Potential protective effect of ALDH-1 stromal expression against early recurrence of operable breast cancers.

Background: The emerging cancer stem cell (CSC) model proposes that the stem cell niche plays a major role in the risk of cancer recurrence. Enzymatic activity of aldehydes, including aldehyde dehydrogenase 1 (ALDH-1), has been used as a marker of normal and malignant breast stem cells (BSCs). However, the clinical implications of the expression of stem cell markers in the stroma have not yet been investigated.

Methods: To determine the relationships of ALDH-1 expression, the currently reliable BSCs marker, with clinical characteristics and survival, we used immunohistochemical staining of tissue microarrays from 180 stroma and epithelial cancer tissues in patients diagnosed with operable early breast cancer (stage 0-III).

Results: ALDH-1 expression was observed in 93.4% of the stromal cells and in 37.2% of the epithelial cells, and the expression levels between the two cell types were significantly correlated (P=0.001). The stromal expression of ALDH-1 was not correlated with any clinical factors, whereas epithelial expression was significantly correlated with a negative estrogen-receptor status (P<0.001), high proliferation based on Ki-67 expression (P<0.001), and younger age (P=0.04). After 27.8 months of follow up, negative stromal expression of ALDH-1 was significantly correlated with shorter overall survival (positive, 56.9±3.0 months . negative, 30.5±3.0 months; P=0.01).

Conclusions: Stromal ALDH-1 expression was not directly correlated with known clinical factors, but its expression may play a protective role against early recurrence. Further observation and large-scale studies are needed to validate the clinical implications of ALDH-1 in breast cancer.