Márcia Grillo Cabral

Immunohistochemical expression of p53, p16 and hTERT in oral squamous cell carcinoma and potentially malignant disorders.

Oral carcinogenesis is a multi-step process. One possible step is the development of potentially malignant disorders known as leukoplakia and erytroplakia. The objective of this study was to use immunohistochemistry to analyze the patterns of expression of the cell-cycle regulatory proteins p53 and p16(INK4a) in potentially malignant disorders (PMD) of the oral mucosa (with varying degrees of dysplasia) and in oral squamous cell carcinomas (OSCC) to correlate them with the expression of telomerase (hTERT). Fifteen PMD and 30 OSCC tissue samples were analyzed. Additionally, 5 cases of oral epithelial hyperplasia (OEH) were added to analyze clinically altered mucosa presenting as histological hyperplasia without dysplasia. p53 positivity was observed in 93.3% of PMD, in 63.3% of OSCC and in 80% of OEH. Although there was no correlation between p53 expression and the grade of dysplasia, all cases with severe dysplasia presented p53 suprabasal immunoexpression. p16(INK4a) expression was observed in 26.7% of PMD, in 43.3% of OSCC and in 2 cases of OEH. The p16(INK4a) expression in OEH, PMD and OSCC was unable to differentiate non-dysplastic from dysplastic oral epithelium. hTERT positivity was observed in all samples of OEH and PMD and in 90% of OSCC. The high hTERT immunoexpression in all three lesions indicates that telomerase is present in clinically altered oral mucosa but does not differentiate hyperplastic from dysplastic oral epithelium. In PMD of the oral mucosa, the p53 immunoexpression changes according to the degree of dysplasia by mechanisms independent of p16(INK4a) and hTERT.

Clinical, histological and immunohistochemical features of ectomesenchymal chondromyxoid tumor

OBJECTIVE Ectomesenchymal chondromyxoid tumor is a rare oral soft tissue neoplasm that should be differentiated from other neural and chondromyxoid entities. The aim of this study was to report the clinical, histological, and immunohistochemical features of 3 additional cases of this condition. METHODS Clinical data were obtained from the clinical records and all cases were evaluated through light microscopy and immunohistochemistry to cytokeratins, vimentin, S100 protein, desmin, smooth muscle actin, and glial fibrilary acidic protein. RESULTS All 3 cases affected the tongue as a long-lasting submucosal swelling and were managed through conservative surgery. They all showed myxoid and chondroid histological patterns, and vimentin, S100, and glial fibrilary acidic protein immunoexpression. CONCLUSIONS These findings reinforce the typical features of ectomesenchymal chondromyxoid tumor previously described, helping to confirm and establish the clinical, histopathological, and immunohistochemical profile of this uncommon lesion.

Immunohistochemical detection of Ki-67 is not associated with tumor-infiltrating macrophages and cyclooxygenase-2 in oral squamous cell carcinoma.

BACKGROUND An inflammatory component consisting of cells and chemical mediators may influence the proliferation and dissemination of the oral squamous cell carcinoma (OSCC). In the present study, we evaluated the possible relationship between Ki-67, tumor-associated macrophages (TAMs), and COX-2 in OSCCs. In addition, the immunodetection of these proteins was associated with different histological grades of malignancy, including invasive and in situ tumors. METHODS Twenty-seven OSCC cases were examined by light microscopy using criteria adopted WHO, and immunohistochemistry for Ki-67, CD68, and COX-2 using EnVision System in invasive and in situ lesions. Immunohistochemical detection of these proteins was assessed and scored for COX-2, and results were compared with their histological grades of malignancy. RESULTS A correlation between Ki-67, COX-2, and CD68 was not found. Histological grade of malignancy (HDM) was associated with the Ki-67 immunostaining (P = 0.00), but this was not observed regarding both CD68 (P = 0.51) and COX-2 (P = 0.89). Furthermore, there was a COX-2 overexpression in 62.96% of the sample, and a high density of TAMs in both OSCCs and in situ carcinomas. CONCLUSIONS Imunolabeling for Ki-67 was directly correlated with less-differentiated tumors, suggesting that this marker may contribute to understand the biological behavior of OSCC, and help to distinguish risk groups of OSCC. Furthermore, the lack of correlation between Ki-67, COX-2, and CD68 indicates that the latter two markers may play a pivotal role in oral carcinogenesis. However, further studies are needed to clarify their contribution for cell proliferation and tumor differentiation.

