Association of PON1, TNF-α and TGF-ß gene polymorphisms with prognosis in oral and oropharyngeal squamous cell carcinoma.

OBJECTIVE: The oral and oropharyngeal squamous cell carcinoma (OOSCC) accounts for 90-95% of tumours in the oral cavity. Single nucleotide polymorphism (SNP) in the coding region of PON1, tumour necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-ß) have been associated with to development of different cancers. Our aim was to investigate the prognostic value of PON1 (rs854560 and rs662), TNF-α (rs1800629 and rs361525) and TGF-ß (rs1800469) SNPs in OOSCC. MATERIALS AND METHODS: We genotyped 163 OOSCC patients and 146 patients from group of control for PON1 (rs854560 and rs662), TNF-α (rs1800629 and rs361525) and TGF-ß (rs1800469) SNPs by real-time polymerase chain reaction (PCR). RESULTS: TNF-α (rs1800629) GG genotype was significantly more frequent in intraoral lesions and clinical stages III and IV, while the polymorphic AA genotype in lip lesion and clinical stages I and II. Moreover, TGF-ß (rs1800469) AG and AA genotypes were significantly more frequent in larger tumours (T3 e T4). TNF-α (rs1800629) AG genotype had poor survival and patients carrying the PON1 (rs662) TT genotype tended to poor survival. CONCLUSIONS: Results suggest that the rs1800629 and rs1800469 could exert influence in the more aggressive behaviour of OOSCC and the genotypes AG of rs1800629, and TT of rs662 could be markers with prognostic value in OOSCC.

Maxillary incisor root morphology in patients with nonsyndromic tooth agenesis: A controlled cross-sectional pilot study.

INTRODUCTION: This study aimed to investigate the association between root morphology of maxillary incisors and nonsyndromic tooth agenesis in patients compared with a control group without agenesis. METHODS: This controlled cross-sectional pilot study (1:4) was performed with a random sample of 335 records from Brazilian applicants for orthodontic treatment, paired by sex and age. Panoramic and periapical radiographs were analyzed to diagnose tooth agenesis and to assess root morphology. The agenesis group (n = 67) included patients with nonsyndromic tooth agenesis, and the control group (n = 268) included patients without tooth agenesis. The statistical analysis included the Student t test and z test, conditional logistic regression, and odds ratio estimates. RESULTS: Occurrence of root morphological changes was significantly higher among patients with agenesis (P <0.05). Significant morphological changes (short, blunt, apically bent, and pipette-shaped roots) were found in the roots of remaining teeth when comparing agenesis and control groups (P <0.05). Patients with agenesis were more likely to show root morphological changes (odds ratio, 74.23; 95% confidence interval, 16.93-325.46; P <0.001). CONCLUSION: Patients with agenesis are more likely to present root morphological changes, which should be considered to minimize problems during orthodontic treatments.

Association of polymorphisms in IL-8, MMP-1 and MMP-13 with the risk and prognosis of oral and oropharyngeal squamous cell carcinoma.

OBJECTIVE: This study investigated the risk and prognostic value of single nucleotide polymorphisms (SNP) inIL-8, MMP-1 and MMP-13 in oral and oropharyngeal squamous cell carcinomas (SCCs). DESIGN: SNPs rs2227532 and rs4073 inIL-8, rs2071230 and rs470558 in MMP-1, and rs2252070 in MMP-13 were genotyped in 125 oral and oropharyngeal SCC patients and 130 healthy controls, using TaqMan allelic discrimination assays. Multiple logistic regression models were used to explore the association between SNPs and cancer development, as well as SNP-SNP interaction and gene-environmental factor (GxE) interaction. Univariate and multivariate methods were applied for survival analyses. RESULTS: With exception of rs2227532, all the SNPs were in Hardy-Weinberg equilibrium in the control. No associations between rs4073 in IL-8 and rs2071230 and rs470558 in MMP-1 were observed, but rs2252070 in MMP-13, in the dominant model, was associated in a protective manner to oral and oropharyngeal SCC (OR: 0.20, 95% CI: 0.06-0.71, p = 0.007). All SNPs interact significantly with cigarette smoking and alcohol consumption on susceptibility to oral and oropharyngeal SCC, but they showed no influence on survival of the patients. CONCLUSIONS: Our results show that rs2252070 inMMP-13 may confer protection effect against oral and oropharyngeal SCC. In addition, the combined effects of IL-8 (rs4073), MMP-1 (rs2071230 and rs470558) and MMP-13 (rs2252070) with environmental carcinogens, such as tobacco and alcohol, are related to increased risk for oral and oropharyngeal SCC development.

