Axillary Skip Metastases and the False-Negative Rate of Sentinel Lymph Node Biopsy in Patients With Breast Cancer Are Related to Negative ALDH-1 Expression and Ki-67 Expression

Breast cancer stem cells (CSCs) have been hypothesized to be the driving force behind tumorigenesis and metastasis. In this study, we evaluated the relationships between CSC expressions in primary breast cancers and corresponding metastatic sentinel and nonsentinel lymph nodes (SLNs and NSLNs). The clinical implications of these relationships were also investigated. CSC expressions were evaluated in 167 breast cancer specimens and associated lymph node biopsies (when present). We used double immunohistochemistry of CD44/CD24 and single immunohistochemistry of ALDH-1 on paraffin-embedded breast tissue, SLN, and NSLN specimens. Seven cases had metastatic NSLNs without SLN involvement—so-called “skip metastasis.” Fifty cases of SLNs (29.9%) and 33 cases of NSLNs (25.7%) had metastases. In the breast cancers, metastatic SLNs, and NSLNs, the expression rates of CD44⁺/CD24⁻ were 47.9%, 26.1%, and 34.6 %, respectively, while the expression rates of ALDH-1⁺ were 42.5%, 36.4%, and 33.3%, respectively. Significant relationships were not observed between CSC expressions in breast cancer and metastatic SLNs or NSLNs. The presence of skip metastasis correlated with negative ALDH-1 in breast cancer (P = .04), as well as several clinicopathologic factors: age >50 years (P = .004), negative lymphovascular tumor emboli (P = .02), and high Ki-67 expression (P = .04). Axillary lymph node metastasis showed no significant relationship with any CSC marker. However, CD44⁺/CD24⁻ and ALDH-1 expressions of metastatic SLNs correlated with CSCs of primary breast cancers. In summary, skip metastasis correlated with negative expression of ALDH-1 in primary breast cancers, which could be promising as a means of assessing the risk of skip metastasis.