Clinicopathologic correlation of cancer stem cell markers CD44, CD24, VEGF and HIF-1α in ductal carcinoma in situ and invasive ductal carcinoma of breast: an immunohistochemistry-based pilot study

Abstract

CD24(-/low)CD44(+) cells have been identified as putative cancer stem cells (CSCs) in breast cancer. However, the expression of these markers, as well as their association with clinical parameters or tumor microenvironment of breast cancer, remains largely unknown. In the present study, we examined the expression of CD44, CD24, VEGF, and HIF-1α in human breast tumor tissues and assessed their clinicopathological correlations. We investigated tissue samples, including 117 cases of invasive ductal carcinoma (IDCa), 14 cases of ductal carcinoma in situ (DCIS), and 15 cases of intraductal hyperplasia (IDH) from breast tissues. The expression of CD44, CD24, HIF-1α, and VEGF was evaluated using immunohistochemical staining. CD24, CD44, HIF-1α, and VEGF were expressed in 49 (41.9%), 51 (43.6%), 32 (27.4%), and 97 cases (82.9%), respectively, in IDCa. CD24(-/low)CD44(+) cells were noted in 48 (41.3%) cases. The levels of CD24 and VEGF expression correlated positively with tumor malignancy (P<0.05). Meanwhile, the expression of CD24, CD44, and VEGF correlated significantly positively with increasing tumor grade (P<0.05). In addition, associations between CD44 and VEGF, CD24 and VEGF, HIF-1α and VEGF, CD24(-/low)CD44(+) and VEGF, CD24(-/low)CD44(+) and HIF-1α were also observed (P<0.05). The HIF-1α expression level was relatively higher in early stage breast cancer patients with CD24(-/low)CD44(+) cells. Taken together, our results suggest that CD24 and VEGF may play important roles in breast tumorigenesis and progression, while HIF-1α may play a role in the early stage of breast carcinogenesis.