Abstract

Abstract Background: The pathogenesis of colorectal cancer in familial adenomatous polyposis (FAP) has been studied genetically. Recently, intestinal stem cell (ISC) or cancer stem cell (CSC) is being focused on colorectal carcinogenesis. The aim of this study is to investigate the immunohistochemical features of stem cell transcription factors on colorectal adenocarcinomas, adenomataous polyps, and normal crypts in patients with FAP. Methods: Lgr5 as an ISC marker, CD133 and CD44 as CSC markers, and NANOG, OCT4, and SOX2 as embryonic stem cell transcription factors were evaluated immunohistochemically. Matched specimens of colorectal adenocarcinoma, adenomatous polyps, and adjacent normal crypts were obtained from individual FAP patients (n=4), to clarify the association between stepwise progression from normal crypt to adenomatous polyp to adenocarcinoma and expression of stem cell transcription factors. Results: Lgr5, NANOG, OCT4, and SOX2 were mainly located in cytoplasm of cancerous and adenomatous cells. CD133 showed cytoplasmic or intraluminal membranous staining in cancerous and adenomatous cells. Immunoreactive CD44 protein was present in cell membrane or cytoplasm of cancerous and adenomatous cells. Immunoreactive positivity and intensity was greater in colorectal adenocarcinomas than in adenomatous polyps, except for NANOG. Adjacent normal crypts showed negative or weak staining of all markers. CD133, CD44, Lgr5, OCT4, and SOX2 were strongly expressed on cancerous cells at the advancing front of colorectal adenocarcinoma. Conclusions: ISC or CSC may be associated with colorectal carcinogenesis of FAP. Stem cell transcription factors may be involved in tumor invasion of colorectal adenocarcinoma in FAP patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3358.

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