Evaluation of the relationship between the expression of AgNOR and Ki67 with the recurrence rate in central granulomatous giant cell lesions: A case-control.

OBJECTIVES: Giant cell granuloma is a local nonneoplastic lesion that is divided into two categories, based on its site of occurrence: Central and peripheral giant cell granuloma. Central giant cell granuloma is an intraosseous lesion that has a tendency to recure even in surgically treated cases. Several studies have proven that there is an association between different lesions clinical behavior and their histological features. The aim of this study was to evaluate the expression of AgNOR and Ki67 in lesions with and without recurrency. MATERIAL AND METHODS: Files and records of 35 patients who had been histologically diagnosed with central giant cell granuloma were investigated. Histological features were studied after performing AgNOR staining and Ki67 marker. The data were analyzed by chi-square, Fisher, and T-test. RESULTS: Acquired data indicated that the count of AgNOR staining and Ki67 marker was significantly higher in lesions with recurrency than the lesions with no recurrency. The same results were attained from Ki67 intensity. CONCLUSION: The current study indicated that AgNOR staining and Ki67 marker have prognostic value in predicting recurrency of central giant cell granuloma lesions.

Giant Cell Tumor and Giant Cell Reparative Granuloma of Bone of the Head: CT and MR Imaging Findings.

BACKGROUND: This study aimed to determine the features and differentiation of Giant Cell Reparative Granuloma (GCRG) and Giant Cell Tumor (GCT) of the head on CT and MRI. METHODS: This retrospective study included six patients with histopathology-confirmed head GCRG and 5 patients with histopathology-confirmed head GCT. All images were independently reviewed by two radiologists. The growth pattern, bone changes, MRI signal intensity, enhancement patterns and other image features were recorded. All patients received CT scans and MR images. RESULTS: All the lesions were located centrally in the bone. Osteolytic bone destruction and expansive growth patterns were observed on CT images. Four of six cases broke the cortical bone with residual cortical bone, and the last two showed a thin cortex in GCRG. Five cases broke the cortical bone with residual cortical bone in GCT. There were enhancing septations in GCT lesions on contrast- enhanced T1-Weighted Images (T1WI) while enhancing septations were not present in GCRG cases. The size of GCT lesions was larger than that of GRCG. GCRG and GCT showed iso-low signals on T1WI and iso-high signals on T2-Weighted Images (T2WI). There was a case with cystic or necrotic lesions in each of the two types of lesions. Osteolytic bone destruction and expansive growth patterns were observed in GCTs and GCRGs. CONCLUSION: The size of the GRCG lesion was smaller than that of the GCT. The presence of enhancing septations and the size of the lesion may distinguish GCTs from GCRG.

Integrated proteomics, phosphoproteomics and metabolomics analyses reveal similarities among giant cell granulomas of the jaws with different genetic mutations.

BACKGROUND: Giant cell granuloma of the jaws are benign osteolytic lesions of the jaws. These lesions are genetically characterized by mutually exclusive somatic mutations at TRPV4, KRAS, and FGFR1, and a fourth molecular subgroup which is wild-type for the three mutations. Irrespective of the molecular background, giant cell granulomas show MAPK/ERK activation. However, it remains unclear if these mutations lead to differences in their molecular signaling in giant cell granulomas. METHODS: Metabolomics, proteomics, and phosphoproteomics analyses were carried out in formalin-fixed paraffin-embedded samples of giant cell granuloma of the jaws. The study cohort consisted of five lesions harboring mutations in FGFR1, six in KRAS, five in TRPV4, and five that were wild-type for these mutations. RESULTS: Lesions harboring KRAS or FGFR1 mutations showed overall similar proteomics and metabolomics profiles. In all four groups, metabolic pathways showed similarity in apoptosis, cell signaling, gene expression, cell differentiation, and erythrocyte activity. Lesions harboring TRPV4 mutations showed a greater number of enriched pathways related to tissue architecture. On the other hand, the wild-type group presented increased number of enriched pathways related to protein metabolism compared to the other groups. CONCLUSION: Despite some minor differences, our results revealed an overall similar molecular profile among the groups with different mutational profile at the metabolic, proteic, and phosphopeptidic levels.

