Cytoplasmic Staining Pattern of Cyclin E and pCDK2 Expression Correlates with Poor Outcome in Breast Cancer (BC) Patients (pts)
Cansu Karakas, Anna Biernacka, Aysegul Sahin, Kelly Hunt, Khandan Keyomarsi. MD Anderson Cancer Center, Houston, TX
Background: Cyclin E, a key regulator of the cell cycle, and its co-activator pCDK2 play an important role in BC biology. Recently, we showed that high levels of cyclin E expression are associated with poor prognosis in BC. Guidelines for cyclin E evalution is lacking. The aim of this study was to identify a biologically significant evaluation method for cyclin E and pCDK2.
Design: Immunohistochemical (IHC) analysis of cyclin E (Santa Cruz 1:1000) and p-CDK2 (Cell Signaling 1:100) was performed on archival sections from 209 pts with stages I-III BC. Cyclin E staining intensity and percentage of positivity were evaluated in the nucleus (N) and cytoplasm (C) and four patterns were distinguished: negative, predominantly N, both N and C and predominantly C. pCDK2 staining was also evaluated in the N and C. Results was correlated with disease-specific survival (DSS).
Results: Among the 209 pts, 119 (57%) showed C cyclin E positivity which was associated with poor outcome compared with outcome in those with C cyclin E-negative tumors. Recurrence was observed in 26/119 pts whose tumor showed C staining but was observed in only 5/90 pts whose tumors showed N staining which was statistically significant (p=0.01). Among the 119 pts with C cyclin E positivity 66 had tumors that were both N and C cyclin E-positive, and 53 had tumors that were only C cyclin E-positive. Recurrence was observed in 14/66 pts whose tumors were both N and C cyclin E-positive, and in 12/53 pts whose tumors were only C cyclin E-positive. Although, both of these groups were associated with poor DSS, the C cyclin E-positive group was more significantly correlated with poor DSS (p=0.006). Furthermore C pCDK2 expression was also associated with poor prognosis. Recurrence was observed in 18/75 pts whose tumor had C pCDK2 staining versus 13/134 pts whose tumor shows no C staining (p=0.004). Pts with tumors positive for both C cyclin E and pCDK2 had the highest recurrence rate (p=0.016).
Conclusions: IHC is a clinically valid method for assessing Cyclin E. C pattern identifies pts with poor prognosis who may benefit from investigational treatment strategies such as CDK2 inhibitors.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 278, Wednesday Morning