Increased expression of α-methylacyl-coenzyme A racemase (AMACR; p504s) and p16 in distal hyperplastic polyps

BACKGROUND: 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 α-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. METHODS: 154 specimen were carefully selected and a micro tissue array (TMA) was constructed. Immunohistochemistry of p16(Ink4a), Ki67, α-methylacyl-coenzyme A racemase (AMACR; p504s), BRAF, CK 20, MLH1 and β-catenin was performed and and immunoexpression was compared among proximal and distal HPs as well as SSAs. RESULTS: 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 p16(Ink4a) (p = 0.028) in distal HPs compared to proximal HPs. In addition AMACR overexpression was associated with increased p16(Ink4a) immunoexpression (p < 0.001). CONCLUSIONS: In this study we describe differential AMACR and p16(Ink4a) in HPs in relation to their localisation. Distal HPs were characterized by AMACR and p16(Ink4a) 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 SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1836116001066768