Immunohistochemical evaluation of IL-1ß, IL-6, TNF-α and IL-17 cytokine expression in peripheral giant cell granuloma and peripheral ossifying fibroma of the jaws.

OBJECTIVE: To examine and compare the immunohistochemical expressions of IL-1ß, IL-6, IL-17 and TNF-α in peripheral giant cell granuloma (PGCG) and peripheral ossifying fibroma (POF). DESIGN: The study included 20 POF and 20 PGCG cases diagnosed at the Pathology Department of Eskisehir Osmangazi University Medical Faculty. Hematoxylin & Eosin-stained slides obtained from each biopsy specimen were re-evaluated, and IL-1ß, IL-6, IL-17 and TNF-α antibodies were investigated immunohistochemically. While staining in stromal cells was examined in POF cases, staining in both stromal spindle cells and multinucleated giant cells was evaluated in PGCG cases. An immunoreactivity score was established for each case by evaluating the staining percentage and intensity for each individual case. The significance level was set at 5% (p < 0.05). RESULTS: The level of IL-6 and TNF-α expressions in the multinucleated giant cells in PGCG lesions was found higher than that in stromal cells (p < 0.005 and p < 0.000, respectively). In PGCG lesions, there was no significant difference between giant cells and stromal cells in terms of IL-1ß and IL-17 expression levels. There was no significant difference between PGCG and POF lesions in terms of IL-1ß and IL-6 expression. TNF-α expression levels were significantly higher in spindle cells of PGCG lesions than that of POF lesions (p < 0.00). However, IL-17 expression levels were significantly lower in PGCG lesions than in POF lesions (p < 0.05). CONCLUSION: The study results showed that TNF-α expression was significantly higher in PGCG lesions and IL-17 expression in POF lesions. IL-1ß, IL-6, IL-17 and TNF-α are involved in the pathogenesis of both PGCG and POF lesions.

Clinical Significance of M1/M2 Macrophages and Related Cytokines in Patients with Spinal Tuberculosis.

BACKGROUND: Macrophages are important immune cells involved in Mycobacterium tuberculosis (M.tb) infection. To further investigate the degree of disease development in patients with spinal tuberculosis (TB), we conducted research on macrophage polarization. METHODS: Thirty-six patients with spinal TB and twenty-five healthy controls were enrolled in this study. The specific morphology of tuberculous granuloma in spinal tissue was observed by hematoxylin-eosin (H&E) staining. The presence and distribution of bacilli were observed by Ziehl-Neelsen (ZN) staining. Macrophage-specific molecule CD68 was detected by immunohistochemistry (IHC). M1 macrophages play a proinflammatory role, including the specific molecule nitric oxide synthase (iNOS) and the related cytokine tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). M2 macrophages exert anti-inflammatory effects, including the specific molecule CD163 and related cytokine interleukin-10 (IL-10). The above markers were all detected by quantitative real-time PCR (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and IHC. RESULTS: Typical tuberculous granuloma was observed in the HE staining of patients with spinal TB. ZN staining showed positive expression of Ag85B around the caseous necrosis tissue and Langerhans multinucleated giant cells. At the same time, IHC results indicated that CD68, iNOS, CD163, IL-10, TNF-α, and IFN-γ were expressed around the tuberculous granuloma, and their levels were obviously higher in close tissue than in the distant tissue. RT-PCR and ELISA results indicated that IL-10, TNF-α, and IFN-γ levels of TB patients were also higher than those of the healthy controls. CONCLUSION: The report here highlights that two types of macrophage polarization (M1 and M2) are present in the tissues and peripheral blood of patients with spinal TB. Macrophages also play proinflammatory and anti-inflammatory roles. Macrophage polarization is involved in spinal TB infection.

Central giant cell granuloma: A clinicopathological and immunohistochemical study of macrophages, blood vessels, lymphatic vessels and regulatory proteins.

