Abstract 893P
Background
Autophagy process, is crucial in ensuring the survival of cells through recyclingof unwanted proteins and/ or generation of energy and is role in the progression of cancer is dual. In the herein presented study, autophagy flux was explored in epithelium and stroma cell populations of various GEP-NENs where existing data are limited, by means of membrane bound LC3B and p62 cytoplasmic proteins which play a major role in regulating the degradation of harmful proteins, aggregates and organelles via autophagy.
Methods
Study was approved by the “Hippokration” General Hospital of Athens Ethics Committee and consisted of 9 patients with Neuroendocrine Carcinomas (pNECs; 6 male, 3 female; mean age:55±7), 16 with Neuroendocrine Tumors (pNETs; 11 male, 5female; mean age: 58.69±3.7)in pancreas (n=19), stomach (n=2), small intestine (n=2) and esophagus (n=1). Immunohistochemistry was performed on 5μm sections of formalin fixed paraffin embedded tissue from pancreatic lesions and normal adjacent (NA) tissue.Staining intensity was multiplied with the percentage of stained cells to obtain the final score. Results were statistically analyzed using IBM SPSS Statistics 28.0.
Results
Although p62 nuclear expression was prominent in NA epithelium (p=0.047), p62 cytoplasmic expression was higher in NENs lesions’ compared to their corresponding NA epithelium (0.92± 0.4 vs 0, p=0.017). Also LC3B expression was induced in lesions’ compared to NA epithelium but this difference was not statistical significance (p=0.1). Nevertheless, LC3B protein expression was significantly increased in NENs lesions’ epithelium compared to their corresponding stroma (5.67±0.9 vs 0.47, p<0.001) and this pattern was more prominent in NEC lesions (NECs: 7.25±1.5 vs 0.62±0.3, p=0.018 vs NETs: 4.67±1.3 vs 0.58±0.3, p=0.016).
Conclusions
Autophagy flux as represented by LC3B and p62 expression profiles is significantly elevated in NEN lesions. This is specifically attributed to NECs and might be associated with their more aggressive behavior in comparison to NETs which are more indolent neoplasms. These results indicate that autophagy can represent a key target for introducing new therapeutic strategies in these patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Kataki Agapi.
Funding
TRANSCAN-2.
Disclosure
All authors have declared no conflicts of interest.