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Prognostic value of K-ras mutations and allelic imbalance on chromosome 18q in patients with resected colorectal cancer

  • Original Contributions
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Diseases of the Colon & Rectum

Abstract

PURPOSE: We designed this study to assess the frequency of K-ras mutations in patients with resected colorectal tumors and their association with survival. A second objective was to analyze the prognostic value of different K-ras genotypes. In a subgroup of patients we also investigated the presence of allelic imbalance on chromosome 18q and its relationship to clinical outcome. METHODS: One hundred fourteen colorectal tumors resected between 1983 and 1986 were analyzed to detect K-ras point mutations at codons 12, 13, and 61 by polymerase chain reaction followed by allele specific oligonucleotide hybridization. A subgroup of 77 tumors was further screened to detect loss of heterozygosity on chromosome 18q using three polymorphic microsatellite markers (D18S67, D18S474 andD18S58). RESULTS: K-ras mutations were detected in 29 percent (33/114) of patients. K-ras mutations correlated with age and preoperative carcinoembryonic antigen levels, and there was some indication that they may be linked to poor survival, especially in Stage II tumors, where a subgroup of patients with aspartic and serine mutations showed significantly reduced survival (P=0.03) compared with K-ras-negative patients. 18q loss of heterozygosity was present in 39 percent (25/63) of tumors. A multivariate analysis of Stage II tumors showed that 18q loss of heterozygosity was significantly associated with a worse prognosis (P=0.006). A significant decrease in survival was identified in ten patients harboring both genetic alterations (K-i mutations and 18q loss of heterozygosity;P=0.02). CONCLUSIONS: In colorectal tumors, K-ras mutations and 18q loss of heterozygosity are two genetic markers which may identify patients with more aggressive behavior, mainly in Stage II tumors. These findings warrant further research, because they can be useful in customizing adjuvant chemotherapy.

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Authors and Affiliations

  1. From the Medical Oncology Service and the Laboratory of Molecular Biology of Cancer, Hospital Germans Trias i Pujol, Badalona

    Albert Font M.D., Albert Abad M.D., Mariano Monzó M.D., Monica Guillot M.D., Jose L. Manzano M.D. &  Rafael Rosell M.D.

  2. Department of Morphological Sciences, Faculty of Medicine, University of Barcelona, Spain

    Mariano Monzó M.D.

  3. Department of Surgery, Hospital Germans Trias i Pujol, Badalona

    Marta Piñol M.D.

  4. Department of Pathology, Hospital Germans Trias i Pujol, Badalona, Barcelona

    Isabel Ojanguren M.D.

  5. Department of Statistics, Free University of Madrid, Madrid, Spain

    Jose J. Sanchez M.D.

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  1. Albert Font M.D.
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  2. Albert Abad M.D.
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  3. Mariano Monzó M.D.
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  4. Jose J. Sanchez M.D.
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  5. Monica Guillot M.D.
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  9. Rafael Rosell M.D.
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Font, A., Abad, A., Monzó, M. et al. Prognostic value of K-ras mutations and allelic imbalance on chromosome 18q in patients with resected colorectal cancer. Dis Colon Rectum 44, 549–557 (2001). https://doi.org/10.1007/BF02234328

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  • DOI: https://doi.org/10.1007/BF02234328

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