Telomerase activity and telomere length in thyroid neoplasia: biological and clinical implications

Despite several recent studies, the biological status and clinical relevanc e of telomerase expression in tumours derived from the thyroid follicular c ell remain controversial. This study has analysed a series of normal, benig n, and malignant thyroid samples using two novel approaches: the use of pur ified epithelial cell fractions to eliminate false-positives due to telomer ase-positive infiltrating lymphocytes; and the simultaneous measurement of telomere length to provide a clearer interpretation of telomere dynamics in thyroid neoplasia, The data obtained support the prediction that the epith elial component of non-neoplastic thyroid and of follicular adenomas is tel omerase-negative, any positive results being explicable by lymphocyte infil tration, In contrast, many malignant tumours, both follicular and papillary , were telomerase-positive, However, serial dilution of extracts indicated a wide spectrum of activity in these cancers, possibly related to variation in the proportion of telomerase-positive cells. Furthermore, an unexpected ly high proportion were telomerase-negative, a finding which was not explic able by technical problems such as TRAP (telomeric repeat amplification pro tocol) assay sensitivity, Many of these apparently telomerase-negative tumo urs had abnormally long telomeres, Correlation of telomerase and telomere l ength data suggests that thyroid cancers fall into three biological groups: telomerase-positive lesions, consistent with the conventional model of tel omere erosion followed by telomerase reactivation; telomerase-negative tumo urs, which maintain telomere length by a mechanism independent of telomeras e; and telomerase-negative tumours which are still undergoing telomere eros ion and may therefore be composed of mortal cancer cells. From a clinical s tandpoint, it is concluded that telomerase detection on unfractionated tiss ue, such as fine needle aspirates, is of no value as a marker of malignancy in follicular lesions, due to both low sensitivity and specificity, Copyri ght (C) 2001 John Wiley & Sons, Ltd.