Abstract 1261: Detection of autophagy in gastric mucosae of Chilean individuals residing in a geographic region characterized by high rates of gastric cancer-related death
Authors: Alejandro Corvalan, Hernan Pulgar, Claudio Cruzat, Nicole Cespedes, Francisco Ruiz, Rodrigo Prado, Nelson E. Brown
Journal: Cancer Research (2018)

Abstract Gastric cancer is the fourth most common cancer worldwide. In Chile, gastric cancer is the first cause of cancer-related deaths, affecting most prominently the southern provinces. Therefore, the elucidation of molecular pathways that might be exploited to improve prognosis and therapies remains an important challenge. There is emerging evidence pointing to the role of autophagy in tumorigenesis. Autophagy, a lysosome-mediated catabolic process, represents a prosurvival process implemented by neoplastic cells in response to stressful stimuli. So far, markers of autophagy have been used as prognosis determinants in early stages of gastric cancer, or have been associated to recurrence and reduced survival in patients with advanced disease. However, the role of autophagy in precursor lesions (chronic gastritis, metaplasia, dysplasia) has not been explored. Our goal was to examine the presence of autophagy (cleaved-LC3A) and proliferation (Ki-67) markers in gastric biopsies obtained from healthy individuals residing in a Chilean geographic zone characterized by a high gastric cancer-related mortality. Toward this goal, 165 asymptomatic individuals, aged 40 to 70, from the Molina area in the south of Chile were subjected to endoscopy and biopsy sampling according to the Operative Link on Gastritis Assessment (OLGA) staging system. Each tissue section was processed for immunohistochemical detection of cleaved-LC3A and Ki67, and the results were correlated with the histopathological findings and the presence or absence of Helicobacter pylori. Our preliminary analyses indicate that 60% of individuals harbor at least one out of five biopsies with the highest score values for cleaved-LC3A staining. Most of these high-scored samples involved the gastric antrum (73.3%) and were also positive for the Ki67 proliferation marker (63.3%). Of note, tissue samples showing the highest score values for cleaved-LC3A staining occurred almost always (93.3%) in the context of chronic gastritis or a combination of chronic gastritis and intestinal metaplasia, even though only 56.7% of cleaved-LC3A positive tissues showed signs of Helicobacter pylori infection. These results seem to indicate that autophagy may allow gastric epithelial cells to circumvent inflammatory stress, highlighting this process as a potential target for the development of anti-cancer or preventive therapies.Grant Support: FIC-30388034-0, CONICYT-FONDAP 115130011, Fondecyt 1151411, PIA-Gastric cancer UTALCA Citation Format: Alejandro Corvalan, Hernan Pulgar, Claudio Cruzat, Nicole Cespedes, Francisco Ruiz, Rodrigo Prado, Nelson E. Brown. Detection of autophagy in gastric mucosae of Chilean individuals residing in a geographic region characterized by high rates of gastric cancer-related death [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1261.