Human telomerase reverse transcriptase gene expression and the surgical management of suspicious thyroid tumors.
OBJECTIVE
Patients with a preoperative cytologic diagnosis of a suspicious thyroid nodule present a therapeutic dilemma because surgery differs for benign and malignant lesions. To address this issue, several molecular markers, including human telomerase reverse transcriptase (TERT), have been tested as markers of thyroid cancer. Because most studies select cases falling into well-defined categories to test new markers, they may overestimate their discriminatory power when applied to samples that are difficult to classify. Fine-needle aspirates (FNAs) of the thyroid with indeterminate cytology are an example of such cases.


METHODS
We examined whether assessing TERT mRNA by reverse transcription-PCR could have improved the surgical management in a cohort of 100 patients undergoing thyroidectomy for indeterminate FNA results.


RESULTS
Ninety percent of 48 cancers were TERT positive, as were 35% of 52 benign lesions. When 10 cases with concomitant lymphocytic thyroiditis were excluded, the overall sensitivity of TERT was 91% (95% confidence interval, 80-98%) and specificity was 79% (64-90%). No clinical or tumor variable contributed to the predictive ability of TERT except for tumor size, which added only marginally. Basing the surgical approach on the TERT assay alone would have reduced lobectomies performed for malignant disease from 11 to 4 cases and reduced total thyroidectomies for benign lesions from to 15 to 9, an overall 50% reduction in suboptimal treatment.


CONCLUSIONS
The overall performance of preoperative differential diagnosis for thyroid tumors with indeterminate FNA results can be substantially improved by the inclusion of molecular markers such as TERT.
Umbricht
Christopher B
CB
Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Conrad
George T
GT
Clark
Douglas P
DP
Westra
William H
WH
Smith
Dañelle C
DC
Zahurak
Marianna
M
Saji
Motoyasu
M
Smallridge
Robert C
RC
Goodman
Steven
S
Zeiger
Martha A
MA
D018263:Adenocarcinoma, Follicular / Q000175:diagnosis / Q000201:enzymology / Q000601:surgery; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D044963:Biopsy, Fine-Needle; D002291:Carcinoma, Papillary / Q000175:diagnosis / Q000201:enzymology / Q000601:surgery; D002648:Child; D015331:Cohort Studies; D004268:DNA-Binding Proteins; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D019098:Telomerase / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000201:enzymology / Q000601:surgery*; D016606:Thyroid Nodule / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D013965:Thyroidectomy; D013966:Thyroiditis / Q000201:enzymology / Q000473:pathology / Q000601:surgery
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C509186:TERT protein, human; D019098:Telomerase