Calcifying epithelial odontogenic tumor (CEOT): a clinicopathologic and immunohistochemical study and comparison with dental follicles containing CEOT-like areas

OBJECTIVE To describe the clinicopathologic, immunohistochemical, and scanning electron microscopic features of 19 cases of calcifying epithelial odontogenic tumor (CEOT) in comparison to 4 cases of dental follicles containing CEOT-like areas (DF-CEOT). STUDY DESIGN A collaborative Latin American retrospective study. RESULTS CEOT and DF-CEOT showed a slight predilection for females, mostly affecting the posterior mandible. CEOTs were classified as epithelium-rich (8 cases), amyloid-rich (4), and calcification-rich (3), and 4 cases showed similar proportion of the 3 components. DF-CEOTs contained odontogenic epithelium, amyloid, calcification, and clear cells. Epithelial cells were positive for cytokeratins CK5 and CK19, E-cadherin, and syndecan 1 (CD138), and focally for amyloid A. In CEOT, amyloid was positive for CD138 and amyloid A, and calcification for CK5, CD138, and amyloid A. In DF-CEOT, calcification was positive for amyloid A. CEOT showed higher Ki-67 protein and minichromosome maintenance complex component 2 (MCM-2) labeling indices than did DF-CEOT. In scanning electron microscopy, CEOT calcified material resembled bone in the 3 cases classified as calcification-rich. CONCLUSIONS CEOT and DF-CEOT showed histomorphologic and immunohistochemical similarities, and the histogenetic significance of these features should be further studied.

Biocompatibility of orthodontic adhesives in rat subcutaneous tissue

Objective The objective of the present study was to verify the hypothesis that no difference in biocompatibility exists between different orthodontic adhesives. Material and Methods Thirty male Wistar rats were used in this study and divided into five groups (n=6): Group 1 (control, distilled water), Group 2 (Concise), Group 3 (Xeno III), Group 4 (Transbond XT), and Group 5 (Transbond plus Self-Etching Primer). Two cavities were performed in the subcutaneous dorsum of each animal to place a polyvinyl sponge soaked with 2 drops of the respective adhesive in each surgical loci. Two animals of each group were sacrificed after 7, 15, and 30 days, and their tissues were analyzed by using an optical microscope. Results At day 7, Groups 3 (Transbond XT) and 4 (Xeno III) showed intense mono- and polymorphonuclear inflammatory infiltrate with no differences between them, whereas Groups 1 (control) and 2 (Concise) showed moderate mononuclear inflammatory infiltrate. At day 15, severe inflammation was observed in Group 3 (Transbond XT) compared to other groups. At day 30, the same group showed a more expressive mononuclear inflammatory infiltrate compared to other groups. Conclusion Among the orthodontic adhesive analyzed, it may be concluded that Transbond XT exhibited the worst biocompatibility. However, one cannot interpret the specificity of the data generated in vivo animal models as a human response.

Immunohistochemical detection of Ki-67 is not associated with tumor-infiltrating macrophages and cyclooxygenase-2 in oral squamous cell carcinoma

BACKGROUND An inflammatory component consisting of cells and chemical mediators may influence the proliferation and dissemination of the oral squamous cell carcinoma (OSCC). In the present study, we evaluated the possible relationship between Ki-67, tumor-associated macrophages (TAMs), and COX-2 in OSCCs. In addition, the immunodetection of these proteins was associated with different histological grades of malignancy, including invasive and in situ tumors. METHODS Twenty-seven OSCC cases were examined by light microscopy using criteria adopted WHO, and immunohistochemistry for Ki-67, CD68, and COX-2 using EnVision System in invasive and in situ lesions. Immunohistochemical detection of these proteins was assessed and scored for COX-2, and results were compared with their histological grades of malignancy. RESULTS A correlation between Ki-67, COX-2, and CD68 was not found. Histological grade of malignancy (HDM) was associated with the Ki-67 immunostaining (P = 0.00), but this was not observed regarding both CD68 (P = 0.51) and COX-2 (P = 0.89). Furthermore, there was a COX-2 overexpression in 62.96% of the sample, and a high density of TAMs in both OSCCs and in situ carcinomas. CONCLUSIONS Imunolabeling for Ki-67 was directly correlated with less-differentiated tumors, suggesting that this marker may contribute to understand the biological behavior of OSCC, and help to distinguish risk groups of OSCC. Furthermore, the lack of correlation between Ki-67, COX-2, and CD68 indicates that the latter two markers may play a pivotal role in oral carcinogenesis. However, further studies are needed to clarify their contribution for cell proliferation and tumor differentiation.

