BMC Cancer 2008, 8:36 http://www.biomedcentral.com/1471-2407/8/36 Table 2: Clinical and Pathologic Characteristics of DCIS Lesions in Study Subjects. P value 0.06* 0.07 0.72 0.66 0.71 P value 0.884 0.422 0.538 0.413 0.726 0.006 0.024 0.257 Page 5 of 11 (page number not for citation purposes) Number of Subjects Mean age (range) Mean size in mm (range) DCIS grade: Grade 1 Grade 2 Grade 3 Free margins (2 mm or greater) Invasive recurrence DCIS recurrence Tamoxifen Use Radiation Therapy *T test, two-tailed p value ~ Margin status missing in 1 case and 5 controls 2 and PPARγ positivity. The results for COX-2 and PPARγ staining are presented in more detail below. COX-2 Expression in DCIS COX-2 expression could be evaluated in 59 samples; cores from 10 samples (6 controls and four cases) were lost in the TMAs. Of the 59 women with evaluable COX-2 stain- ing, 45.7% had strong COX-2 expression. (Fig 1) There was a significant difference in the proportion of cases that expressed COX-2 by immunohistochemistry compared to controls. (P = 0.006). Strong cytoplasmic COX-2 staining was found to be associated with ipsilateral breast recur- rence after breast-conserving treatment of DCIS. The odds ratio (OR) on univariate analysis was 5.11 (95% CI 1.7– 15.5). We did not see a significant association between strong COX-2 expression and histological grade of the lesions, although the majority of Grade 1 lesions were COX-2 negative (9/13, 69%). In the 10 samples where COX-2 expression data were missing due to core loss, the mean size of the DCIS lesions was smaller in the 4 cases (7.25 mm, range 4–15 mm) than in the six controls (12.8 mm, range 2–25 mm). Although this study lacked the statistical power to exam- ine non-invasive and invasive recurrences separately, it is noteworthy that four of the six cases with invasive recur- Table 3: Proportion of Cases and Controls with Positive Staining of DCIS Lesions for Markers of Interest Molecular Markers Cases N (% positive) Controls N (% positive) Total (N) ER PR HER-2/neu P53 Cyclin D1 COX-2 PPARγ P21 20 (77%) 21 (81%) 14 (56%) 17 (74%) 16 (64%) 18 (67%) 1 (4%) 9 (37%) 22 (79%) 20 (71%) 18 (64%) 19 (63%) 16 (59%) 9 (29%) 7 (27%) 7 (23%) 54 54 53 53 52 59 51 54 Cases N (%) 31 51 (36–77) 17.7 (4–73) 5 (16.) 16 (52.) 10 (33) 28 (90) 8 (26) 23 (74) 10 (32) 20 (65) Controls N (%) 38 50.5 (35–79) 11.9 (2–31) 13 (34) 18 (47) 7 (18) 30 (79) - - 12 (32) 23 (61) rences were COX-2 positive. (One of the six was negative and the other case was lost during processing). There was no difference in COX-2 expression between younger women and older women (using an age threshold of 50 years). Although other studies have indicated that HER-2/ neu over-expression is associated with DCIS recur- rence[7], we did not find an association between HER-2/ neu over-expression and ipsilateral DCIS recurrence (p = 0.538). The expression of HER-2/neu and COX-2 was con- cordant in 29/52 lesions that could be assessed for both proteins (12 lesions were positive for both and 17 lesions were negative for both). Dual negativity for COX-2 and HER-2/neu was significantly associated with control sta- tus (17 of 27 controls were dual negative, p = 0.024). Dual positivity for COX-2 and HER-2/neu was not associated with an increase in recurrence risk over COX-2 positivity alone. PPARγ Expression in DCIS PPARγ positivity was evaluable in 51 women (25 cases and 26 controls); nuclear staining was seen by immuno- histochemistry in eight of 51 women (15.6%). This includes patients who have nuclear staining alone or nuclear and cytoplasmic staining (Fig 2). Only one of the cases expressed nuclear PPARγ gamma, compared to seven of 26 (27%) of controls. This difference was statistically