Abstract 1525: Nuclear homeoprotein SIX1 is associated with stage and grade of endometrial carcinoma.

Abstract

Abstract Introduction: SIX1 is a member of the homeoprotein gene family encoding transcription factors involved in normal embryogenesis. These proteins function in the cell nucleus to regulate transcription of genes that drive differentiation. SIX1 is also aberrantly expressed in numerous human malignancies, including breast, ovarian and cervical carcinomas. In a mouse model, SIX1 initiates transformation of mammary epithelial cells to diverse histologic types of carcinoma. SIX1 has not yet been studied in endometrial carcinoma, which is the most common gynecologic malignancy in the United States. Thus, our goal was to evaluate SIX1 in clinical samples of endometrial carcinoma and determine if there was an association with stage and grade. Methods: A tissue microarray (TMA) was created using endometrial carcinoma cases (n=55) and benign controls (i.e. proliferative, secretory and atrophic endometrium) (n=12). Endometrioid and serous histologic types were included in the carcinoma cases. The TMA was stained using a rabbit polyclonal anti-SIX1 antibody (Sigma). The TMA was then scored in a blinded manner by a single pathologist, using presence versus absence of nuclear staining for the stromal cells and the epithelial cells. Clinical data was collected on these samples to include height, weight, BMI, grade (FIGO 1, 2 or 3) and stage (1A, 1B-2B, 3A-4B). Results: Few controls had nuclear SIX1 in epithelial cells while all controls had nuclear SIX1 in stromal cells. In endometrial cancer samples, there was significantly increased nuclear SIX1 staining in the epithelial cells compared to controls, while there was less nuclear SIX1 in stromal cells. This finding was more pronounced with increasing grade and stage of tumor (Table 1). Conclusions: Nuclear SIX1 expression is associated with increased grade and stage of endometrial cancer. These findings suggest that SIX1 may play a role in the progression of this common cancer and have utility as a marker of more aggressive disease. Table 1. Percentage of uterine samples with nuclear SIX1 staining in epithelial and stromal cells Grade Stage Epithelial Stromal Epithelial Stromal Control 3/12 (25) 12/12 (100) Control 3/12 (25) 12/12 (100) Grade 1 16/22 (72) 13/22 (59) 1A 5/11 (46) 10/11 (91) Grade 2 15/16 (94) 6/16 (38) 1B-2B 26/31 (84) 13/31 (42) Grade 3 14/17 (82) 7/17 (41) 3A-4B 12/13 (92) 3/13 (23) Citation Format: Sara E. Wobker, Wendy N. Jefferson, Carmen J. Williams, Victoria L. Bae-Jump. Nuclear homeoprotein SIX1 is associated with stage and grade of endometrial carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1525. doi:10.1158/1538-7445.AM2013-1525