Mutations of the APC gene in human sporadic colorectal cancers.

Abstract:

BACKGROUND:Mutations of the APC gene are reported to occur frequently in sporadic colorectal adenomas and adenocarcinomas. We studied APC gene mutations in cases of human sporadic colorectal cancer in order to evaluate their correlation with pathologic characteristics and clinical prognosis. METHODS:Most of the mutations of the APC gene (95%) are nonsense or frame shift mutations, encoding for truncated APC proteins. For this reason, mutation detection of the APC gene was performed using the in vitro synthesized protein (IVSP) assay, analysing the region between nucleotide 2058 and nucleotide 5079 of the gene, containing the mutation cluster region. RESULTS:Out of 58 cases of colorectal cancer, 29 presented a mutated form of APC (mutation frequency 50%). We did not find a statistically significant correlation between APC gene mutation and age, sex, localization of the primary tumour, grading, Crohn-like lymphoid reaction or presence of residual adenoma. Tumours with low invasivity (Dukes' stages A and B) were less frequently mutated (12/27, 44.5%) than tumours of Dukes' stage C (15 out of 21, 71.4%), which developed macroscopically secondary metastasis with variable latency after surgery. Highly invasive tumours with synchronous metastases (Dukes' stage D) had, instead, a low frequency of APC mutations (20%, 2/10) (P = 0.02, compared with Dukes' stages A, B and C). CONCLUSIONS:These data suggest that more aggressive Dukes' stage D tumours develop metastasis by means of an unknown mechanism, independent of APC mutation.

journal_name

Scand J Gastroenterol

authors

De Filippo C,Luceri C,Caderni G,Pacini M,Messerini L,Biggeri A,Mini E,Tonelli F,Cianchi F,Dolara P

doi

10.1080/003655202320378248

subject

Has Abstract

pub_date

2002-09-01 00:00:00

pages

1048-53

issue

9

eissn

0036-5521

issn

1502-7708

journal_volume

37

pub_type

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