The prognostic role of the human embryonic stem cell protein, NANOG, in breast cancer

Abstract

Breast cancer is a heterogenous disease. Recent cDNA microarray studies classified breast cancer into three main groups, which have been shown to be of prognostic importance: luminal (usually estrogen receptor (ER) and progesterone receptor (PR) positive), HER2 and basal-like subtypes. Basal-like tumors have the worst prognosis and are usually triple negative (ER\PR\HER2 negative). NANOG is a transcription factor that plays an important role in human embryonic stem cell pluripotency and self-renewal (Ezeh, 2005). It is located at chromosome 12p13, a region frequently gained in basal-like breast tumors (Bergmaschi, 2006). Given that NANOG is upregulated by SOX2, which is preferentially expressed in basal-like breast carcinomas (Rodriguez-Pinilla, 2007), the objective of our study was to assess whether NANOG protein expression was related to basal-like breast cancers, tumor recurrence and patient survival. Cohort study. Sporadic node-negative invasive breast carcinomas were analyzed by immunohistology and tissue microarrays for ER, PR, HER2 and NANOG protein expression (n = 117). Tumors were considered to have basal-like phenotype if they were triple negative (ER\PR\HER2-). We correlated NANOG tissue expression with breast cancer outcome. Kaplan-Meier survival curves (NANOG+ vs. NANOG-) for disease free and overall survivals were compared using Log-rank test. Preliminary analysis of 22 (13 NANOG+, 9 NANOG-) triple negative samples revealed longer mean disease-free (7.0 vs. 4.9 years) and overall (12.1 vs. 9.0 years) survival in the NANOG + group. The difference did not reach statistical significance (Figure 1, Figure 2). Preliminary data indicate that NANOG protein expression may be of prognostic importance in basal-like (ER, PR, and HER2 -) breast cancer. We intend to confirm the significance of this study in a larger cohort.