COX-2 and PPARγ expression are potential markers of recurrence risk in mammary duct carcinoma in-situ

Swati Kulkarni, Deepa B. Patil, Leslie K. Diaz, Elizabeth L. Wiley, Monica Morrow, Seema A. Khan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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.

Original languageEnglish (US)
Article number36
JournalBMC cancer
Volume8
DOIs
StatePublished - 2008

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Cancer Research

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