Al-Mulla F et al. (2006) Genetic profiling of stage I and II colorectal cancer may predict metastatic relapse. Mod Pathol 19: 648–658

Al-Mulla F et al. (2006) Metastatic recurrence of early-stage colorectal cancer is linked to loss of heterozygosity on chromosomes 4 and 14q. J Clin Pathol 59: 624–630

Patients who present with early-stage colorectal cancer without metastasis (Dukes' stage A or B) typically undergo surgery without adjuvant therapy. Despite having apparently low-risk disease, 10–40% of these patients relapse after surgery, and up to 50% die from complications or metastasis. Molecular markers that can predict relapse in patients with early-stage colorectal cancer are being investigated, but previous studies analyzed only a few candidate markers.

Al-Mulla and colleagues' study enrolled 70 patients with early-stage, nonmetastatic colorectal cancer. Tumor samples from 27 patients who relapsed after surgery were compared with samples from 43 patients who did not relapse during follow-up (range 2–9 years). The authors used comparative genomic hybridization to identify chromosomal aberrations in a total of 61 tumors; their findings were confirmed by DNA microarray analysis of 10 tumors.

This genome-wide analysis identified many abnormalities that correlated with relapse of early-stage colorectal cancer after surgery, including loss of chromosomes 1p, 4, 5q, 8p, 9p, 14q, and 18p, and gain of chromosomes 1q, 8q, and 13q. Notably, samples from patients who relapsed were more likely to have multiple aberrations (e.g. loss of both 8p and 18q, and loss of both 4 and 14q). These specific multiple aberrations were associated with markedly short survival after surgery. Loss of chromosome 4 independently predicted poor survival.

The same team has recently used an unrelated technique (analysis of highly polymorphic microsatellite markers) to narrow down the deletions on chromosomes 4 and 14 to specific regions.