OBJECTIVE: This study seeks to investigate immunohistochemical parameters that could distinguish non-aggressive Central giant cell granuloma (CGCG) from aggressive CGCG, two groups of lesions which differ in their clinical and radiographic features and prognosis. MATERIAL AND METHODS: 12 cases of non-aggressive CGCG and 11 cases of aggressive CGCG were investigated and associated the immunohistochemical expression of macrophages (CD68 and CD163), blood vessels (CD34 and CD105), lymphatic vessels (D2-40) and regulator proteins (p63 and Ki-67). Clinical and radiographic features were also studied. RESULTS: Associations between all proteins in non-aggressive and aggressive CGCG were not significant (p > 0.05). With respect to non-aggressive CGCG, there were no significant correlations, while in aggressive CGCG there was a significant positive correlation between CD68 and CD163 (p = 0.031), between CD34 and D2-40 proteins (p = 0.04), whereas a significant negative correlation was observed between CD105 and CD68 (p = 0.040). However, regardless of aggressiveness of CGCG, there was a significant positive correlation between CD68 and CD163 (p = 0,04). Among the clinical and immunohistochemical aspects, only the symptomatology was a significant risk factor for the occurrence of aggressive CGCG (OR = 12.00/p = 0.016). CONCLUSION: Macrophages and angiogenesis contribute to their maintenance and development of CGCG. In addition, immunohistochemistry used here was not able to differentiate their aggressiveness. However, symptomatology was proved to be a risk factor for the occurrence of aggressive CGCG. It is possible that clinical features, particularly symptomatology, represent the most appropriate parameter to attempt to distinguish GCCG.

C/EBPß regulates Vegf gene expression in granulosa cells undergoing luteinization during ovulation in female rats.

The ovulatory LH-surge increases Vegf gene expression in granulosa cells (GCs) undergoing luteinization during ovulation. To understand the factors involved in this increase, we examined the roles of two transcription factors and epigenetic mechanisms in rat GCs. GCs were obtained from rats treated with eCG before, 4 h, 8 h, 12 h and 24 h after hCG injection. Vegf mRNA levels gradually increased after hCG injection and reached a peak at 12 h. To investigate the mechanism by which Vegf is up-regulated after hCG injection, we focused on C/EBPß and HIF1α. Their protein expression levels were increased at 12 h. The binding activity of C/EBPß to the Vegf promoter region increased after hCG injection whereas that of HIF1α did not at this time point. The C/EBPß binding site had transcriptional activities whereas the HIF1α binding sites did not have transcriptional activities under cAMP stimulation. The levels of H3K9me3 and H3K27me3, which are transcriptional repression markers, decreased in the C/EBPß binding region after hCG injection. The chromatin structure of this region becomes looser after hCG injection. These results show that C/EBPß regulates Vegf gene expression with changes in histone modifications and chromatin structure of the promoter region in GCs undergoing luteinization during ovulation.

Computer-assisted analysis of immunohistological parameters in oral giant cell granulomas.

OBJECTIVE: The aim of this study was to examine the relationship between active osteoclasts, as defined by positive nuclear NFATc1 signals, and the clinical behaviors of oral giant cell granulomas. MATERIALS AND METHODS: NFATc1 immunohistochemical and TRAP-Cbfa1 double immunofluorescence stainings were performed on 9 cases of peripheral giant cell granulomas (PGCGs), 9 cases of central giant cell granulomas (CGCGs) with a recurrent history, and 10 cases of CGCGs without a recurrent history. The results were photographed and quantified by ImageJ. Nine osteoclast- and osteoblast-related parameters were analyzed with conventional statistics and with Rapidminer, an open data analysis platform for computer predictive modeling. RESULTS: Peripheral giant cell granulomas had a significantly lower percentage of active osteoclasts than CGCGs. The recurrent CGCG subgroup had the highest active osteoclast density in comparison with non-recurrent CGCG subgroup and PCCGs. CONCLUSIONS: The study strongly indicates that the status of osteoclasts, as defined by the subcellular NFATc1 signal, has an association with the clinical behavior of oral giant cell granulomas. NFATc1 staining may be useful as a biomarker to predict recurrence of CGCGs. The study also illustrates the potential application of data science tools in studying pathology to facilitate the discovery of disease-associated biomarkers.

