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

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.

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.

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).

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.