Abstract 5044: Role of obesity in Leptin-Notch crosstalk (NILCO) in endometrial cancer from African American and Chinese women

Abstract

Abstract Introduction: Endometrial cancer is the most common gynecological malignancy of the female reproductive tract. Endometrial cancer is classified into two groups: Type I, which is estrogen dependent, and Type II, which is usually associated with endometrial atrophy and is estrogen independent. Type II is the more aggressive form with a poor prognosis and is often observed more in African American women. Obesity, characterized by high levels of leptin, is a major risk factor for endometrial cancer, which suggests that leptin may play a role in endometrial cancer pathogenesis. Over-expression of Notch, IL-1 and leptin and the signaling crosstalk (NILCO) among these pro-angiogenic factors is associated with metastasis and decreased survival rates in breast cancer patients. However, much is unknown whether this association is found in endometrial cancer. Objective: In this investigation, we aim to determine whether NILCO components are differentially expressed in Type I and Type II endometrial cancer. We hypothesize that there is a positive correlation between endometrial cancer etiology and higher BMI and NILCO expression. We further hypothesize that the correlation is more evident in Type II endometrial cancer. Methods: Expression levels of Notch1, 2, 3 & 4, Jagged-1, DLL4, Survivin, Hey2, IL-1R tI, Leptin, and Ob-R were determined via immunohistochemistry (IHC) in endometrial cancer from overweight/obese African American patients and compared to endometrial cancer tissue array from Chinese women (70 cases of carcinoma and 5 cases of non-malignant duplicated cores per case, US Biomax, Inc). Staining intensity was assigned using semi-quantitative HSCORE [∑pi (i+1), where “i” is the intensity with a value of 1, 2, or 3 (weak, moderate or strong, respectively and “pi” is the percentage of stained cells for each intensity] calculated by two independent observers in 3 different fields (100 cells/each). Western Blot and qPCR analyses of tissue lysates from cancer samples and benign surrounding tissues were also used to examine the expression levels of NILCO components.Student t-test was used to determine statistical differences between samples. Results: IHC results showed that Notch1 and 4, DLL4, Survivin, and Jagged-1 were expressed higher in Type II endometrial cancer patients. IL-1R tI was expressed higher in non-malignant compared to malignant tissue samples. Western blot and qPCR analyses further corroborated these results. Conclusion: The results support our hypothesis that obesity affects the expression of NILCO components, which could be involved in endometrial cancer progression and aggressiveness. [Partially supported by NIH/NCI 1SC1CA138658-05; NIH RR03034,1C06 RR18386, NIH/NCRR 1G12RR026250-03 and MSM/Tuskegee Univ/UAB Cancer Center Partnership grant 5U54CA118638. The National Center for Advancing Translational Sciences of the NIH Award UL1TR000454]. Citation Format: Danielle Daley-Brown, Regina Lee, Gabriela Oprea-Ilies, Emerald Screws, Roland Matthews, Roland Pattillo, Ruben Rene Gonzalez-Perez. Role of obesity in Leptin-Notch crosstalk (NILCO) in endometrial cancer from African American and Chinese women. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5044. doi:10.1158/1538-7445.AM2014-5044