Presence of CD3-positive T-cells in oral premalignant leukoplakia indicates prevention of cancer transformation.

AIM: Leukoplakias (LPLs) are lesions in the oral mucosa that have a potential to transform into oral squamous cell carcinoma (OSCC). As the degree of immunosurveillance may be important for this transformation to occur, the aim of this study was to determine the presence of immune cells in LPLs with dysplasia in relation to later development of OSCC. MATERIALS AND METHODS: Biopsies from 16 patients with clinical diagnosis of LPL and histopathological diagnosis of hyperkeratosis with dysplasia were immunostained with antibodies to detect CD3(+) T cells, CD1a(+) LCs, Ki-67(+) and p53-expressing cells. Patients were divided into two groups: LPL with dysplasia that transformed into OSCC (LPL-dys) and that which did not (LPL-ca). RESULTS: Quantitative analyses showed significantly lower numbers of CD3(+) T-cells in LPL-ca than in LPL-dys. No significant differences were detected when comparing LPL-dys and LPL-ca regarding CD1a(+), p53(+) and Ki-67(+) cells. CONCLUSION: The number of CD3-expressing T-cells may be important for preventing malignant transformation of LPL.

Expression of high mobility group A proteins in oral leukoplakia.

BACKGROUND: Oral leukoplakia (LPL) is considered a potentially malignant disorder in the oral cavity and the gastric tract. High mobility group A (HMGA) proteins are important in the transformation of normal cells into cancer cells, but there is a lack of knowledge on their importance in oral cancer development. The aim of the current project was to investigate HMGA expression in LPLs with different levels of dysplasia. MATERIALS AND METHODS: Biopsies were histologically processed to visualize the expression of HMGA1 and HMGA2 using immunohistochemistry. RESULTS: An increase of HMGA1-positive cells correlating to the degree of dysplasia was registered in the epithelium and in the connective tissue. HMGA2 expression was seen in the epithelium and in the connective tissue but with no obvious correlation to the level of dysplasia. CONCLUSION: This is, to our knowledge, the first study showing the expression of HMGA proteins in healthy and non-healthy oral mucosa.

Loss of 5-hydroxymethylcytosine and TET2 in oral squamous cell carcinoma.

AIM: Epigenetic modifications, such as DNA methylation, are considered important in the regulation of target genes in cancer development. 5-Hydroxymethylcytosine (5hmC) was recently discovered to be related to the process of malignant transformation. The influence of DNA methylation in oral squamous cell carcinomas (OSCC) is not fully-understood. Therefore, the aim of the present study was to investigate the DNA methylation pattern in OSCC compared to healthy oral epithelium. MATERIALS AND METHODS: Oral mucosal samples from patients with OSCC (n=15) and healthy mucosa (n=12) were analyzed using immunohistochemistry with antibodies against 5hmC, 5mC and ten-eleven-translocation-2 (TET2). RESULTS: A significant decrease in 5hmC and TET2 expression was found in OSCC compared to healthy oral epithelium. In contrast, there was a significant increase in 5mC expression in OSCC compared to healthy epithelium. CONCLUSION: Our results indicate that loss of 5hmC is an epigenetic event of OSCC.

Squamous cell carcinoma in a patient with oral lichen planus treated with topical application of tacrolimus.

Oral lichen planus (OLP) is a chronic mucosal disorder of unclear etiology. The mainstay of therapy is topical use of steroids but other immuno-modulating therapies have also been tried. One such example is topical application of tacrolimus. Tacrolimus was in 2000 approved for treatment of atopic dermatitis, but in 2005 a boxed warning was included because of a potential risk of cancer development and for lack of long-term studies of the safety of the drug. The present study describes a patient who in 2003 was diagnosed with OLP and where treatment has included an intermittent use of tacrolimus. Five years after diagnosis, the patient developed a squamous cell carcinoma in the region where tacrolimus had been applied. The possible relationship between the use of tacrolimus and cancer development and rationale to include tacrolimus in OLP treatment is discussed.

Oral mucoceles; extravasation cysts and retention cysts. A study of 298 cases.

