Expression of apoptosis-inducing factor (AIF) in keratoacanthomas and squamous cell carcinomas of the skin

Abstract:  The complex biological trait ‘susceptibility to apoptosis’ is a nosological feature distinguishing squamous cell carcinomas (SCC) from keratoacanthomas (KA). The purpose of this study was to compare the expression of apoptosis-inducing factor (AIF), a major effector of the caspase-independent apoptosis pathway, in formalin-fixed SCC (N = 23) and KA (N = 29) resection specimens. SCC express statistically significant more AIF than KA both as proportion of AIF+ cells by immunohistochemistry (median: 54% vs 33%; P < 0.01) and as total AIF protein content by western blot quantification (six-fold increased; P < 0.01). However, the contribution of AIF to apoptosis, measured as fraction of apoptotic nuclei with overt DNA fragmentation by the TUNEL method that co-express AIF translocated to nucleus, is significantly less prevalent among SCC (median: 19% vs 48% in KA; P < 0.01). These findings indicate to a distinctive involvement of AIF in the progression of certain epithelial skin tumors that might be exploited as a promising treatment target.