Impact of C-FOS/C-JUN Transcriptional Factors Co-Expression in Non-small Cell Lung Carcinoma.

Abstract

Background/aim: Significant transcription factors - including c-Fos (gene locus: 14q24.3) and c-Jun (gene locus: 1p32-p31) - regulate cell homeostasis preventing abnormal signal transduction to nucleus. Their over-activation seems to be associated with an aggressive phenotype in non-small cell lung carcinomas (NSCLCs). In the current study, our aim was to co-analyze c-FOS/c-JUN protein expression in a series of NSCLCs correlating them to the corresponding clinico-pathological features.

Materials and methods: A set of fifty (n=50) paraffin embedded NSCLC tissue sections were selected comprising of adenocarcinomas (n=25) and squamous cell carcinomas (n=25), respectively. Immunocytochemistry (IHC) for the c-FOS/c-JUN markers was implemented. Digital image analysis (DIA) was also performed for evaluating objectively the corresponding immunostaining intensity levels of the examined proteins.

Results: All the examined tissue samples expressed the markers in different protein levels. High staining intensity levels were detected in 34/50 (68%) and 24/50 (48%), respectively. C-FOS over expression was statistically significant correlated to stage (p=0.033), whereas C-JUN over expression was associated with NSCLC histotype (p=0.05) and with maximum tumor diameter (p=0.046).

Conclusion: C-FOS/C-JUN co- over activation is observed frequently in NSCLC, playing potentially a central role in the aggressiveness of the malignancy's phenotype (advanced stage, increased metastatic potential). Development and implementation of novel agents that target these transcription factors is a promising approach for applying targeted therapeutic strategies in NSCC patients based on specific genetic signatures and protein profiles.