ORIGINAL ARTICLESAlpha-Methylacyl-CoA Racemase A Novel Tumor Marker Over-expressed in Several Human Cancers and Their Precursor LesionsZhou, Ming M.D., Ph.D.; Chinnaiyan, Arul M. M.D., Ph.D.; Kleer, Celina G. M.D.; Lucas, Peter C. M.D., Ph.D.; Rubin, Mark A. M.D.Author Information From the Departments of Pathology (M.Z., A.M.C., C.G.K., P.C.L., M.A.R.) and Urology (A.M.C., M.A.R.), University of Michigan School of Medicine, Ann Arbor, Michigan, U.S.A. Supported by Specialized Program of Research Excellence for Prostate Cancer (S.P.O.R.E.) NCI Grant P50CA69568. Address correspondence and reprint requests to Mark A. Rubin, MD, 1500 East Medical Center Drive, CCGC 7314, Ann Arbor, MI 48109, U.S.A.; e-mail: [email protected]; web site: http://rubinlab.cancer.med.umich.edu The American Journal of Surgical Pathology: July 2002 - Volume 26 - Issue 7 - p 926-931 Buy Abstract α-Methylacyl-CoA racemase (AMACR) is a mitochondrial and peroxisomal enzyme involved in the metabolism of branched-chain 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. © 2002 Lippincott Williams & Wilkins, Inc.