Title:High Survivin Expression in Ductal Carcinoma In Situ (DCIS): A Potential Therapeutic Target
Volume: 8
Issue: 3
Author(s): Graves Holly, Mick Rosemarie, Sharma Anupama, Lewis Robert, Roberts Shelley, Fitzpatrick Elizabeth, Xu Shuwen, Zhang Paul and Czerniecki J. Brian
Affiliation:
Keywords:
Biomarkers, Breast Cancer, Ductal Carcinoma in Situ (DCIS), Histopathologic Grade, Survivin
Abstract: 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.
