Cancer stem cell and epithelial-mesenchymal transition markers predict worse outcome in metaplastic carcinoma of the breast.

Abstract

Metaplastic breast carcinomas are known to overexpress markers of epithelial-mesenchymal transition and cancer stem cells. We evaluated their immunohistochemical expression, correlating with clinicopathological parameters and survival outcomes. The study cohort comprised 63 cases diagnosed at the Department of Pathology, Singapore General Hospital. Tumor size, grade, lymph node stage, and metaplastic components were reviewed. Immunohistochemistry was performed on sections cut from tissue microarray blocks. Antibodies to ER, PR, HER2, CK14, EGFR, 34βE12, cancer stem cell markers (CD44, CD24, ALDH1A1), epithelial-mesenchymal transition markers (Twist and E-cadherin), were applied. Survival outcomes were correlated with immunohistochemical findings. T2 tumors accounted for 74.7% of cases, with grade 3 tumors predominating (71.4%). Triple negativity occurred in 87.3%, and basal-like subtype in 69.8% of tumors. CD44+, CD44+CD24-, ALDH1A1+, loss of membranous E-cadherin (Ecadloss) and positive Twist expression was found in 82.5, 73.0, 77.8, 54.0, and 57.1% of tumors, respectively. Combinational phenotypes of CD44+EcadlossTwist+, CD44+CD24-EcadlossTwist+, and ALDH1A1+EcadlossTwist+ were observed in 28.6, 25.4, and 2.6% of tumors. Histologic grade was significantly correlated with E-cadherin loss (p=0.042), Twist positivity (P=0.001), CD44+EcadlossTwist+ (P=0.010), CD44+CD24-EcadlossTwist+ (P=0.018), and ALDH1A1+EcadlossTwist+(P=0.010). Lymph node stage was significantly associated with CD44+EcadlossTwist+(P=0.044) and CD44+CD24-EcadlossTwist+ (P=0.044). Basal-like phenotype was significantly correlated with CD44 expressing (P=0.004) and CD44+CD24- tumors (P=0.049). Tumors harboring CD44+EcadlossTwist+ and CD44+CD24-EcadlossTwist+ phenotypes disclosed early recurrence (P=0.027, P=0.006) and poorer overall survival (P=0.037, P=0.006), respectively. Expression of cancer stem cell and epithelial-mesenchymal transition markers in metaplastic breast cancers correlates with adverse pathological parameters and outcome.