Serum vitamin D levels of patients with oral squamous cell carcinoma (OSCC) and expression of vitamin D receptor in oral precancerous lesions and OSCC

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.

Serum levels of 25‐hydroxy‐vitamin D in patients with oral squamous cell carcinoma: Making a case for chemoprevention

“…In the present study, we focused on the estimation of serum vita- what was previously reported by other authors (Anand et al, 2017;Bochen et al, 2018 andGrimm et al, 2015). Grimm et al (2015) reported that among the 42 OSCC patients in their study in a Cauca- et al, 2013). This makes the findings of this study even more significant and relevant to this population.…”

“…The chemopreventive and therapeutic roles of vitamin D in a wide range of human cancers have been suggested in the literature (Bikle, Oda, & Teichert, 2011;Kamradt et al, 2003). Indeed, many of these malignant lesions including OSCC have been shown to express the receptor for 1,25 Dihydroxyvitamin D 3 ; also known as VDR (vitamin D receptor) (Adisa et al, 2017;Grimm et al, 2013 and2015;Osafi et al, 2014 andRussel et al, 2010). The suggested mechanism of action may be through its effect on p53-mediated DNA damage in cases of skin squamous cell carcinoma (Reichrath & Reichrath, 2013).…”

“…This, they claim, confers a "protective autophagy" on these cancer cells and therefore prolong their lifespans. This is believed to be responsible for the cancer metastasis, recurrence, and resistance to both chemotherapy and radiotherapy (Grimm et al, 2015;Sinha et al, 2013). Therefore, treatment options that will promote apoptosis will indeed help in the management of OSCC (Grimm et al, 2015).…”

“…The active form of vitamin D (1-alpha, 25-dihydroxycholecalciferol) (VD) has been shown through several studies to affect normal and cancerous cells by enhancing anti-proliferation and pro-apoptotic factors, as well as inhibition of cell-cycle promoters and growth factor signaling pathways (Grimm et al, 2015;Grimm, Alexander, Munz, Hoffmann, & Reinert, 2013;Osafi et al, 2014 andRussel, Rassnick, Erb, Vaughan, &McDonough, 2010). This means that it is pro-apoptotic and is a useful anti-neoplastic agent in the management of several malignancies including those of the head and neck region (Grimm et al, 2015;Osafi et al, 2014 andRussel et al, 2010). Serum level of vitamin D has also been used as a predictor for cancer development (Grimm et al, 2015; Tuohimaa & Lou, 2012).…”

“…This means that it is pro-apoptotic and is a useful anti-neoplastic agent in the management of several malignancies including those of the head and neck region (Grimm et al, 2015;Osafi et al, 2014 andRussel et al, 2010). Serum level of vitamin D has also been used as a predictor for cancer development (Grimm et al, 2015; Tuohimaa & Lou, 2012).…”