Abstract 3546: Prevalence of Lynch Syndrome among Middle Eastern endometrial cancer using targeted next generation sequencing

Endometrial carcinoma (EC) is the second most common gynecologic cancer worldwide. Although most ECs are sporadic, 2%-5% tend to be familial, with Lynch syndrome (LS) being the most commonly associated. The purpose of this study was to identify the incidence of LS in a large cohort of Middle eastern ECs and determine the feasibility of microsatellite instability (MSI) screening by immunohistochemistry (IHC) followed by molecular screening in deficient cases. We performed screening of 436 unselected EC for MSI status using IHC, followed by Target Capture sequencing of MSI deficient cases. MLH1 methylation analysis was performed by Real-time PCR, for cases showing deficient MLH1 by IHC. Complete loss of tumor nuclear protein expression in at least one of the four MMR genes was noted in 12.2% (53/436) of EC cases with 32 cases being MLH1 deficient, 10 MSH2 deficient, five MSH6 deficient and six PMS2 deficient. Of the 53 EC cases showing loss of expression in MMR genes, germline MMR mutations were found in four cases (0.9%). Promoter methylation analysis of 32 MLH1 deficient cases showed four cases to be unmethylated (12.5%). Our current study highlights the incidence of LS among patients with EC in Saudi Arabia. Screening of all EC patients using immunohistochemistry and reflex MLH1 promoter methylation testing followed by gene sequencing is feasible and desirable. Citation Format: Sandeep K. Parvathareddy, Abdul K. Siraj, Rong Bu, Tariq Masoodi, Saud Azam, Wael Haqawi, Khadija Alobaisi, Maha Alrasheed, Valorie Balde, Nabil Siraj, Mark R. Diaz, Laila Ghazwani, Felisa DeVera, Hassan AlDossari, Khawla S. Al-Kuraya. Prevalence of Lynch Syndrome among Middle Eastern endometrial cancer using targeted next generation sequencing [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3546.