcription-PCR of the hTERT gene revealed expression in 15 (79%) of 19 malignant thyroid neoplasms, including 6 of 6 follicular carcinomas and 9 of 13 papillary carcinomas. In contrast, hTERT gene expression was detected in only 5 (28%) of 18 benign thyroid nodules, including 2 of 7 follicular adenomas and 3 of 11 hyperplastic nodules. All five benign thyroids exhibiting hTERT gene expression had lymphocytic thyroiditis. No normal thyroids exhibited hTERT gene expression. Telomerase enzyme activity was examined in all 37 nodules and was found to correlate with hTERT gene expression in 35 (95%) nodules. The two cases in which telomerase activity and hTERT expression results were discrepant were in two papillary carcinomas that were telomerase activity negative and hTERT positive. Finally, we have demonstrated that hTERT gene expression can be measured in in vivo FNA samples. These results suggest that hTERT expression may be more accurate than telomerase activity in distinguishing benign from malignant and may be measured in FNA samples from suspicious thyroid lesions.
authors.affiliation: Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. motosaji@welchlink.welch.jhu.edu
authors.forename: M
authors.initials: M
authors.lastname: Saji
authors.forename: S
authors.initials: S
authors.lastname: Xydas
authors.forename: W H
authors.initials: WH
authors.lastname: Westra
authors.forename: C K
authors.initials: CK
authors.lastname: Liang
authors.forename: D P
authors.initials: DP
authors.lastname: Clark
authors.forename: R
authors.initials: R
authors.lastname: Udelsman
authors.forename: C B
authors.initials: CB
authors.lastname: Umbricht
authors.forename: S
authors.initials: S
authors.lastname: Sukumar
authors.forename: M A
authors.initials: MA
authors.lastname: Zeiger
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D004268:DNA-Binding Proteins; D015870:Gene Expression; D006801:Humans; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D012313:RNA; D012680:Sensitivity and Specificity; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics*; D016606:Thyroid Nodule / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase