High Survivin Expression in Ductal Carcinoma In Situ (DCIS): A Potential Therapeutic Target

Introduction: Survivin, a member of the Inhibitor of Apoptosis Proteins (IAP), is involved in cell proliferation, apoptosis suppression, and angiogenesis. Survivin is highly expressed in many cancers and its expression is often correlated with more aggressive disease and worse outcomes. Our goal was to characterize survivin expression in ductal carcinoma in situ (DCIS) with a specific interest in correlation to histopathologic grade, hormone receptor (HR) and HER2 status, and the presence of invasion or microinvasion. Methods: Immunohistochemistry was performed on paraffin-embedded tissue containing clinical DCIS (n = 91). Survivin expression was evaluated for intensity (1-3+) as well the percentage of tumor staining (0-100%). A numerical score was calculated by multiplying the staining intensity by the percentage of tumor cells staining giving an overall score (0 -300). Immunoreactivity was scored separately for cytoplasm and nuclei. Results: Cytoplasmic survivin expression was found in 89/91 (97.8%) DCIS patients. There was a positive correlation between cytoplasmic survivin expression and histopathologic grade (p < 0.001). HR positive DCIS showed higher levels of nuclear survivin than HR negative DCIS (p = 0.02), while HER2 positive DCIS showed lower levels of nuclear expression than HER2 negative DCIS (p = 0.03). Survivin expression did not correlate with the presence of invasion. Conclusion: Increasing levels of cytoplasmic survivin expression appear to correlate with higher histopathologic grade. Survivin may be involved in the transition from a low to higher grade lesion. Since survivin is highly expressed in DCIS, survivin could serve as an excellent therapeutic target for the treatment and prevention of early breast cancer.