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Head and Neck Pathology

, Volume 13, Issue 4, pp 635–642 | Cite as

Expanded Expression of Toll-Like Receptor 2 in Proliferative Verrucous Leukoplakia

  • Joon Koh
  • Zoya B. KuragoEmail author
Original Paper

Abstract

Proliferative verrucous leukoplakia (PVL) is a premalignant condition of the oral mucosa with > 70% chance of progression to squamous cell carcinoma (SCC), while lacking the common risks and behavior seen in non-PVL oral squamous carcinogenesis. PVL follows a multi-stage slow, relentless and usually multifocal expansion of surface epithelial thickening that over time takes on a verrucous architecture, eventually leading to verrucous carcinoma and/or dysplasia followed by “conventional” SCC, a process that takes years and is notoriously difficult to manage. As mucosal surfaces and carcinomas arising at these sites, are colonized by microorganisms, host receptors for microbial products have received attention as potential contributors to carcinogenesis. Studies show that microbial pattern recognition toll-like receptor (TLR)2 in various epithelial cells is upregulated in premalignant lesions and in malignant cells and can activate oncogenic pathways. Because of the highly progressive nature of PVL, we examined TLR2 expression in well-characterized PVL samples by immunohistochemistry. We found that, similar to epithelial dysplasia and SCC, PVL keratinocytes throughout the epithelial thickness showed diffuse TLR2 expression even in early stage lesions prior to onset of dysplasia. In contrast, oral mucosal samples in the absence of hyperorothokeratosis or dysplasia, expressed TLR2 primarily in the basal and parabasal layers. Given the high rates of PVL transformation and the previously established pro-cancer role of high TLR2 expression in malignant oral squamous cells, it is important to determine how its’ expression and functions are regulated in the oral squamous epithelium, and what is the specific TLR2 role in carcinogenesis.

Keywords

Proliferative verrucous leukoplakia PVL Verrucous hyperplasia Toll-like receptor 2 TLR2 Squamous epithelium Squamous cell carcinoma Oral cancer 

Abbreviations

CD282

Cluster of differentiation 282

DAB

Diaminobenzidine

ERK

Extracellular signal regulated kinase

Gneg

Gram-negative

Gpos

Gram-positive

H&E

Hematoxylin and eosin

HPV

Human papillomavirus

IHC

Immunohistochemistry

MAPK

Mitogen-activated protein kinase

PBS

Phosphate buffered saline

PVL

Proliferative verrucous leukoplakia

SCC

Squamous cell carcinoma

TLR

Toll-like receptor

Notes

Acknowledgements

We thank Ms. Regina Hand, histotechnologist at the Dental College of Georgia, for providing sections of archival specimens for the study. This study was supported by Augusta University Pilot Project Grant.

Compliance with Ethical Standards

Conflict of interest

Authors have no conflicts of interest to disclose.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Dental College of GeorgiaAugusta UniversityAugustaUSA
  2. 2.Medical College of Georgia, Georgia Cancer CenterAugusta UniversityAugustaUSA

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