Clinicopathological, immunohistochemical and molecular correlation of neural crest transcription factor SOX10 expression in triple-negative breast carcinoma

Hum Pathol. 2018 Oct:80:163-169. doi: 10.1016/j.humpath.2018.06.007. Epub 2018 Jun 9.

Abstract

The transcription factor SOX10 mediates the differentiation of neural crest-derived cells, and SOX10 by immunohistochemistry (IHC) is used primarily for the diagnosis of melanoma. SOX10 expression has been previously documented in benign breast myoepithelial cells. However there is limited literature on its expression in triple-negative breast carcinoma (TNBC). The aim was to study the clinical, pathologic and molecular profiles of SOX10+ tumors in TNBC. Tissue microarrays of TNBC were evaluated for SOX10 expression in 48 cases. SOX10 expression was correlated with clinical and pathologic features such as age, grade, and stage. Gene expression was analyzed on RNA extracted from formalin-fixed paraffin-embedded (FFPE) specimens with Affymetrix 2.0 HTA. Co-expression of SOX10 with androgen receptor (AR), WT1, gross cystic disease fluid protein-15 (GCDFP-15), mammaglobin, epidermal growth factor receptor (EGFR), CK5/6 and GATA transcription factor 3 (GATA3) were also assessed. The mean age was 59.38 (range, 28-90 years). Overall, 37.5% cases (18/48) were SOX10+. There was no association between SOX10 expression and age, grade or stage of patients; 6 of 10 (60%) cases of basal-like 1 (BL1), and 5 of 8 cases of unstable (UNS) molecular subtype were SOX10+. One of 5 basal-like-2 (BL2), 1 of 6 immunomodulatory (IM), 1 of 4 mesenchymal (M), 1 of 5 luminal androgen receptor (LAR) and 2 of 8 mesenchymal stem cell (MSL) showed lower frequencies of SOX10 expression. There was negative correlation between SOX10 and AR+ subtypes (P < .002). SOX10 was positively correlated with WT1 (P = .05). SOX10 did not show significant correlation with mammaglobin, GCDFP15, EGFR, CK5/6 and GATA3. SOX10 expression in the basal-like and unstable molecular subtypes supports the concept that these neoplasms show myoepithelial differentiation.

Keywords: Androgen receptor; Basal-like; Molecular subtypes; SOX10; Triple-negative breast cancer; WT1.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis
  • Female
  • GATA3 Transcription Factor / metabolism
  • Humans
  • Immunohistochemistry / methods
  • Middle Aged
  • Neural Crest / pathology*
  • SOXE Transcription Factors / genetics
  • SOXE Transcription Factors / metabolism*
  • Triple Negative Breast Neoplasms / diagnosis
  • Triple Negative Breast Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • SOX10 protein, human
  • SOXE Transcription Factors