BMC Cancer Research article COX-2 and PPARγ expression are potential markers of recurrence risk in mammary duct carcinoma in-situ Swati Kulkarni2, Deepa B Patil1, Leslie K Diaz4, Elizabeth L Wiley5, Monica Morrow3 and Seema A Khan*1 BioMed Central Open Access Address: 1Lynn Sage Breast Center and Feinberg School of Medicine of Northwestern University, Chicago USA, 2Department of Surgery Roswell Park Cancer Institute, Buffalo USA, 3Department of Surgery, Fox Chase Cancer Center Philadelphia USA, 4Department of Pathology Abbott Northwestern Hospital, Minneapolis USA and 5Department of Pathology, University of Illinois Medical Center Chicago USA Email: Swati Kulkarni - swati.kulkarni@roswellpark.org; Deepa B Patil - d-patil@northwestern.edu; Leslie K Diaz - Leslie.diaz@allina.com; Elizabeth L Wiley - ewiley@uic.edu; Monica Morrow - Monica.morrow@fccc.edu; Seema A Khan* - skhan@nmh.org * Corresponding author Published: 31 January 2008 BMC Cancer 2008, 8:36 doi:10.1186/1471-2407-8-36 This article is available from: http://www.biomedcentral.com/1471-2407/8/36 Received: 6 July 2007 Accepted: 31 January 2008 © 2008 Kulkarni et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: In women with duct carcinoma in-situ (DCIS) receiving breast conservation therapy (BCT), in-breast recurrences are seen in approximately 10%, but cannot be accurately predicted using clinical and histological criteria. We performed a case-control study to identify protein markers of local recurrence risk in DCIS. Methods: Women treated for DCIS with BCT, who later developed in-breast recurrence (cases) were matched by age and year of treatment to women who remained free of recurrence (controls). Results: A total of 69 women were included in the study, 31 cases and 38 controls. Immunohistochemical evaluation of DCIS tissue arrays was performed for estrogen receptor, progesterone receptor, HER-2/neu, cyclin D1, p53, p21, cycloxygenase-2 (COX-2) and peroxisome proliferator activated receptor γ (PPARγ). Two markers were significantly different between cases and controls on univariate analysis: strong COX-2 expression was associated with increased risk of recurrence, with 67% vs. 24% positivity in cases and controls p = 0.006; and nuclear expression of PPARγ was associated with protection from recurrence with 4% vs. 27% positivity in cases and controls, p = 0.024. In a multivariate model which included size, grade, COX- 2 and PPARγ positivity, we found COX-2 positivity to be a strong independent risk factor for recurrence (OR 7.90, 95% CI 1.72–36.23)., whereas size and grade were of borderline significance. PPARγ expression continued to demonstrate a protective trend, (OR 0.14, 95% CI 0.06–1.84). Conclusion: Our findings suggest that COX-2 and PPARγ should be investigated further as biologic markers to predict DCIS recurrence, particularly since they are also potential therapeutic targets. Background With the widespread use of screening mammography, the incidence of ductal carcinoma in-situ (DCIS) has increased steadily[1], so that DCIS now accounts for up to 20% of newly diagnosed breast cancers[2]. Management of localized DCIS has evolved from total mastectomy Page 1 of 11 (page number not for citation purposes)