P5-11-16: CD44 and CD24 Expression in Ductal Invasive Breast Carcinomas, Classified by Molecular Subtypes and Its Association with Prognostic Factors.
Authors: Bernardi MA , Logullo AF , Pasini FS , Nonogaki S , Soares FA , do Socorro Maciel M , Brentani MM 
Published: June 2012

Abstract
Backgound: Breast carcinomas (BC) exhibit intra tumoral heterogeneity being stratified into several subgroups based in gene expression profiles or histochemical biomarkers. It was suggested that this heterogeneity is derived in part from the transformation of different subsets of cancer stem cells (CSC) in each intrinsic subgroup. The presence of CSC can be evidenced by phenotypic analysis of CD44 e CD24. This study aimed to identify the CD24 and CD44 immunophenotypes within invasive ductal breast carcinoma (IDC) subgroups defined by immunohistochesmistry markers and determine its influence on prognosis as well as its association with the expression of Ki67, citokeratins (CK5 and CK18) and claudin-7. Methods: Immuno expression of CD44 and CD24 alone or in combination was investigated in 95 IDC cases arranged in a tissue microarray (TMA). The association with subgroups defined as luminal A and B;HER2 rich and triple negative, or with the other markers and prognosis was analyzed. Results: CD44+/CD24- and CD44-/CD24+ were respectively present in 8.4% and 16.8% of the tumors, a lack of both proteins was detected in 6.3%, while CD44+/CD24+ was determined in 45.3% of the tumors. Although there was no significant correlation between subgroups and different phenotypes, the CD44+/CD24-phenotype was more common in the basal subgroups but absent in HER2 tumors, whereas luminal tumors are enriched in CD44-/CD24+ and CD44+/CD24+ cells. The frequency of CD44+/CD24- or CD44-/CD24+ have not been associated with clinical characteristics or biological markers. There was also no significant association of these phenotypes with the event free (DFS) and overall survival (OS). Single CD44+ was evident in 57.9% and was marginally associated to grading and not to any other tumor characteristics, while CD24+ was positive in 74.7% of the tumors, showing a significant association with ER, PR and Ki67 and a marginal association with CK18 and claudin-7. Expression of claudin-7 and Ki67 did not associate with the cancer subgroups, while a positive association between CK18 and the luminal subgroups was found (p=0.03). CD44+ was not significantly associated with OS and DFS whereas CD24+ frequency although not significantly associated with OS was associated with a decrease in DFS (p=0.07). CK5, CK18 and Ki67 expression had no influence in OS or DFS, claudin-7 positive was associated with reduced DFS (p=0.05). Conclusions: There was no significant correlation between CD44+/CD24- tumor cells frequency and event-free or OS. However, a tendency toward a favorable prognosis, was noted. Contrariwise the presence of CD44-/CD24+ suggested a worse prognosis. Both single CD24 and claudin-7 positivity were associated with reduced time of reccurence, suggesting a contribution of these markers to aggressiveness. Supported by FAPESP and CNPq.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-11-16.