Clinicopathological significance of SNPs in RAD51 and XRCC3 in oral and oropharyngeal carcinomas.

BACKGROUND: This study investigated the influence of single nucleotide polymorphisms (SNP) in RAD51 and XRCC3 on susceptibility to oral and oropharyngeal squamous cell carcinomas (SCC) and determined their clinicopathological significance. SUBJECTS AND METHODS: SNPs rs1801320 and rs1801321 in RAD51 and rs861539 in XRCC3 were genotyped in 81 patients presenting oral SCC, 45 presenting oropharyngeal SCC, and 130 healthy controls, using TaqMan allelic discrimination assays. Multiple logistic regression models were used to explore the association between SNPs and cancer development, as well as gene-gene (GxG) interaction and gene-environmental factor (GxE) interaction. Clinicopathological associations were verified through the chi-square test, and univariate and multivariate methods were applied for survival analyses. RESULTS: Although allelic and genotypic models and the GxG interaction analysis were nonsignificant, the GxE analysis revealed synergistic effects of the risk alleles of rs1801320, rs1801321, and rs861539 with smoking and alcohol consumption on susceptibility to oral and oropharyngeal SCC. Furthermore, oropharyngeal SCC patients carrying the XRCC3 rs861539 GT/TT genotype (T risk allele) presented a shorter overall survival than GG genotype carriers. CONCLUSION: Combined effects of RAD51 (rs1801320 and rs1801321) and XRCC3 (rs861539) SNPs with environmental carcinogens (tobacco and alcohol) are associated with oral and oropharyngeal SCC development.

Polymorphisms associated with oral clefts as potential susceptibility markers for oral and breast cancer.

OBJECTIVE: To evaluate the association of single nucleotide polymorphisms (SNPs) in genes/loci consistently altered in nonsyndromic oral clefts in patients with oral and breast cancer in a Brazilian population. DESIGN: This case-control study evaluated the association of SNPs in IRF6 (rs642961), WNT3A (rs708111), GSK3ß (rs9879992), 8q24 (rs987525) and WNT11 (rs1533767), representing regions consistently identified as of susceptibility for oral clefts, with oral cancer (oral squamous cell carcinoma) and breast cancer. Logistic regression analyses were used for confounding adjustments, and p values ≤0.01 were considered statistically significant (Bonferroni correction = 0.05/5 polymorphic markers). RESULTS: The minor G allele of rs9879992 in GSK3ß was associated with oral cancer risk (p = 0.02), whereas rs1533767 in WNT11 showed a protective effect against it (p = 0.04). Several SNP-SNP interactions containing GSK3ß rs9879992 were significantly associated with oral cancer after 1000 permutation test. To breast cancer, the A allele of rs987525 was associated with increase risk in early stage (p = 0.02) and SNP-SNP interactions involving the 5 SNPs were significantly observed, with the most significant interaction among rs708111, rs1533767, rs9879992 and rs642961 (p1000permutation<0.001). CONCLUSION: Our results reveal associations of SNPs consistently altered in oral cleft with oral and breast cancer risk, raising interesting possibilities to identify risk markers for those tumors.

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.

Immunoexpression of transforming growth factor beta and interferon gamma in radicular and dentigerous cysts.

