p53 Expression in Triple Negative Breast Carcinomas: Evidence of Racial and Age-Related Differences.
Simone Davion, Megan Sullivan, Stephen M Rohan, Kalliopi P Siziopikou. Northwestern University Feinberg School of Medicine, Chicago, IL
Background: The triple negative subtype of breast carcinomas (TNBC), defined in the molecular classification of breast cancer as estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2) negative, is a heterogeneous group of lesions with different pathological characteristics, molecular alterations, clinical features and biologic behavior. TNBC is thought to be associated with a higher recurrence rate and poor overall prognosis. In this study we evaluated the role of p53, a mediator of cellular response to DNA damage, in this high risk and therapeutically challenging group of breast carcinomas.
Design: Our patient population consisted of 197 patients diagnosed with TNBC at Northwestern Memorial Hospital (2005-2010, mean age: 54, range 29-93). Electronic medical records were reviewed to determine the demographics. Pathologic tumor characteristics were reviewed and included histologic type, tumor grade, tumor size, presence of lymphatic invasion (LVI), lymph node status and p53 expression (by immunohistochemistry (IHC), Ventana, Bp53-11). Tissue microarrays (in triplicate including controls) were made from 99 of these TNBC for IHC evaluation of basal cytokeratin expression (CK5/6, DAKO DS/16B4).
Results: Overall, TNBC were almost exclusively infiltrating ductal carcinomas (182/197, 92.3%) of high histologic grade. 163/197 were grade 3 tumors, and the remaining were grade 2. p53 was expressed in 54.7% and was not associated with the tumor grade, tumor size, presence of LVI nor lymph node status. However, a higher percentage (60.4%) of the basal phenotype TNBC cases expressed p53 compared to just half (51.4%) of the non-basal phenotype TNBC. In addition, more than three quarters (77.7%) of African- American (AA) patients with TNBC expressed p53 compared to just over half (57.1%) of Caucasians (p<0.01). Of interest 50% of the TNBC patients younger than 50 expressed the basal/p53 positive phenotype compared with only 23.4% of the TN patients older than 50 (p<0.01).
Conclusions: 1. p53 is expressed in over half of the TNBC studied. 2. AA patients are more likely to have a basal phenotype TNBC with high expression of p53. 3. TNBC patients younger than 50 years of age are twice as likely to have p53 expressing TNBC of the basal phenotype than patients older than 50 y.o. These findings suggest that p53 mutations may play a role in the aggressive behavior of TNBC in young and AA patients. In addition, the results suggest that p53 status may be a specific prognostic indicator in these subgroups of TNBC patients.
Monday, February 28, 2011 1:00 PM
Poster Session II # 74, Monday Afternoon