Oral mucoceles can be divided in two different forms, extravasation and retention cysts. The aim of this study was to identify the frequency of each form, sex- and age distribution, location, recurrences, referent and the differences between the two forms. A total of three-hundred-five cases were retrieved from the Department of Oral Pathology at the Institution of Odontology, The Sahlgrenska Academy at Göteborg University between 1993 and 2003. Seven referrals were disregarded because there was insufficient information, leaving 298 cases for this study. In relation to other studies, our study investigated a larger number of cases. Extravasation cysts were the most common type (258 cases). There was a slight predominance among women (55%) and the most frequent location was the lower lip (71%). 84% occurred between the ages of 0 and 40 years with peak incidence in the second decade (34%). 62% of the referrals came from specialists, 28% from general practitioners, and 10% from the Department of Oral Medicine. Retention cysts were not found as frequently as extravasation cysts (40 cases) and the occurrence in women was also a bit higher (58%). We found a more even distribution regarding age and location. The most common locations were floor of the mouth (25%), cheek (20%), and lower lip (18%). They occurred more often between the ages of 11 and 30 (31%), and between 50 and 80 (50%). 75% of the referrals came from specialists, 15% from general practitioners,and 10% from the Department of Oral Medicine. Recurrences were unusual for both cyst types. 17 cases of extravasation cysts were reported as recurrences and one case of retention cyst.

Expression modes and clinical manifestations of latent membrane protein 1, Ki-67, cyclin-B1, and epidermal growth factor receptor in nonendemic nasopharyngeal carcinoma.

BACKGROUND: We aimed to identify clinical significance of latent membrane protein 1 (LMP1), Ki-67, cyclin-B1, and epidermal growth factor receptor (EGFR), in nonendemic nasopharyngeal carcinoma (NPC). METHODS: The relation between expression of the markers in 45 NPC specimens and clinicopathological and survival variables was statistically analyzed. RESULTS: LMP1 was present in 33% of the tumors, and its presence was associated with advanced nodal and disease stages. Overexpression was defined as labeling index > or = median value for Ki-67, > or = 15% for cyclin-B1, and > or =50% for EGFR, and it was displayed in 50%, 55%, and 80% of the specimens, respectively. Strong EGFR staining intensity and not overexpression of the 3 markers was the variable with statistically significant impact on treatment outcomes in terms of worse local and locoregional tumor control rates. CONCLUSIONS: Our results suggest that the evaluation of EGFR staining intensity in patients with NPC may identify a subgroup of patients with poor prognosis.

Langerin-expressing and CD83-expressing cells in oral lichen planus lesions.

OBJECTIVE: Dendritic Langerhans cells (LCs) have been attributed a role in the pathogenesis of lichen planus as autoantigen-presenting cells initiating expansion of autoreactive T cells. Langerin and CD83, which are cell molecules expressed on LCs, are associated with antigen presentation. The present study examined expression of Langerin and CD83 molecules on LCs in patients with oral lichen planus (OLP). MATERIAL AND METHODS: Biopsies were obtained from seven patients with OLP. Oral mucosa from seven healthy subjects served as controls. Monoclonal antibodies (mAbs) were used in standard immunohistochemical procedures to visualize CD1a-, Langerin-, and CD83-molecule-expressing cells. RESULTS: CD1a+ and Langerin+ cells were found in significantly higher frequencies in OLP epithelium compared with healthy oral epithelium (p<0.01 and p<0.05, respectively); however, the frequency of CD83+ cells did not differ (p>0.05). The connective tissue in OLP lesions showed significantly higher frequencies of CD1a+, Langerin+, and CD83+ cells compared with healthy connective tissue (p<0.01, p<0.01, and p<0.05). CD1a+ and Langerin+ cells in OLP and healthy epithelium had a dendritic morphology. CONCLUSIONS: The study shows increased numbers of CD1a- and Langerin-expressing LCs in OLP compared with healthy controls. In the connective tissue, CD83+ cells with dendritic morphology were localized to regions of lymphocyte clusters. The presence of CD83+ dendritic cells in areas of lymphocyte clusters in the connective tissue of OLP lesions indicates the possibility of ongoing autoantigen presentation.