INTRODUCTION: The aim of this study was to evaluate and compare the immunohistochemical expression of transforming growing factor beta (TGF-ß) and interferon gamma (IFN-γ) between radicular cysts (RCs) and dentigerous cysts (DCs). METHODS: Twenty RCs and DCs were selected for analysis of the immunoexpression of TGF-ß and IFN-γ in the epithelium and capsule. RESULTS: The cell reactivity of TGF-ß and IFN-γ in the lining epithelium and capsule of RCs showed no significant differences when compared with DCs (P > .05). There was a tendency of a higher expression of TGF-ß in the capsule of DCs. CONCLUSIONS: Our results showed the presence of TGF-ß and IFN-γ in RCs and DCs, supporting the hypothesis that both participate in the development of these lesions, where IFN-γ usually plays a role in bone resorption, which is counterbalanced by the osteoprotective activity performed by TGF-ß.

Immunohistochemical detection of receptor activator nuclear κB ligand and osteoprotegerin in odontogenic cysts and tumors.

PURPOSE: The aim of the present study was to compare the immunohistochemical detection of receptor activator nuclear κB ligand (RANKL) and osteoprotegerin (OPG) in radicular cysts (RCs), dentigerous cysts (DCs), solid ameloblastomas (SAs), and keratocystic odontogenic tumors (KOTs). MATERIALS AND METHODS: A total of 20 RCs, 20 DCs, 20 KOTs, 14 dental follicles (DFs), and 18 SAs were evaluated by immunohistochemistry using anti-RANKL and anti-OPG antibodies. The analysis was quantitative, and the number of positive cells was counted in 10 microscopic high-power fields (400×). RESULTS: The DFs, KOTs, and SAs showed higher expression of RANKL than did the RCs and DCs in the epithelium (P < .05). The epithelial expression of OPG was higher in the DFs, KOTs, RCs, and DCs than in the SAs (P < .05). The ratio of OPG less than RANKL was more frequent in SAs and OPG greater than RANKL in DCs (P < .05). CONCLUSIONS: Our results have shown differences in RANKL and OPG detection in the odontogenic cysts and tumors studied. The higher RANKL and lower OPG detection in SA could play a role in bone resorption, compatible with the tumor's biologic behavior.

Immunoexpression of RANK, RANKL, OPG, VEGF, and vWF in radicular and dentigerous cysts.

BACKGROUND: Radicular (RC) and dentigerous cysts (DC) can show a range from little to quite extensive primary/secondary inflammation and it is possible that the variation seen in the fibrous capsule of these cysts might reflect differences in the osteolytic activity. Moreover, the presence of hemorrhagic areas in the fibrous capsule of DC could also contribute to the increase in osteolytic activity. The aim of this study was to compare immunohistochemical expression of nuclear factor κappaB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG), vascular endothelial growth factor (VEGF) and angiogenic index in RC and DC. METHODS: These proteins were evaluated in 20 RC and DC by immunohistochemistry. Angiogenic index was determined by microvessel count (MVC) using anti-von Willebrand factor antibody. RESULTS: RANK and RANKL were higher in DC than RC in fibrous capsule. RC showed higher expression of VEGF in the epithelium and capsule. DC exhibited higher MVC than RC. CONCLUSIONS: Ours results suggest that RANK and RANKL play an important role in bone resorption in DC and the hemorrhagic areas in the capsule of DC could be explained by increased vessel's number. The higher VEGF expression in RC might be related to nature of these lesions, where the inflammatory process contributes significantly to these findings.

Immunohistochemical study of integrin α5ß1, fibronectin, and Bcl-2 in normal oral mucosa, inflammatory fibroepithelial hyperplasia, oral epithelial dysplasia, and oral squamous cell carcinoma.