Comparative Study of Correlation between Angiogenesis Markers (CD31) and Ki67 Marker with Behavior of Aggressive and Nonaggressive Central Giant Cell Granuloma with Immunohistochemistry Technique

Background: The central giant cell granuloma (CGCG) is generally considered a non-neoplastic lesion. However, some cases show aggressive behavior like neoplasms. Based on clinical observations, a number of researchers have classified this lesion into aggressive and non- aggressive types. This study was aimed to investigate the association between clinical behavior and histopathological features using immunohistochemical vascular CD31 and cellular proliferation Ki67 markers. Materials and methods: In this descriptive-analytical, clinicopathological and immunohistochemical study, 50 CGCGs, including 25 aggressive and 25 non-aggressive types were selected according to Chuong's classification. The samples were then subjected to immunohistochemical staining to analyze positivity for CD31 and Ki67 markers. Numbers of blood vessels and percentage proliferation of underlying fibroendothelial cells were assessed, and the obtained results were analyzed with the t-test and the Mann-Whitney test. Results: The results showed a significant difference between aggressive and non-aggressive CGCG lesions in the mean incidences of Ki67 (p=0.044). and CD31 (p=0.003) positivity. Conclusion: The present evaluation of expression rates for the vascular CD31 and cellular proliferation Ki67 markers showed there might be a positive relation between the clinical features and histopathology of CGCG. Furthermore, clinical behavior may be predicted based on features such as the number of blood vessels and proliferation of fibroendothelial cells.

Immunoexpression of calcitonin and glucocorticoid receptors in central giant cell lesions of the jaws.

BACKGROUND: This study analyzed the immunoexpression of calcitonin receptor (CTR) and glucocorticoid receptor (GR) in central giant cell lesions (CGCLs) and verified potential associations with patient's response to clinical treatment with intralesional injection of triamcinolone. MATERIALS AND METHODS: Fifty-four cases of CGCLs, including 22 non-aggressive, and 32 aggressive, were investigated by immunohistochemistry. RESULTS: Surgery was the therapeutic choice for 53.1% of the aggressive CGCLs, and 46.9% were submitted to the conservative treatment with intralesional triamcinolone injections. Among patients submitted to conservative treatment, 60% (n = 9) showed favorable response. CTR expression was observed in 68.51%, and GR in 94.44% of the total sample. There were no differences in the expression of CTR, neither GR in mononucleated stromal cells (MSCs) or multinucleated giant cells (MGCs), in relation to aggressiveness, treatment performed for and the response to conservative treatment. Both markers showed a positive correlation between their expression in MSCs and MGCs in the total sample (P < 0.0001). CTR expression on MSCs showed a positive correlation with MGCs in the aggressive and non-aggressive groups (P < 0.0001). CONCLUSIONS: Calcitonin receptor and GR expression were diffuse and similar in non-aggressive and aggressive cases, and it did not influence the response to clinical treatment with triamcinolone in the sample studied.

Are CD68 and Factor VIII-RA Expression Different in Central and Peripheral Giant Cell Granuloma of Jaw: An Immunohistochemical Comparative Study.

OBJECTIVE: Central giant cell granuloma and peripheral giant cell granuloma of the jaw and oral cavity are identical in histopathologic features, although they are different in pathogenesis and clinical behavior. The aim of present study was to compare CD 68 and factor VIII related antigen (VIII-RA ) immunoreactivity in central giant cell granuloma and peripheral giant cell granuloma to determine the biologic nature and clinical behavior of these lesions which may lead to a better or new treatment modality. MATERIAL AND METHOD: CD68 and factor VIII-RA expression were examined immunohistochemically in 22 cases of central giant cell granuloma (10 aggressive and 12 non- aggressive ) and 19 cases of peripheral giant cell granuloma. The Kruskal-Wallis test followed by the Dunn test was used for data analysis. RESULTS: CD68 expression was observed in approximately 100% of multinucleated giant cells and 50% of mononuclear cells. Overexpression of factor VIII-RA in the endothelial cells of capillary like vessels in the periphery of the lesions was prominent. A statistical significant difference for CD68 intensity score in mononuclear cells among three groups (P=0.016) was observed. Indeed, factor VIII-RA intensity score in the endothelial cells of central giant cell granuloma and peripheral giant cell granuloma showed significant difference (P=0.004). CONCLUSION: These findings support the histiocyte/macrophage nature of multinucleated giant cells and mononuclear cells. Overexpression and high intensity score of CD68 in mononuclear cells and the high intensity score of factor VIII-RA in endothelial cells represent less aggressive behavior in central giant cell granuloma.

