The expression and prognostic value of stem cell markers Bmi-1, HESC5:3, and HES77 in human papillomavirus-positive and -negative oropharyngeal squamous cell carcinoma

Tumour Biol. 2019 Mar;41(3):1010428319840473. doi: 10.1177/1010428319840473.

Abstract

Human papillomavirus is detected in over 50% of oropharyngeal squamous cell carcinomas. Human papillomavirus-positive oropharyngeal squamous cell carcinomas differ from human papillomavirus-negative tumors, and both expression patterns are classified as distinct entities. The Bmi-1 oncogene is a well-known member of the mammalian polycomb-group family. HESC5:3 and HES77 are newly developed monoclonal antibodies produced against undifferentiated embryonic stem cells. Our aim was to explore their roles in both human papillomavirus-positive and -negative oropharyngeal squamous cell carcinomas. Our cohort comprised 202 consecutive oropharyngeal squamous cell carcinoma patients diagnosed and treated with curative intent. We used tissue microarray tumor blocks to study the immunohistochemical expression of Bmi-1, HESC5:3, and HES77. We compared the expressions of these stem cell markers with p16 immunoexpression and human papillomavirus status, as well as with other characteristics of the tumor, and with patients' clinical data and follow-up data. Human papillomavirus- and p16-positive tumors expressed less Bmi-1 and more HESC5:3 than the negative tumors. HES77 expression was high in human papillomavirus-positive oropharyngeal squamous cell carcinoma, but it did not correlate with p16 positivity. In our multivariable model, Bmi-1 and HESC5:3 were still associated with human papillomavirus, but the association between human papillomavirus and HES77 remained absent. In conclusion, Bmi-1, HESC5:3, and HES77 may have a different role in human papillomavirus-positive and human papillomavirus-negative tumors. There was no correlation between Bmi-1, HESC5:3, and HES77 expression and survival.

Keywords: Cancer; human papillomavirus; immunohistochemistry; oropharynx; p16.

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / virology
  • Cyclin-Dependent Kinase Inhibitor Proteins / biosynthesis*
  • Cyclin-Dependent Kinase Inhibitor Proteins / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Humans
  • Oropharyngeal Neoplasms / pathology*
  • Oropharyngeal Neoplasms / virology*
  • Papillomaviridae / isolation & purification*
  • Papillomavirus Infections / virology
  • Polycomb Repressive Complex 1 / biosynthesis*

Substances

  • Antibodies, Monoclonal
  • BMI1 protein, human
  • Cyclin-Dependent Kinase Inhibitor Proteins
  • Polycomb Repressive Complex 1