Markers of squamocolumnar junction cells in normal tonsils and oropharyngeal cancer with and without HPV infection
Patrizia Morbini1,2, Gianluca Capello2, Paola Alberizzi2, Marco Benazzo3, Chiara Paglino4, Patrizia Comoli5 and Paolo Pedrazzoli4
1Department of Molecular Medicine, Unit of Pathology, University of Pavia, 2Department of Pathology IRCCS Policlinico S. Matteo Foundation, 3Department of Otolaryngology, University of Pavia and IRCCS Policlinico S. Matteo Foundation, 4Department of Oncology, IRCCS Policlinico S. Matteo Foundation and 5Pediatric Hematology/Oncology, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy
Offprint requests to: Patrizia Morbini, MD, PhD, Department of Molecular Medicine, Unit of Pathology, Via Forlanini 16, 27100 Pavia, Italy. e-mail: firstname.lastname@example.org
Summary. 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 squamo-columnar (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. Histol Histopathol 30, 833-839 (2015)
Key words: HPV-associated oropharyngeal carcinoma, Squamocolumnar junction, Tonsillar crypt, Anterior gradient 2, Cytokeratin 7