Abstract

Background: Resistance to programmed cell death (apoptosis) is a crucial factor for the carcinogenesis of oral squamous cell carcinoma (OSCC). Vitamin D (calcitriol) may overcome apoptosis resistance in tumor cells of OSCC. Vitamin D receptor (VDR) expression in oral precancerous lesions of OSCC has not been analyzed and serum vitamin D level seems to be a predictor of cancer development. Material and Methods: Expression of VDR was analyzed in normal oral mucosa (n=5), oral precursor lesions (simple hyperplasia, n=11; squamous intraepithelial neoplasia, SIN I-III, n=35), and OSCC specimen (n=42) by immunohistochemistry (IHC). Moreover, serum vitamin D levels were measured by 25(OH)D3 (calcidiol) in patients with OSCC (n=42) and correlated with IHC results. Results: Expression of VDR was significantly increased in precancerous and OSCC compared with normal tissue. Compared with SIN I-III lesions VDR expression significantly decreased in OSCC. Severe vitamin D deficiency was detected in our OSCC patient cohort but there was no significant correlation analyzed between serum vitamin D levels and corresponding immunohistochemically detected VDR expression in OSCC. Conclusions: Our survey provides the first evidence of VDR expression in precancerous lesions of OSCC. Apoptosis induction of VDR+ cells in oral precancerous lesions and OSCC by natural vitamin D or synthetic vitamin D compounds could be useful for chemoprevention. Moreover, systemically and/or locally applied, these compounds may act as sensitizers for apoptosis mediated by radio-, and chemotherapy treatment in OSCC. Key words:Oral cancer, oral precancer, lichen planus, leukoplakia, apoptosis, serum 25(OH)D3, vitamin D receptor, chemoprevention, multistep carcinogenesis.

Highlights

  • The development of oral squamous cell carcinoma (OSCC) is a multistep process that influence key cellular pathways involved in tumor development and growth

  • Vitamin D receptor (VDR) expression in oral precancerous lesions of OSCC has not been analyzed and serum vitamin D level seems to be a predictor of cancer development

  • Severe vitamin D deficiency was detected in our OSCC patient cohort but there was no significant correlation analyzed between serum vitamin D levels and corresponding immunohistochemically detected VDR expression in OSCC

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Summary

Introduction

The development of oral squamous cell carcinoma (OSCC) is a multistep process that influence key cellular pathways involved in tumor development and growth. Serum vitamin D levels (calcidiol) were measured and correlated with tissue-related VDR expression in OSCC patients. Material and Methods - Patients and Tumor Specimen The records of healthy individuals (normal oral mucosal tissues, n=5), patients with oral precursor lesions (simple hyperplasia, n=11; squamous intraepithelial neoplasia SIN I, n=5; SIN II, n=9; SIN III, severe dysplasia, n=10; SIN III, carcinoma in situ, n=11), and patients with invasive OSCC (n=42, Table 1) were retrospectively assessed from January 2009 to December 2013. - Serum 25(OH)D3 (calcidiol) values in patients with OSCC and correlation with corresponding immunohistochemically detected VDR expression No patient (n=0/42, 0%) showed normal (>35 ng/ml) serum vitamin D levels or mild (25-35 ng/ml) vitamin D deficiency.

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