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

Research output: Contribution to journalArticle

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.A ll 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 HPVsusceptible cells and related OPC.

Original languageEnglish
Pages (from-to)833-839
Number of pages7
JournalHistology and Histopathology
Volume30
Issue number7
DOIs
Publication statusPublished - 2015

Fingerprint

Tonsillar Neoplasms
Oropharyngeal Neoplasms
Intercellular Junctions
Guanine Deaminase
Carcinoma
Infection
Palatine Tonsil
Neoplasms
Matrix Metalloproteinase 7
Keratin-7
Tongue
Cervix Uteri
Squamous Cell Carcinoma
Carcinogenesis
Epithelium
Epithelial Cells
Immunohistochemistry
Antibodies
Population

Keywords

  • Anterior gradient 2
  • Cytokeratin 7
  • HPV-associated oropharyngeal carcinoma
  • Squamocolumnar junction
  • Tonsillar crypt

ASJC Scopus subject areas

  • Histology
  • Pathology and Forensic Medicine

Cite this

@article{a67c69a8c8a94f8e81ba040a5ed496df,
title = "Markers of squamocolumnar junction cells in normal tonsils and oropharyngeal cancer with and without HPV infection",
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.A ll 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 HPVsusceptible cells and related OPC.",
keywords = "Anterior gradient 2, Cytokeratin 7, HPV-associated oropharyngeal carcinoma, Squamocolumnar junction, Tonsillar crypt",
author = "Patrizia Morbini and Gianluca Capello and Paola Alberizzi and Marco Benazzo and Chiara Paglino and Patrizia Comoli and Paolo Pedrazzoli",
year = "2015",
doi = "10.14670/HH-11-590",
language = "English",
volume = "30",
pages = "833--839",
journal = "Histology and Histopathology",
issn = "0213-3911",
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T1 - Markers of squamocolumnar junction cells in normal tonsils and oropharyngeal cancer with and without HPV infection

AU - Morbini, Patrizia

AU - Capello, Gianluca

AU - Alberizzi, Paola

AU - Benazzo, Marco

AU - Paglino, Chiara

AU - Comoli, Patrizia

AU - Pedrazzoli, Paolo

PY - 2015

Y1 - 2015

N2 - 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.A ll 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 HPVsusceptible cells and related OPC.

AB - 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.A ll 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 HPVsusceptible cells and related OPC.

KW - Anterior gradient 2

KW - Cytokeratin 7

KW - HPV-associated oropharyngeal carcinoma

KW - Squamocolumnar junction

KW - Tonsillar crypt

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