Immunohistochemical Comparative Study of Aggressive and Non-aggressive Central Giant Cell Lesions of the Jaws Based on the Tenascin-C Expression Profile.

The purpose of this study was to compare the immunohistochemical expression of tenascin-C (Tn-C) regarding clinicopathological variables and its association with the clinical behavior of central giant cell lesions (CGCLs). Forty-eight paraffin-embedded samples of CGCLs were selected. Based on clinical and radiographic features, the lesions were classified as aggressive (A-CGCLs) and non-aggressive (NA-CGCLs) subtypes. Histological assessment included the microvessel count (MVC), multinucleated giant cell (MGC) count, and the proportion of tissue area involved by mononuclear stromal cells/interstitial fibrosis. Immunoreactivity, immunolocalization, and distribution patterns of Tn-C were studied immunohistochemically. The association between Tn-C expression and clinicopathological characteristics was analyzed separately and adjusted for confounders using logistic regression models. A significantly greater proportion of cases with moderate-to-intense, intracellular, and diffuse staining of Tn-C was observed in A-CGCLs. CGCLs with a size ≥3.3 cm, fast growth, cortical disruption, high MVC/MGC counts, and low interstitial fibrosis showed a significantly greater frequency of moderate-to-intense, intracellular, and diffuse staining. Logistic regression analysis indicated a strong/independent association of these three immunohistochemical parameters with the aggressiveness of lesions. These data appear to suggest a possible role for Tn-C in the etiopathogenesis of CGCLs of the jaws, where its upregulation might favor the destructive behavior of A-CGCLs.

Association analysis between rs6184 and rs6180 polymorphisms of growth hormone receptor gene regarding skeletal-facial profile in a Colombian population.

Background/Objective: There is strong evidence that genetic factors may affect the craniofacial morphology. This study aimed to examine the association between the rs6184 and rs6180 polymorphic variants of the growth hormone receptor (GHR) gene and skeletal-facial profile in a Colombian population. Subjects/Methods: Saliva samples from 306 individuals ranging in age from 15 to 53 (mean 24.33) years were collected. Cephalometric parameters were used to categorize the participants as Class I, Class II, or Class III skeletal-facial profile. The polymerase chain reaction-restriction fragment length polymorphism method was used to identify genotypes of the rs6184 and rs6180 single nucleotide polymorphisms (SNPs). The association of polymorphisms with the skeletal-facial profile was assessed separately and adjusted for confounding using a multivariate binary logistic regression model, alongside with analysis of linkage disequilibrium and haplotype associations. Results: Although individuals carrying the CA genotype of the rs6184 SNP showed both significantly decreased values for ANB angle and increased measures concerning mandibular body length and mandibular length, no significant differences amongst genotype groups of rs6180 SNP were observed. Moreover, chi-square test and logistic regression analysis revealed that the CA genotype of rs6184 SNP and the A-A haplotype were highly associated with Class III skeletal-facial profile. Conclusions: Although these results do not support that rs6180 SNP could be identified as a predictor for skeletal-facial profile, they suggest that the allele A of rs6184 SNP alone or in combination with other SNPs in the GHR gene yields significant horizontal and longitudinal variations of the mandibular morphology and might be a strong/independent prognostic indicator for Class III skeletal-facial profile in the present population.

Immunoexpression of NF-ĸB and their inhibitory subunits IĸBα and IĸBß in giant cell lesions of the jaws: implications for their clinical behavior.

BACKGROUND: The unpredictable behavior of giant cell lesions (GCLs) of the jaws parallels its controversial histogenesis. This study evaluated a possible association between the immunohistochemical expression of NF-ĸB, the inhibitory subunits IĸBα/IĸBß, and clinicopathological variables with the behavior of central and peripheral GCLs of the jaws. MATERIALS AND METHODS: Paraffin-embedded samples of GCLs of the jaws (n = 68) were prepared for histological/immunohistochemical assessment. Demographic and clinicopathological parameters were assessed to determine the behavior of the lesions. A staining-intensity-distribution (SID) score was used to assess the immunomarkers reactivity. The association between significant candidate immunohistochemical predictor variables regarding clinical behavior was analyzed individually and adjusted for confounding using a binary logistic regression model. RESULTS: While univariate analysis revealed a positive association of NF-ĸB SID score, NF-ĸB nuclear expression, IĸBα SID score, and NF-ĸB to inhibitors average ratio with the aggressive status of GCLs, after bivariate logistic regression analysis, only NF-ĸB nuclear expression, IĸBα SID score, and NF-ĸB to inhibitors average ratio remained as robust predictors of aggressiveness. Confounding and interaction effects regarding clinicopathological candidate predictor variables were also noted. CONCLUSION: It looks that clinical behavior of GCLs of the jaws may be strong/independently linked to the increased nuclear expression of NF-ĸB, higher NF-ĸB to inhibitors average ratio, and decreased IĸBα SID score. Notwithstanding, there are simultaneously synergistic and opposing interactive effects with respect to age stratum, growth rate, multinucleated giant cells count, and mononuclear stromal cells density in the susceptible host that may increase the tissue destruction observed in aggressive GCLs.

