Association of p27kip1 Expression and BRCA Status among Women with Breast Cancer: A Single Institution Study
Michelle Schneider, Constance Albarracin, Banu Arun, Angelica M Gutierrez Barrerra, Roland Bassett, Shaheenah Dawood, Dealla Saab, Lucy Gao, Isabelle Bedrosian, Daniel Rosen. Baylor College of Medicine, Houston; The University of Texas MD Anderson Cancer Center, Houston; Dubai Hospital, Dubai, United Arab Emirates
Background: p27kip1, a cyclin dependent kinase inhibitor that is transactivated by normally functioning BRCA1, acts as a potent tumor suppressor protein in many malignancies including breast cancer. Decreased p27kip1 expression has been associated with poor prognostic outcome among various groups of breast cancer patients, including BRCA mutation carriers. The objective of this study was to correlate p27kip1 expression in patients with known BRCA mutation status with clinico-pathological characteristics, hormonal receptor status and expression of human epidermal growth factor receptor 2 (HER2).
Design: Samples from 94 patients with known BRCA mutation status (age range 31-82 years) were assessed for p27kip1 expression using a tissue microarray (TMA). This TMA included the following subgroups: BRCA non-carrier (n=15), BRCA1 mutation carrier (n=19), BRCA2 mutation carrier (n=21), and sporadic breast cancer (n=39). Expression of p27kip1, estrogen receptor (ER), progesterone receptor (PR), and HER2 was evaluated by digital image analysis. Mean nuclear p27kip1 expression was defined as the average percent of positively stained tumor nuclei in a patient subgroup.
Results: The mean nuclear p27kip1 expression was observed in BRCA non-carriers, BRCA1 and 2 mutation carriers and sporadic patient populations at 95.6% (SD), 76.3% (SD), 94.3% (SD), and 91.2% (SD) respectively. Lower p27kip1 expression was significantly associated with BRCA1 mutation carriers (p=0.0007), grade III tumors (p=0.0047), ER negative tumors (p<0.0001), and PR negative tumors (p= 0.0187). HER2 expression was not associated with p27kip1 expression (p=0.8702).
Conclusions: The results of this single institution study indicate that p27kip1 expression is decreased among BRCA1 mutation carriers, which supports a role for altered p27kip1 expression in BRCA1-associated breast cancer. Decreased nuclear p27kip1 is also associated with higher grade and hormone receptor negative tumors; all factors that are associated with a poor prognostic outcome. Further studies are warranted to analyze the prognostic and predictive significance of these findings. In particular, to determine if p27kip1 plays a unique role in clinical outcome.
Monday, March 19, 2012 11:30 AM
Platform Session: Section B, Monday Morning