Mikrosatellitenanalyse und p53-Mutationsanalyse zur Responseprädiktion bei lokal fortgeschrittenen neoadjuvant therapierten Magenkarzinomen
Former published data of our group suggested that a high rate of LOH in the tumors including LOH at chromosome 17p13 might be associated with good clinical response to neoadjuvant cisplatinum-based chemotherapy in gastric cancer . In this study we extended our analysis to evaluate the influence of chromosomal instability and p53-mutation on therapy response.
Pretherapeutic biopsies of 53 patients were studied at 11 microsatellite loci. A peak allele ration < 0.6 was considered as LOH. p53 mutation analysis was performed by DHPLC (denaturating high pressure chromatography) and direct sequencing.
53 patients were included. 49 Patients were resected. 21 were clinical responders. In respect to histopathological response 14 of the 49 resected patients were classified as responders. 3 tumors showed high microsatellite instability and were not included in LOH and FAL analysis. 15 of the 45 informative tumors exhibited LOH at TP 53. There was a strong assosiation of LOH and clinical response (p = 0.014) and histopathological response (p = 0.02). Tumors of 19 patients had p53 mutations. There was no correlation between response and p53 mutation. Patients with high rate of LOH (FAL > 0,25) showed a significant improved survival (59 vs. 22 months; p = 0.008).
Tumors with a high rate of LOH seem to be more sensitive to this type of therapy. In respect to p53 mutation no association was found.
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