Autophagy related markers (Beclin-1 and ATG4B) are strongly expressed in Wilms' tumor and correlate with favorable histology

Abstract

Background. Wilms’ tumor treatment has achieved great success in the last decade. Nevertheless, some cases still fail to respond to the current multimodality therapy. These cases fall mainly in the unfavorable histology group with very few belonging to the favorable histology group. In recent years, autophagy manipulation whether inhibition or stimulation has been shown to affect cancer cell behavior and has emerged as a novel mechanism to improve cancer cell response to currently used therapeutic regimens. Objective. The current study aimed to investigate the expression of autophagy related markers (ATG4B and Beclin1) in WT, its association with the different clinicpathological parameters and its impact on patient survival. Methods. Twenty-one formalin fixed paraffin embedded (FFPE) WT specimens were immunohistochemically stained using autophagy related markers; Beclin-1 and ATG4B. All clinical, radiological and follow up data were retrieved from the patient records. Results. All specimens showed positive expression of both Beclin-1 and ATG4B. The staining score for Beclin1 varied between 50 and 300, and its expression was significantly associated with favorable histology (p=0.007). Similarly, ATG4B expression was significantly higher in favorable histology tumors compared to unfavorable histology (p=0.046). A statistically significant positive correlation between Beclin-1 and ATG4B expression was observed. The cumulative disease-free survival in patients with favorable histology was significantly higher compared to patients with unfavorable histology (p=0.0027). Conclusions. Beclin-1 and ATG4B expression were both found to be statistically significant discriminators of survival. Collectively these findings suggest that the expression of autophagy-related markers is associated with a favorable histology and could predict better survival in these patients