SOX10 belongs to the SOX family of transcription factors. It is an important regulator of early neural crest development, melanocyte differentiation and melanoma biology. Triple-negative (TN)/basal-like breast cancer is a clinically heterogeneous group lacking in prognostic biomarkers and therapeutic targets. Recent studies reported that SOX10 is over-expressed in these tumours. The aims of the current study were: i) to investigate prognostic significance of SOX10 expression in a large cohort of invasive breast cancers (n=449) with long-term clinical follow up data (25 years); ii) to investigate SOX10 mRNA expression in published datasets (e.g. TCGA); and iii) to evaluate SOX10 protein expression in normal and tumour-adjacent normal breast.
At the mRNA level, SOX10 expression is enriched in the basal-like molecular subtype and shows a bimodal distribution. At the protein level, we found SOX10 was predominantly expressed in subsets of TN (44%; 32/73) and basal-like (49%; 28/57) breast cancers, and associated with markers of poor outcome (e.g. tumour grade, lymph node status). SOX10 expression predicted poor survival (p<0.0001; Kaplan Meier analysis) and was the most powerful prognostic indicator in a multivariate (stepwise Cox Proportional Hazards) model after excluding TN status (p=0.0004). Critically, it also predicted poor survival within the TN/basal-like group (p=0.0168; n=54). In both normal (reduction mammoplasty; n=18) and tumour-associated normal (n=19) breast, SOX10 localised to luminal or myoepithelial compartments, or both, but this was mutually exclusive with whole lobules displaying the same expression pattern. Interestingly, this in situ analysis revealed a striking correlation between SOX10 and c-kit expression, and an inverse association with ER. Future studies will focus on investigating whether SOX10 may play a role in regulating luminal progenitor cell function.