TERT Expression and Clinical Outcome in Pulmonary Carcinoids.
Abstract
PURPOSE 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 telomerase reverse transcriptase ( TERT ) is decisive in determining the course of disease. We therefore investigated whether TERT expression defines the clinical fate of patients with pulmonary carcinoid. METHODS TERT expression was examined by RNA sequencing in a test cohort and a validation cohort of pulmonary carcinoids (n = 88 and n = 105, respectively). A natural TERT expression cutoff was determined in the test cohort on the basis of the distribution of TERT expression, and its prognostic value was assessed by Kaplan-Meier survival estimates and multivariable analyses. Telomerase activity was validated by telomere repeat amplification protocol assay. RESULTS Similar to neuroblastoma, TERT expression exhibited a bimodal distribution in pulmonary carcinoids, separating tumors into TERT -high and TERT- low subgroups. A natural TERT cutoff discriminated unfavorable from favorable clinical courses with high accuracy both in the test cohort (5-year overall survival [OS], 0.547 ± 0.132 v 1.0; P < .001) and the validation cohort (5-year OS, 0.788 ± 0.063 v 0.913 ± 0.048; P < .001). In line with these findings, telomerase activity was largely absent in TERT -low tumors, whereas it was readily detectable in TERT- high carcinoids. In multivariable analysis considering TERT expression, histology (typical v atypical carcinoid), and stage (≤IIA v ≥IIB), high TERT expression was an independent prognostic marker for poor survival, with a hazard ratio of 5.243 (95% CI, 1.943 to 14.148; P = .001). CONCLUSION 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.
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BibTeX
@article{werr2026tert,
title = {{TERT Expression and Clinical Outcome in Pulmonary Carcinoids.}},
author = {Lisa Werr and Christoph Bartenhagen and Carolina Rosswog and Maria Cartolano and Catherine Voegele and Alexandra Sexton-Oates and Alex Di Genova and Angela Ernst and Yvonne Kahlert and Nadine Hemstedt and Stefanie Höppner and Audrey Mansuet Lupo and Giuseppe Pelosi and Luka Brcic and Mauro Papotti and Julie George and Graziella Bosco and Alexander Quaas and Laura H Tang and Kenneth Robzyk and Kyuichi Kadota and Mee Sook Roh and Rachel E Fanaroff and Christina J Falcon and Reinhard Büttner and Sylvie Lantuejoul and Natasha Rekhtman and Charles M Rudin and William D Travis and Nicolas Alcala and Lynnette Fernandez-Cuesta and Matthieu Foll and Martin Peifer and Roman K Thomas and Matthias Fischer},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
year = {2026},
month = oct,
doi = {10.1200/jco.23.02708},
url = {https://hal.science/hal-05842838v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - TERT Expression and Clinical Outcome in Pulmonary Carcinoids.
AU - Lisa Werr
AU - Christoph Bartenhagen
AU - Carolina Rosswog
AU - Maria Cartolano
AU - Catherine Voegele
AU - Alexandra Sexton-Oates
AU - Alex Di Genova
AU - Angela Ernst
AU - Yvonne Kahlert
AU - Nadine Hemstedt
AU - Stefanie Höppner
AU - Audrey Mansuet Lupo
AU - Giuseppe Pelosi
AU - Luka Brcic
AU - Mauro Papotti
AU - Julie George
AU - Graziella Bosco
AU - Alexander Quaas
AU - Laura H Tang
AU - Kenneth Robzyk
AU - Kyuichi Kadota
AU - Mee Sook Roh
AU - Rachel E Fanaroff
AU - Christina J Falcon
AU - Reinhard Büttner
AU - Sylvie Lantuejoul
AU - Natasha Rekhtman
AU - Charles M Rudin
AU - William D Travis
AU - Nicolas Alcala
AU - Lynnette Fernandez-Cuesta
AU - Matthieu Foll
AU - Martin Peifer
AU - Roman K Thomas
AU - Matthias Fischer
PY - 2026
DA - 2026/10/28
JO - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
DO - 10.1200/jco.23.02708
UR - https://hal.science/hal-05842838v1
AB - PURPOSE 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 telomerase reverse transcriptase ( TERT ) is decisive in determining the course of disease. We therefore investigated whether TERT expression defines the clinical fate of patients with pulmonary carcinoid. METHODS TERT expression was examined by RNA sequencing in a test cohort and a validation cohort of pulmonary carcinoids (n = 88 and n = 105, respectively). A natural TERT expression cutoff was determined in the test cohort on the basis of the distribution of TERT expression, and its prognostic value was assessed by Kaplan-Meier survival estimates and multivariable analyses. Telomerase activity was validated by telomere repeat amplification protocol assay. RESULTS Similar to neuroblastoma, TERT expression exhibited a bimodal distribution in pulmonary carcinoids, separating tumors into TERT -high and TERT- low subgroups. A natural TERT cutoff discriminated unfavorable from favorable clinical courses with high accuracy both in the test cohort (5-year overall survival [OS], 0.547 ± 0.132 v 1.0; P < .001) and the validation cohort (5-year OS, 0.788 ± 0.063 v 0.913 ± 0.048; P < .001). In line with these findings, telomerase activity was largely absent in TERT -low tumors, whereas it was readily detectable in TERT- high carcinoids. In multivariable analysis considering TERT expression, histology (typical v atypical carcinoid), and stage (≤IIA v ≥IIB), high TERT expression was an independent prognostic marker for poor survival, with a hazard ratio of 5.243 (95% CI, 1.943 to 14.148; P = .001). CONCLUSION 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.
ER -