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EPV139/#616 TP53 mutations differentially affect prognosis of endometrial cancer: an in-silico approach
  1. D Das Ghosh1,2,
  2. R Roy Chowdhury1,3 and
  3. S Roychoudhury1,2
  1. 1Kolkata Gynecological Oncology Trials and Translational Research Group (KolGOTrg), Endometrial Cancer, Kolkata, India
  2. 2Saroj Gupta Cancer Centre and Research Institute, Basic and Translational Research, Kolkata, India
  3. 3Saroj Gupta Cancer Centre and Research Institute, Gynecoloic Oncology, Kolkata, India


Objectives The Cancer Genome Atlas cohort of endometrial carcinoma (TCGA-UCEC) consists of 40.3% (214/530) of TP53-mutants. TP53 mutation-spectrum consists of missense and truncated mutations yielding loss-of-function/gain-of-function (GOF) and only loss-of-function effects, respectively. of the four TCGA-defined molecular categories, namely, prognostically superior POLE, MSI, ‘copy number low’ and prognostically worst ‘copy number high’, the last includes TP53-mutants. We have compared progression free survival (PFS) among missense, truncated and most frequent GOF TP53-mutants, in the context of overlapping mutations in POLE and/or MSI-specific genes.

Methods Our study is based on mutation-analysis from TCGA-UCEC categorizing cases into TP53-mutants, POLE-mutants and MSI-specific gene-mutants. Mutational overlap is termed as ‘mixed’. MSI-status is based on mutations in MSH2/MSH3/MSH6/MLH1/MLH3/PMS1/PMS2.

Results PFS of TP53 truncated-only (n=37) and TP53 truncated-mixed (group-A) (n=12) differed significantly (p,log-rank=0.013) unlike that among TP53 missense-only (n=123), TP53 truncated-only, and TP53 missense-mixed (n=21) (p,log-rank=0.305). GOF TP53 Y220C (group-B) (n=6) depicted better PFS. There was no difference in PFS of group-A or group-B from those having POLE mutated wild-type TP53 (group-C) (p,log-rank=0.582) (n=9). Together, group-A and group-B showed lower risk (HR=0.087; 95%CI = 0.012 - 0.638; p=0.016) and better PFS compared to other TP53 mutations (p,log-rank=0.010).

Conclusions Clinically, group-A and group-B behave like group-C, having better prognosis. Therefore, these patients may escape adjuvant therapy despite their TP53-mutant status. The subset of cases who would benefit from this comprise 8.41% (group-A + group-B = 18/214*100) of the TP53-mutant cases or 3.39% (group-A + group-B = 18/530*100) as opposed to the repoetedly acclaimed 1.69% (group-C = 9/530*100) of total cases.

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