Recurrent bilateral gingival peripheral calcifying epithelial odontogenic tumor (Pindborg tumor): A case report

Calcifying epithelial odontogenic tumor (CEOT) is an extremely rare, benign neoplasm, accounting for approximately 1% of all odontogenic tumors. Peripheral CEOTs commonly resemble oral hyperplastic or reactive lesions and are histologically similar to their intraosseous counterparts. We report an unusual case of multifocal peripheral CEOT. A 40-year-old female presented with bilateral soft, painful, erythematous, gingival swellings localized in premolar areas of the mandibular gingiva. The presumptive diagnosis was bilateral pyogenic granuloma. The masses were surgically excised under local anesthesia without bone curettage and both recurred 12 months later. Morphologic features, and histochemical and immunohistochemical tests revealed bilateral peripheral calcifying odontogenic epithelial tumor. There is no clinical or radiographic evidence of recurrence 3.5 years after excision. This multifocal phenomenon has been reported previously only for intraosseous CEOT. Gingival masses must be carefully evaluated for clinical and histologic evidence of neoplasia.

Clinicopathologic analysis and syndecan-1 and Ki-67 expression in calcifying cystic odontogenic tumors, dentinogenic ghost cell tumor, and ghost cell odontogenic carcinoma

OBJECTIVE Benign and malignant tumor cells can express altered adhesion properties, and these features can be associated with their proliferative and invasive characteristics. This study aimed to evaluate syndecan-1 and Ki-67 expression in ghost cell-containing odontogenic tumors. STUDY DESIGN Clinical data were retrieved from laboratory records, and hematoxylin-eosin-stained slides and sections, labeled with monoclonal antibodies anti-syndecan-1 and anti-Ki-67 using the immunoperoxidase technique, were evaluated. RESULTS Included were 21 central calcifying cystic odontogenic tumors (CCOTs) (4 associated with odontoma), 2 peripheral CCOTs, 1 dentinogenic ghost cell tumor, and 1 ghost cell odontogenic carcinoma (GCOC). Syndecan-1 was mainly expressed in cells resembling stellate reticulum and in stromal cells from the fibrous capsule. The mean Ki-67 labeling index was 4.1% (49.3% for GCOC), but it was not associated with syndecan-1 expression. CONCLUSIONS Syndecan-1 is variably expressed in cells resembling the stellate reticulum, stromal cells, and basal cells and might be associated with the biology of these tumors.

Tumor-Infiltrating Macrophage and Microvessel Density in Oral Squamous Cell Carcinoma

Tumor-associated macrophages (TAM) are the main cellular component in stroma of many tumors and participate in tumor angiogenesis. The aim of present study was to compare the microvascular density (MVD) and infiltrating macrophage density (IMD) in oral squamous cell carcinomas (OSCCs) with different histological grades. A histomorphometric analysis was performed after immunohistochemistry using antibodies such as von-Willebrand factor and CD68. A significant difference in MVD was found between well and moderately differentiated OSCCs (p<0.05). TAM were largely present in all studied tumors and the IMD was not different among OSCCs with different histological grades (p=0.381). Significant correlation between MVD and IMD was not observed (p=0.870). In conclusion, these results suggest that TAM and angiogenesis have an influence at different histological grades of OSCC. However, the lack of correlation between MVD and IMD could suggest that angiogenesis does not depend on the number of macrophages present in OSCC, but their predominant phenotype. Further studies involving distinct phenotypes of macrophages should be done to better understand the influence of TAM on the tumor angiogenesis.

Histopathological Features of Keratocystic Odontogenic Tumor A Descriptive Study of 177 Cases From a Brazilian Population

The aim of this study was to describe the clinicopathologic features of 177 keratocystic odontogenic tumors (KCOTs) diagnosed in a Brazilian population. A total of 177 KCOTs were reviewed and affected 158 patients with ages ranging from 5 to 79 years (mean age = 32 years) with a slight female predominance. Mandible was the most common affected site (69.3%), and a unilocular radiolucency was the most common radiographic image. Microscopically, all cases showed at least focal areas of classic KCOT, but several histological aspects were also observed, including diffuse and focal epithelial lining hyperplasia (48.6%), epithelial budding (12.4%), reactive cytological alterations (11.3%), dystrophic calcification (7.9%), daughter cysts (7.8%), odontogenic epithelial remnants (4.5%), focal areas of orthokeratinization (2.8%), and ameloblastomatous epithelium (1.7%). These variations may make KCOT diagnosis challenging in some cases, so careful full-sample analysis and knowledge of these uncommon histological features associated with KCOT are essential for correct diagnosis.