As reported in the Journal of Clinical Oncology by Werr et al, high telomerase reverse transcriptase (TERT) expression has been found to be associated with poorer survival in patients with pulmonary carcinoids.
As stated by the investigators: “The clinical course of pulmonary carcinoids ranges from indolent to fatal disease, suggesting that specific molecular alterations drive progression toward the fully malignant state. A similar spectrum of clinical phenotypes occurs in pediatric neuroblastoma, in which activation of … TERT is decisive in determining the course of disease.”
Study Details
The multi-institutional study involved determination of TERT expression by RNA sequencing in 88 patients in a test cohort and 105 patients in a validation cohort. A TERT expression cutoff was determined in the test cohort on the basis of distribution of TERT expression, and associations with overall survival were analyzed.
Key Findings
As stated by the investigators: “Similar to neuroblastoma, TERT expression exhibited a bimodal distribution in pulmonary carcinoids, separating tumors into TERT-high and TERT-low subgroups.
In the test cohort, the 5-year overall survival was 56% among 26 patients with TERT-high tumors (n = 26) vs 100% among those with TERT-low tumors (n = 62; P < .001). In the validation cohort, the 5-year overall survival was 91% among patients with TERT-low tumors (n = 55) vs 79% among those with TERT-high tumors (n = 50; P < .001).
Consistent with these findings, telomerase activity measured by a telomere repeat amplification assay showed that telomerase activity was predominantly absent in TERT-low tumors and readily detectable in TERT-high tumors.
In a multivariate analysis, high TERT expression was an independent marker for poorer overall survival vs low TERT expression (hazard ratio [HR] = 5.24, 95% confidence interval [CI] = 1.94–14.15, P = .001). Histology was also an independent marker (HR for atypical carcinoid vs typical carcinoid = 2.64, 95% CI = 1.05–2.64, P = .039).
The investigators concluded: “Our data demonstrate that high TERT expression defines clinically aggressive pulmonary carcinoids with fatal outcome, similar to neuroblastoma, indicating that activation of TERT may be a defining feature of lethal cancers.”
Matthias Fischer, MD, of the Center for Molecular Medicine Cologne, University of Cologne, Germany, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by the German Research Foundation and others. For full disclosures of the study authors, visit ascopubs.org.
