SIAH as a Potential Prognostic Marker for Recurrence in Patients with Ductal Carcinoma In Situ (DCIS)
KC Behling, AH Tang, S Kadiaka, K Nguyen, M Potoczek, SC Peiper, GF Schwartz, AK Witkiewicz. Thomas Jefferson University Hospital, Philadelphia, PA
Background: Seven in absentia homolog (SIAH) is an E3 ubiquitin ligase that acts as a common downstream mediator of EGFR/Her2 and Ras signaling. The exact mechanism of SIAH in tumorgenesis is unknown, however, increased SIAH expression is seen in both neoplastic and non-neoplastic proliferating cells. Studies using shRNA and dominant negative SIAH have shown that decreased SIAH function results in decreased lung and pancreatic tumor growth in vitro and in vivo. There has been no prior examination of SIAH protein expression in breast carcinoma.
Design: Formalin fixed, paraffin embedded resection specimens from sixty-five patients with DCIS were stained with an anti-SIAH antibody (24E6H3, 1:100 dilution), and the percentage of tumor cells and normal adjacent tissue positive for SIAH nuclear staining was recorded. All patients were treated with wide excision only. Statistical analysis was performed comparing SIAH staining in tumor cells to disease recurrence, histologic type (comedo vs. non-comedo), necrosis, hormone receptor status (estrogen receptor and progesterone receptor), and Her2/neu status (Wilcoxon two-sample test), as well as nuclear grade (Kruskal-Wallis test). Correlation of SIAH expression in tumor cells with SIAH expression in normal adjacent tissue and age (Spearman correlation coefficient) was also examined.
Results: Expression level of SIAH in tumors cells was significantly higher in specimens from patients with recurrence (median=19 %) as compared to patients without recurrence (7%)(p<0.001). There was also significantly increased SIAH expression in comedo type DCIS (13.5% in comedo DCIS vs. 7% in other histologic types, p=0.014). No significant association was observed between SIAH expression and estrogen receptor, progesterone receptor, and Her2/neu status. There was a significant correlation between SIAH expression in tumors and normal adjacent tissue (Spearman correlation = 0.58, p<0.001) as well as between SIAH expression in normal adjacent tissue and patient age (Spearman correlation = -0.59, p <0.001). No significant correlation was identified between patient age and SIAH expression in tumors.
Conclusions: SIAH is a promising biomarker for disease recurrence in patients with DCIS.
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 14, Wednesday Afternoon