Using moderate or strong staining intensity as positive (score = 3 or 4), evaluation of AMACR protein expression in 94 prostate needle biopsy specimens demonstrated 97% sensitivity and 100% specificity for detecting prostate cancer.
To extend the utility of this marker for prostate cancer diagnosis, we combined staining for cytoplasmic AMACR with staining for the nuclear protein, p63, a basal cell marker in the prostate that is absent in prostate cancer.
To test this hypothesis, we sequenced all five exons, exon-intron junctions, the promoter region, and 3'-untranslated region of AMACR in germ-line DNA samples of 96 probands from hereditary CaP (HPC) families.
Small interference RNA (siRNA) against AMACR, but not the control inverted siRNA, reduced the expression of AMACR and significantly impaired proliferation of the androgen-responsive PCa cell line LAPC-4.
Performing a supervised analysis to identify potential comarkers of PDGFR-beta in PCa, we identified a set of genes whose expression was associated with PDGFR-beta status including early growth response 1 (Egr1), an upstream effector of PDGF (4.2-fold upregulation), alpha-methylacyl-CoA racemase, as well as v-Maf and neuroblastoma suppressor of tumorigenicity (both with a 2.2-fold downregulation).
Here, we report that an enzyme downstream from AMACR in the peroxisomal branched chain fatty acid beta-oxidation pathway-D-bifunctional protein (DBP)-is also upregulated in prostate cancer at both mRNA and protein levels, accompanied by increased enzymatic activity.
Combined quantitative expression analysis of ERG with two other genes commonly overexpressed in CaP, AMACR and DD3, revealed overexpression of at least one of these three genes in virtually all CaP specimen (54 of 55).
However, promoter deletion analysis identified an 8-bp nonclassic CCAAT enhancer element located approximately 80 bp upstream of the transcriptional initiation site that is responsible for AMACR expression in both prostate cancer cell lines and cell lines of liver origin.
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.
These genes include several that have recently become associated with carcinogenesis, such as Krüppel-like factor (KLF)4, a gut-enriched transcription factor associated with induction of differentiation and reduction in cellular proliferation; DNA (cytosine-5-)-methyltransferase 1, associated with methylation; and alpha-methylacyl-CoA racemase (AMACR), a marker associated with the development of colon and prostate cancer.
AMACR was the best single marker of prostate cancer but in 7 of the 59 total cases the expression of AMACR was not significantly elevated while PSGR and/or PSGR2 were substantially elevated.
Since the latter clearly predominate in the laboratory routine, PCR-based detection of AMACR has the potential to gain widespread acceptance as a suitable future tool for monitoring prostate cancer patients.
The protective associations observed among ibuprofen users suggest that AMACR gene variants may enhance the chemopreventive effects of ibuprofen on prostate cancer risk.
In a study of brothers discordant for the diagnosis of prostate cancer (including 449 affected and 394 unaffected men) from 332 familial and early-onset prostate cancer families, we used conditional logistic regression and family-based association tests to investigate the association between prostate cancer and five single nucleotide polymorphisms (SNPs) tagging common haplotype variation within the coding and regulatory regions of AMACR.
Identification of prostate cancer associated-gene expression alterations such as AMACR, Kallikrein gene family and genes associated with androgen signaling such as PDEF and STEAP were consistent with previous findings reported in prostate cancer.