Abstract 1793: POLE gene mutations confer good progression free survival in Asian women with FIGO grade 3 endometrioid endometrial carcinoma
Authors: Wong Adele , Kuick Chik Hong , Wong Wai Loong , Tham Jill M. , Mansor Sorsiah , Eva Loh , Jain Sudhanshi , Chan Sock Hoai , Tan Sze Huey , Li Shao Tzu , Vikas Nadkarni N. , Chew Sung Hock , Ngeow Joanne , Hong Wanjin 
Published: July 2016

Introduction: Endometrial carcinoma (EC) is the most common gynaecological cancer in developed countries. Mortality rates of patients with FIGO grade 3 endometrioid ECs are almost similar to that of uterine serous carcinoma and clear cell carcinoma. In 2013, the Cancer Tumour Genome Atlast (TGCA) identified POLE gene mutations in a subset of ECs, predominantly in the endometrioid subtype with high FIGO grade. While it has been suggested that POLE mutation confers good prognosis, the data remains conflicting. Our study aims to evaluate the association between the POLE gene mutations and progression free survival in Asian women with FIGO grade 3 endometrioid EC.

Methods: Forty-five Asian patients diagnosed with FIGO Grade 3 endometrioid EC between 2009 and 2013 were included. Next generation sequencing (NGS) performed utilizing the Ion Torrent Personal Genome Machine (PGM) and custom designed AmpliSeq panel for formalin fixed embedded (FFPE) tissue was performed. Using the Ion Reporter, mutations with at least 10% allele frequency and present in the COSMIC database were deemed to be pathogenic. All other mutations, excluding silent mutations, were considered as variants of unknown significance (VUS). Survival curves for pathogenic somatic POLE mutated and wild-type tumors were estimated by Kaplan-Meier method and compared using logrank test.

Results: All detected pathogenic and VUS POLE gene mutations were missense mutations. Our results provide further evidence to corroborate the mutation effect of POLE gene with 100% recurrence free survival in FIGO Grade 3 endometrioid EC patients with pathogenic POLE gene mutations, extends to South East Asian women as well (median follow-up POLE vs wild type; 52.5 vs 45; p = 0.2). Pathogenic somatic POLE gene mutations were present in 25.5% (12/45) patients with Grade 3 endometrioid EC. All were still alive at the time of censure with no reports of relapse following initial treatment. Three of these women harbored mutations outside exons 9 to 14 with one mutation listed as pathogenic in colorectal carcinomas. Among women without the pathogenic somatic POLE mutation, recurrence was seen in 24.2% (8/33) with 15.1% (5/33) subsequently dying of the disease.

Conclusion: POLE gene mutations confer a good prognosis for FIGO grade 3 endometrioid EC and will be important in clinical decision making. POLE wild-type patients potentially show have closer follow-up and should be considered for newer targeted chemotherapeutic agents.

Citation Format: Adele Wong, Chik Hong Kuick, Wai Loong Wong, Jill M. Tham, Sorsiah Mansor, Loh Eva, Sudhanshi Jain, Sock Hoai Chan, Sze Huey Tan, Shao Tzu Li, Nadkarni N. Vikas, Sung Hock Chew, Joanne Ngeow, Wanjin Hong. POLE gene mutations confer good progression free survival in Asian women with FIGO grade 3 endometrioid endometrial carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1793.