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Introduction: Prostaglandin E2 (PGE2), a major metabolite produced by cylooxygenase 2(COX-2), plays a role in tumor development and progression. PGE2 is the ligand for 4 prostaglandin type E (EP) receptor subtypes, EP1 to EP4. The expression patterns of these receptors on a variety of cell types accounts for the diverse functions of PGE2. Over-expression of COX2 and PGE2 has been observed in colorectal cancer (CRC) and PGE2 binding to EP2 receptors on endothelial cells in blood vessels of tumors directly impact tumor angiogenesis by enhancing cell survival. Also, COX-2/PGE2 contributes to VEGF and CXCL1 mediated angiogenesis which is necessary for tumor growth. There is also evidence that COX2 derived PGE2 promotes colorectal cancer growth via activation of epidermal growth factor receptor (EGFR) signaling. Elevated levels of EGF, VEGF, and CXCL1 have been noted in CRC patients; however, plasma PGE2 levels in CRC patients have not been well studied. This study’s purpose was to compare preoperative plasma PGE2 levels in populations of CRC and benign colonic disease patients.Methods: Patients(pts) undergoing colorectal resection for benign colonic disease or adenocarcinoma were prospectively enrolled in an IRB approved tissue and data banks. Preoperative blood samples, basic demographic data, type of resection performed, other clinical information, and pathology results were prospectively collected. Blood samples were processed in a timely manner and plasma was stored at -800C until further use. Plasma PGE2 was determined in duplicate via ELISA, and results are reported as mean ± SD. A t-test was used to compare PGE2 levels between groups. Significance was defined as p<0.05.Results: A total of 148 pts were enrolled; 78 CRC (83% colon, 17% rectal) and 70 benign condition pts (51% diverticulitis, 44% adenoma). The mean male to female ratios in the groups were comparable, but the CRC pts were older (p=0.002). The final cancer staging in the CRC group: stage 1, 24 (31%); stage 2, 28 (36%); stage 3, 18 (23%); stage 4, 8 (10%). The mean PGE2 level was significantly higher in the CRC group than the benign group (676.8±582.5 pg/ml vs. 472.5±424.8 pg/ml, p=0.002). No significant differences in PGE2 levels were noted between the different stage groups, however, plasma levels were higher in stage-4 pts.Conclusion: Preoperative plasma PGE2 levels were evaluated in CRC pts and compared to those in benign colorectal disease pts. The mean plasma PGE2 level in CRC pts was 43% higher than the mean level in benign pts. The higher levels in CRC pts could be attributed to tumor-related inflammation, progression, and angiogenesis. Further studies with a larger population of cancer free control and CRC pts, including more stage-4 patients, are necessary to better determine whether PGE2 levels correlate with Cancer stage and prognosis.