Age and Expression of CD163 and Colony-Stimulating Factor 1 Receptor (CD115) Are Associated With the Biological Behavior of Central Giant Cell Granuloma.

PURPOSE: Central giant cell granulomas (CGCGs) are clinically classified as nonaggressive (nA-CGCGs) and aggressive (A-CGCGs). However, histopathologically, all lesions feature spindle mononuclear cells (MCs) and multinuclear giant cells (GCs) in a hemorrhage-rich stroma. We aimed to investigate the presence of cells with a monocyte- or macrophage-related phenotype and, together with clinical variables, to examine their predictive potential for the biological behavior of CGCGs. PATIENTS AND METHODS: For our investigation, we implemented a retrospective cohort study. Sections were immunohistochemically stained for colony-stimulating factor 1 receptor (CSF-1R) (CD115), CD163, CD68, and nuclear factor κB. The clinical variables included age, gender, and location of lesions. Associations between immunostains, clinical variables, and CGCG aggressiveness were analyzed by the Wilcoxon (Mann-Whitney) exact test and t test. Significant variables were further analyzed by a logistic regression model followed by receiver operating characteristic (ROC) curve analysis for diagnostic sensitivity. Significance was set at P < .05. RESULTS: Patients with A-CGCGs (n = 36) were younger than those with nA-CGCGs (n = 31) (P = .002). Logistic regression showed that CD163-GC (ß = -0.870, P = .031) and CD115-MC (ß = -0.783, P = .027) had a significant protection effect (odds ratio, 0.419 [95% confidence interval, 0.190 to 0.925], and odds ratio, 0.457 [95% confidence interval, 0.229 to 0.913], respectively). ROC curve analysis showed that CD163-GC and CSF-1R (CD115)-MC combined were the best predictor in distinguishing nA-CGCGs from A-CGCGs (area under ROC curve, 0.814; P < .001). At the optimal cutoff value (0.408), sensitivity was 87% and specificity, 65%. CONCLUSIONS: Increasing age and high expression of CD163-GC and CSF-1R (CD115)-MC can serve as significant predictors of nA-CGCGs. A functional link between CD163-GC and the characteristic areas of extravasation of erythrocytes is discussed.

Involvement of mast cells and microvessels density in reactive lesions of oral cavity: A comparative immunohistochemical study.

In view of the similarity of clinicopathological features between reactive lesions of the oral cavity, the objective of the present study was to investigate the density of MCs (mast cells) and microvessels in a series of these lesions. Thirty-seven cases of reactive lesions including fibrous hyperplasia (FH, n=10), inflammatory fibrous hyperplasia (IFH, n=10), peripheral giant cell lesion (PGCL, n=10) and lobular capillary hemangioma (LCH, n=7) were investigated using immunohistochemistry for mast cell tryptase and CD34. For comparative purposes, central giant cell lesions (CGCL, n=5) were included. A higher MC density was observed in LCH (37.01), while CGCL exhibited the lowest density (n=8.14). There was a significant difference in MC density when all reactive lesions were compared to CGCL (p=0.001). The largest mean density of microvessels was observed in LCH (n=21.69). The smallest number was observed in CGCL (n=6.24). There was a significant difference in microvessel density when the reactive lesions were compared to CGCL (p=0.003). There was a significant and direct correlation between the density of MCs and microvessels only for IFH (p=0.048) and CGCL (p=0.005). A significant and direct correlation between the mean density of MCs and microvessels was observed when the reactive lesions were analyzed as a whole (p=0.005). Our results suggest that mast cells contribute to the connective tissue framework and angiogenic function, as well as the development, of reactive lesions of the oral cavity, including FH, IFH, LCH and PGCL.

