PMID- 16475686
OWN - NLM
STAT- MEDLINE
DCOM- 20060309
LR  - 20060214
IS  - 0250-7005 (Print)
IS  - 0250-7005 (Linking)
VI  - 26
IP  - 1A
DP  - 2006 Jan-Feb
TI  - Aberrant crypt foci.
PG  - 107-19
AB  - Colon cancer evolves through epithelial cell deregulation and inappropriate 
      proliferation. These histopathological characteristics are exemplified in the 
      biochemical, immunohistochemical, genetic and epigenetic elements detected within 
      colonic mucosa. Early detection is paramount for the prevention of colon cancer 
      deaths. Aberrant crypt foci (ACF) are thought to be the earliest identifiable 
      neoplastic lesions in the colon carcinogenetic model. The progression of ACF to 
      polyp and, subsequently, to cancer parallels the accumulation of several 
      biochemical alterations and mutations whereby a small fraction of ACF evolve to 
      colon cancer. Recent data indicate that, not uncommonly, some ACF bypass the 
      polyp stage in their carcinogenesis thus reinforcing the importance of their 
      early detection and our understanding of their pathogenesis. Since ACF were first 
      detected in carcinogen-treated mice, research efforts have focused on these 
      microscopically visible lesions both in animal and human models. ACF show 
      variable histological features, characterized by Kudo (20) and, therefore, can be 
      grouped into differing categories by in vivo examination with 
      high-magnification-chromoscopic-colonoscopy (HMCC). As expected, ACF are more 
      frequently detected in distal animal and human colons coinciding with the 
      geographic distribution of colorectal cancer (CRC). Various proteomic (Prot) 
      markers may be altered within ACF suggesting possible prospective pathological 
      changes. These markers include Calreticulin, Transgelin, Serotransferrin, 
      Triphosphate isomerase and Carbonic anhydrase II. Other markers of importance 
      include carcinoembryonic antigen (CEA), B-catenin, placental cadherin 
      (P-cadherin), epithelial cadherin (E-cadherin), inducible nitric oxide synthase 
      (iNOS), cyclooxygenase (COX-2) and P16INK4a. Genetic mutations of K-ras, B-Raf 
      APC and p53 have been demonstrated in ACF as well as the epigenetic alterations 
      of CpG island methylation. Genomic instabilities (GI), illustrated by a higher GI 
      Index (GII), microsatellite instability (MSI), loss of heterozygosity (LOH) and 
      defects in mismatch repair (MMR) systems, are also expressed. These 
      transformations may lead to the identification of the earliest pathological 
      features initiating colon tumorigenesis. In this review, the advances in ACF 
      research as precursors of CRCs are highlighted.
FAU - Alrawi, Sadir J
AU  - Alrawi SJ
AD  - Division of Gastrointestinal Surgery, Department of Surgical Oncology, Roswell 
      Park Cancer Institute, Buffalo, NY 14263, USA. Sadir.Alrawi@RoswellPark.org
FAU - Schiff, Michael
AU  - Schiff M
FAU - Carroll, Robert E
AU  - Carroll RE
FAU - Dayton, Merril
AU  - Dayton M
FAU - Gibbs, John F
AU  - Gibbs JF
FAU - Kulavlat, Mahmood
AU  - Kulavlat M
FAU - Tan, Dongfeng
AU  - Tan D
FAU - Berman, Kevin
AU  - Berman K
FAU - Stoler, Daniel L
AU  - Stoler DL
FAU - Anderson, Garth R
AU  - Anderson GR
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
SB  - IM
MH  - Animals
MH  - Colorectal Neoplasms/genetics/metabolism/*pathology
MH  - Humans
MH  - Intestinal Mucosa/metabolism/pathology
MH  - Precancerous Conditions/genetics/metabolism/*pathology
RF  - 158
EDAT- 2006/02/16 09:00
MHDA- 2006/03/10 09:00
CRDT- 2006/02/16 09:00
PHST- 2006/02/16 09:00 [pubmed]
PHST- 2006/03/10 09:00 [medline]
PHST- 2006/02/16 09:00 [entrez]
PST - ppublish
SO  - Anticancer Res. 2006 Jan-Feb;26(1A):107-19.