High frequency of p16 and SOX10 coexpression but not androgen receptor expression in triple-negative breast cancers

Hum Pathol. 2020 Aug:102:13-22. doi: 10.1016/j.humpath.2020.06.004. Epub 2020 Jun 18.

Abstract

Triple-negative breast cancers (TNBCs) represent approximately 12-17% of all breast cancers and have distinctively aggressive clinical courses. Because routine biomarkers for breast cancer do not apply for TNBCs, it is essential to find novel prognostic markers and potential targets for therapeutic agents. p16 and SOX10 are emerging biomarkers with relatively unexplored expressions in TNBCs. We present an analysis of the expression of p16 and SOX10 in combination with that of androgen receptor (AR) and cytokeratin (CK) 5/6 in TNBCs. In addition, we used tissue microarrays (TMAs) to compare frequencies of p16 and SOX10 between TNBCs and non-TNBCs. Fifty-six TNBC samples with clinical data were stained immunohistochemically with p16, SOX10, AR, and CK5/6. Fifty-four cases (96.4%) were invasive ductal carcinoma, not otherwise specified, and 46 cases (82.1%) were Nottingham histologic grade 3. The majority of TNBC cases were positive for p16 (n = 44; 78.6%) and SOX10 (n = 48; 85.7%). AR was positive in 15 cases (26.8%). CK5/6 was positive in 24 cases (42.9%), which were classified as basal-like breast cancer (BLBC) subtype. The frequencies of p16 and SOX10 expression in BLBC and non-BLBC subtypes did not reveal significant statistical difference in a separate analysis. Using archived TNBC and non-TNBC TMAs, we observed that 56% of TNBC cases were positive for p16 compared with 16% of non-TNBC cases (p-value <0.0001). SOX10 was positive in 80% of TNBC cases compared with 35% of non-TNBC cases (p-value <0.0001). A significant correlation was observed between p16 and SOX10 coexpression in TNBC cases (n = 56/80, p = 0.02) but not in non-TNBC cases (n = 23/348; p = 0.626). In conclusion, p16 and SOX10 are frequently expressed in TNBC, regardless of CK5/6 expression. Furthermore, p16 and SOX10 are often coexpressed in TNBCs compared with non-TNBCs.

Keywords: AR; Basal-like breast cancer; Biomarkers; Breast Cancer; SOX10; Triple negative breast cancer; p16.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Cyclin-Dependent Kinase Inhibitor p16 / biosynthesis*
  • Female
  • Humans
  • Keratin-5 / biosynthesis
  • Keratin-6 / biosynthesis
  • Middle Aged
  • Receptors, Androgen / biosynthesis*
  • SOXE Transcription Factors / biosynthesis*
  • Triple Negative Breast Neoplasms / pathology*

Substances

  • AR protein, human
  • Biomarkers, Tumor
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Keratin-5
  • Keratin-6
  • Receptors, Androgen
  • SOX10 protein, human
  • SOXE Transcription Factors