ASSESSMENT OF GENOMIC DAMAGE IN COLORECTAL-CANCER BY DNA-FINGERPRINTING - PROGNOSTIC APPLICATIONS

Purpose: Here we evaluate the prognostic significance of the relative value of genomic damage assessed by DNA fingerprinting in colorectal c ancer. Materials and Methods: Sixty-three tumor and paired normal muco sa samples were included in the study, Genomic damage was assessed by comparative analysis of paired normal and tumor tissue DNA fingerprint s by the arbitrarily primed polymerase chain reaction (AP-PCR). Decrea ses and increases of intensity in bands were computed and referred to the total number of visualized bands per case, An index reflecting the genomic damage fraction (GDF), with separated values for losses and g ains, was obtained for each tumor. This index was used to determine mo lecular and clinicopathologic correlates after exclusion of eight case s displaying microsatellite instability. Results: Fifty-five cases wer e considered for the statistical analysis. The average fraction of alt ered bands per tumor was 0.287 +/- 0.121, When losses and gains were c omputed separately, the average fraction of changes was 0.126 +/- 0.11 3 and 0.161 +/- 0.120, respectively. Tumors lacking a ras mutation sho wed an increased GDF, primarily because of a higher fraction of gains, Tumors that were at advanced Dukes' stages and that were poorly diffe rentiated also displayed a higher GDF. Finally, disease-free survival was significantly diminished in tumors with a GDF greater than 0.314 ( P<.001). The prognostic significance of the GDF was independent of Duk es' stage (Cox multivariate analysis, P = .005). Conclusion: The degre e of genomic damage assessed by unbiased DNA fingerprinting correlates with genotypic, phenotypic, and clinical variables in colorectal carc inoma and may be useful in assessing prognosis in colorectal cancer. ( C) 1997 by American Society of Clinical Oncology.