TERT promoter mutations indicate poor outcomes in differentiated thyroid cancer | Endocrinology

TERT promoter mutations indicate poor outcomes in differentiated thyroid cancer | Endocrinology:

Melo M. J Clin Endocrinol Metab. 2014;doi:10.1210/jc.2013-3734.

Telomerase reverse-transcriptase promoter mutations could be a major indicator of tumor aggressiveness in differentiated thyroid carcinomas. In a retrospective observational study, they were associated with distant metastases, poor response to treatment and outcomes.

The study included 647 tumors and tumor-like lesions in 469 patients with follicular cell-derived thyroid carcinomas treated and followed in five university hospitals.

The telomerase reverse-transcriptase (TERT) promoter mutations were observed in 7.5% of papillary carcinomas (PTC), 17.1% of follicular carcinomas (FTC), 29% of poorly differentiated carcinomas (DTC) and 33.3% of anaplastic thyroid carcinomas, according to data.

“The detection of such mutations appears to be, per se, a promising prognostic indicator in DTC and PTC,” researchers wrote.

In the group with DTC, TERT-mutated tumors were associated with older age (P<.001) and larger tumors (P=.002). In addition, TERT promoter mutations were significantly associated with distant metastases (P<.001) and higher stage (P<.001), researchers wrote.

Patients with DTC and TERT promoter mutations tended to be exposed to more radioiodine treatments (P=.009) with a greater cumulative dose (P=.004), and administered more treatment modalities (P=.001), researchers wrote.

“The most important added value of the present study is that we found evidence showing that patients with TERT mutated tumors had decreased survival when compared with patients with tumors harboring wild-type TERT and, moreover, that this holds true for the whole DTC series, as well as for PTC and FTC independently,” researchers wrote.

At 7.8 years follow-up, researchers found that patients with TERT-mutated DTC were more likely to display persistent disease (P=.001); TERT promoter mutations were significantly associated with disease-specific mortality among patients with follicular cell-derived thyroid carcinomas (P<.001), DTC (P<.001), PTC (P=.001), and FTC (P<.001).

After adjustments for age at diagnosis and sex, researchers wrote that the HR was 10.35 (95% CI, 2.01-53.24) in DTC and 23.81 (95% CI, 1.36-415.76) in PTC.
“Our findings suggest a link between telomerase activity and metastatic capacity may exist,” researchers wrote.
Disclosure: The researchers report no relevant financial disclosures.