944P - POLE mutations and MSI were positive predictive factors for progression free survival in endometrial cancer patients at the risk of recurrence

Date 09 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Endometrial Cancer
Gynaecologic Malignancies
Translational Research
Presenter Akihiro Nyuya
Citation Annals of Oncology (2017) 28 (suppl_5): v330-v354. 10.1093/annonc/mdx372
Authors A. Nyuya1, J. Haraga2, T. Nagasaka3, K. Nakamura2, T. Haruma2, T. Nishida2, K. YASUI3, T. Fujiwara1, A. Goel4, H. Masuyama2
  • 1Department Of Gastroenterological Surgery, Okayama University Hospital, 700-8558 - Okayama/JP
  • 2Department Of Obstetrics And Gynecology, Okayama University Hospital, 700-8558 - Okayama/JP
  • 3Gastroenterological Surgery, Okayama University Hospital, 700-8558 - Okayama/JP
  • 4Center For Gastrointestinal Research Center For Translational Genomics And Oncology, CeBaylor Scott & White Research Institutenter for Translational Genomics and Oncology, 75246 - Texas/US

Abstract

Background

The Cancer Genome Atlas (TCGA) reported the genomic subgroups of endometrial cancer (EC); POLE mutation, Microsatellite instability (MSI), copy number low, and copy number high. Cancer with POLE mutation or MSI indicates hyper or high mutated, and they are considered to have some potential for good prognosis through immunoactivity in tumor microenvironment. In this study, we investigated the POLE mutation and MSI status in EC, and the correlation between the subtypes and prognosis and considered about the necessity of adjuvant therapy to good prognosis group.

Methods

In this study, we extracted tumor DNA from formalin-fixed, paraffin-embedded tissue of 325 EC tissues surgically resected at Okayama University Hospital.Then, we analyzed MSI status from 4 mononucleotide markers by a multiplex PCR assay and POLE mutation status by Sanger sequence for hot spot mutations (V411L and P286R), and compared with the clinical and pathological outcomes obtained from medical records retrospectively.

Results

MSI cancer accounted for 24.9% (81/325 cases) and POLE mutation cancer accounted for 7.4% (24/325 cases) of the cohort. Progression free survival (PFS) was significantly better in POLE mutation group, followed by MSI group, and the others group. All the 24 POLE mutation patients had no recurrence during the observation period (median: 46.5 months [1∼111months]). Next, we investigated prognosis of the cases limited to those who usually need adjuvant therapy (except for stage IA and G1/2) among three genotype groups. POLE mutation and MSI group was the positive predictive factors for PFS in multivariate analysis.

Conclusions

POLE mutations and MSI were good prognostic factors for EC patients, especially, for EC patients at the risk of recurrence. Our results recommend prospective clinical trials whether adjuvant chemotherapy decreases the risk of recurrence in EC patients with POLE mutations or MSI.

Clinical trial identification

Legal entity responsible for the study

Takeshi Nagasaka

Funding

None

Disclosure

All authors have declared no conflicts of interest.