title: COX-2 and PPARgamma expression are potential markers of recurrence risk in mammary duct carcinoma in-situ.
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 gamma (PPARgamma). 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 PPARgamma 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 PPARgamma 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. PPARgamma expression continued to demonstrate a protective trend, (OR 0.14, 95% CI 0.06-1.84).
  
  
  CONCLUSIONS
  Our findings suggest that COX-2 and PPARgamma should be investigated further as biologic markers to predict DCIS recurrence, particularly since they are also potential therapeutic targets.
authors.affiliation: Lynn Sage Breast Center and Feinberg School of Medicine of Northwestern University, Chicago USA. swati.kulkarni@roswellpark.org
authors.forename: Swati
authors.initials: S
authors.lastname: Kulkarni
authors.forename: Deepa B
authors.initials: DB
authors.lastname: Patil
authors.forename: Leslie K
authors.initials: LK
authors.lastname: Diaz
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Wiley
authors.forename: Monica
authors.initials: M
authors.lastname: Morrow
authors.forename: Seema A
authors.initials: SA
authors.lastname: Khan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002278:Carcinoma in Situ / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D047495:PPAR gamma / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D047495:PPAR gamma; D051546:Cyclooxygenase 2