TERT expression and clinical outcome in pulmonary carcinoids Journal Article
| Authors: | Werr, L.; Bartenhagen, C.; Rosswog, C.; Cartolano, M.; Voegele, C.; Sexton-Oates, A.; Di Genova, A.; Ernst, A.; Kahlert, Y.; Hemstedt, N.; Höppner, S.; Mansuet Lupo, A.; Pelosi, G.; Brcic, L.; Papotti, M.; George, J.; Bosco, G.; Quaas, A.; Tang, L. H.; Robzyk, K.; Kadota, K.; Roh, M. S.; Fanaroff, R. E.; Falcon, C. J.; Büttner, R.; Lantuejoul, S.; Rekhtman, N.; Rudin, C. M.; Travis, W. D.; Alcala, N.; Fernandez-Cuesta, L.; Foll, M.; Peifer, M.; Thomas, R. K.; Fischer, M.; on behalf of the Lung NEN Network |
| Article Title: | TERT expression and clinical outcome in pulmonary carcinoids |
| Abstract: | PURPOSEThe 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.METHODSTERT 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.RESULTSSimilar 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).CONCLUSIONOur 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. © 2024 American Society of Clinical Oncology. |
| Keywords: | immunohistochemistry; adolescent; adult; cancer survival; controlled study; human tissue; protein expression; aged; middle aged; young adult; major clinical study; overall survival; genetics; histopathology; mortality; cancer patient; cancer staging; diagnostic accuracy; phenotype; metabolism; cell infiltration; lung neoplasms; tumor differentiation; cohort analysis; pathology; enzyme activity; telomerase; tumor marker; risk factor; risk assessment; lung tumor; neuroblastoma; telomerase reverse transcriptase; carcinoid; kaplan meier method; carcinoid tumor; immunocompetent cell; kaplan-meier estimate; clinical outcome; typical carcinoid; tert protein, human; cancer prognosis; humans; prognosis; human; male; female; article; rna sequencing; biomarkers, tumor; protein expression level; pulmonary carcinoid |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 43 |
| Issue: | 2 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2025-01-10 |
| Start Page: | 214 |
| End Page: | 225 |
| Language: | English |
| DOI: | 10.1200/jco.23.02708 |
| PUBMED: | 39348606 |
| PROVIDER: | scopus |
| PMCID: | PMC11709002 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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