title: LC3A-positive light microscopy detected patterns of autophagy and prognosis in operable breast carcinomas.
abstract: 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.
authors.affiliation: Department of Pathology, Democritus University of Thrace and University General Hospital of Alexandroupolis, Alexandroupolis, Greece.
authors.forename: Efthimios
authors.initials: E
authors.lastname: Sivridis
authors.forename: Michael I
authors.initials: MI
authors.lastname: Koukourakis
authors.forename: Christos E
authors.initials: CE
authors.lastname: Zois
authors.forename: Ioanna
authors.initials: I
authors.lastname: Ledaki
authors.forename: David J P
authors.initials: DJ
authors.lastname: Ferguson
authors.forename: Adrian L
authors.initials: AL
authors.lastname: Harris
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Gatter
authors.forename: Alexandra
authors.initials: A
authors.lastname: Giatromanolaki
mesh_terms: D000328:Adult; D000368:Aged; D001343:Autophagy; D001943:Breast Neoplasms / Q000378:metabolism* / Q000601:surgery; D002277:Carcinoma / Q000378:metabolism* / Q000601:surgery; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008854:Microscopy, Electron / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D009368:Neoplasm Transplantation; D016896:Treatment Outcome
chemical_list: C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins
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