Mast Cell Concentrations in Peripheral and Central Giant Cell Granulomas: Is there any Angiogenetic Role?

BACKGROUND: In the maxillofacial region, giant cell granulomas occur in 2 clinical forms, central and peripheral. Despite histopathological similarity between these 2 forms totally different clinical behaviors have been reported. The present study was undertaken to compare mast cell and vascular concentrations in these pathologic lesions. MATERIALS AND METHODS: In this cross-sectional descriptive study, 20 pathological samples of central giant cell granuloma (CGCG) and 20 samples of peripheral giant cell granuloma (PGCG) were selected and examined through toluidine blue staining for mast cell assessment and immunohistochemical staining by VEGEF antibody for comparing the number of mast cells. T-test, chi-squared test and backward multivariate linear regression were used for statistical analysis using SPSS 20. Statistical significance was set at P<0.05. RESULTS: This study showed significantly greater VEGF expression and mast cell concentrations in CGCG compared to PGCG cases. Also there was a significant correlation between VEGF expression and the concentration of mast cells. No relation was found between age, sex and site of the lesion and concentration of mast cells or VEGF expression. CONCLUSIONS: It is feasible that higher concentrations of mast cells in CGCG versus PGCG samples might lead to more aggressive clinical behavior via vascular proliferation and angiogenesis. However, other biologic mechanisms should be considered in this situation.

Immunoexpression of Glucose Transporters 1 and 3 and Macrophage Colony-Stimulating Factor in Central and Peripheral Giant Cell Lesions of the Jaws.

PURPOSE: The peripheral giant cell lesion (PGCL) is a reactive process associated with a local irritating factor that shows low recurrence after treatment, especially if the irritating factor is eliminated. In contrast, the central giant cell lesion (CGCL) presents variable clinical behavior ranging from slow and asymptomatic growth without recurrence to rapid, painful, and recurrent growth. The immunoexpression of glucose transporter (GLUT)-1, GLUT-3, and macrophage colony-stimulating factor (M-CSF) was compared in CGCL and PGCL. MATERIALS AND METHODS: Twenty nonaggressive CGCLs, 20 aggressive CGCLs, and 20 PGCLs were selected for analysis of the immunoexpression of GLUT-1, GLUT-3, and M-CSF in multinuclear giant cells (MGCs) and mononuclear cells (MCs). RESULTS: There was a difference in the percentage of immunoreactive cells of GLUT-1 and GLUT-3 in MC components among lesions and in the intensity of GLUT-1 in MCG and MC components, GLUT-3 in MGC components, and M-CSF in MC components. CONCLUSIONS: These results suggest that GLUT-1, GLUT-3, and M-CSF could play a role in the pathogenesis of the lesions studied. The stronger immunostaining of these proteins in MCs shows that these cells have greater metabolic activity and osteoclastogenesis, especially in aggressive CGCL. The MCs showed a stronger relation than the MGCs to the pathogenesis of the studied lesions.

Immunohistochemical expression of alpha-smooth muscle actin and glucocorticoid and calcitonin receptors in central giant-cell lesions.

