title: Alpha-methylacyl-CoA racemase protein expression is associated with the degree of differentiation in breast cancer using quantitative image analysis.
abstract: Alpha-methylacyl-CoA racemase (AMACR) is an enzyme involved in the metabolism of fatty acids and is an important tissue biomarker in the prostate to distinguish normal glands from prostate cancer. Here, for the first time, we evaluated the expression of AMACR protein in normal breast, ductal carcinoma in situ, and invasive carcinomas. By immunofluorescence and immunohistochemistry, AMACR was seen in cytoplasmic granules consistent with a mitochondrial and peroxisomal localization. AMACR expression was determined by immunohistochemistry on 160 invasive carcinomas with long follow-up, using a high-density tissue microarray, and evaluated by two methods: standard pathology review and quantitative image analysis. AMACR was overexpressed in 42 of 160 (26%) invasive carcinomas, and it was associated with a decrease in tumor differentiation, a feature of aggressive breast cancer. Quantitative analysis allowed for better discrimination and more accurate evaluation of low-intensity staining. In conclusion, AMACR protein is expressed in normal breast and its expression seems to increase in invasive carcinomas. We observed stronger AMACR protein expression in high-grade carcinomas when compared with low-grade ones. Quantitative image analysis is a novel way to accurately and reproducibly evaluate immunohistochemistry in breast tissue samples using high-density tissue microarrays.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Agnieszka K
authors.initials: AK
authors.lastname: Witkiewicz
authors.forename: Sooryanarayana
authors.initials: S
authors.lastname: Varambally
authors.forename: Ronglai
authors.initials: R
authors.lastname: Shen
authors.forename: Rohit
authors.initials: R
authors.lastname: Mehra
authors.forename: Michael S
authors.initials: MS
authors.lastname: Sabel
authors.forename: Debashis
authors.initials: D
authors.lastname: Ghosh
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
authors.forename: Celina G
authors.initials: CG
authors.lastname: Kleer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics* / Q000473:pathology; D005260:Female; D005348:Fibrocystic Breast Disease / Q000235:genetics / Q000473:pathology; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D019998:Racemases and Epimerases / Q000096:biosynthesis*; D015203:Reproducibility of Results
chemical_list: D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase