Pantelis Varvaki Rados

Odontogenic Cysts: Analysis of 680 Cases in Brazil

The purpose of this study was to evaluate the prevalence of 680 odontogenic cysts diagnosed in Porto Alegre, RS, Brazil, and to compare results with findings in the literature. Data of odontogenic cysts diagnosed from 1985 to 2005 were collected from the files of the Oral Pathology Laboratory of Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil, and entered in a standardized form for later comparisons. The most prevalent odontogenic cysts were radicular (72.50%), dentigerous (22.20%) and residual (4.26%) cysts. The mandible of white patients was the anatomic site and ethnic group most frequently affected by this disease. Four of the six types of cysts were more frequent in the second and fourth decades of life, and no significant differences were found between sexes in the diagnosis of odontogenic cysts. In conclusion, the prevalence of odontogenic cysts was similar to that reported in the literature, which shows that inflammatory cysts are the most frequent.

Comparison of histometric and morphometric analyses of bone height in ligature-induced periodontitis in rats

The purpose of this study was to compare histologic and morphometric procedures of bone height measurement. Microscopic measurements are the most frequent methods in periodontal studies with animals, but have limited capacity to identify bone levels associated with both healthy tissues and periodontal disease. Ligatures were placed in the maxillary left second molars of 10 male 60-day-old Wistar rats for 30 days. Left and right maxillary sides of 5 rats were processed for histologic analysis (H), sectioned buccolingually, and stained with HE. The maxillae of the other 5 rats were defleshed and used for morphometric analysis (M). Histometric measurements from the cementoenamel junction to the bone crest were performed. Standardized photographs were used for morphometric analysis. The t test was used for dependent or independent samples (alpha = 0.05%). Distances from cementoenamel junction to bone crest were 0.95 +/- 0.25 and 1.07 +/- 0.30 mm for H and M, respectively. Buccal measurements were 0.92 +/- 0.16 and 1.08 +/- 0.35 mm for H and M. The values obtained using H and M for areas without ligatures were 0.44 +/- 0.15 and 0.47 +/- 0.11 mm for lingual measurements and 0.23 +/- 0.08 and 0.41 +/- 0.10 mm for buccal measurements. No significant differences were found between the two methods in the detection of bone height associated with the placement of ligatures in rats.

Prevalence and risk indicators of oral mucosal lesions in an urban population from South Brazil.

OBJECTIVE The objective of the study was to assess the prevalence of oral mucosal lesions (OML) and to perform a multivariable risk assessment of demographic, socioeconomic, behavioral, and oral risk indicators for its occurrence in an urban population in South Brazil. METHODS This cross-sectional study selected 1586 subjects (719M/867F, age: 14-104 years) using a multistage probability sampling strategy (65.1% response rate). Prevalence, odds ratios (OR), and confidence intervals (95% CI) were calculated accounting for the survey design. RESULTS Leukoplakia and lichen planus were observed in 1.01% and 1.02% of subjects, respectively. In the multivariable analysis, these lesions were significantly associated with moderate/heavy smoking (OR = 9.0, 95% CI = 2.1-39.1) and heavy drinking (OR = 2.0, 95% CI = 1.1-3.7). Candidiasis and proliferative lesions were observed in 14.09% and 3.80% of the subjects, respectively. These lesions were significantly associated with female gender (OR = 2.2, 95% CI = 1.5-3.2 and OR = 1.7, 95% CI = 1.0-2.8), older age (OR=22, 95% CI = 8.0-60.8 and OR = 8.9, 95% CI = 3.4-23.7), and low socioeconomic status (OR = 1.9, 95% CI = 1.0-3.5 and OR = 3.0, 95% CI = 1.2-7.2). CONCLUSIONS This population is in need of OML prevention and treatment. Future studies should validate the findings that premalignant lesions are causally related to smoking and alcohol consumption, and that other OML are associated with socioeconomic-demographic disparities in this and similar populations.

