AMACR is associated with advanced pathologic risk factors in sporadic colorectal adenomas

Laboratory of Pathology, Georgios Gennimatas General Hospital, Thessaloniki 54635, Greece.
World Journal of Gastroenterology (Impact Factor: 2.37). 05/2010; 16(20):2476-83.
Source: PubMed


To analyze alpha-methylacyl CoA racemase (AMACR) expression in relation to various dysplasia phenotypes and clinicopathological parameters of sporadic colorectal adenomas.
Fifty-five cases of sporadic colorectal adenomas were categorized according to the Vienna classification for Gastrointestinal Neoplasia. These corresponded to a total of 98 different intra-lesion microscopic fields that were further independently assigned a histological grade based on the old nomenclature (mild, moderate, severe dyplasia and carcinoma in situ). AMACR expression was evaluated by immunohistochemistry and statistical analysis was performed to investigate possible associations with various clinicopathologic parameters of adenomas i.e. gender, age, localization, grade of dysplasia, size and configuration.
Patient age ranged from 41 to 84 years (mean 65 +/- 13.2 years); 37 patients were males and 18 were females. Adenomas ranged in size between 0.5 and 30 cm (mean 2 +/- 1.3 cm), including 18 tubular, 16 villous, 20 mixed or tubulovillous, and 1 giant sessile villous adenoma. AMACR expression was observed in 3 out of 16 (18.8%) of low-grade vs 23 out of 35 (62.8%) of high-grade lesions (P = 0.002). Most adenomas exhibiting high grade dysplasia with in situ carcinoma-like areas stained positive for AMACR (15/17 or 88.2%) as compared to adenomas with high grade dysplasia which contained severe dysplasia-like foci (6/15 or 40%), (P = 0.005). In AMACR positive adenomas featuring severe dysplasia-like or in situ carcinoma-like areas, AMACR staining was not necessarily observed in the in situ component. Positivity in intra-lesion of mild, moderate or severe dysplasia-like foci was more often encountered in adenomas harboring in situ, intramucosal or infiltrative carcinoma [21/33 (63.6%) vs 9/40 (22.5%), P < 0.001]. Strong AMACR expression was found in 11 out of 17 villous adenomas, but in only 1 out of 18 tubular lesions (P = 0.005). Larger lesions, i.e. > 1 cm stained more frequently for AMACR than smaller ones [27/45 (60%) vs 2/10 (20%), P = 0.02]. Overall, AMACR expression was associated with the grade of dysplasia, as well as with the size and configuration of adenomas, i.e. the consensus risk factors applied to colorectal adenoma patient surveillance.
It may be worthy to further evaluate the possible use of AMACR as an additional risk factor for the assessment of colorectal adenoma patients.

Download full-text


Available from: Sotiris Lakis, Apr 11, 2014
  • Source
    • "AMACR is a mitochondrial and peroxisomal enzyme that is part of the degradation of branched chained fatty acid derivates. AMACR is essential for the completion of the β-oxidation pathway [15] and has recently been shown to upregulated in colorectal cancer and adenoma [16-18]; 4) BRAF, MLH1 and β-catenin as additional markers involved in the serrated adenocarcinoma carcinogenesis. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Hyperplastic polyps (HP) and sessile serrated adenomas (SSA) share morphological similarities. In this immunohistochemical study we chose a panel of potential relevant and promising biomarkers including alpha-methylacyl-coenzyme A racemase (AMACR;p504s) , which is involved in the degradation of branched chained fatty acids derivates, and analysed a cohort of HPs and SSAs in order to identify different immunophenotypes in relation to lesion localisation. 154 specimen were carefully selected and a micro tissue array (TMA) was constructed. Immunohistochemistry of p16Ink4a, Ki67, alpha-methylacyl-coenzyme A racemase (AMACR;p504s), BRAF, CK 20 , MLH1 and beta-catenin was performed and and immunoexpression was compared among proximal and distal HPs as well as SSAs. None of the markers revealed a differential expression among HPs and SSAs. However, the study demonstrates a significant overexpression of AMACR (p = 0.004) and p16Ink4a (p = 0.028) in distal HPs compared to proximal HPs. In addition AMACR overexpression was associated with increased p16 Ink4a immunoexpression (p < 0.001). In this study we describe differential AMACR and p16 Ink4a in HPs in relation to their localisation. Distal HPs were characterized by AMACR and p16Ink4a overexpression in contrast to proximal HPs, although morphological identically. Thus AMACR overexpression points towards a pathobiological relevance of the protein in distal HPs. In context of recently published data this suggest distal HPs as potential precursor lesions of certain adenoma subtypes. However, at this point of time this finding remains speculative and needs to be confirmed by further studies.Virtual slidesThe virtual slide(s) for this article can be found here:
    Diagnostic Pathology 10/2013; 8(1):178. DOI:10.1186/1746-1596-8-178 · 2.60 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Prostate cancer (PCa) has become to have the highest incidence and the second mortality rate in western countries, affecting men's health to a large extent. Although prostate-specific antigen (PSA) was discovered to help diagnose the cancer in an early stage for decades, its specificity is relative low, resulting in unnecessary biopsy for healthy people and over-treatment for patients. Thus, it is imperative to identify more and more effective biomarkers for early diagnosis of PCa in order to distinguish patients from healthy populations, which helps guide an early treatment to lower disease-related mortality by noninvasive or minimal invasive approaches. This review generally describes the current early diagnostic biomarkers of PCa in addition to PSA and summarizes the advantages and disadvantages of these biomarkers.
    Asian Journal of Andrology 05/2014; 16(4). DOI:10.4103/1008-682X.129211 · 2.60 Impact Factor