β-catenin expression and allelic loss at APC in sporadic colorectal carcinogenesis

被引:25
作者
Hao, XP [1 ]
Frayling, IM
Willcocks, TC
Han, W
Tomlinson, IPM
Pignatelli, MN
Pretlow, TP
Talbot, IC
机构
[1] St Marks Hosp, Acad Dept Pathol, Harrow, Middx, England
[2] St Marks Hosp, Imperial Canc Res Fund, Colorectal Canc Unit, Harrow, Middx, England
[3] Biogenex, San Ramon, CA 94583 USA
[4] Univ Westminster, Sch Biosci, London W1R 8AL, England
[5] Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA
[6] Imperial Canc Res Fund, Mol & Populat Genet Lab, London WC2A 3PX, England
[7] Hammersmith Hosp, Imperial Coll, Sch Med, Dept Histopathol, London, England
[8] Univ Cambridge, Addenbrookes Hosp, Dept Med Genet, Mol Genet Lab, Cambridge CB2 2QQ, England
关键词
APC; allele loss; beta-catenin; colorectum; adenoma; carcinoma;
D O I
10.1007/s00428-001-0570-0
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
beta-catenin is involved in E-cadherin-mediated cell adhesion, intracellular signal transduction, and also interacts with adenomatous polyposis coli (APC) protein. We previously found that 31% of colorectal adenomas and 84% of carcinomas showed reduced membranous staining of beta-catenin, while 46% of adenomas and 79% of carcinomas displayed beta-catenin nuclear expression. Importantly, a reciprocal relationship between reduced membranous and increased nuclear beta-catenin expression was demonstrated in the development from adenoma to carcinoma. To clarify whether this relates to an abnormality of the APC gene (APC), we have now studied allele loss in microdissected tissues from 74 adenomas and 21 carcinomas (sporadic cases, previously immunostained for P-catenin) by analysis of the microsatellites D5S346, D5S82 and D5S299. Fifty-five tumors (57.8%) showed allele loss at APC (no difference between adenomas and carcinomas). Thirty-one of these 55 (31/55, 56.4%) displayed both increased nuclear localization and reduced membranous staining of beta-catenin, and thirteen tumors (13/55, 23.6%) manifested either nuclear expression without changes in membranous expression or reduced membranous staining without nuclear expression (9 and 4 cases, respectively), while 11 (11/55, 20.0%) preserved normal membranous expression. Adenomas and carcinomas showing both nuclear and reduced membranous expression of beta-catenin, compared with those with normal membranous expression, tended to show allele loss (P<0.01). In addition, 24 (24/95, 25.6%) tumors showed a change in the pattern of beta-catenin expression, but did not exhibit allele loss. These results suggest that although there may be a number of mechanisms responsible for changes in beta-catenin expression in colorectal tumors, dysfunction of APC may be the major cause of this phenomenon.
引用
收藏
页码:362 / 366
页数:5
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