The objective of this study was to compare the immunoexpression of integrin α5ß1, fibronectin, and the Bcl-2 protein in normal oral mucosa (NOM), inflammatory fibroepithelial hyperplasia (IFH), oral epithelial dysplasia (OED), and oral squamous cell carcinoma (OSCC). Eleven cases of NOM, 16 IFH, 20 OED, and 27 OSCC were selected for analysis of the immunoexpression of integrin α5ß1, fibronectin, and bcl-2 protein. There was an association between the intensity and location of the integrin α5ß1 expression, especially in the OSCC, that 48.1% of cases showed weak immunoreactivity and 40.7% in the suprabasal layer (P < 0.05). There was an association between the pattern and distribution of fibronectin expression in basement membrane, where 90% of NOM showed a pattern of linear continuous and 80% of OED exhibited focal distribution (P < 0.05). The fibronectin expression in connective tissue was predominantly intense with an association of staining pattern among the different specimens, where 37% of OSCC showed a reticular pattern (P < 0.05). There was an association of bcl-2 protein among the types of specimens, especially in IFH and OSCC, where 100% of the cases exhibited scores 1 of staining (P < 0.05). Within this context, the interaction of integrin α5ß1 with its main ligand in the extracellular matrix, fibronectin, is suggested to influence the survival of tumor cells and to favor their proliferation by modulating apoptosis through the upregulation of antiapoptotic proteins or the suppression of apoptotic mediators.

Adenomatoid odontogenic tumor: retrospective study of 15 cases with emphasis on histopathologic features.

Adenomatoid odontogenic tumor (AOT) is an uncommon benign epithelial lesion of odontogenic origin and, thus far, only few studies regarding the frequency of its many histopathologic features have been published in the literature. Thus, the aim of this study was to perform a retrospective analysis in a case series of AOT, with emphasis on the histopathological features. Fifteen cases of AOT were studied considering their clinical, radiographic and histopathologic aspects. Twelve cases affected females and the mean age was 16.2 years. The anterior maxilla was the most common site (66.6 %) and radiographically most cases showed a unilocular radiolucency with well-defined borders (57.1 %). Histologically, most cases exhibited predominantly a solid growth pattern (46.7 %) or a similar proportion of solid and cribriform patterns (46.7 %). Eosinophilic amorphous material ("tumor droplets") was found in all cases (100 %). Most tumors showed duct-like spaces (93.3 %) and convoluted structures (60.0 %) whereas a minor proportion of cases presented calcifying epithelial odontogenic tumor (CEOT)-like areas (26.7 %). Variable amounts of calcified material were found in most AOTs (80.0 %) whereas osteodentin and perivascular hyalinization were seen only rarely (6.7 % each one). Five (33.3 %) cases had areas mimicking a dentigerous cyst and most of these were diagnosed in females (80.0 %). Regarding the histopathologic features, our results suggest that AOTs usually show predominance of solid pattern or a similar proportion of solid and cribriform patterns while osteodentin and perivascular hyalinization are rarely seen in these tumors. In addition, areas mimicking a dentigerous cyst and CEOT-like areas are relatively infrequent findings in AOTs.

Immunoexpression of TNF-α and TGF-ß in central and peripheral giant cell lesions of the jaws.

BACKGROUND: 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. On the other hand, central giant cell lesion (CGCL) presents a variable clinical behavior ranging from slow and asymptomatic growth without recurrence to rapid, painful and recurrent growth. Our aim was to compare the immunoexpression of tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-ß) in CGCL and PGCL. METHODS: Twenty CGCL and 20 PGCL were selected for analysis of the immunoexpression of TNF-α and TGF-ß in multinucleated giant cells (MGC) and mononucleated cells (MC). RESULTS: The PGCL showed lightly higher expression of TNF-α than CGCL. In comparison with PGCL, the CGCL showed higher expression of TGF-ß in MC and MGC (P < 0.05) and in total cells (P < 0.05). Significant positive correlation was found between expressions of TGF-ß and TNF-α in CGCL (P < 0.05). CONCLUSIONS: Our results suggest that, in CGCL, coordinated interactions between TGF-ß and TNF-α may be important for osteoclastogenesis and bone resorption. PGCL occasionally cause bone resorption but to a lower extent, a fact that might be explained by the lower expression of TGF-ß in these lesions.

Analysis of inflammatory infiltrate, perineural invasion, and risk score can indicate concurrent metastasis in squamous cell carcinoma of the tongue.

