Alpha-methylacyl-CoA racemase: A novel tumor marker over-expressed in several human cancers and their precursor lesions

Ming Zhou, Arul M. Chinnaiyan, Celina G. Kleer, Peter C. Lucas, Mark A. Rubin

Research output: Contribution to journalArticle

226 Citations (Scopus)

Abstract

α-Methylacyl-CoA racemase (AMACR) is a mitochondrial and peroxisomal enzyme involved in the metabolism of branchedchain fatty acid and bile acid intermediates. Recently, AMACR has been demonstrated to be over-expressed in localized and metastatic prostate cancer, suggesting that it may be an important tumor marker. This study examines AMACR expression in a variety of human cancers and their precursor lesions. A survey of online Expressed Sequence Tags (ESTs) and Serial Analysis of Gene Expression (SAGE) databases revealed that AMACR was over-expressed in multiple cancers. The findings were confirmed by AMACR immunohistochemistry performed on several tissue microarrays containing common human tumors, including prostate, colon, and breast. Based on prior work, AMACR protein expression was divided into two categories: Negative (negative to weak staining intensity) and positive (moderate to strong staining intensity). AMACR protein over-expression was found in a number of cancers, including colorectal, prostate, ovarian, breast, bladder, lung, and renal cell carcinomas, lymphoma, and melanoma. Greatest over-expression was seen in colorectal and prostate cancer with positive staining in 92% and 83% cases, respectively. AMACR over-expression was present in 44% of breast cancer cases. AMACR was also over-expressed in precursor lesions. Sixty-four percent of high-grade prostatic intraepithelial neoplasia and 75% colonic adenomas demonstrated positive AMACR protein expression. Reverse transcriptase-polymerase chain reaction for AMACR using laser capture microdissected prostate tissue confirmed gene over-expression at the mRNA level. In conclusion, our study suggests that AMACR is potentially an important tumor marker for several cancers and their precursor lesions, especially those linked to high-fat diets.

Original languageEnglish (US)
Pages (from-to)926-931
Number of pages6
JournalAmerican Journal of Surgical Pathology
Volume26
Issue number7
DOIs
StatePublished - Jul 20 2002

Fingerprint

Tumor Biomarkers
Prostate
Staining and Labeling
Colorectal Neoplasms
Neoplasms
Prostatic Neoplasms
Breast
Prostatic Intraepithelial Neoplasia
Racemases and Epimerases
Gene Expression
Proteins
Expressed Sequence Tags
High Fat Diet
Coenzyme A
Reverse Transcriptase Polymerase Chain Reaction
Bile Acids and Salts
Renal Cell Carcinoma
Adenoma
Melanoma
Lymphoma

Keywords

  • α-Methyacyl
  • Breast cancer
  • CoA racemase (AMACR)
  • Colorectal adenoma
  • Colorectal cancer
  • Prostate cancer
  • Prostatic intraepithelial neoplasia
  • Tumor marker

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine

Cite this

Alpha-methylacyl-CoA racemase : A novel tumor marker over-expressed in several human cancers and their precursor lesions. / Zhou, Ming; Chinnaiyan, Arul M.; Kleer, Celina G.; Lucas, Peter C.; Rubin, Mark A.

In: American Journal of Surgical Pathology, Vol. 26, No. 7, 20.07.2002, p. 926-931.

Research output: Contribution to journalArticle

Zhou, Ming ; Chinnaiyan, Arul M. ; Kleer, Celina G. ; Lucas, Peter C. ; Rubin, Mark A. / Alpha-methylacyl-CoA racemase : A novel tumor marker over-expressed in several human cancers and their precursor lesions. In: American Journal of Surgical Pathology. 2002 ; Vol. 26, No. 7. pp. 926-931.
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abstract = "α-Methylacyl-CoA racemase (AMACR) is a mitochondrial and peroxisomal enzyme involved in the metabolism of branchedchain fatty acid and bile acid intermediates. Recently, AMACR has been demonstrated to be over-expressed in localized and metastatic prostate cancer, suggesting that it may be an important tumor marker. This study examines AMACR expression in a variety of human cancers and their precursor lesions. A survey of online Expressed Sequence Tags (ESTs) and Serial Analysis of Gene Expression (SAGE) databases revealed that AMACR was over-expressed in multiple cancers. The findings were confirmed by AMACR immunohistochemistry performed on several tissue microarrays containing common human tumors, including prostate, colon, and breast. Based on prior work, AMACR protein expression was divided into two categories: Negative (negative to weak staining intensity) and positive (moderate to strong staining intensity). AMACR protein over-expression was found in a number of cancers, including colorectal, prostate, ovarian, breast, bladder, lung, and renal cell carcinomas, lymphoma, and melanoma. Greatest over-expression was seen in colorectal and prostate cancer with positive staining in 92{\%} and 83{\%} cases, respectively. AMACR over-expression was present in 44{\%} of breast cancer cases. AMACR was also over-expressed in precursor lesions. Sixty-four percent of high-grade prostatic intraepithelial neoplasia and 75{\%} colonic adenomas demonstrated positive AMACR protein expression. Reverse transcriptase-polymerase chain reaction for AMACR using laser capture microdissected prostate tissue confirmed gene over-expression at the mRNA level. In conclusion, our study suggests that AMACR is potentially an important tumor marker for several cancers and their precursor lesions, especially those linked to high-fat diets.",
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