Immunohistochemical evidence for an impairment of autophagy in tumorigenesis of gastric carcinoids and adenocarcinomas in rodent models and patients
- Autores: Reidar Alexander Vigen, Yosuke Kodama, Trond Viset, Reidar Fossmark, Mark Kidd, Timothy C Wang, Irvin M. Modlin, Duan Chen, Chun Mei Zhao
- Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 28, Nº. 4, 2013, págs. 531-542
- Idioma: español
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Resumen
Background/Aim: Autophagy has dual roles in tumorigenesis: tumor-promoting or tumor-suppressing. The aim of the present study was to examine autophagy-related markers by immunohisto-chemistry in gastric carcinoids and adenocarcinomas in rodent models and patients.
Methods: Gastric carcinoids in Mastomys were induced by loxtidine treatment. Spontaneously developed gastric adenocarcinomas in Japanese cotton rats and INS-GAS transgenic mice were included. Patient tissue samples of gastric carcinoids or adenocarcinomas were collected. Immunohistochemistry was performed against autophagy-related gene protein-6 (ATG-6, also called beclin-1), ATG-5 and ATG-16.
Results: In tumor-free Mastomys, ATG-5, ATG-16 and beclin-1 were immunepositive in the gastric mucosa. In tumor-bearing Mastomys, ATG-5 and ATG-16 were negative in the tumors, whereas beclin-1 was positive in four of five animals. In carcinoid patients, ATG-5 was negative in six of ten, ATG-16 negative in nine of ten, and beclin-1 negative in three of ten patients. In cotton rats, ATG-5 and ATG-16 were negative in all tumors. Beclin-1 was negative in three of five rats. In INS-GAS mice, ATG-5 and beclin-1 were positive in the tumor area, but the numbers of immunopositive cells per gland were reduced by about 50% in comparison with wild-type mice. In adenocarcinoma patients, ATG-5 and ATG-16 were negative in eight of ten, and beclin-1 positive in all ten patients.
Conclusions: An impaired autophagy took place at the stage of formation of ATG-5-ATG-12-ATG-16 complex in both gastric carcinoids and adenocarcinoma of both rodent models and patients. ATG-5 and ATG-16 might be better markers than beclin-1 in assessing autophagy in these lesions
