Expression of the Cancer Stem Cell Marker ALDH1 in Triple Negative Breast Cancer: Prognostic Impact and Tumor Microenvironment.
Marina De Brot, Rafael M Rocha, Fernando A Soares, Helenice Gobbi. Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Hospital A.C. Camargo, Sao Paulo, Brazil
Background: Triple negative breast cancer (TNC; ER, PR, and HER2-negative) is a high risk cancer that lacks the benefit of specific treatment. Emerging studies suggest that some malignancies may obey a cancer cell hierarchy similar to that observed in normal tissues. The theory of cancer stem cells (CSC) in breast cancer and its association with tumor initiation and drug resistance can have implications on targeted therapy. We characterized expression of ALDH1, a putative CSC marker, in a cohort of 140 patients with TNC to examine its association with clinicopathological features, prognosis, and outcome.
Design: Clinical and pathological data were obtained. A TMA containing 2 cores of each tumor was constructed and IHC for ER, PR, HER2, CK5, CK14, EGFR, p63, caveolin, p53 and ALDH1 was performed. Both tumor cell and stromal expression of ALDH1 was evaluated.
Results: The majority of tumors were high grade (83.7%) and of ductal/no special type (80.8%). Tumor cells exhibited cytoplasmic expression of ALDH1 in 26/140 (18.7%) cases, while stromal expression was detected in 117/140 (83.6%) cases. ALDH1 expression in tumor cells was not associated with overall survival or disease-free survival (OS; DFS) in our series. In contrast, stromal expression was significantly associated with best OS (p=0.044). Cox multivariate analysis was carried out and ALDH1 stromal expression was shown to be an independent prognostic factor (RR=0,382;p=0.003;IC=0,202-0,723). Tumor cell and stromal expression of ALDH1 did not correlate with any of the other parameters examined, including age, tumor size, type, histological grade, nodal status, metastases, and relapse. Moreover, triple-negative tumors also express CK5 (75.0%), CK14 (29.0%), EGFR (28.6%), p63 (28.6%), caveolin (14.3%), and p53 (67.1%). We considered basal-like cancers to be any tumor ER/PR/HER2-negative, CK5 and/or CK14-positive. A basal-like phenotype was detected in 105/140 (75.0%) triple negative tumors and ALDH1 expression was demonstrated in both tumor cells (21/105 cases; 20.0%) and stroma (87/105 cases; 82.9%).
Conclusions: ALDH1 is more frequently seen in stromal cells than in epithelial tumor cells. Additionally, stromal expression is associated with best OS in our series of TNCs. Stromal cells expressing ALDH1within the tumor could represent one of the means through which tumor microenvironment play a role in determining prognosis in TNC.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 4, Tuesday Afternoon