Markers of squamocolumnar junction cells in normal tonsils and oropharyngeal cancer with and without HPV infection

Histol Histopathol. 2015 Jul;30(7):833-9. doi: 10.14670/HH-11-590. Epub 2015 Feb 3.

Abstract

HPV infection has been identified recently as the causative agent of a subset of squamous cell carcinomas arising in oropharyngeal tonsils. Factors influencing the susceptibility of tonsillar epithelium to HPV-induced oncogenesis are far from being elucidated. A 5-protein signature including cytokeratin (CK)7, anterior gradient (AGR)2, cluster differentiation (CD)63, matrix metalloproteinase (MMP)7, and guanine deaminase (GDA) has recently been found to identify a residual embryonic cell population in the squamocolumnar (SC) junction of the cervix, susceptible to HPV infection, and cancers originating from these cells. The expression of SC junction markers was investigated with immunohistochemistry in normal tonsils and in oropharyngeal carcinomas (OPC) fully characterised for HPV. All markers were constantly expressed in the reticulated epithelial cells of the tonsillar crypts, with variable diffusion and intensity; in OPC, positivity was observed in 36,5%, 29,2%, 39%, 17%, and 25% of cases with respectively AGR2, CK7, GDA, CD63, and MMP7 antibodies. No OPC was positive for all markers; 6 were completely negative. AGR2 and CK7 showed significant association with tumor- and HPV-related parameters. AGR2 expression was associated with tumor origin in the tongue base (p=0.013); CK7 was associated with non-keratinising morphology (p=0.013). p16 tumor cell expression was associated with AGR2 (p=0.021); transcriptionally active HPV infection was associated with AGR2 and CK7 (p=0.024 and 0.043). Expression of SC junction markers in tonsillar crypt cells might be related to the embryological development of tonsillar structures; their partial association with HPV oncogenic infection could help to identify HPV-susceptible cells and related OPC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Carcinoma, Squamous Cell / etiology*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Female
  • Guanine Deaminase / metabolism
  • Humans
  • Immunohistochemistry
  • Keratin-7 / metabolism
  • Male
  • Matrix Metalloproteinase 7 / metabolism
  • Middle Aged
  • Mucoproteins
  • Oncogene Proteins
  • Oropharyngeal Neoplasms / etiology*
  • Oropharyngeal Neoplasms / metabolism*
  • Oropharyngeal Neoplasms / pathology
  • Palatine Tonsil / cytology
  • Palatine Tonsil / metabolism*
  • Papillomaviridae / pathogenicity
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / metabolism*
  • Papillomavirus Infections / pathology
  • Proteins / metabolism
  • Tetraspanin 30 / metabolism

Substances

  • AGR2 protein, human
  • Biomarkers
  • CD63 protein, human
  • GDA protein, human
  • Keratin-7
  • Mucoproteins
  • Oncogene Proteins
  • Proteins
  • Tetraspanin 30
  • MMP7 protein, human
  • Matrix Metalloproteinase 7
  • Guanine Deaminase