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. 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.
authors: Department of Molecular Medicine, Unit of Pathology, University of Pavia and Department of Pathology IRCCS Policlinico S. Matteo Foundation, Pavia, Italy. patrizia.morbini@unipv.it.
authors: Patrizia
authors: P
authors: Morbini
authors: Department of Pathology IRCCS Policlinico S. Matteo Foundation.
authors: Gian Luca
authors: GL
authors: Capello
authors: Department of Pathology IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.
authors: Paola
authors: P
authors: Alberizzi
authors: Department of Otolaryngology, University of Pavia and IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.
authors: Marco
authors: M
authors: Benazzo
authors: Department of Oncology, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.
authors: Chiara
authors: C
authors: Paglino
authors: Pediatric Hematology/Oncology, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.
authors: Patrizia
authors: P
authors: Comoli
authors: Department of Oncology, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.
authors: Paolo
authors: P
authors: Pedrazzoli
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006148:Guanine Deaminase / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053552:Keratin-7 / Q000378:metabolism; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D008875:Middle Aged; D009088:Mucoproteins; D015513:Oncogene Proteins; D009959:Oropharyngeal Neoplasms / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D014066:Palatine Tonsil / Q000166:cytology / Q000378:metabolism*; D027383:Papillomaviridae / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000378:metabolism; D060149:Tetraspanin 30 / Q000378:metabolism
chemical_list: C502296:AGR2 protein, human; D015415:Biomarkers; C554586:CD63 protein, human; C402297:GDA protein, human; D053552:Keratin-7; D009088:Mucoproteins; D015513:Oncogene Proteins; D011506:Proteins; D060149:Tetraspanin 30; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; D006148:Guanine Deaminase