Saji M, Xydas S, Westra W H, Liang C K, Clark D P, Udelsman R, Umbricht C B, Sukumar S, Zeiger M A
Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Clin Cancer Res. 1999 Jun;5(6):1483-9.
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.
甲状腺细针穿刺抽吸活检（FNA）中有10%被细胞病理学家判定为对恶性肿瘤“不确定”或“可疑”，但这些病变大多为良性。因此，其他恶性肿瘤标志物可能会成为有用的辅助手段。端粒酶的催化成分，即人类端粒酶逆转录酶（hTERT），已在永生化细胞系中被发现重新激活。hTERT基因的逆转录聚合酶链反应显示，19例甲状腺恶性肿瘤中有15例（79%）表达，包括6例滤泡癌中的6例以及13例乳头状癌中的9例。相比之下，18例良性甲状腺结节中只有5例（28%）检测到hTERT基因表达，包括7例滤泡性腺瘤中的2例以及11例增生性结节中的3例。所有呈现hTERT基因表达的5例良性甲状腺均有淋巴细胞性甲状腺炎。正常甲状腺均未呈现hTERT基因表达。对所有37个结节检测了端粒酶活性，发现35个结节（95%）中端粒酶活性与hTERT基因表达相关。端粒酶活性和hTERT表达结果不一致的2例为2例乳头状癌，端粒酶活性阴性而hTERT阳性。最后，我们证明了hTERT基因表达可在体内FNA样本中检测。这些结果表明，hTERT表达在区分良性与恶性方面可能比端粒酶活性更准确，并且可在可疑甲状腺病变的FNA样本中检测。
