Prognostic impact of the cancer stem cell related markers ALDH1 and EZH2 in triple negative and basal-like breast cancers

• Published in: Pathology 2012-06, Vol.44 (4), p.303-312
• Main Authors: De Brot, Marina, Rocha, Rafael M., Soares, Fernando A., Gobbi, Helenice
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - mortality; Adenocarcinoma - secondary; Adult; ALDH1; basal-like breast cancer; Biomarkers, Tumor - metabolism; Brazil - epidemiology; breast neoplasms; Breast Neoplasms - diagnosis; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; DNA-Binding Proteins - metabolism; Enhancer of Zeste Homolog 2 Protein; EZH2; Female; followup; Humans; immunohistochemistry; Isoenzymes - metabolism; Kaplan-Meier Estimate; Lymph Nodes - metabolism; Lymph Nodes - pathology; Lymphatic Metastasis; Neoplasm Staging; neoplastic stem cells; Neoplastic Stem Cells - metabolism; Polycomb Repressive Complex 2; Prognosis; Receptor, ErbB-2 - metabolism; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Retinal Dehydrogenase - metabolism; Stromal Cells - metabolism; Stromal Cells - pathology; survival; Survival Rate; Tissue Array Analysis; Transcription Factors - metabolism; triple negative breast cancer; Tumor Microenvironment
• ISSN: 0031-3025; 1465-3931
• DOI: 10.1097/PAT.0b013e3283534bcb

We assessed the expression of ALDH1 and EZH2, cancer stem cell (CSC) related markers, in triple negative and basal-like breast cancers, investigating their association with clinicopathological features and outcome. Clinicopathological data were obtained from 140 cases of triple negative breast cancer. A tissue microarray was constructed and immunohistochemistry for ER, PR, HER2, ALDH1, EZH2, CK5, CK14, EGFR, p63, caveolin, and p53 was performed. Tumour cell and stromal expression of ALDH1 were evaluated. Multivariate analysis was conducted, including all significant variables. The majority of triple negative breast cancers were invasive ductal carcinomas of no special type (NST) (116/140). Tumour cells exhibited cytoplasmic expression of ALDH1 in 26 of 140 cases, while stromal expression was detected in 117 of 140 cases. Tumour cell expression did not correlate with any of the parameters. Conversely, stromal expression was associated with better overall survival (p = 0.044). Assessment by Cox Regression Model showed a HR of 2.80 (HR = 1/0.357 = 2.80; 95%CI 0.178-0.714; p = 0.004) for breast cancer death when ALDH1 was not found in the stromal compartment of tumours, independent of age, histological type/grade, nodal status, stage, relapse, and expression of basal markers. High EZH2 expression was noted in 120 of 140 triple negative breast cancers and was not associated with other variables. Basal-like cancers comprised 75% (105/140) of triple negative breast cancers. Interestingly, we found association between EZH2 and CK14 expression (p = 0.041). ALDH1 expression is frequent in tumour-associated stromal cells of triple negative breast cancer and is associated with better outcome. Tumour microenvironment should be considered when studying prognostic impact of CSCs in breast cancer.