Disease relevance of AMACR

• Sequence analysis of AMACR cDNA from the patients identified two different mutations that are likely to cause disease, based on analysis in Escherichia coli [1].
• OBJECTIVES: To determine the expression and clinical utility of alpha-methylacyl coenzyme A racemase (AMACR), a gene identified as being overexpressed in prostate cancer by global profiling strategies [2].
• Both untreated metastases (n = 32 patients) and hormone refractory prostate cancers (n = 14 patients) were generally strongly positive for AMACR [3].
• Examination of colorectal cancer, which is not hormone regulated, demonstrated high levels of AMACR expression in well to moderately differentiated tumors and weak expression in anaplastic colorectal cancers [4].
• We observed stronger AMACR protein expression in high-grade carcinomas when compared with low-grade ones [5].

High impact information on AMACR

• RESULTS: Three of 4 independent DNA microarray analyses (n = 128 specimens) revealed significant overexpression of AMACR in prostate cancer (P<.001) [2].
• AMACR up-regulation in prostate cancer was confirmed by both RT-PCR and immunoblot analysis [2].
• Expression profiling identifies a novel alpha-methylacyl-CoA racemase exon with fumarate hydratase homology [6].
• Moreover, simultaneous inhibition of both the AMACR pathway by siRNA and androgen signaling by means of androgen withdrawal or antiandrogen suppressed the growth of LAPC-4 cells to a greater extent than either treatment alone [7].
• Overexpressed AMACR from both clinical tissues and PCa cell lines is wild type by sequence analysis and functionally active by enzymatic assay [7].

Chemical compound and disease context of AMACR

• Alpha-methylacyl-CoA racemase as an androgen-independent growth modifier in prostate cancer [7].
• BACKGROUND: Alpha-methylacyl-CoA-racemase (AMACR), a recently discovered tumor marker for prostate cancer, is being used increasingly in conjunction with hematoxylin and eosin (H&E) histology and basal cell markers in the workup of difficult prostate needle biopsies [8].
• The histogenesis of mucinous tubular and spindle cell carcinoma from the distal nephron continues to be debatable, as our study showed the expression of the proximal convoluted tubule-related marker AMACR among these tumors [9].
• Alpha-methylacyl-CoA racemase (AMACR) catalyzes the racemization of alpha-methyl, branched carboxylic coenzyme A thioesters, and is overexpressed in a variety of neoplasms, such as prostate and colon cancer [10].
• AMACR expression can also be identified in high grade prostatic intraepithelial neoplasia (PIN), prostatic atrophy, AAH, and benign prostatic glands, and accordingly, a diagnosis of PC should not be based solely on a positive AMACR immunostain, especially when the luminal staining is weak and/or noncircumferential [11].

Biological context of AMACR

• One particular AMACR probeset was derived from an alternatively spliced exon with 88% identity to a 521-bp sequence that spans four exons of the fumarate hydratase [6].
• 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 [7].
• 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 [12].
• We emphasize the interpretation of the AMACR immunohistochemical results in routine surgical pathology practice and also discuss the potential future applications of this marker and the possible role of AMACR in the pathogenesis of cancer development [13].
• Alpha-methyacyl-CoA racemase (AMACR), a mitochondrial and peroxisomal enzyme essential in lipid metabolism, is overexpressed in prostate cancer [14].

Anatomical context of AMACR

• By immunofluorescence and immunohistochemistry, AMACR was seen in cytoplasmic granules consistent with a mitochondrial and peroxisomal localization [5].
• 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 [15].
• The high degree of specificity of AMACR for dysplasia/carcinoma in BE and IBD suggests that it may be useful to detect neoplastic epithelium in these conditions [10].
• Weak or focal AMACR immunoreactivity was detected in only 4 of 51 (8%) papillary carcinomas arising in other organs (2 of 14 thyroid, 2 of 13 lung, 0 of 6 breast, 0 of 6 endometrium, 0 of 6 ovary, and 0 of 6 pancreas) [16].
• Two hundred and fifty cases of adenocarcinomas from lung, breast, pancreas, bile duct, adrenal gland, salivary gland, ovary, thyroid and endometrium were negative or rarely positive for AMACR [17].

Associations of AMACR with chemical compounds

• Immunohistochemistry was carried out with antibodies specific for alpha-methyl-coenzyme A racemase (AMACR) and glutathione S-transferase alpha (clear-cell RCC marker) [18].
• Conversely, pristanic acid and, to a much lesser extent, phytanic acid markedly increased AMACR protein levels selectively in the LNCaP cell line, but not the NPrEC cell line [19].
• The usefulness of our approach based on virtual microscopy can be evaluated on the website , which also serves as an educational tool for self-learning the correlation between hematoxylin and eosin stained tissue morphology, and AMACR/p63 IHC in prostate biopsies [20].
• Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissue sections, with a primary prediluted rabbit monoclonal anti-AMACR antibody [21].
• Neither the biologically potent androgen 5alpha-dihydrotestosterone nor 17beta-estradiol had any apparent effect on AMACR expression at the protein or transcriptional levels in either cell line [19].

Other interactions of AMACR

• AMACR IIA contains an alternative fifth exon that has extensive homology to the human fumarate hydratase (FH) and encodes a 288-amino acid protein (Mw 32 kDa, pI 9.6) [14].
• Data from Western blotting and luciferase-based reporter assays suggest that the function and expression of AMACR are independent of androgen receptor-mediated signaling [7].
• METHODS AND RESULTS: The expression levels of AMACR mRNA were measured by real-time polymerase chain reaction [22].
• Most of the adenomas (82%, 31/38) stained strongly for AMACR in a fashion similar to that of PRCC [18].
• Foci of ASAP found in the absence of cancer were assessed with additional sectioning, high-molecular weight keratin (CK903), and alpha-methylacyl coenzyme A racemase (AMACR) immunohistochemistry [23].

Analytical, diagnostic and therapeutic context of AMACR

• Clinical utility of AMACR was evaluated using 94 prostate needle biopsy specimens [2].
• A lead candidate gene, AMACR, was validated at the transcript level by reverse transcriptase polymerase chain reaction (RT-PCR) and at the protein level by immunoblot and immunohistochemical analysis [2].
• The findings were confirmed by AMACR immunohistochemistry performed on several tissue microarrays containing common human tumors, including prostate, colon, and breast [12].
• AMACR is not helpful in differentiating MA from Wilms' tumor, but CD57 is helpful in this differential diagnosis [24].
• AMACR protein expression was determined by immunohistochemistry using an image analysis system on two localized prostate cancer cohorts consisting of 204 men treated by radical prostatectomy and 188 men followed expectantly [25].

References