Immunoexpression of RANK, RANKL and OPG in sporadic odontogenic keratocysts and their potential association with recurrence.

BACKGROUND: Odontogenic keratocysts (OKCs) are clinically aggressive lesions with relatively high recurrence rates. Dysregulation of functional equilibrium in the RANK/RANKL/OPG system is responsible for osteolysis associated with the development of OKCs. Previously published findings imply that immunoexpression of these 3 proteins may correlate with bone resorption activity in OKCs. OBJECTIVES: The rationale behind this study was to assess the potential for receptor activator of nuclear factor kappa-B (RANK), receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) expression, as well as RANKL/OPG expression ratio, to serve as prognostic indicators for OKC recurrence. MATERIAL AND METHODS: We investigated the immunoexpression patterns of RANK, RANKL and OPG, and their correlation with recurrence rates, in 41 patients with OKCs treated with enucleation. RESULTS: We found no statistically significant differences between recurrent and non-recurrent cysts in terms of either: epithelial (p = 0.404) and stromal (p = 0.469) immunoreactivity of RANK; epithelial (p = 0.649) and stromal (p = 0.198) immunoreactivity of RANKL; or epithelial (p = 1) and stromal (p = 0.604) immunoreactivity of OPG. We also did not find significant differences in the distribution of cases with respect to ratios of RANKL/OPG immunostaining scores between recurrent and non-recurrent OKCs, both in the epithelium and in the connective tissue (p = 1 and p = 0.237, respectively). CONCLUSIONS: Our results suggest that immunoexpression levels of RANK, RANKL and OPG at the time of pathological diagnosis, as well as the RANKL/OPG ratio, are not useful as prognostic markers for OKC recurrence.

Evaluation of Proinflammatory, NF-kappaB Dependent Cytokines: IL-1α, IL-6, IL-8, and TNF-α in Tissue Specimens and Saliva of Patients with Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a life-threatening disease. It could be preceded by oral potentially malignant disorders (OPMDs). It was confirmed that chronic inflammation can promote carcinogenesis. Cytokines play a crucial role in this process. The aim of the study was to evaluate interleukin-1alpha (IL-1α), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α) in tissue specimens and saliva of patients with OSCC and OPMDs. METHODS: Cytokines were evaluated in 60 tissue specimens of pathological lesions (OSCCs or OPMDs) and in 7 controls (normal oral mucosa, NOM) by immunohistochemistry and in saliva of 45 patients with OSCC or OPMDs and 9 controls (healthy volunteers) by enzyme-linked immunosorbent assays. RESULTS: Immunohistochemical analysis revealed significantly higher expression of IL-8 in OSCC specimens and TNF-α in OSCCs and OPMDs with dysplasia as compared to NOM. Moreover, expression of TNF-α was significantly higher in oral leukoplakia and oral lichen planus without dysplasia, whereas expression of IL-8 only in oral leukoplakia without dysplasia in comparison with NOM. Salivary concentrations of all evaluated cytokines were significantly higher in patients with OSCC than in controls. Moreover, levels of IL-8 were significantly higher in saliva of patients with OPMDs with dysplasia as compared to controls and in OSCC patients as compared to patients with dysplastic lesions. There was also significant increase in salivary concentrations of IL-6, IL-8 and TNF-α in patients with OSCC as compared to patients with OPMDs without dysplasia. CONCLUSION: The study confirmed that proinflammatory, NF-kappaB dependent cytokines are involved in pathogenesis of OPMDs and OSCC. The most important biomarker of malignant transformation process within oral mucosa among all assessed cytokines seems to be IL-8. Further studies on a larger sample size are needed to corroborate these results.

Evaluation of enzymatic and non-enzymatic antioxidant status and biomarkers of oxidative stress in saliva of patients with oral squamous cell carcinoma and oral leukoplakia: a pilot study.

Objective: The study aimed to evaluate total antioxidant capacity as well as levels of various enzymatic and non-enzymatic antioxidants, and oxidative stress markers in saliva of patients with oral squamous cell carcinoma (OSCC) and oral leukoplakia (OL). Material and methods: Twenty patients with OSCC, 20 patients with OL and 20 healthy subjects were enrolled into this prospective study. Total Antioxidant Capacity (TAC), activity of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) as well as levels of total glutathione (tGSH), reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG ratio, uric acid (UA), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) were estimated in saliva using appropriate biochemical methods. Results: The activity of SOD was significantly higher in OSCC group in comparison with OL and control groups. The levels of GSH were markedly lower in OSCC and OL patients as compared to the control group. Likewise, we found that GSH/GSSG ratio was markedly lower in the OSCC and OL groups. Levels of some biomarkers were influenced by clinical staging of OSCC and OL as well as by sociodemographic factors. Conclusions: The results of this pilot study suggest that salivary activity of SOD is higher in OSCC patients, whereas levels of GSH and GSH/GSSG ratio are lower in saliva of patients with OSCC and OL. Clinical staging of OSCC and OL, as well as some sociodemographic factors may also influence salivary antioxidant status.

Investigation of clinicopathological parameters and expression of COX-2, bcl-2, PCNA, and p53 in primary and recurrent sporadic odontogenic keratocysts.

OBJECTIVES: Odontogenic keratocyst (OKC) presents considerable variation in aggressiveness and propensity for recurrence, yet hitherto, no explicit clinicopathological features have been determined to clearly demonstrate the potential for relapse. This retrospective study aims to investigate the prognostic relevance of various clinicopathological features as well as immunoexpression of COX-2, bcl-2, PCNA, and p53 in sporadic OKC. MATERIALS AND METHODS: Among 41 patients with OKC treated by enucleation, the frequency of recurrence for various clinicopathological features as well as immunoexpression for COX-2, bcl-2, PCNA, and p53 was evaluated. RESULTS: The mean follow-up was 8.49 years, and recurrences were ascertained in 29.27% of cases. We found significant differences between recurrent and non-recurrent cysts in terms of multilocularity (P = 0.029), cortical perforation (P = 0.001), and lesion size (P < 0.001). Hazard risk for the recurrence was 3.362 (95% CI 1.066-10.598) for multilocular cysts, 7.801 (95% CI 2.1-28.985) for evidence of cortical perforation, and 1.004 (1.002-1.006) for 1 mm2 of lesion size on panoramic radiographs. We also found that immunoexpression of PCNA significantly correlates with the radiographic evidence of cortical perforation (P = 0.048) and that there is significant positive correlation between expression of COX-2 and bcl-2 (P = 0.001) as well as significant negative correlation between immunoexpression of COX-2 and age (P = 0.002). None of the other analyzed factors were associated with the recurrence. CONCLUSIONS: Larger size, multilocularity, and cortical perforation in sporadic OKC may be correlated with the relapse. CLINICAL RELEVANCE: Immunohistochemical analyses of COX-2, bcl-2, PCNA, and p53 lack prognostic utility in sporadic OKC.