Clinical significance of mutator phenotype and chromosome 17p and 18q allelic loss in gastric cancer

Background: Tumour stage is the only reliable prognostic factor for gastric cancer. The molecular anomalies involved in this process have the potential to serve as additional prognostic markers. Methods: Forty-four gastric cancers, treated by surgery alone, have been analysed for chromosome 17p and 18q allelic loss and for the presence of microsatellite instability (MSI), using microsatellite markers and DNA from paraffin-embedded tumours. Results: Eight cancers showed a MSI-positive (MSI+) phenotype. Among the 36 MSI-negative cancers, chromosome 17p and 18q allelic losses were found in 22 of 34 and 19 of 33 informative cases respectively. Multivariate survival analysis indicated MSI status to be an independent prognostic factor along with the tumour stage. MSI+ cancers were associated with longer patient survival, whereas MSI-negative cancers had a significantly poorer prognosis (P = 0.007), with a median actuarial survival of 24 months. Conclusion: MSI status is an independent prognostic factor among gastric cancers at the same stage. Chromosome 17p and 18q status added no additional prognostic information to that of tumour stage. The combined use of tumour stage and MSI status may help in deciding whether patients with advanced gastric cancer require additional therapy other than surgery alone.