Abstract

BackgroundHyperplastic 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.Methods154 specimen were carefully selected and a micro tissue array (TMA) was constructed. Immunohistochemistry of p16Ink4a, 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.ResultsNone 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 p16Ink4a immunoexpression (p < 0.001).ConclusionsIn this study we describe differential AMACR and p16Ink4a 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: http://www.diagnosticpathology.diagnomx.eu/vs/1836116001066768

Highlights

  • Hyperplastic polyps (HP) and sessile serrated adenomas (SSA) share morphological similarities

  • AMACR immunostaining was located in the cytoplasm of upper and basal crypt cells

  • In addition a comparison of all SSAs versus all HPs revealed no differences in AMACR expression (p = 0.448)

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Summary

Introduction

Hyperplastic polyps (HP) and sessile serrated adenomas (SSA) share morphological similarities. Hyperplastic polyps have been considered benign and harmless lesions for several decades [1] It is known, that besides of the classical adenomaadenocarcinoma pathway described by Vogelstein [2], an additional (non-hereditary) pathways exists, called. Molecular key features of the classical adenomaadenocarcinoma include KRAS and p53, whereas in the serrated pathway BRAF mutations appear to be an early event [2,7,8,9]. In addition this initial event is often followed by hypermethylation of CpG-island in gen promoters. A subset of HPs may be precursor lesions of SSAs

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