Genomic instability and oncogene amplifications in colorectal adenomas predict recurrence and synchronous carcinoma

Individual colorectal adenomas have different propensities to progress to invasive disease. Here, we explored if these differences could be explained by gene copy number alterations. We evaluated 18 adenomas of patients without synchronous or subsequent carcinoma (6.5 years follow up), 23 adenomas of carcinoma patients and six related carcinomas. All samples were measured for their DNA ploidy status. Centromere probes for chromosome 17 and 18 as well as gene specific probes for SMAD7, EGFR, NCOA3, TP53, MYC, and RAB20 were assessed by multi-colour fluorescence in-situ hybridization. An increased genomic instability index of CEP17, SMAD7 and EGFR as well as TP53 deletions and MYC amplifications defined adenomas of patients with synchronous carcinoma (p<0.05). Diploid NCOA3 signal counts were associated with longer adenoma-recurrence free surveillance (p=0.042). In addition, NCOA3-, MYC-, EGFR- and RAB20- amplifications as well as TP53 deletions correlated with increased DNA stem line values and/or aneuploidy in adenomas (p<0.05). Aberrations of NCOA3, MYC, and RAB20 were furthermore associated with histopathologically defined high-risk adenomas (p<0.05). RAB20 amplifications were also correlated with high-grade dysplastic adenomas (p=0.002). We conclude that genomic instability in colorectal adenomas is reflected by EGFR-, MYC-, NCOA3-, and RAB20-amplifications that do correlate with histomorphological features and are indicative for adenoma recurrence and the presence of synchronous carcinomas.