for performing real-time quantitative PCR, Western blot and migra- tion assay. Results: Seventy-four genes (threshold of P b 0.05) including matrix metallopeptidase 1 (MMP1) were down-regulated in lapatinib- treated endometrial cancer cell lines ARK1 and ARK2 (expressed high level of HER2). Further validation showed that lapatinib- suppressed MMP1 expression at the level of both transcription and translation in ARK1 and ARK2 cell lines. Comparing to ARK1 and ARK2, lapatinib-resistant endometrial cancer cell lines of Ishikawa and RL95-2 exhibited lower levels of MMP1. Lapatinib treatment resulted in dephosphorylation of EGFR and HER2, and deactivation of ERK1/2 and PI3K pathway in ARK2 cell line. Knockdown of HER2 and EGFR decreased 2-fold lapatinib-reduced MMP1 expression. MMP1 was also shown to have significantly higher expression (n=24, p = 0.024) and histoscores (n = 30, p = 0.0059) in the endometrial cancer than in normal endometrial tissues using quantitative real- time PCR analysis and IHC, respectively. Conclusions: We conclude that lapatinib may induce deactivation of ERK1/2 and PI3K linked to HER2 signaling, and that MMP1 could play a potential role in the tumorigenesis of endometrial cancer cells. doi:10.1016/j.ygyno.2011.12.336 336 Role of synaptotagmin-like 2 (SYTL2) in ovarian cancer progression S. Kim 1 , V. Vathipadiekal 2 , J. Kikuchi 2 , G. Mohapatra 2 , H. Cho 1 , E. Nam 1 , S. Kim 1 , J. Kim 1 , Y. Kim 1 , M. Birrer 2 . 1 Yonsei University College of Medicine, Seoul, Republic of Korea, 2 Massachusetts General Hospital/ Harvard University, Boston, MA. Objective: To delineate the role of SYTL2 in modulating ovarian cancer growth and aggressiveness. Methods: SYTL2 was identified as a highly differentially expressed gene in tumors compared to normal ovarian surface epithelial cells (p=0.0097) with a hazard ratio of 3.65 and Cox score of 13.95 (Mok, et al., 2009). Expression of SYTL2 was evaluated by Kaplan–Meier analysis using microarray intensity of 1000 to stratify the 53 patients. TCGA data was analyzed for DNA copy number alteration along 11q. For tumor biology, two human ovarian epithelial cancer cell lines (A2780 and A224) with relatively low SYTL2 expression were used. We tested the effect of SYTL2 over-expression in A2780 and A224 cell lines on cellular proliferation, migration, invasion, and anchorage- independent colony formation in vitro and tumor growth in vivo. To identify potential mechanisms, we conducted Affymetrix U133 plus 2.0 GeneChip microarrays with SYTL2 up-regulated A2780 cells and their corresponding control cells. We generated common gene list and the potential pathway was identified using Pathway Studio software. Results: SYTL2 maps to 11q14.1, a region known to be associated with high level amplification in high grade serous ovarian carcinoma (HGSOvCa). DNA copy number analysis using 338 HGSOvCa from the TCGA project indicated that SYTL2 maps to the amplicon on 11q14.1. Further analysis of 42 TCGA tumors containing high level amplification allowed mapping of the amplicon structure along 11q and defined the minimal region of amplification. SYTL2 mapped to the minimal region of the amplicon along 11q14.1 and was found to be amplified in 25% of the tumors. High SYTL2 expression (median survival 17 months) group showed a significantly shorter survival than the low SYTL2 expression (median survival 32 months) group (p=0.0097). Ovarian cancer cell lines (A2780 and A224) with SYTL2 over-expression, compared to corresponding control cells, had increased cell proliferation (p=0.001 and 0.02), migration (p=0.007 and 0.01), invasion (p=0.001 and 0.18) and colony formation (p = 0.003 and 0.02) in vitro and increased growth of xenograft tumors (p=0.01). Pathway analysis suggested that SYTL2 up-regulation may induce activation of WNT signaling pathway through Wnt3A transport facilitating tumor growth and aggressive- ness. Wnt3A expression in conditioned media was higher compared to A2780 clone and vector pool. Conclusions: SYTL2 is associated with HGSOvCa growth and aggressiveness and may serve as a survival-associated target. doi:10.1016/j.ygyno.2011.12.337 337 Utilization of genomic signatures to identify Fludarabine and Temsirolimus as candidate drugs with high efficacy to chemo-refractory endometrial cancers T. Baba 1 , B. Kharma 1 , M. Mandai 1 , Y. Yoshioka 1 , J. Hamanishi 1 , N. Matsumura 1 , K. Yamaguchi 1 , S. Murphy 2 , I. Konishi 1 . 1 Kyoto University, Kyoto, Japan, 2 Duke University Medical Center, Durham, NC. Objective: Endometrial cancer is one of the most common gyneco- logic malignancies, and the numbers of patients has been increased almost twice in this decade in Japan. Accompanied with the increasing rate, we sometimes encountered patients of high histolo- gical grade resistant to conventional chemotherapy with platinum agents, and it is keen to discover new drugs which are effective to chemo-refractory cases. Methods: The response of the NCI-60 cell lines to 26 clinically-used drugs was analyzed with respective 50% Growth Inhibitory concen- tration (GI50; http://www.dtp.nci.nih.gov/webdata.html) to generate response signature of each drug from gene expression data using Bayesian binary regression, to calculate susceptibility score of every sample in endometrial cancer data in vivo (GSE2019; http:// www.ncbi.nlm.nih.gov/geo) and in vitro (GSE25458), and to identify candidates for chemo-refractory cases. Using this candidate, cell proliferation assay, apoptosis assay, and caspase assay were per- formed in vitro. Tumor growth inhibitory effect of the candidate was also assessed in vivo using nude mice. Results: Through the microarray analysis, Fludarabine and Temsir- olimus showed higher susceptibility scores in high grade cases compared with cisplatin, doxorubicin, and paclitaxel. Fludarabine inhibited cells proliferation and increased apoptosis rate more significantly in a cisplatin-resistant endometrial cancer cell line, HEC-1A, than HEC-50B (p b 0.001). By Fludarabine treatment, Caspase 3/7 activity was induced higher in HEC-1A than HEC-50B (p b 0.001), and the growth of HEC-1A inoculated tumor was superior inhibited than cisplatin (p b 0.05). Conclusions: These results indicate that utilization of genomic signatures is convenient to identify new candidates potentially effective to chemo-resistant cases, and both Fludarabine and Temsirolimus may play a potent role in the future anti-tumor strategy of endometrial cancer. doi:10.1016/j.ygyno.2011.12.338 338 LKB1, a novel transcriptional target of p53, is down-regulated in high-grade endometrial carcinoma N. Co, D. Iglesias, R. Schmandt, K. Lu. The University of Texas, MD Anderson Cancer Center, Houston, TX. Objective: LKB1 is a serine/threonine kinase that regulates cell polarity, proliferation and energy metabolism via the AMPK pathway. We have previously shown that 19% of human endometrial cancers exhibited Abstracts / Gynecologic Oncology 125 (2012) S3–S167 S138