Anti-AMACR monoclonal antibody

BACKGROUND. Alpha-methylacyl CoA racemase (AMACR) is an enzyme involved in fatty acids metabolism. One of AMACRs primary substrates, phytanic acid, is principally obtained from dietary red meat/dairy, which are associated with prostate cancer (PCa) risk. AMACR is also a tumor tissue biomarker over-expressed in PCa. In this study, we explored the potential relationship between AMACR polymorphisms, red meat/dairy intake, and PCa risk. METHODS. Caucasian participants from two population-based PCa case-control studies were included. AMACR single nucleotide polymorphisms (SNPs) were selected to capture variation across the gene and regulatory regions. Red meat and dairy intake was determined from food frequency questionnaires. The odds ratio (OR) of PCa (overall and by disease aggressiveness) was estimated by logistic and polytomous regression. Potential interactions between genotypes and dietary exposures were evaluated. RESULTS. Data from 1,309 cases and 1,267 controls were analyzed. Carriers of the variant T allele (rs2287939) had an OR of 0.81 (95% CI 0.68-0.97) for less aggressive PCa, but no alteration in risk for more aggressive PCa. Red meat consumption was positively associated with PCa risk, and the association was stronger for more aggressive disease (lowest vs. highest tertile OR = 1.55, 95% CI 1.10-2.20). No effect modification of AMACR polymorphisms by either dietary red meat or dairy intake on PCa risk was observed. CONCLUSIONS. PCa risk varied by level of red meat intake and by one AMACR SNP, but there was no evidence for gene-environment interaction. These findings suggest that the effects of AMACR polymorphisms and red meat and dairy on PCa risk are independent. Prostate 71: 498-506, 2011. (C) 2010 Wiley-Liss, Inc.

Current laboratory and morphological differential diagnosis of prostate cancer is based on the use of sensitive tumor-specific markers. One of the most promising tumor markers is alpha-methylacyl-CoA racemase (AMACR), and studies indicate a positive correlation between AMACR expression, degree of tumor differentiation, and tumor progression. Most commonly, AMACR is detected by immunohistochemical means. Here, we took advantage of the adjuvant properties of colloidal gold nanoparticles to prepare rabbit polyclonal anti-AMACR antibodies and compare them with commercially available monoclonal anti-AMACR antibodies. The sensitivity of both antibody types, as determined by ELISA, was comparable and close to 1 mu g mL(-1), whereas a gold nanoshell-aided immunodot assay demonstrated eight times higher sensitivity for polyclonal gold-derived anti-AMACR antibodies. The rabbit polyclonal anti-AMACR antibodies were used in immunohistochemical analysis of biopsy specimens collected from patients with different prostate pathologies. The intensity of AMACR detection in prostate epithelium cytoplasm differed significantly between the groups of patients with prostate adenoma and with prostate cancer.