FAS/FAS-ligand Apoptotic Complex Deregulation in Laryngeal Squamous Cell Carcinomas

FAS/FAS-ligand (FAS-L) complex is implicated in critical cell functions including programmed cell death (apoptosis) and immune response regulation. FAS and FAS-ligand are members of the tumor necrosis factor (TNF) superfamily. Their activation triggers the caspase-mediated apoptotic cataract. The aim of this study was to investigate the role of their altered co-expression in a series of laryngeal squamous cell carcinomas (LSCCs).

A set of fifty (n=50) LSCC archival tissue sections was analyzed by performing a combination of immunohistochemistry (IHC) and digital image analysis (DIA) assays for determining the expression of FAS/FAS-L expression.

A broad spectrum of FAS/FAS-L expression values were detected across the examined cases. A significant negative correlation was found between FAS and FAS-L overall expression (p<0.001) indicating that higher FAS expression is associated with lower FAS-L expression. Furthermore, the expression of FAS was highest in stage IV carcinomas, whereas FAS-L was higher in stage III tumors, however, the differences were not statistically significant (p=0.260, p=0.101, respectively). Concerning the size of the examined malignancies (max diameter), the FAS/FAS-L expression showed a statistically significant difference in both (p=0.001, p=0.011, respectively). According to their expression status, larger tumors tend to demonstrate higher levels of FAS protein, whereas smaller tumors exhibit overexpression of FAS-L.

FAS/FAS-L apoptotic system deregulation is a relatively frequent event in LSCCs. Dysregulation of the system - due to altered FAS and FAS-L co-expression levels - negatively affects the normal apoptotic mechanism. Additionally, this abnormality is clearly observed in aggressive phenotypes (advanced stage, enlarged tumor volume).