Abstract
Abstract Endometrial cancer is the most common gynecologic malignancy. The most common histological type is endometrioid endometrial cancer (EEC). While the majority of patients present with early-stage and low-grade EEC and have an excellent prognosis, a subset has metastatic disease at presentation, or develops distant recurrence after initial treatment of the primary. However, the lack of prognostic biomarkers for metastatic EEC is a critical barrier. We have developed a genetically engineered mouse model for metastatic EEC that implicates coexistent Pten and Mig-6 mutations in EEC. Pten mutation in the uterus is not sufficient for distant metastasis, but mice with concurrent ablation of Mig-6 and Pten develop distant metastasis. Arginase 1 (ARG1) regulates the last step of the urea cycle, and an increase in ARG1 has been correlated as a poor prognostic factor in a variety of cancers including ovarian carcinoma, colorectal cancer, and neuroblastoma. In the present study, ARG1 expression was evaluated with immunohistochemistry in endometrial hyperplasia and cancer of mice with Pten mutation as well as Pten and Mig-6 double mutations. Our immunostaining analysis revealed that the expression of ARG1 in early stage of EEC from mice deficient in Mig-6 and Pten mutations significantly increased compared to Pten mutation in the uterus. High levels of ARG1 are associated with distant metastatic endometrial cancer. The results demonstrate that a high level of ARG1 is associated with poor prognosis in association with EEC of mouse. ARG1 has the potential to identify patients that require additional treatment at an early stage of endometrial cancer. Citation Format: Jae-Wook Jeong, Dinh Tran, Valery Rozen, Tae Hoon Kim, Jung-Yoon Yoo. ARG1 is potential prognostic biomarker for development of distant metastatic endometrial cancer in mice with Pten deficiency [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2470.
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