Prognostic significance of K- ras and TP53 mutations in the ... : Diseases of the Colon & Rectum (original) (raw)

Original Contributions: PDF Only

Prognostic significance of K- ras and TP53 mutations in the role of adjuvant chemotherapy on survival in patients with dukes C colon cancer

Bleeker, W. A. M.D.1; Hayes, V. M. Ph.D.2; Karrenbeld, A. M.D., Ph.D.3; Hofstra, R. M. W. Ph.D.2; Verlind, E. Ph.D.2; Hermans, J. Ph.D.4; Poppema, S. M.D., Ph.D.3; Buys, C. H. C. M. Ph.D.2; Plukker, J.Th M. M.D., Ph.D.1

1From the Department of Surgery/Surgical Oncology

University Hospital Groningen

Groningen

2the Department of Medical Genetics

University Hospital Grontingen

Groningen

3the Department of Pathology

University Hospital Grontingen

Groningen

4Department of Medical Statistics

Leiden University Medical Center

Leiden

the Netherlands

Supported by a grant form the Netherlands Cancer Foundation (NKB/KWF).

Presented at the European Cancer Conference, Vienna, Austria, Sept 13 to 16, 1999.

Abstract

PURPOSE:

Mutations in K- ras and TP53 genes are common in colorectal cancer. They affect biologic behavior and might influence chemotherapy susceptibility in these tumors. We investigated whether the survival of patients with Dukes C colon cancer treated with adjuvant chemotherapy is influenced by K- ras and TP53 mutations.

METHODS:

Mutation screening of the hot spots of the K- ras gene and of the evolutionarily conserved regions of the TP53 gene was performed by denaturing gradient gel electrophoresis technique in formalin-fixed paraffin-embedded specimens of 55 consecutive patients with Dukes C colon cancer treated with adjuvant 5-fluorouracil-based chemotherapy. The median follow-up was 47 (range, 32-66) months.

RESULTS:

Alterations in the mutation hot spots of K- ras were found at codon 12 (n=11) and 13 (n=4) in 15 of the 55 carcinomas (27 percent). No mutation was found at codon 61. Mutations of a probably causative nature in the evolutionarily conserved regions (exons 5-8) of the TP53 gene were found in 24 tumors (44 percent). K- ras and TP53 mutations were found equally in the group with recurrent disease (7/26 (26 percent) and 12/27 (44 percent), respectively) and in the group without recurrences (8/28 (24 percent) and 12/28 (43 percent), respectively). Cancer-specific survival did not differ significantly between patients with K- ras or TP53 or both mutated and nonmutated tumors, respectively (log-rank test: K- ras, P =0.72 and TP53, P =0.77; K- ras and TP53, P =0.8). Also, potentially aggressive K- ras codon 12 and 13 mutations had the same survival as tumors without these mutations (log-rank test; P =0.73).

CONCLUSIONS:

Patients with K- ras or TP53 or both mutated Dukes C colon tumors have the same survival as nonmutated tumors when treated with adjuvant chemotherapy. These data suggest that mutations in K- ras or TP53 alone are not prognostic indicators in patients with Dukes C colon cancer receiving adjuvant 5-Fluorouracil-based therapy.