Odontogenic Epithelium: Immunolabeling of Ki-67, EGFR and Survivin in Pericoronal Follicles, Dentigerous Cysts and Keratocystic Odontogenic Tumors

The aim of this study was to evaluate the biological profile of odontogenic epithelium by immunolabeling of epidermal growth factor receptor (EGFR), Ki-67 and survivin in keratocystic odontogenic tumors (KOT), dentigerous cysts (DC), and pericoronal follicles (PF). Immunohistochemical analysis was performed in 13 KOTs, 14 DCs and 9 PFs. Immunolabeling was analyzed in the basal and suprabasal layers of KOTs and DCs, and in the islands of odontogenic epithelium and/or reduced enamel epithelium of PFs. KOTs showed the highest proliferation rate among the three groups, mainly in suprabasal layers. EGFR immunolabeling was observed mainly in the cytoplasm in basal and suprabasal layers of KOTs and in the suprabasal layer of DCs. Immunolabeling in both membrane and cytoplasm was greater in PFs. In PFs, membrane-only staining was observed. Survivin immunolabeling showed a greater percentage of positive cells (scoring +++) in the suprabasal layer of KOTs. In DCs, both layers showed similar percentages of cells scoring +++; PFs showed the highest percentage of these cells. In KOTs, epithelial cells showed stimulus-independent neoplastic proliferative characteristics, suggesting the presence of a suprabasal proliferative compartment, maintained by inhibition of apoptosis. In DCs, the basal layer seemed to proliferate in response to stimulus. Although PFs showed low proliferative activity, the expression of EGFR indicates that some cells have a high capacity to respond to stimuli, which could probably explain the origin of odontogenic lesions.

Exposure to alcohol or tobacco affects the pattern of maturation in oral mucosal cells: a cytohistological study

Objective: To assess the maturation pattern of oral mucosal cells of patients exposed to tobacco and alcohol.

Loss of SOX2 expression induces cell motility via vimentin up‐regulation and is an unfavorable risk factor for survival of head and neck squamous cell carcinoma

Recurrent gain on chromosome 3q26 encompassing the gene locus for the transcription factor SOX2 is a frequent event in human squamous cell carcinoma, including head and neck squamous cell carcinoma (HNSCC). Numerous studies demonstrated that SOX2 expression and function is related to distinct aspects of tumor cell pathophysiology. However, the underlying molecular mechanisms are not well understood, and the correlation between SOX2 expression and clinical outcome revealed conflicting data. Transcriptional profiling after silencing of SOX2 expression in a HNSCC cell line identified a set of up‐regulated genes related to cell motility (e.g. VIM, FN1, CDH2). The inverse regulation of SOX2 and aforementioned genes was validated in 18 independent HNSCC cell lines from different anatomical sites. The inhibition of cell migration and invasion by SOX2 was confirmed by constant or conditional gene silencing and accelerated motility of HNSCC cells after SOX2 silencing was partially reverted by down‐regulation of vimentin. In a retrospective study, SOX2 expression was determined by immunohistochemical staining on tissue microarrays containing primary tumor specimens of two independent HNSCC patient cohorts. Low SOX2 expression was found in 19.3% and 44.9% of primary tumor specimens, respectively. Univariate analysis demonstrated a statistically significant correlation between low SOX2 protein levels and reduced progression‐free survival (Cohort I 51 vs. 16 months; Cohort II 33 vs. 12 months) and overall survival (Cohort I 150 vs. 37 months; Cohort II 33 vs. 16 months). Multivariate Cox proportional hazard model analysis confirmed that low SOX2 expression serves as an independent prognostic marker for HNSCC patients. We conclude that SOX2 inhibits tumor cell motility in HNSCC cells and that low SOX2 expression serves as a prognosticator to identify HNSCC patients at high risk for treatment failure.

Glucose-Regulated Protein 78 (Grp78) Confers Chemoresistance to Tumor Endothelial Cells under Acidic Stress

Objectives This study was designed to investigate the activation of the unfolded protein response (UPR) in tumor associated endothelial cells (TECs) and its association with chemoresistance during acidic pH stress. Materials and Methods Endothelial cells from human oral squamous cell carcinomas (OSCC) were excised by laser capture microdissection (LCM) followed by analysis of UPR markers (Grp78, ATF4 and CHOP) using quantitative PCR. Grp78 expression was also determined by immunostaining. Acidic stress was induced in primary human dermal microvascular endothelial cells (HDMECs) by treatment with conditioned medium (CM) from tumor cells grown under hypoxic conditions or by adjusting medium pH to 6.4 or 7.0 using lactic acid or hydrochloric acid (HCl). HDMEC resistance to the anti-angiogenic drug Sunitinib was assessed with SRB assay. Results UPR markers, Grp78, ATF4 and CHOP were significantly upregulated in TECs from OSCC compared to HDMECs. HDMECs cultured in acidic CM (pH 6.0–6.4) showed increased expression of the UPR markers. However, severe acidosis led to marked cell death in HDMECs. Alternatively, HDMECs were able to adapt when exposed to chronic acidosis at pH 7.0 for 7 days, with concomittant increase in Grp78 expression. Chronic acidosis also confers drug resistance to HDMECs against Sunitinib. Knockdown of Grp78 using shRNA resensitizes HDMECs to drug treatment. Conclusions UPR induction in ECs under acidic pH conditions is related to chemoresistance and may contribute to therapeutic failures in response to chemotherapy. Targeting Grp78, the key component of the UPR pathway, may provide a promising approach to overcome ECs resistance in cancer therapy.

A 10-year study of specimens submitted to oral pathology laboratory analysis: lesion occurrence and demographic features

The purpose of the present paper was to describe the range of lesions histologically diagnosed in an oral pathology laboratory in southern Brazil. A retrospective study of 8,168 specimen analyses recorded between 1995 and 2004 was conducted. The records were retrieved from the Oral Pathology Laboratory, School of Dentistry, Federal University of Rio Grande do Sul, RS, Brazil. A total of 6,831 valid cases (83.63%) were examined. Of these, inflammatory lesions were the most common occurrences (n = 4,320; 63.24%). Benign and malignant tumors accounted for 7.66% (n = 523) and 1.9% (n = 130) of the occurrences, respectively. Significant associations were observed between nonneoplastic proliferative disorders and benign mesenchymal tumors in females, and between squamous cell carcinoma and leukoplakia in males. Most diagnoses were benign in nature and had an inflammatory etiology. The association of some demographic characteristics with the occurrence of lesions suggests that these characteristics should be considered in performing differential diagnoses.

Peripheral clear cell variant of calcifying epithelial odontogenic tumor affecting 2 sites: report of a case

A case of clear cell variant of calcifying epithelial odontogenic tumor (CEOT) affecting 2 different extraosseous sites is described. A 43-year-old female patient presented with 2 gingival lesions (1 in the upper premolar and 1 in the lower incisor area), which were clinically diagnosed as inflammatory hyperplasia and surgically removed. Microscopically, both lesions were composed of polyhedral cells (some with clear cytoplasm); hyaline material and areas of calcification were also observed. The diagnostic hypotheses raised were clear cell variant of CEOT, hyalinizing clear cell carcinoma, and renal metastasis. The hyaline material was positive for Congo red, crystal violet, and Lugols iodine stains, but negative for Coomassie blue; the clear cells showed positively stained granules with PAS stain. Based on these results, the conclusive diagnosis for both lesions was clear cell variant of CEOT. No evidence of recurrence was observed after 1 year of follow-up.

Effect of nifedipine on gingival enlargement and periodontal breakdown in ligature-induced periodontitis in rats

OBJECTIVE A recent consensus report could not find specific reports of the effect of nifedipine on the destruction of the periodontal tissues. The aim of the present study was to evaluate the effect of nifedipine on gingival enlargement and periodontal breakdown using a ligature-induced periodontitis in rats. MATERIALS AND METHODS Fifty, male, 60 days old, Wistar rats, were divided into six groups. Cotton sutures were placed around the upper second molars. Two groups of 10 rats each did not receive ligatures and were treated daily with either saline solution or nifedipine 50mg/kg/day. Two groups of 10 rats received ligatures and were also treated daily with saline solution or nifedipine 50mg/kg/day. Two additional groups (nifedipine 10 and 100mg/kg/day) were included to explore a possible dose-response relationship. Animals were euthanatised at 30 days. Internal and oral epithelium, total and inflamed connective tissue, gingival thickness and height, and bone loss were assessed histologically. RESULTS Nifedipine alone was not sufficient to promote gingival enlargement or periodontal destruction in the absence of the ligature. Compared to animals with ligatures only, the group that received ligatures and nifedipine 50mg/kg/day showed significant higher estimates for total and inflamed connective tissue, gingival thickness and height. No significant differences were observed for bone loss between these experimental groups. The other dosages of nifedipine did not provide additional information. CONCLUSION Nifedipine itself did not lead to gingival enlargement in rats. In the presence of biofilm accumulation, nifedipine yielded greater gingival enlargement and periodontal inflammation, but it did not increase periodontal destruction.