Abstract P6-01-13: SOX10 and folate receptor alpha are frequently expressed in triple negative and progesterone receptor negative breast cancers

Abstract

Abstract Background: Specific biomarkers can be essential for developing effective treatments for aggressive breast cancers, especially triple negative subtypes, for which treatment options are limited. Folate receptor alpha (FRα), a critical membrane protein for DNA synthesis and cell metabolism, has been suggested to participate in the transformation of breast cancer into aggressive subtypes. It has been shown to be strongly associated with poor prognosis in triple negative breast cancers (TNBC) as well as estrogen receptor (ER) positive and progesterone receptor (PR) negative subtypes. SOX10 is a nuclear transcription factor that participates in neural crest development and in the differentiation of cells of melanocytic lineage. Data suggests that SOX10 may contribute in stem cell or progenitor cell maintenance. Recently, SOX10 expression has also been documented in benign breast myoepithelial cells and in aggressive breast cancers. The correlation of FRα and SOX10 in breast cancer is not fully known. This is the first study to compare FRα and SOX10 immunohistochemical profiles in breast cancers with emphasis in TNBC. Design: 166 cases of whole breast cancer tissues were classified according to their ER, PR, and HER2 immunohistochemical (IHC) status. These same cases were then IHC stained for mouse monoclonal SOX10 and FRα. Cut-off values of 1% and 5% for SOX10 and FRα, respectively, were used to determine positivity. Results: SOX10 achieved a sensitivity of 42.1% (8/19) in ER+/PR-/HER2- cases and was negative in all ER+/PR-/HER2+ cases (p<0.05). FRα was positive in 7.6% (7/92) of ER+/PR+/HER2- cases and was negative in all ER+/PR+/HER2+ cases. SOX10 identified more ER+/PR-/HER2- cases (42.1%, 8/19) than ER+/PR+/HER2+ cases (7.7%, 1/13) (p<0.05). Similarly, FRα stained 52.6% (10/19) of ER+/PR-/HER2- cases and was negative in all ER+/PR+/HER2+ cases (p<0.005). SOX10 and FRα were observed in 3.3% (1/30) and 20% (6/30) of HER2+ cases, respectively. In ER-/PR-/HER2- (triple negative) cases, both markers were highly expressed with 40.0% (10/25) and 52.0% (13/25) positive cases with SOX10 and FRα, respectively, with 24.0% (6/25) of cases positive with both markers. Approximately one half of TNBC cases expressed SOX10 and FRα; however, most SOX10 positive TNBC cases did not overlap with FRα positive TNBC cases. Table 1: SOX10 and FRα expression in breast cancer subtypesER/PR/HER2 ClassificationSOX10+ (%)FRα+ (%)Co-expression of SOX10 and FRα (%)ER+/PR+/HER2+ (n=13)1 (7.7%)0 (0.0%)0 (0.0%)ER+/PR+/HER2- (n=92)6 (6.5%)7 (7.6%)2 (2.2%)ER+/PR-/HER2+ (n=10)0 (0%)5 (50.0%)0 (0.0%)ER+/PR-/HER2- (n=19)8 (42.1%)10 (52.6%)5 (26.3%)HER2+ (n=30)1 (3.3%)6 (20.0%)0 (0.0%)ER-/PR-/HER2- (n=25)10 (40.0%)13 (52.0%)6 (24.0%) Conclusion: SOX10 and FRα were frequently expressed in triple negative breast cancers and in progesterone receptor negative breast cancers. Our data suggests that there may be different mechanisms by which SOX10 and FRα are implicated in aggressive breast cancers. These findings may help achieve a better understanding of the two different pathways involving stem cells (SOX10) and growth factors (FRα), their potential prognosis and their therapeutic management in the future. Citation Format: Laura L Hoang, Weimin Qi, Charlie Yu, David Tacha. SOX10 and folate receptor alpha are frequently expressed in triple negative and progesterone receptor negative breast cancers [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-01-13.