We analyzed a group of gastric
carcinomas treated with a
cisplatin-based
neoadjuvant chemotherapy regimen for
microsatellite instability (MSI) and loss of heterozygosity (LOH) to determine whether there is any relation between microsatellite alterations and
therapy response. Pretherapeutic endoscopic biopsies of 37 patients were studied at 11 microsatellite loci. Thirteen (35%) had a complete or partial clinical response (responders), and 24 (65%) had only a minor or no response (nonresponders). High-grade MSI was found in two
tumors, both nonresponders, whereas low-grade MSI was found in five biopsies, including three non-responders and two responders. Regarding LOH, the most obvious differences between the groups were observed on chromosome 17p13, the location of the p53 gene, with 7 of 12 (58%) and 3 of 20 (15%) of the informative
tumors exhibiting LOH in responders and nonresponders, respectively (P = 0.018). A statistically significant difference was also observed in the fractional allelic loss (FAL) ratio of the groups. Among the 13 responding patients, 7 (54%)
tumors exhibited high FAL (>0.5-0.75), 2 (15%) showed medium FAL (>0.25-0.5), and 4 (31%) demonstrated low FAL values (0-0.25), whereas among the 22 nonresponding patients, 2 (9%)
tumors showed high FAL, 5 (23%) showed medium FAL, and 15 (68%) showed low FAL (P = 0.020). These data suggest that LOH at chromosome 17p13 is associated with a good clinical response to
cisplatin-based
chemotherapy, suggesting that altered p53 function might render cells more sensitive to
therapy. Furthermore, the association of FAL with
therapy response indicates that gastric
carcinomas with a high level of chromosomal alteration may be more sensitive to this type of
chemotherapy.