Expression of Potential Cancer Stem Cell Markers CD44+/CD24- in the Molecular and Genetic Subgroups of Breast Cancer
AL Bane, AM Mulligan, D Pinnaduwage, A Viloria-Petit, FP O'Malley, IL Andrulis. Samuel Lunenfeld Research Institution, Toronto, ON, Canada; St. Michael's Hospital, Toronto, ON, Canada; Mount Sinai Hospital, Toronto, ON, Canada
Background: In the stem cell model of carcinogenesis it is the small population of cancer stem cells (CSC) in a tumor that is believed to be the driver of tumorigenesis, the source of metastasis and the cause of relapse and therapy resistance. In breast cancer a population of cells identified as CD44+/CD24- have been demonstrated to have CSC properties in vitro and in vivo. Breast cancer is a highly heterogenous disease at the clinical and molecular level, with distinct molecular subtypes strongly correlated with clinical outcome. We hypothesize that a correlation exists between the expression of CD44+/CD24- representing CSCs and the adverse molecular subtypes of breast cancer and with tumor parameters known to portend a poor prognosis.
Design: Tissue microarrays (TMAs) were constructed using 58 BRCA1-associated, 64 BRCA2-associated and 242 non-BRCA1/2 breast tumors. Immunohistochemical profiling of all tumors was performed with antibodies against ER, PR, CK8/18, CK5, CK14 and EGFR to determine the molecular subtype and CD44 and CD24 to determine if CSCs were present. Statistical comparison was made using the Chi-Square test or Fisher's Exact test.
Results: 81/364 (22%) of tumors were basal-like, 32/364 (9%) were HER2/neu overexpressing, 218/364 (60%) were luminal and the remaining 32 (9%) were unclassifiable. Expression of CD44+/CD24- was positively correlated with the basal-like subgroup (p=0.04); 27% of basal-like tumors, 3.4% of HER2/neu overexpressing and 13% of luminal tumors contained CD44+/CD24- CSCs. Furthermore expression of CD44+/CD24- was positively correlated with adverse prognosis features including high tumor grade (p=0.002), lymphatic invasion (p=0.01) and lymph node positivity (p=0.01). BRCA1-associated tumors are known to be enriched for basal-like tumors, and when we examined this subgroup we found expression of CD44+/CD24- was positively associated with BRCA1-associated tumors (p=0.01); 28% of BRCA1-associated tumors contained CD44+/CD24- cells compared to 13% of non-BRCA1 tumors.
Conclusions: This study demonstrates that basal-like and BRCA1-associated tumors are more likely to express CD44+/CD24- than non-basal and non-BRCA1-associated tumors. Furthermore expression of CD44+/CD24- correlates with poor histopathologic and/or prognostic characteristics.
Monday, March 9, 2009 1:30 PM
Platform Session: Section B, Monday Afternoon