LC3A-positive light microscopy detected patterns of autophagy and prognosis in operable breast carcinomas.

Autophagy is a self-degradation mechanism by which cells recycle their own cytoplasmic constituents and dispose of excess or defective organelles after starvation and oxygen deprivation. An antibody to the microtubule-associated protein 1 light chain 3 (LC3A), recognizing both the soluble (LC3A-I) a...

Full description

Bibliographic Details
Main Authors: Sivridis, E, Koukourakis, M, Zois, C, Ledaki, I, Ferguson, D, Harris, A, Gatter, K, Giatromanolaki, A
Format: Journal article
Language:English
Published: 2010
_version_ 1797050891364204544
author Sivridis, E
Koukourakis, M
Zois, C
Ledaki, I
Ferguson, D
Harris, A
Gatter, K
Giatromanolaki, A
author_facet Sivridis, E
Koukourakis, M
Zois, C
Ledaki, I
Ferguson, D
Harris, A
Gatter, K
Giatromanolaki, A
author_sort Sivridis, E
collection OXFORD
description Autophagy is a self-degradation mechanism by which cells recycle their own cytoplasmic constituents and dispose of excess or defective organelles after starvation and oxygen deprivation. An antibody to the microtubule-associated protein 1 light chain 3 (LC3A), recognizing both the soluble (LC3A-I) and the membrane-bound form (LC3A-II) of the protein, was used to detect autophagic activity in 102 breast carcinomas. Three distinct patterns were recognized: (1) diffuse cytoplasmic, (2) cytoplasmic/juxta-nuclear, and (3) "stone-like" pattern--dense, rounded, amorphous structures, 5 microm on average, typically enclosed within cytoplasmic vacuoles. The diffuse cytoplasmic pattern showed a direct association with estrogen and progesterone receptor expression. The juxta-nuclear pattern indicated a similar association with hormone receptors, an inverse association with tumor size, and a favorable prognosis. By contrast, an increased number of stone-like structures, probably representing an excessive autophagic response, was related to high-grade tumors and a less favorable outcome. Interestingly, 60 additional epithelial tumors of nonbreast origin disclosed identical autophagic patterns, and so did MDA231 breast cancer xenografts and HCT116 colon tumor spheroids (also analyzed by electron microscopy). Moreover, MCF-7 human breast cancer cell lines confirmed induction of LC3A by anoxia and Thapsigargin. It is concluded that autophagy can be readily recognized in breast carcinomas by light microscopy, after immunohistochemical staining with LC3A, but the significance of the various patterns expressed would need further evaluation.
first_indexed 2024-03-06T18:11:55Z
format Journal article
id oxford-uuid:0353fe5b-6859-4275-84c9-459c4f8be485
institution University of Oxford
language English
last_indexed 2024-03-06T18:11:55Z
publishDate 2010
record_format dspace
spelling oxford-uuid:0353fe5b-6859-4275-84c9-459c4f8be4852022-03-26T08:45:29ZLC3A-positive light microscopy detected patterns of autophagy and prognosis in operable breast carcinomas.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0353fe5b-6859-4275-84c9-459c4f8be485EnglishSymplectic Elements at Oxford2010Sivridis, EKoukourakis, MZois, CLedaki, IFerguson, DHarris, AGatter, KGiatromanolaki, AAutophagy is a self-degradation mechanism by which cells recycle their own cytoplasmic constituents and dispose of excess or defective organelles after starvation and oxygen deprivation. An antibody to the microtubule-associated protein 1 light chain 3 (LC3A), recognizing both the soluble (LC3A-I) and the membrane-bound form (LC3A-II) of the protein, was used to detect autophagic activity in 102 breast carcinomas. Three distinct patterns were recognized: (1) diffuse cytoplasmic, (2) cytoplasmic/juxta-nuclear, and (3) "stone-like" pattern--dense, rounded, amorphous structures, 5 microm on average, typically enclosed within cytoplasmic vacuoles. The diffuse cytoplasmic pattern showed a direct association with estrogen and progesterone receptor expression. The juxta-nuclear pattern indicated a similar association with hormone receptors, an inverse association with tumor size, and a favorable prognosis. By contrast, an increased number of stone-like structures, probably representing an excessive autophagic response, was related to high-grade tumors and a less favorable outcome. Interestingly, 60 additional epithelial tumors of nonbreast origin disclosed identical autophagic patterns, and so did MDA231 breast cancer xenografts and HCT116 colon tumor spheroids (also analyzed by electron microscopy). Moreover, MCF-7 human breast cancer cell lines confirmed induction of LC3A by anoxia and Thapsigargin. It is concluded that autophagy can be readily recognized in breast carcinomas by light microscopy, after immunohistochemical staining with LC3A, but the significance of the various patterns expressed would need further evaluation.
spellingShingle Sivridis, E
Koukourakis, M
Zois, C
Ledaki, I
Ferguson, D
Harris, A
Gatter, K
Giatromanolaki, A
LC3A-positive light microscopy detected patterns of autophagy and prognosis in operable breast carcinomas.
title LC3A-positive light microscopy detected patterns of autophagy and prognosis in operable breast carcinomas.
title_full LC3A-positive light microscopy detected patterns of autophagy and prognosis in operable breast carcinomas.
title_fullStr LC3A-positive light microscopy detected patterns of autophagy and prognosis in operable breast carcinomas.
title_full_unstemmed LC3A-positive light microscopy detected patterns of autophagy and prognosis in operable breast carcinomas.
title_short LC3A-positive light microscopy detected patterns of autophagy and prognosis in operable breast carcinomas.
title_sort lc3a positive light microscopy detected patterns of autophagy and prognosis in operable breast carcinomas
work_keys_str_mv AT sivridise lc3apositivelightmicroscopydetectedpatternsofautophagyandprognosisinoperablebreastcarcinomas
AT koukourakism lc3apositivelightmicroscopydetectedpatternsofautophagyandprognosisinoperablebreastcarcinomas
AT zoisc lc3apositivelightmicroscopydetectedpatternsofautophagyandprognosisinoperablebreastcarcinomas
AT ledakii lc3apositivelightmicroscopydetectedpatternsofautophagyandprognosisinoperablebreastcarcinomas
AT fergusond lc3apositivelightmicroscopydetectedpatternsofautophagyandprognosisinoperablebreastcarcinomas
AT harrisa lc3apositivelightmicroscopydetectedpatternsofautophagyandprognosisinoperablebreastcarcinomas
AT gatterk lc3apositivelightmicroscopydetectedpatternsofautophagyandprognosisinoperablebreastcarcinomas
AT giatromanolakia lc3apositivelightmicroscopydetectedpatternsofautophagyandprognosisinoperablebreastcarcinomas