Original Articles
Copyright ©The Author(s) 2001. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 15, 2001; 7(3): 352-356
Published online Jun 15, 2001. doi: 10.3748/wjg.v7.i3.352
APC and K-ras gene mutation in aberrant crypt foci of human colon
Ping Yuan, Meng-Hong Sun, Jin-Sheng Zhang, Xiong-Zeng Zhu, Da-Ren Shi
Ping Yuan, Jin-Sheng Zhang, Department of Pathology, Medical College of Fudan University
Meng-Hong Sun, Xiong-Zeng Zhu, Da-Ren Shi, Department of Pathology, Cancer Hospital/Cancer Institute, Fudan University, Shanghai 200032, China
Author contributions: All authors contributed equally to the work.
Correspondence to: Dr. Meng Hong Sun, Department of Pathology, Cancer Hospital/Cancer Institute, Fudan University, Shanghai 200032, China. menghongs@hotmail.com and pingyuan61@hotmail.com
Telephone: +86-21-64175590 Fax: 0086-21-64174774
Received: July 17, 2000
Revised: September 3, 2000
Accepted: September 19, 2000
Published online: June 15, 2001

AIM: To study the genetic alteration in ACF and to define the possibility that ACF may be a very early morphological lesion with molecular changes, and to explore the relationship between ACF and colorectal adenoma even carcinoma.

METHODS: DNA from 35 CRC, 15 adenomas, 34 ACF and 10 normal mucus was isolated by means of microdissection. Direct gene sequencing of K-ras gene including codon 12, 13 and 61 as well as the mutation cluster region (MCR) of APC gene was performed.

RESULTS: K-ras gene mutation frequency in ACF, adenoma and carcinoma was 17.6% (6/34), 13.3% (2/15), and 14.3% (5/35) respectively, showing no difference (P > 0.05) in K-ras gene mutation among three pathologic procedures. The K-ras gene mutation in adenoma, carcinoma and 4 ACF restricted in codon 12 (GGT→GAT), but the other 2 mutations from ACF located in codon 13 (GGC→GAC). K-ras gene mutation was found more frequently in older patients and patients with polypoid cancer. No mutation in codon 61 was found in the three tissue types. Mutation rate of APC gene in adenoma and carcinoma was 22.9% (8/35) and 26.7% (4/15), which was higher than ACF (2.9%) (P < 0.05). APC gene mutation in carcinoma was not correlated with age of patients, location, size and differentiation of tumor.

CONCLUSION: ACF might be a very early morphological lesion in the tumorogenesis of colorectal tumor. The morphological feature and gene mutation status was different in ACF and adenoma. ACF is possibly putative "microadenoma" that might be the precursor of adenoma. In addition, the development of a subgroup of colorectal carcinomas might undergo a way of "normal epithelium→ACF→carcinomas".

Keywords: colorectal carcinoma, aberrant crypt foci (ACF), adenoma, K-ras, APC, DNA sequencing