K-ras2 activation and genome instability increase proliferation and size of FAP adenomas

The possible role of K-ras2 mutations and aneuploidy toward increase of pro liferation and adenoma size in Familial Adenomatous Polyposis (FAP) adenoma s is not known. The present study addresses these issues by investigating 1 47 colorectal adenomas obtained from four FAP patients. The majority of ade nomas had size lower than or equal to 10 mm (86%), low grade dysplasia (63% ), and were preferentially located in the right colon (60%). Normal mucosa samples were obtained from 19 healthy donors. Three synchronous adenocarcin omas were also investigated. K-ras2 mutation spectrum was analysed by PCR a nd Sequence Specific Oligonucleotide (SSO) hybridization, while flow cytome try (FCM) was used for evaluating degree of DNA ploidy and S-phase fraction . Overall, incidences of K-ras2 mutations, DNA aneuploidy and high S-phase values (>7.2%) were 6.6%, 5.4% and 10.5%, respectively. In particular, amon g the adenomas with size lower than 5 mm, K-ras2 mutation and DNA aneuploid y frequencies were only slightly above 1%. Statistically significant correl ations were found between K-ras2 and size, DNA ploidy and size and K-ras2 a nd S-phase (p < 0.001). In particular, among the wild type K-ras2 adenomas, high S-phase values were detected in 8% of the cases versus 57% among the K-ras2 mutated adenomas (p = 0.0005). The present series of FAP adenomas in dicates that K-ras2 activation and gross genomic changes play a role toward a proliferative gain and tumour growth in size.