Association of CD44 and CD24 phenotype with lymph node metastasis and survival in triple-negative breast cancer

Abstract

Background: CD44⁺CD24^-/low phenotypes are associated with poor outcome of triple-negative breast cancer (TNBC); however, the role of the CD44⁺CD24^-/low phenotype in lymph node metastasis and survival has not been fully understood in TNBC.

Methods: A total of 51 TNBC patients were included. CD44 and CD24 expression was determined using immunohistochemistry by which CD44 and CD24 were double-immunostained. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method.

Results: The proportion of the CD44⁺CD24^-/low phenotype was 33.3% in TNBC specimens without lymph node metastases and 69.0% in those with lymph node metastases. In addition, the CD44⁺CD24^-/low phenotype correlated significantly with tumor size, histologic classification, TNM stage, and lymph node metastasis (P < 0.05). The CD44⁺CD24^-/low phenotype was detected in 69.0% of TNBC patients with lymph node metastases, and 51.7% of TNBC patients without lymph node metastases. In TNBC patients without lymph node metastases, the median DFS and OS were 18.2 and 28 months in cases with a CD44⁺CD24^-/low phenotype and 26.5 and 42.5 months in those without a CD44⁺CD24^-/low phenotype (P < 0.05), and in TNBC patients with lymph node metastases, the median DFS and OS were 17.2 and 25.7 months in cases with a CD44⁺CD24^-/low phenotype and 24.5 and 39.3 months in those without a CD44⁺CD24^-/low phenotype, respectively (P < 0.05).

Conclusions: CD44 and CD24 are independent prognostic markers for patients with TNBC. The CD44⁺CD24^-/low phenotype correlates with more aggressive clinicopathologic features and is strongly associated with poor prognosis in patients with TNBC.

Keywords: CD24; CD44; Triple-negative breast cancer; cancer stem cells; lymph node metastasis; survival.

Figure 1

Immunostaining of CD44 and CD24 in triple-negative breast cancer specimens with and without lymph node metastases. A1 and A3. Positive CD44 staining in triple-negative breast cancer specimens without lymph node metastases; A2 and A4. Negative CD24 staining in triple-negative breast cancer specimens without lymph node metastases; B1 and B3. Positive CD44 staining in triple-negative breast cancer specimens with lymph node metastases; B2 and B4. Negative CD24 staining in triple-negative breast cancer specimens with lymph node metastases. * indicates tumor foci in triple-negative breast cancer specimens with and without lymph node metastases, and the arrows show positive CD44 expression and negative CD24 expression. A1, A2, B1 and B2. Magnification of × 10; A3, A4, B3 and B4. Magnification of × 40.

Figure 2

Double immunostaining of CD44 and CD24 in triple-negative breast cancer specimens with and without lymph node metastases (× 40). Circumferential membranous staining (permanent brown staining) shows CD44 expression, and low (A) or negative CD24 staining (B) is found in the membrane and cytoplasm.

Figure 3

Kaplan-Meier curves of disease-free survival and overall survival in triple-negative breast cancer patients. A. Comparison of disease-free survival between patients without lymph node metastases positive and negative for the CD44⁺CD24^-/low phenotype; B. Comparison of overall survival between patients without lymph node metastases positive and negative for the CD44⁺CD24^-/low phenotype; C. Comparison of disease-free survival between patients with lymph node metastases positive and negative for the CD44⁺CD24^-/low phenotype; D. Comparison of overall survival between patients with lymph node metastases positive and negative for the CD44⁺CD24^-/low phenotype.