Caruso Rosario Alberto, Angelico Giuseppe, Irato Eleonora, de Sarro Rosalba, Tuccari Giovanni, Ieni Antonio
a Department of Human Pathology in Adult and Developmental Age "Gaetano Barresi", Section of Anatomic Pathology , University of Messina , Messina , Italy.
Ultrastruct Pathol. 2018 Jan-Feb;42(1):10-17. doi: 10.1080/01913123.2017.1388322. Epub 2017 Dec 1.
Autophagy represents a catabolic process in which cellular protein and organelles are engulfed into autophagosomes, digested in lysosomes and reutilized for the cellular metabolism. In neoplastic conditions, autophagy may act either as a tumour suppressor avoiding the accumulation of damaged proteins and organelles or as a mechanism of cell survival promoting the tumour growth. Although enhanced autophagy has been reported in hypoxic areas of solid tumors, there are only few ultrastructural reports concerning the relationships between autophagy and tumor grade. In the present study, we have performed an ultrastructural investigation aimed to document autophagy in a cohort of advanced gastric carcinomas of tubular type, correlating the observed findings with low and high tumor grade. Among 71 surgically resected cases of advanced gastric carcinomas, we have selected twelve low-grade and thirteen high-grade tubular adenocarcinomas. Autophagic vacuoles (AV) were only occasionally found in low-grade tubular carcinomas, while they constituted a frequent finding in high-grade ones (p < 0.01). Moreover, in high-grade tubular adenocarcinomas, our data revealed a morphologic association between autophagy and nuclear changes, such as multinucleation, micronucleation and nuclear buds, largely considered as ultrastructural aspects of mitotic instability. However, an increased autophagy was associated with organelle-poor cytoplasm or a senescent phenotype, characterized by lipofuscin granules and cytoplasmic vacuoles. In the light of our observations, it may be suggested that autophagy should be considered a phenomenon mainly related to the cellular differentiation and tumor progression.
自噬是一种分解代谢过程，其中细胞蛋白质和细胞器被吞噬进自噬体，在溶酶体中被消化并重新用于细胞代谢。在肿瘤状态下，自噬既可以作为一种肿瘤抑制机制，避免受损蛋白质和细胞器的积累，也可以作为一种促进肿瘤生长的细胞存活机制。尽管在实体瘤的缺氧区域已报道自噬增强，但关于自噬与肿瘤分级之间关系的超微结构报告却很少。在本研究中，我们进行了一项超微结构研究，旨在记录一组管状型晚期胃癌中的自噬情况，并将观察结果与低级别和高级别肿瘤分级相关联。在71例手术切除的晚期胃癌病例中，我们选择了12例低级别和13例高级别管状腺癌。自噬泡（AV）在低级别管状癌中仅偶尔发现，而在高级别管状癌中则是常见现象（p < 0.01）。此外，在高级别管状腺癌中，我们的数据显示自噬与核变化之间存在形态学关联，如多核化、微核化和核芽，这些在很大程度上被视为有丝分裂不稳定的超微结构特征。然而，自噬增加与细胞器贫乏的细胞质或衰老表型相关，其特征为脂褐素颗粒和细胞质空泡。根据我们的观察结果，可能提示自噬应被视为一种主要与细胞分化和肿瘤进展相关的现象。
