title: Telomerase activity and telomere length in thyroid neoplasia: biological and clinical implications.
abstract: Despite several recent studies, the biological status and clinical relevance of telomerase expression in tumours derived from the thyroid follicular cell remain controversial. This study has analysed a series of normal, benign, and malignant thyroid samples using two novel approaches: the use of purified epithelial cell fractions to eliminate false-positives due to telomerase-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 epithelial component of non-neoplastic thyroid and of follicular adenomas is telomerase-negative, any positive results being explicable by lymphocyte infiltration. 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 unexpectedly high proportion were telomerase-negative, a finding which was not explicable by technical problems such as TRAP (telomeric repeat amplification protocol) assay sensitivity. Many of these apparently telomerase-negative tumours had abnormally long telomeres. Correlation of telomerase and telomere length data suggests that thyroid cancers fall into three biological groups: telomerase-positive lesions, consistent with the conventional model of telomere erosion followed by telomerase reactivation; telomerase-negative tumours, which maintain telomere length by a mechanism independent of telomerase; and telomerase-negative tumours which are still undergoing telomere erosion and may therefore be composed of mortal cancer cells. From a clinical standpoint, it is concluded that telomerase detection on unfractionated tissue, such as fine needle aspirates, is of no value as a marker of malignancy in follicular lesions, due to both low sensitivity and specificity.
authors.affiliation: Department of Pathology, University of Wales College of Medicine, Cardiff CF14 4XN, UK.
authors.forename: P
authors.initials: P
authors.lastname: Matthews
authors.forename: C J
authors.initials: CJ
authors.lastname: Jones
authors.forename: J
authors.initials: J
authors.lastname: Skinner
authors.forename: M
authors.initials: M
authors.lastname: Haughton
authors.forename: C
authors.initials: C
authors.lastname: de Micco
authors.forename: D
authors.initials: D
authors.lastname: Wynford-Thomas
mesh_terms: D000236:Adenoma / Q000175:diagnosis; D000328:Adult; D001707:Biopsy, Needle; D002291:Carcinoma, Papillary / Q000175:diagnosis; D018265:Carcinoma, Papillary, Follicular / Q000175:diagnosis; D004796:Clinical Enzyme Tests; D020732:Cytogenetic Analysis; D005260:Female; D006044:Goiter, Nodular / Q000201:enzymology; D006111:Graves Disease / Q000201:enzymology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D019098:Telomerase / Q000032:analysis*; D016615:Telomere / Q000648:ultrastructure*; D013961:Thyroid Gland / Q000201:enzymology; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000648:ultrastructure
chemical_list: D019098:Telomerase