Loss of heterozygosity and microsatellite instability as predictive markers for neoadjuvant treatment in gastric carcinoma

We analyzed a group of gastric carcinomas treated with a cisplatin-based ne oadjuvant chemotherapy regimen for microsatellite instability (MSI) and los s of heterozygosity (LOH) to determine whether there is any relation betwee n microsatellite alterations and therapy response. Pretherapeutic endoscopi c biopsies of 37 patients were studied at II 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 nonresponders and two responders. Regarding LOH, the most obvious differences between the groups were observed on chromosom e 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 o bserved 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 showe d high FAL, 5 (23%) showed medium FAL, and 15 (68%) showed low FAL (P = 0.0 20), These data suggest that LOH at chromosome 17p13 is associated with a good c linical response to cisplatin-based chemotherapy, suggesting that altered p 53 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 t ype of chemotherapy.