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Genetic Tumor Markers With Prognostic Impact in Dukes’ Stages B and C Colorectal Cancer Patients

Chieu B. Diep, Lin Thorstensen, Gunn Iren Meling, Eva Skovlund, Torleiv O. Rognum, Ragnhild A. Lothe

From the Department of Genetics, Institute for Cancer Research, and the Department of Surgery, The Norwegian Radium Hospital; Institute of Forensic Medicine, The National Hospital; and Section of Medical Statistics, University of Oslo, Oslo, Norway.

Address reprint requests to Ragnhild A. Lothe, PhD, Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway; email: rlothe{at}radium.uio.no.

Purpose: To examine several genetic changes in primary colorectal carcinomas (CRCs) from patients with 10 years of follow-up and associate the findings with clinicopathologic variables.

Material and Methods: DNA from 220 CRCs were analyzed for allelic imbalances at 12 loci on chromosome arms 1p, 14q, 17p, 18q, and 20q, and the microsatellite instability (MSI) status was determined. The clinical significance of the tumor protein 53 (TP53) mutations was re-evaluated.

Results: Patients with tumors containing 17p or 18q deletions had shorter survival than those without these alterations (P = .021, P = .008, respectively). This was also significant for the Dukes’ B group (P = .025, P = .010, respectively). Furthermore, patients with tumors showing losses of both chromosome arms revealed an even poorer disease outcome than those with either 17p or 18q loss. Patients with low increase in 20q copy number in their tumors had longer survival compared with those without changes (P = .009) or those with a high increase of copy number (P = .037). This was also evident for the Dukes’ C group (P = .018, P = .030, respectively). MSI was seemingly a beneficial marker for survival (P = .071). A significant association between mutations affecting the L3 zinc-binding domain of TP53 and survival was confirmed in this cohort after 10 years of follow-up, and also was found to apply for patients in the Dukes’ B group. Several associations were found among genetic and pathologic data.

Conclusion: The present study indicates that 17p, 18q, and 20q genotypes, and TP53 mutation status add information in the subclassification of Dukes’ B and C patients and may have impact on the choice of treatment.

Supported by the Norwegian Foundation for Health and Rehabilitation (C.B.D.) and the Norwegian Cancer Society (L.T., R.A.L.).

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