Stromal CD10 and SPARC Expression Predict Recurrence of Ductal Carcinoma In Situ
W Rizzo, S Kadakia, I Chervoneva, K Nguyen, M Potoczek, S Peiper, G Schwartz, A Witkiewicz. Thomas Jefferson University Hospital, Philadelphia, PA
Background: Ductal carcinoma in situ (DCIS) currently accounts for 20-30% of newly diagnosed breast cancers. The current classification of DCIS based on nuclear grade, architectural differentiation and the presence of necrosis does not adequately predict the likelihood of recurrence after breast conserving therapy. Therefore there is a critical need to identify novel predictors of DCIS progression. Recently, the stromal proteins CD10 and SPARC (secreted protein acid rich in cysteine), identified in invasive breast carcinoma, have been correlated with decreased survival. There have been no studies addressing the clinical significance of stromal CD10 and SPARC expression in DCIS. Our study evaluated these proteins in DCIS and examined their association with clinicopathological variables and DCIS recurrence.
Design: Eighty five cases of DCIS were included in the study. All patients were treated with wide local excision alone. CD10 and SPARC expression in tumor stroma was assessed by standard immunoperoxidase method with anti-CD 10 (1:200 dilution, Burlingame, CA) and anti-SPARC (1:200 dilution, AbCam, Cambridge, MA)) antibodies. The staining was scored semi-quantitatively as negative (0; no staining), weak (1; either diffuse weak staining or strong staining in less than 30% of stromal cells) and strong (2; defined as strong staining of 30% of stromal cells). Statistical analysis was performed using the Fisher's exact test. Multivariable analysis was conducted utilizing Exact Logistic Regression software (SAS 9.1 and LogExact).
Results: The recurrence rate for our study population was 28%. There was a significant association between stromal CD10 expression and DCIS recurrence (p<0.001, Fisher's exact test). Recurrence was observed in 5% of patients with the CD10 stromal score 0 and in 63% of patients with the score 2. There was also a significant association between stromal SPARC expression and recurrence (p<0.001, Fisher's exact test). Among patients with the stromal SPARC score 0, only 7% had a recurrence whereas recurrence occurred in 50% of patients with the stromal score 2. There was no association between CD10 or SPARC expression and DCIS type, nuclear grade, estrogen receptor, progesterone receptor or HER2 status. In multivariate analysis stromal CD10 but not SPARC expression remained a strong predictor of DCIS recurrence.
Conclusions: Our results indicate that stromal CD10 and to a lesser extent SPARC are potentially novel biomarkers predicting DCIS recurrence.
Monday, March 22, 2010 11:30 AM
Platform Session: Section C, Monday Morning