Autophagy and hypoxia in colonic adenomas related to aggressive features

作者：Giatromanolaki A^*; Koukourakis M I; Koutsopoulos A V; Harris A L; Gatter K C; Sivridis E

来源：Colorectal Disease, 2013, 15(5): E223-E230.

DOI：10.1111/codi.12147

• Autophagy
• colon cancer
• adenoma
• hypoxia

Aim The study investigated whether autophagic activity and hypoxia parallel the adenomacarcinoma sequence. Method The study comprised 120 tubular adenomas with high-grade dysplasia, including 22 with questionable evidence of invasion, 37 with definite stromal invasion and 29 with severely dysplastic adenoma, 10 traditional serrated adenomas and 22 classical tubular adenomas lacking aggressive features. The samples were stained immunohistochemically for autophagy (LC3A and Beclin-1) and hypoxia-inducible factor1-alpha (HIF1) markers. Results LC3A was detected as diffuse cytoplasmic staining and as dense stone-like structures (SLS) within cytoplasmic vacuoles. Beclin-1 reactivity was purely cytoplasmic, whereas that of HIF1 was both cytoplasmic and nuclear. SLS counts in noninvasive, nontransformed areas of tubular adenomas were consistently low (median SLS=0.5; 200x magnification), whereas a progressive increase was noted from areas of equivocal invasion (median SLS=1.3; 200x magnification) and intramucosal carcinoma (median SLS=1.4; 200x magnification) to unequivocal invasive foci (median SLS=2.1; 200x magnification) (P<0.0001). A similar association was shown for Beclin-1 and HIF1 expression (P<0.05). Traditional serrated adenomas yielded low SLS counts and weak HIF1 reactivity, but high cytoplasmic LC3A and Beclin-1 expression (P<0.01). Conclusion A hypoxia-driven autophagy in adenomatous polyps, when particularly intense and localized, is commonly associated with early invasion or severely dysplastic adenoma.

• 出版日期2013-5