PURPOSE: In this retrospective study, the aim was to compare individual histopathologic parameters of malignancy between nonmetastatic and metastatic squamous cell carcinoma of the tongue. MATERIALS AND METHODS: Sixty-two cases of squamous cell carcinoma of the tongue were selected and examined according to the system established by Brandwein-Gensler et al (Am J Surg Pathol 29:167, 2005) and included the pattern of invasion (most to least favorable), lymphocytic infiltration, perineural invasion, risk score, keratinization, eosinophilia, perivascular invasion, and tumor thickness. RESULTS: The least favorable pattern had no association with nodal metastasis (P > .05). The scarcity or density of the lymphocytic infiltration, perineural invasion, and a risk score ≥ 3 were associated with nodal metastasis (P < .05). Keratinization, eosinophilia, perivascular invasion, and tumor thickness had no association with nodal metastasis (P > .05). A significant positive correlation was found between the pattern of invasion and perineural invasion and between the pattern of invasion and tumor thickness (P < .05). CONCLUSIONS: The scarcity or density of the lymphocytic infiltration, perineural invasion, and histopathologic risk score may be helpful as parameters of histologic malignancy for the evaluation of metastatic and nonmetastatic squamous cell carcinoma of the tongue.

Central odontogenic fibroma.

Odontogenic fibroma (OF) is a benign odontogenic tumor characterized by various amounts of odontogenic epithelium in a mature fibrous stroma. Two variants can be distinguished: an intraosseous or central OF (COF) and an extraosseous or peripheral. The intraosseous variant is an extremely rare tumor that presents clinical, radiographic, and histopathologic variable findings. A thorough review of the English literature revealed 78 cases of COF so far. Thus, we report an additional case of COF occurring in the maxilla of a 36-year-old woman. In addition, we performed a brief description and discussion of the cases reported in the maxilla and mandible.

Nonodontogenic cysts of the oral and maxillofacial region: demographic profile in a Brazilian population over a 40-year period.

The aim of the study was to determine the distribution of histologically diagnosed nonodontogenic cysts (nOCs) over a 40-year period in a Brazilian population. Biopsy records from patients with nOC from the files of the Oral Pathology Service during the period of 1970-2009 were evaluated. Among 10,311 oral biopsies, 58 met the criteria of nOCs. The most frequent nOCs were nasopalatine duct cysts (32.8%), followed by epidermoid cysts (20.7%) and oral lymphoepithelial cysts (17.2%). Nasopalatine duct cysts showed predominance among females (68.4%). Epidermoid cysts were most commonly found in the floor of the mouth (36.4%), tongue (27.3%), and buccal mucosa (27.3%). Oral lymphoepithelial cysts exhibited female prevalence (80.0%) and were commonly located in the tongue (44.4%). The frequency of nOCs found in the population studied here is slightly different from those reported in other case series. Nasopalatine duct cysts, epidermoid cysts, and oral lymphoepithelial cysts were the most common nOCs found, accounting for 70.7% of all nOCs.

Sialolipoma in minor salivary gland: case report and review of the literature.

Sialolipoma is a rare benign neoplasm characterized by a well-circumscribed mass composed of neoplastic mature adipose tissue and non-neoplastic salivary gland elements. A 72-year-old woman presented with a painless swelling located in the hard palate, which had been identified 15 days earlier. Microscopically, the tumor was well-circumscribed consisting of lobular proliferation of the lipomatous tissue with thin fibrous tissue septa containing clustered salivary gland elements. Both the glandular and adipose components were found in almost equal proportion. No atypia in the adipose tissue was observed. The definitive diagnosis was sialolipoma. The patient showed no signs of recurrence 8 months after surgical excision. Including the present case, 35 cases of sialolipoma have been reported in the English literature. Of these 35 cases, 16 cases were located in minor salivary glands. Gender was identified in 14 of these cases with 4 males (28.5%) and 10 females (71.5%). The age distribution was from 27 to 84 years (mean, 61.6 years) and the tumor size ranged from 0.9 to 4 cm (mean, 1.7 cm). The most frequently reported clinical presentation was of a painless swelling (56.3%).