α-methylacyl-CoA racemase protein expression is associated with the degree of differentiation in breast cancer using quantitative image analysis

Agnieszka K. Witkiewicz, Sooryanarayana Varambally, Ronglai Shen, Rohit Mehra, Michael S. Sabel, Debashis Ghosh, Arul M. Chinnaiyan, Mark A. Rubin, Celina G. Kleer

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Abstract

α-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.

Original languageEnglish (US)
Pages (from-to)1418-1423
Number of pages6
JournalCancer Epidemiology Biomarkers and Prevention
Volume14
Issue number6
DOIs
StatePublished - Jun 2005

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Racemases and Epimerases
Coenzyme A
Breast Neoplasms
Carcinoma
Immunohistochemistry
Proteins
Breast
Cytoplasmic Granules
Carcinoma, Intraductal, Noninfiltrating
Fluorescent Antibody Technique
Prostate
Prostatic Neoplasms
Fatty Acids
Biomarkers
Pathology
Staining and Labeling
Enzymes
Neoplasms

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

α-methylacyl-CoA racemase protein expression is associated with the degree of differentiation in breast cancer using quantitative image analysis. / Witkiewicz, Agnieszka K.; Varambally, Sooryanarayana; Shen, Ronglai; Mehra, Rohit; Sabel, Michael S.; Ghosh, Debashis; Chinnaiyan, Arul M.; Rubin, Mark A.; Kleer, Celina G.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 14, No. 6, 06.2005, p. 1418-1423.

Research output: Contribution to journalArticle

Witkiewicz, Agnieszka K. ; Varambally, Sooryanarayana ; Shen, Ronglai ; Mehra, Rohit ; Sabel, Michael S. ; Ghosh, Debashis ; Chinnaiyan, Arul M. ; Rubin, Mark A. ; Kleer, Celina G. / α-methylacyl-CoA racemase protein expression is associated with the degree of differentiation in breast cancer using quantitative image analysis. In: Cancer Epidemiology Biomarkers and Prevention. 2005 ; Vol. 14, No. 6. pp. 1418-1423.
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