C-Myc protein expression indicates unfavorable clinical outcome in surgically resected small cell lung cancer
(2024) In World Journal of Surgical Oncology 22(1).- Abstract
Background: By being highly involved in the tumor evolution and disease progression of small cell lung cancer (SCLC), Myc family members (C-Myc, L-Myc, and N-Myc) might represent promising targetable molecules. Our aim was to investigate the expression pattern and prognostic relevance of these oncogenic proteins in an international cohort of surgically resected SCLC tumors. Methods: Clinicopathological data and surgically resected tissue specimens from 104 SCLC patients were collected from two collaborating European institutes. Tissue sections were stained by immunohistochemistry (IHC) for all three Myc family members and the recently introduced SCLC molecular subtype-markers (ASCL1, NEUROD1, POU2F3, and YAP1). Results: IHC analysis... (More)
Background: By being highly involved in the tumor evolution and disease progression of small cell lung cancer (SCLC), Myc family members (C-Myc, L-Myc, and N-Myc) might represent promising targetable molecules. Our aim was to investigate the expression pattern and prognostic relevance of these oncogenic proteins in an international cohort of surgically resected SCLC tumors. Methods: Clinicopathological data and surgically resected tissue specimens from 104 SCLC patients were collected from two collaborating European institutes. Tissue sections were stained by immunohistochemistry (IHC) for all three Myc family members and the recently introduced SCLC molecular subtype-markers (ASCL1, NEUROD1, POU2F3, and YAP1). Results: IHC analysis showed C-Myc, L-Myc, and N-Myc positivity in 48%, 63%, and 9% of the specimens, respectively. N-Myc positivity significantly correlated with the POU2F3-defined molecular subtype (r = 0.6913, p = 0.0056). SCLC patients with C-Myc positive tumors exhibited significantly worse overall survival (OS) (20 vs. 44 months compared to those with C-Myc negative tumors, p = 0.0176). Ultimately, in a multivariate risk model adjusted for clinicopathological and treatment confounders, positive C-Myc expression was confirmed as an independent prognosticator of impaired OS (HR 1.811, CI 95% 1.054–3.113, p = 0.032). Conclusions: Our study provides insights into the clinical aspects of Myc family members in surgically resected SCLC tumors. Notably, besides showing that positivity of Myc family members varies across the patients, we also reveal that C-Myc protein expression independently correlates with worse survival outcomes. Further studies are warranted to investigate the role of Myc family members as potential prognostic and predictive markers in this hard-to-treat disease.
(Less)
- author
- organization
- publishing date
- 2024-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Immunohistochemistry, Molecular subtypes, Myc family, Small cell lung cancer
- in
- World Journal of Surgical Oncology
- volume
- 22
- issue
- 1
- article number
- 57
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:38369463
- scopus:85185451395
- ISSN
- 1477-7819
- DOI
- 10.1186/s12957-024-03315-7
- language
- English
- LU publication?
- yes
- id
- ed4926e4-3f41-4708-9ac2-7fe0287dceaf
- date added to LUP
- 2024-03-13 14:26:14
- date last changed
- 2024-04-24 10:12:09
@article{ed4926e4-3f41-4708-9ac2-7fe0287dceaf,
abstract = {{<p>Background: By being highly involved in the tumor evolution and disease progression of small cell lung cancer (SCLC), Myc family members (C-Myc, L-Myc, and N-Myc) might represent promising targetable molecules. Our aim was to investigate the expression pattern and prognostic relevance of these oncogenic proteins in an international cohort of surgically resected SCLC tumors. Methods: Clinicopathological data and surgically resected tissue specimens from 104 SCLC patients were collected from two collaborating European institutes. Tissue sections were stained by immunohistochemistry (IHC) for all three Myc family members and the recently introduced SCLC molecular subtype-markers (ASCL1, NEUROD1, POU2F3, and YAP1). Results: IHC analysis showed C-Myc, L-Myc, and N-Myc positivity in 48%, 63%, and 9% of the specimens, respectively. N-Myc positivity significantly correlated with the POU2F3-defined molecular subtype (r = 0.6913, p = 0.0056). SCLC patients with C-Myc positive tumors exhibited significantly worse overall survival (OS) (20 vs. 44 months compared to those with C-Myc negative tumors, p = 0.0176). Ultimately, in a multivariate risk model adjusted for clinicopathological and treatment confounders, positive C-Myc expression was confirmed as an independent prognosticator of impaired OS (HR 1.811, CI 95% 1.054–3.113, p = 0.032). Conclusions: Our study provides insights into the clinical aspects of Myc family members in surgically resected SCLC tumors. Notably, besides showing that positivity of Myc family members varies across the patients, we also reveal that C-Myc protein expression independently correlates with worse survival outcomes. Further studies are warranted to investigate the role of Myc family members as potential prognostic and predictive markers in this hard-to-treat disease.</p>}},
author = {{Lang, Christian and Megyesfalvi, Zsolt and Lantos, Andras and Oberndorfer, Felicitas and Hoda, Mir Alireza and Solta, Anna and Ferencz, Bence and Fillinger, Janos and Solyom-Tisza, Anna and Querner, Alessandro Saeed and Egger, Felix and Boettiger, Kristiina and Klikovits, Thomas and Timelthaler, Gerald and Renyi-Vamos, Ferenc and Aigner, Clemens and Hoetzenecker, Konrad and Laszlo, Viktoria and Schelch, Karin and Dome, Balazs}},
issn = {{1477-7819}},
keywords = {{Immunohistochemistry; Molecular subtypes; Myc family; Small cell lung cancer}},
language = {{eng}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{World Journal of Surgical Oncology}},
title = {{C-Myc protein expression indicates unfavorable clinical outcome in surgically resected small cell lung cancer}},
url = {{http://dx.doi.org/10.1186/s12957-024-03315-7}},
doi = {{10.1186/s12957-024-03315-7}},
volume = {{22}},
year = {{2024}},
}