111 Malaysian J Pathol 2010; 32(2) : 111 – 116 Histomorphology of aberrant crypt foci in colorectal carcinoma D NORLIDA A Ojep MBBS, MPath, and PHANG Koon Seng* MBBS, DCPath Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak and *Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia Abstract Colorectal carcinogenesis is a complex multistep process that includes changes in histomorphological appearance of the colonic mucosa and changes at molecular level. Aberrant crypt foci (ACF) was first described by Bird in 1987 on examination of methylene-blue-stained colonic mucosa of azoxymethane-treated mice under light microscopy. Since then ACF was considered as the earliest preneoplastic change that can be seen in the colonic mucosa. The aim of this study was to look at the histomorphology and distribution of ACF in colorectal carcinoma. 50 formalin-fixed archival colectomy specimens for colorectal carcinoma were examined under light microscopy after staining with 0.2% methylene blue. ACF was identified by larger and darker crypts with thickened epithelium, and often elevated from adjacent normal mucosa. ACF was found in 41 of 50 colectomy specimens examined. There were 328 ACF consisting of 36 (11.0%) ACF without hyperplasia or dysplasia, 263 (80.2%) ACF with hyperplasia and 29 (8.8%) ACF with dysplasia. Of these 29 ACF with dysplasia, 25 showed low grade dysplasia and four high grade dysplasia. The density of ACF was higher in the left colon, those older than 65 years of age and among males but these findings were statistically not significant. The crypt multiplicity of hyperplastic ACF (30.149, SD 28.395) was larger than dysplastic ACF (20.613, SD 40.128). The spectrum of histological changes observed probably represent the evolution of ACF in colorectal carcinogenesis. Keywords: Aberrant crypt foci, colorectal carcinoma, dysplasia, hyperplasia Address for correspondence and reprint requests: Dr Dayangku Norlida Awang Ojep, Department of Pathology, Faculty of Medicine and Health Sciences, University Malaysia Sarawak, Lot 77, Jalan Tun Ahmad Zaidi Adruce, 93150 Kuching, Sarawak. Tel + 60 82 292132. Fax + 60 82 422564. Email: aodnorlida@fmhs.unimas.my ORIGINAL ARTICLE INTRODUCTION Colorectal carcinogenesis is a complex multistep process that includes changes in both histomorphological appearances of the colonic mucosa and at molecular level. It is believed that there are two pathogenetically distinct pathways for the development of colon cancer. 1,2 The first pathway is characterised by chromosomal instability resulting in stepwise accumulation of mutations in a series of oncogenes and tumour suppressor genes. The molecular evolution of colon cancer in this pathway can be seen through a series of morphologically identifiable stages: initial localised colonic epithelial hyperplasia, followed by formation of adenomas that progressively enlarge and ultimately develop into invasive cancers i.e. the adenoma-carcinoma sequence. The second pathway is characterised by genetic lesions in DNA mismatch repair genes (microsatellite instability). Aberrant crypt foci (ACF) was first described by Bird in 1987 on examination of methylene- blue-stained whole-mount preparations of colonic mucosa of azoxymethane-treated mice under light microscopy. 3 ACF was characterised by larger and darker crypts, a thickened layer of epithelium which was slightly elevated, having slit-like lumina with an increased pericryptal space from the surrounding normal crypts. 4 ACF was considered a precursor lesion of carcinoma, reinforced by the presence of dysplasia, 5 – 9 monoclonality 10 and gene mutations (k-ras, APC). 11, 12 – 14 This study was to identify this earliest change (ACF), and to see its histological pattern and distribution in colorectal carcinoma specimens. MATERIALS AND METHODS Fifty (50) archival formalin-fixed colonic resections of colorectal carcinoma diagnosed