Abstract 5350: Aldehyde dehydrogenase 1 is useful for identifying some subtypes of non-basal triple negative breast cancer

Abstract

Abstract BACKGROUND Triple negative breast cancer (TNBC) is heterogeneous and consists of tumors associated with basal-type and cancer stem cell (CSC) phenotypes. Identifying these specific phenotypes is important for treating TNBC. The expression of aldehyde dehydrogenase 1 (ALDH-1), a biomarker of CSC phenotype, is observed more frequently in TNBC than non-TNBC and is associated with biologically aggressive features. AIM In order to categorize types of breast cancer, especially TNBC, ALDH-1 was examined in terms of 1) its association with pathological factors and 2) the genes significantly expressed in ALDH-1 positive cells. METHODS 1) The expression of ALDH-1 and its association with the other pathological factors of ER, PgR, HER2, p53, Ki-67, CK5/6, EGFR were examined immunohistochemically in 87 breast cancer samples. Histological grade was assigned to each of the samples.2) ALDH-1 positive and negative cells were collected by microdissection from formalin-fixed paraffin- embedded samples of 5 ALDH-1 positive breast cancer cases. mRNA was extracted and the expression profile of approximately 5,000 genes was assessed by cDNA microarray (Affymetrix GeneChip®, Human Genome U133 Plus 2.0 Array). By comparing gene expressions of ALDH-1 positive and negative cells in the same sample, characteristic genes related to CSC were identified. RESULTS 1) ALDH-1 was inversely correlated with ER (p=0.0006) and PgR (p=0.0054), while positively correlated with Ki67 (p=0.0023) and TopoII (p=0.0014). No association was found between ALDH-1 with CK5/6 or with EGFR. 2) Approximately 800 annotated genes were significantly up- or down- regulated. Several characteristic genes related to ALDH-1 have been presently confirmed by other methodologies. CONCLUSION CK5/6 and EGFR are currently used to identify basal-type TNBC. Because ALDH-1 was not associated with CK5/6 or EGFR, ALDH-1 and related genes may be helpful in identifying some non-basal types of TNBC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5350. doi:1538-7445.AM2012-5350