Abstract: |
Background: Chromosome imbalances occur in many cancers and represent important biological properties of tumours. However, measurements of such imbalances are difficult. We used a new, quantitative approach to investigate the prognostic value of chromosome imbalances in early-stage colorectal cancers. Methods: We studied 180 patients with no evidence of lymph-node or distant metastases at the time of surgery. DNA from paraffin-embedded tumours was tested for imbalances of chromosome 8p and 18q by digital SNP (single-nucleotide polymorphism) - a technique in which each allele in a sample is directly counted. Surviving patients had median follow-up of 68 months, and disease recurrence was used as the clinical endpoint. Findings: Tumours were divided into three groups: "L" tumours (n = 93) had allelic imbalances of chromosomes 8p and 18q, "L/R" tumours (n = 60) had allelic imbalances of either chromosome 8p or 18q but not both, and "R" tumours (n = 27) retained allelic balance for both chromosomes. 5-year disease-free survival was 100% (95% CI 80-100) for patients with R tumours, 74% (61-87) for patients with L/R tumours, and 58% (47-69) for those with L tumours. These differences were significant (p < 0.0001) and were independent of other variables - eg, Duke's stage A tumours of class L were much more likely to recur than Duke's stage B tumours of class R (p = 0.002). Interpretation: In patients without metastasis, allelic imbalance is a better predictor of prognosis than histopathological stage. |
Keywords: |
adult; cancer survival; controlled study; human tissue; aged; disease-free survival; middle aged; survival rate; major clinical study; single nucleotide polymorphism; polymorphism, single nucleotide; disease course; histopathology; cancer staging; follow up; lymph node metastasis; colorectal cancer; allele; metastasis; neoplasm recurrence, local; gene frequency; heterozygote; chromosomes, human, pair 8; prediction; colorectal neoplasms; chromosome aberration; neoplasm metastasis; recurrent disease; chromosome 8p; tumor; technique; genetic markers; chromosome 18q; chromosomes, human, pair 18; allelic imbalance; humans; prognosis; human; male; female; priority journal; article
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