OP0012 Expression of the pluripotency transcription factor SOX2 in primary breast cancers: Correlation with clinicopathological features and recurrence

Abstract

Background SOX2 is one of the pluripotency transcription factors expressed by stem cells, playing a central role in maintenance of stemness and overexpressed in a variety of solid tumours. In breast cancer, SOX2 expression has mainly been reported in the basal-like subtype. We evaluated a heterogenous group of breast cancer tissues to determine whether the expression of SOX2 and other pluripotency transcription factors correlated with clinicopathological factors and recurrence. Methods 140 primary invasive breast cancer specimens were collected. mRNA expression for SOX2, OCT4, NANOG, and GDF3 genes was assessed by RT-PCR. Immunohistochemistry was done for SOX2. Correlations with molecular subtypes, menopausal status, grading, ER, PR, ki67 (⩽20%), HER2, T-size, and node status were evaluated. Association of SOX2 expression and disease-free survival was estimated by univariate and multivariate analysis (p ⩽ 0.05). Findings In 117 samples assessable by RT-PCR we found the following correlations: NANOG and grade 2, GDF3 and node-negative, SOX2 and higher ki67 (p = 0.019, p = 0.029, p = 0.035, respectively). At univariate analysis of disease-free survival, SOX2 expression (hazard ratio (HR) 2.36; p = 0.002), ki67 (HR 2.19; p = 0.028), T-size ⩾1 (HR 2.06; p = 2.011), node-status (HR 2.21; p = 0.014); ER/PR (HR 0.58/HR 0.59, p = 0.065/p = 0.068) were statistically significant. At multivariate analysis, SOX2 (HR 2.99; 95% confidence interval (CI) 1.41–6.30; p = 0.004), node-status (HR 2.44; 95% CI 1.25–4.76; p = 0.009), and T-size ⩾1 (HR 1.77; 95% CI 0.99–3.13; p = 0.051) were associated with increased risk of recurrence. An earlier recurrence was observed in SOX2 + (median 34.9 months; 95% CI 7.5–62.2) than SOX2- patients (median: 60.3 months; 95% CI 32.6–88.1; p = 0.017); overall survival was shorter in SOX2 + patients than in those who were SOX-(68.2 months, 95% CI 63.7–151.4 versus 145.3 months, 95% CI: 80.5–210.2) although this was not significant (p = 0.104). IHC showed SOX2 protein expression in all of 11 samples; no expression was noted in 20 randomly selected SOX2- samples. Interpretation Our analysis confirms that expression of pluripotency transcription factors correlates with specific clinicopathological factors (grade, node-status, and ki67). SOX2 expression was associated with an increased risk of recurrence, irrespective of other clinicopathological factors.