5034 Background: A practical serum-based screening test for endometrial and ovarian carcinomas could greatly improve their early diagnosis, but developing such a test has proved elusive. Herein, we describe methods offering increased statistical power over conventional ‘batch’ analyses, via paired patient serum samples to identify biomarkers specific for uterine endometriod carcinomas (UEA). Methods: Paired serum samples (collected pre- and post- surgery) were prepared from patients undergoing UEA resection. A Ciphergen SELDI-TOF mass spectrometer was used to generate the patient serum proteomic profiles with data acquisition optimized to the 5,000–40,000 m/z (mass) range. Spectra quality was assessed using a specific function within the R-project statistical platform (v2.2.0), whereas data analyses were performed using Bioconductor, an extension of the R statistical platform; all in a blinded manner. Raw spectra were processed as follows: spectra pair normalization, baseline subtraction, and differential peak detection (with calibrated alignment). Aligned peaks were sorted into groups, based on tumor pathology and pre- vs. post-operative specimen type, and compared using a two tailed homoscedastic t-test in Microsoft Excel 2003. Results: Pre- and post-operative serum from 10 patients with UEA had their serum proteomic profiles evaluated for peaks lost after surgery. These values were then compared with a set of ‘normal’ samples (i.e. patients undergoing surgery for benign gynecologic disease). Even with our small sample size we identified 16 serum components that were significantly reduced or absent (p < 0.04) after tumor resection; 10 unique to UEA (p <0.04). From this group, species at m/z values of 4291.9, 4414.2, 5036.1, 9,615.0, and 25,508.8 seem most promising, based on their high level of significance (p < 0.02), for 10/10 patients. Conclusions: These results validate the power of our pre-and post-operative sample sets for the identification of new serum biomarker candidates for UEA. Work is in progress to increase the patient sample size, expand the study to patients with serous uterine and ovarian carcinomas, and identify the reported biomarker candidates via tandem mass spectrometry No significant financial relationships to disclose.