Abstract 2875: ATAD2 overexpression indentifies aggressive endometrial carcinomas

Abstract

Abstract Background Upregulation of the gene ATAD2 has been implicated in cancer development and progression in a number of tissues, and reported to be a member of prognostic gene-signatures in breast (van 't Veer et al, 2002; Wang et al, 2005) and endometrial cancers (Salvesen et al, 2009). We have investigated ATAD2 protein expression in relation to prognosis and gene expression alterations relevant for potential biological driver mechanisms and treatment targets in endometrial cancer. Methods: A total of 564 endometrial carcinoma primary lesions were prospectively collected and explored for ATAD2 protein expression in relation to survival and established markers for aggressive disease. Transcriptional alterations related to ATAD2 protein level were investigated by microarray analysis for 236 freshly frozen samples in parallel. Differentially expressed genes were identified using the significance analysis of microarray (SAM) method, and GSEA analysis was performed using the MSigDB version 4.0 C2 collection http://www.broadinstitute.org/gsea/msigdb/index.jsp). Results: High ATAD2 expression is significantly associated with the established clinical-pathological variables for aggressive endometrial cancer high FIGO stage, non-endometrioid subtype, high grade, aneuploidy, loss of hormone receptors and poor overall survival (all P-values≤0.001), also in the subset of ERα positive tumors. mRNA and protein expression for ATAD2 was highly correlated (p<0.001), suggesting that immunohistochemical staining may represent a more clinically applicable measure for mRNA levels for ATAD2 level in routinely collected formalin fixed paraffin embedded specimens. Gene expression alterations in samples with high ATAD2 expression revealed upregulation of several cancer-related genes (CDCs, E2Fs) and gene sets that previously has been linked to aggressive disease and potential for targeting new therapies. Conclusion: Our results support that immunohistochemical staining for ATAD2 may be a clinically applicable biomarker reflecting clinical phenotype and targetable alterations in endometrial carcinomas to be further explored in controlled clinical trials. Salvesen HB et al (2009) Proc Natl Acad Sci U S A 106(12): 4834-9 van 't Veer LJ et al (2002) Nature 415(6871): 530-6 Wang Y et al (2005) Lancet 365(9460): 671-9 Citation Format: Camilla Krakstad, Ingvild Løberg Tangen, Maria B. Raeder, Erling Hoivik, Kanthida Kusonmano, June X. Zou, Anne M. Øyan, Jone Trovik, Hongwu Chen, Karl Henning Kalland, Helga B. Salvesen. ATAD2 overexpression indentifies aggressive endometrial carcinomas. [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 2875. doi:10.1158/1538-7445.AM2014-2875