BACKGROUND: Central giant-cell lesions (CGCLs) are reactive lesions that consist histologically of spindle-shaped stromal cells, (fibroblasts and myofibroblasts) loosely arranged in a fibrous stroma, multinucleated giant cells and mononuclear cells with haemorrhagic areas. This study identified the immunoexpression of alpha-smooth muscle actin in spindle-shaped stromal cells, and glucocorticoid and calcitonin receptors in multinucleated giant cells and mononuclear cells. Their association with the clinical and radiographic characteristics of these lesions was identified. METHODS: Thirty-five cases of CGCLs were studied. Expression of alpha-smooth muscle actin, glucocorticoid and calcitonin was evaluated by immunohistochemistry. The labelling index was 100 times the quotient of the number of positive cells divided by the total number of cells of each type. Logistic regression analysis was applied. RESULTS: Alpha-smooth muscle actin was positive (54%) for spindle stromal cells (myofibroblasts). A significant association was observed with root resorption (P = 0.004) and cortical bone destruction (P = 0.024). Glucocorticoid immunoexpression was positive for 99% of the giant cells and 86.7% of the mononuclear cells. Glucocorticoid immunoexpression in the mononuclear cells was associated with root resorption (P = 0.031). A longer evolution time was associated with lower immunoexpression of glucocorticoid (OR 12.4: P = 0.047). Calcitonin immunoexpression was positive in 86% of the giant cells. Immunoexpression of calcitonin was associated with age (P = 0.040). CONCLUSIONS: Myofibroblasts are important components of CGCLs, stromal cells and alpha-smooth muscle. Actin immunoexpression was associated with root and cortical bone resorption.

S100, bcl2 and myeloperoxid protein expirations during periodontal inflammation.

BACKGROUND: Periodontal inflammation is characterized by injuries in collagen, epithelial, bone tissues. The hypotheses to be tested were relationship between the s100, bcl2 and myeloperoxidase in gingival tissues (MPO does affect the level of s100, bcl2). The object of this study was to investigate of s100 expression, bcl2 expression and myeloperoxidase expression in periodontal inflammation. METHODS: 27 patients (giant-cell epulis) and 30 patients (acute and chronic inflammations) were included in the study for s100 expression, bcl2 expression and myeloperoxidase expression by immunohistochemistry and hematoxylin--eosin. RESULTS: Giant-cells in epulis positivity for myeloperoxidase has been observed in 100% However, only 75.31% of giant-cells were positive for bcl2 expression. Acute 98.2%, and chronic 89.28% inflammation was a significant positive for myeloperoxidase. The immunohistochemical findings of s100, bcl 2 and myeloperoxidase in epithelial layers have showed the result of 100%, 82,2%, 100% positive cells in acute and 100%, 78.25%, 100% in chronic process of inflammation respectively. CONCLUSION: The results indicate that the pathogenesis of periodontal inflammation might involve inhibition of cell death, through the overexpression of bcl-2, due to identifying factors myeloperoxidase (result in the DNA damage by the product of catalysis). The highest levels of s100 activity have been found at sites with chronic inflammation.

Immunohistochemical comparison of p53, Ki-67, CD68, vimentin, α-smooth muscle actin and alpha-1-antichymotry-psin in oral peripheral and central giant cell granuloma.

INTRODUCTION: Giant cell lesions are characterised histologically by multinucleated giant cells in a background of ovoid to spindle-shaped mesenchymal cells. There is a major debate whether these lesions are separate entities or variants of the same disease. Our aim was to study the nature of multinucleated and mononuclear cells from peripheral giant cell granuloma (PGCG), and central giant cell granuloma (CGCG) and giant cell tumor (GCT) of long bones using immunohistochemistry evaluation and to determine whether there is a correlation between recurrence and the markers used. MATERIALS AND METHODS: Ki-67, p53, Vimentin, smooth muscle specific actin, CD68 and alpha-1-antichymotrypsin were used to study 60 giant cell lesions. These included 26 CGCG, 28 PGCG, and 6 GCT cases using an avidin-biotin-complex immunohistochemistry standard method. RESULTS: All studied cases showed the same results except the percentage of Ki-67 positive mononuclear cells in PGCG was significantly higher than that of both CGCG and GCT (p<0.05). Interestingly, no statistical correlation between recurrence and the markers used was found. CONCLUSION: Our results may suggest that these lesions have the same histogenesis. The mononuclear stromal cells, both histiocytic and myofibroblastic, are thought to be responsible for the behavior of these lesions whereas the multinucleated cells are considered as reactive. This might support the argument that PGCG, CGCG and GCT are different variants for the same disease. Further studies using molecular techniques are required to elucidate why some of these lesions behave aggressively than others.

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.