Genomic alterations (LOH, MI) on chromosome 17q21-23 and prognosis of sporadic colorectal cancer

Genomic alterations at the long arm of chromosome 17, and in particular at the nm23 locus, are still controversial in colorectal cancer (CRC). Our aim was to investigate the possible relationship of loss of heterozygosity (LO H) and microsatellite instability (MI), at 4 microsatellite loci spanning t he 17q21-23 region, to the risk of liver metastasis and nm23 protein expres sion. Genomic DNA extracted from 58 primary and 54 liver secondary formalin -fixed and paraffin-embedded CRCs was obtained from 82 patients. A fluoresc ent PCR coupled with an automated DNA sequencer was applied. Increasing fra ction of loci showing LOH was positively associated with risk of liver meta stases (logrank test for trend, p, = 0.005); this remained independent afte r adjusting to T-stage (Cox regression, p = 0.022), N-stage (p = 0.007), or Dukes' stage (p = 0.012). Conversely, increasing frequency of MI was assoc iated with a reduced risk of liver metastases in Dukes' B tumours (logrank test for trend, p = 0.032). When comparing 30 primary and matched liver sec ondary lesions, we found concordant genomic alteration in 72% (NMEI) to 43% (D 17S579). Finally, we observed a trend in association between the propor tion of loci with LOH and nm23 positivity (chi(2) test for trend, p = 0.024 ). Our findings suggest that genomic alterations in the 17q21-23 region may affect prognosis of CRC as well as regulation of the nm23 protein expressi on via an unknown underlying mechanism. (C) 2000 Wiley-Liss, Inc.