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Analytical Cellular Pathology
Volume 19 (1999), Issue 1, Pages 39-46

K-ras2 Activation and Genome Instability Increase Proliferation and Size of FAP Adenomas

Anna Rapallo,1 Andrea Sciutto,1 Elio Geido,1 Roberto Orecchia,1 Edmondo Infusini,1 Natalija Pujic,1 Emanuele S.G. d’Amore,2 Roberto Monaco,3 Mauro Risio,4 Francesco P. Rossini,5 and Walter Giaretti1

1Laboratory of Biophysics and Cytometry, National Cancer Institute (IST), Genoa, Italy
2Pathology Service, University of Padua, Italy
3Pathology Service, Cardarelli Hospital, Naple, Italy
4Pathology Service, National Institute for Cancer Research and Treatment, Candiolo, Turin, Italy
5Service of Gastroenterology, ASL1, S. Giovanni Vecchio Hospital, Turin, Italy

Received 10 August 1999; Accepted 23 September 1999

Copyright © 1999 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The possible role of K‐ras2 mutations and aneuploidy toward increase of proliferation and adenoma size in Familial Adenomatous Polyposis (FAP) adenomas is not known. The present study addresses these issues by investigating 147 colorectal adenomas obtained from four FAP patients. The majority of adenomas 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 adenocarcinomas were also investigated. K‐ras2 mutation spectrum was analysed by PCR and Sequence Specific Oligonucleotide (SSO) hybridization, while flow cytometry (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, among the adenomas with size lower than 5 mm, K‐ras2 mutation and DNA aneuploidy frequencies were only slightly above 1%. Statistically significant correlations were found between K‐ras2 and size, DNA ploidy and size and K‐ras2 and S‐phase (p). 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 indicates that K‐ras2 activation and gross genomic changes play a role toward a proliferative gain and tumour growth in size.