Therefore, the pedigree was diagnosed as an FAP family with a novel APC germline mutation which had different gastric phenotypes depending on the status of HP infection.
To investigate the role of a defective 8-oxo-G repair we performed a germline mutation screening in the genes OGG1, MTH1 and MUTYH, in 81 patients with a clinical phenotype ranging from attenuated or atypical adenomatous polyposis coli including hyperplastic polyps to hereditary non-polyposis colorectal cancer (HNPCC) type X syndrome without mono- or biallelic mutations in either APC, MUTYH or the DNA mismatch repair genes.
Thus, we performed immunohistochemical analysis of hyperplastic polyps (HP), serrated adenomas (SA), and classical adenomas (tubular adenomas - TA and tubulovillous adenomas - TVA) and carcinomas developed from adenomas (CA) using expression of p53, Ki-67, c-myc, APC, MSH2 and Ets-1 proteins.
We examined the presence of HPs and sessile serrated adenomas (SSAs) in 17 MAP patients and studied the occurrence of G:C-->T:A transversions in the APC and K-ras gene in these polyps.
In this study, 46 serrated adenomas from 39 patients, 32 conventional (nonserrated) adenomas from 31 patients, and 18 hyperplastic polyps from 16 patients were evaluated for loss of heterozygosity (LOH) of APC, p53, p16, and 3p and for K-ras mutations of codons 12, 13, and 61 by polymerase chain reaction (PCR) analysis.
In all samples of normal human and mouse colonic mucosa and in human hyperplastic polyps both APC and beta-catenin immunoreactivity were present in colonocytes.
This subset combines features of the suppressor and mutator pathways, may be more dependent on K-ras than on the APC gene in the early stages of neoplastic evolution, and a proportion may be related histogenetically to the serrated (hyperplastic) polyp.
Four hamartomatous polyps (three from JP and one from PJS) showed seven, new mutations and one common APC variant (codon 486), whereas no hyperplastic polyps demonstrated mutation.
Four patients had a germ-line E1317Q missense variant of APC that was not present in controls; one of these individuals had an unusually large number of metaplastic polyps of the colorectum.
Moreover, the presence of somatic APC mutations in fundic gland polyps suggests that inactivation of the APC gene plays a role not only in forming adenomas but also in forming hyperplastic polyps in fundic gland mucosa, and there may be some additional steps to the adenoma-carcinoma sequence.