Effect of TP53 mutation status on survival in the MAGIC trial.

Abstract

71 Background: In oesophagogastric cancer TP53 mutation may be prognostic and/or predict for chemoresistance, however available data are conflicting. We hypothesised that TP53 status would impact on survival for patients (pts) randomised to surgery alone or perioperative ECF chemotherapy in the MRC MAGIC trial. Methods: Genomic DNA FFPE tissue sections were extracted with QIAmp DNA FFPE Tissue Kit (Qiagen, Hilden, Germany). Mutations in exons 4-9 were screened for by fluorescent PCR -amplification of genomic DNA, followed by Capillary Electrophoresis-Single Strand Conformational Analysis (CE-SSCA). Mutations were characterised by bi -directional Sanger sequencing analysis performed on an independent PCR -reaction and the sequencing results were compared to the reference sequences in the COSMIC database. TP53 status was correlated with demographics and survival. Results: TP53 results were available on 154 pts (50% of pts with available DNA). The remainder failed CE-SSCA due to degraded DNA. Pts with/without TP53 data had similar demographics and survival. TP53 mutation was detected in 51/154 (33%) samples. Exon 4, 5, 6, 7 and 8 mutations occurred in 4%, 42%, 8%, 36% and 10% of specimens with a TP53 result. Pts with TP53 mutations were more likely to have an oesophageal or junctional tumor (vs. gastric) than TP53 wild type (WT) pts (38% vs. 17% respectively p = 0.016). Survival from surgery was comparable for pts with mutant and WT TP53 tumors in both arms of the trial (See Table). P-value for interaction between treatment group and TP53 status was 0.776, indicating no interaction was present. Conclusions: In the MAGIC trial, TP53 mutation status was not prognostic, and did not predict for lack of benefit from chemotherapy. Further study is required in order to evaluate the effect of differing TP53 mutations on treatment and survival. [Table: see text]