Abstract
Individual colorectal adenomas have different propensities to progress to invasive disease. In this study, we explored whether 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 6 related carcinomas. All samples were measured for their DNA ploidy status. Centromere probes for chromosomes 17 and 18, as well as gene-specific probes for SMAD7, EGFR, NCOA3, TP53, MYC, and RAB20 were assessed by multicolor 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). Furthermore, aberrations of NCOA3, MYC, and RAB20 were 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.
| Original language | English |
|---|---|
| Journal | Modern Pathology |
| Volume | 24 |
| Issue number | 4 |
| Pages (from-to) | 542-555 |
| Number of pages | 14 |
| ISSN | 0893-3952 |
| DOIs | |
| Publication status | Published - 01.04.2011 |
Funding
We express our gratitude to Timo Gemoll, Buddy Chen and Joseph Cheng for IT support, to Ulla Aspenblad and Inga Maurin for excellent assistance with immunohistochemistry, to Marco Gerling and Gisela Grosser-Pape for excellent assistance with image cytometry, and to Elke Gheribi and Regina Kaatz for clinical sample and data collection. This project was supported by the Intramural Research Program of the NIH, National Cancer Institute and by the Werner und Klara Kreitz-Foundation, Schles-wig-Holstein, Germany. CAB received a stipend by the DAAD (Deutscher Akademischer Austausch-dienst) and a travel grant by the Boehringer Ingelheim Fond (BIF), Germany. This study was performed in collaboration with the North German Tumorbank Colorectal Cancer (DKH no. 108446) and the Surgical Center for Translational Oncology— Lübeck (SCTO-L).