Time-related changes in salivary levels of the osteotropic factors sRANKL and OPG through orthodontic tooth movement.

INTRODUCTION: In this study, we aimed to determine whether the variations in salivary concentrations of soluble receptor activator of nuclear factor kappa B ligand (sRANKL) and osteoprotegerin (OPG), and their ratios, might be linked with the different phases of orthodontic tooth movement. METHODS: Twenty healthy subjects who required fixed appliance therapy not involving tooth extractions or surgical procedures were selected. Unstimulated whole saliva samples were collected from each patient before fitting the orthodontic appliances, and at 24 to 48 hours, 2 weeks, 5 weeks, and 8 weeks after the activation. Salivary sRANKL and OPG concentrations were determined by enzyme-linked immunosorbent assays. The data were analyzed by using nonparametric statistics. RESULTS: Overall, median values of sRANKL showed significant increases, median OPG salivary values showed a significant downward trend, and the sRANKL/OPG ratio tended to increase significantly over time after the activation visit. However, clear fluctuations in the immunoenzymatic findings were noted at the different sampling times, indicating nonlinear trends in the levels of the biomarkers through time. Post-hoc pairwise comparisons showed significant differences between (1) all sRANKL values relative to those of the 8-week sampling time; (2) baseline/8-week OPG salivary levels; and (3) baseline, 24 to 48 hours, and 2-week sRANKL/OPG ratios compared with those of the 8-week test. CONCLUSIONS: The findings indicate that variations in salivary concentrations of sRANKL and OPG and their ratios might be linked to the different phases of orthodontic tooth movement. Hence, these analytes might serve in a panel of salivary functional biomarkers that could assist in the screening of orthodontic treatment in clinical practice.

Overexpression of matrix metalloproteinase (MMP)-1 and -9 in central giant cell lesions of the jaws: implications for clinical behavior.

OBJECTIVE: The aim of this study was to investigate the relationship between the immunohistochemical expression of MMP-1 and MMP-9 with the clinical behavior of central giant cell lesions (CGCLs) of the jaws. STUDY DESIGN: Paraffin-embedded tissue from 30 aggressive and 12 nonaggressive CGCLs was assessed for the expression of MMP-1 and MMP-9 using immunohistochemistry. RESULTS: Although cellular immunolocalization patterns of MMP-1 and MMP-9 were similar, mean values of expression estimation/SID scores of each protease were significantly higher in aggressive CGCLs in comparison with nonaggressive lesions. Moreover, linear regression analysis showed that there was a reasonably good correlation not only between the expression estimation but also among SID scores of the 2 proteolytic enzymes. CONCLUSION: The findings of this study suggest a role for MMP-1 and MMP-9 in the resorptive activity of different cellular groups in CGCLs and indicate that differences in immunoreactivity of these 2 proteolytic enzymes may underlie the distinct clinical behavior.

Expression of hMLH1 and hMSH2 proteins in pleomorphic adenoma of minor salivary glands: relationship with clinical and histologic findings.

OBJECTIVE: The aim was to examine the relationship between clinicopathological features and immunoexpression of hMLH1 and hMSH2 proteins in pleomorphic adenoma (PA) of minor salivary glands. STUDY DESIGN: Paraffin-embedded samples of typically benign PA lesions (n = 35) were prepared for histologic and immunohistochemical assessment. Based on the clinicopathologic features, the samples were categorized into low- and high-risk subtypes for their estimated potential for malignant transformation. RESULTS: Immunohistochemical analysis revealed strong correlations regarding the expression estimation and staining-intensity distribution (SID) scores between the two proteins. Although there was no relationship between marker immunoexpression and SID scores regarding clinical parameters, statistically significant variations for these parameters were evident regarding some histologic criteria or for risk stratification subtypes. CONCLUSION: The findings of this study could suggest the relationship of a DNA mismatch repair deficiency with high-risk subtypes of PA and the implication of its role in the origin and progression of these subtypes.

Cytomorphometric and immunohistochemical comparison between central and peripheral giant cell lesions of the jaws.

OBJECTIVE: To determine whether cytomorphometric differences of multinucleated giant cells (MGCs) and CD68 reactivity of both MGCs and infiltrating macrophages may be associated with the clinical behavior of central and peripheral giant cell lesions of the jaws. STUDY DESIGN: Paraffin-embedded samples of central giant cell lesions (CGCLs; n = 20) and peripheral giant cell lesions (PGCLs; n = 20) were prepared for cytomorphometric analysis and immunohistochemistry. RESULTS: The nuclei in CGCLs were more numerous, larger, and more irregular than those in PGCLs. Furthermore, CD68 expression and the ratio of CD68(+) macrophage to MGCs were significantly greater in CGCLs than in PGCLs. Statistical correlations between CD68 expression and the staining-intensity distribution score within the diagnostic groups were significant in CGCLs and not significant in PGCLs. CONCLUSION: Although the CGCLs share some histopathologic similarities with PGCLs, differences in both nuclear morphometric parameters of MGC and CD68 immunoreactivity may underlie the distinct clinical behavior.