Gas chromatography-mass spectrometry determination of the pentafluorobenzoyl derivative of methylhydrazine in false morel (Gyromitra esculenta) as a monitor for the content of the toxin gyromitrin.

The main toxic compound found in false morel (Gyromitra esculenta) is acetaldehyde-N-methyl-N-formylhydrazone (gyromitrin). This paper describes a method of determining the total hydrazones content based on acid hydrolysis of gyromitrin and other related hydrazones in air-dried false morel followed by derivatisation of methylhydrazine with pentafluorobenzoyl chloride. The derivative, tris-pentafluorobenzoyl methylhydrazine (tris-PFB-MH) is analyzed by gas chromatography-mass spectrometry. The overall precision of the method is better than 10% (relative standard deviation) for 0.5 ng/microl methylhydrazine in solution. The minimum detectable concentration of methylhydrazine (tris-PFB-MH) by this method is estimated to be approximately 12 pg/microl, which is equal to 0.3 microg/g dry matter (DM) of false morel.

Accuracy of proximal caries depth measurements: comparison between limited cone beam computed tomography, storage phosphor and film radiography.

The aim of this study was to compare the accuracy of limited cone beam computed tomography (LCBCT), an image plate system and F-speed film in assessing the depth of proximal carious lesions. Radiographs of a dry mandible with sound and carious teeth were obtained with all three methods. In 41 molar and premolar proximal surfaces, 2 observers independently measured lesion depth on the images from the three modalities. The correlation of measurements was assessed with Pearson's correlation analysis. Results from imaging modalities and histological sectioning (gold standard) were compared using Bland-Altman plots. Overall comparison of the depth measurements from the imaging modalities and the gold standard was done using repeated-measures ANOVA. Pairwise comparisons of systems were done by the Bonferroni t test. The correlation between the measurements of the two observers was 0.977 for film, 0.997 for image plate system and 0.998 for LCBCT. Bland-Altman plots revealed that LCBCT agreed very closely with the gold standard while the agreement between the latter and the image plate--or film--images was moderate. The mean difference and 95% limits of agreement between LCBCT and the gold standard were smaller than those between either image plate or F-speed film and the gold standard. The LCBCT method appears as a promising tool for detection and monitoring of proximal carious lesions.

Preradiotherapy hemoglobin level but not microvessel density predicts locoregional control and survival in laryngeal cancer treated with primary radical radiotherapy.

PURPOSE: To evaluate the roles of preradiotherapy hemoglobin level and microvessel density (MVD) as predictive factors for tumor control and survival in patients with laryngeal cancer treated with primary radiotherapy. EXPERIMENTAL DESIGN: Two hundred and fourteen patients with stage I-IV laryngeal cancer were included in the analysis. Patients were treated with once daily fractionated radiotherapy over 6.5 weeks or twice daily fractionated radiotherapy over 4.5 weeks up to total doses of 62 to 68 Gy. Preradiotherapy hemoglobin levels were obtained from patient journals, and pretreatment tumor biopsies were stained with CD34 antibody for the counting of microvessels. The prognostic implication of preradiotherapy hemoglobin level and MVD on tumor control and survival was tested. RESULTS: Five-year locoregional control probability was 88.9% for patients with preradiotherapy hemoglobin levels >137.5 g/L (median) and 64.4% for patients with preradiotherapy hemoglobin levels <137.5 g/L (P = 0.01). The corresponding figures for disease-free survival were 87.8 and 62.8% (P = 0.007), respectively, and for overall survival 58.1 and 40.3% (P < 0.001), respectively. In multivariate analysis, tumor stage and preradiotherapy hemoglobin level were significant prognostic factors for locoregional control and disease-free survival, whereas tumor stage, preradiotherapy hemoglobin-level, gender, and age were significant prognostic factors for overall survival. No correlation was found between MVD and tumor control and survival. CONCLUSION: Preradiotherapy hemoglobin level, but not MVD, predicts locoregional control and survival in patients with laryngeal cancer treated with radiotherapy.

Overexpression of cell cycle regulatory proteins correlates with advanced tumor stage in head and neck squamous cell carcinomas.

Squamous cell carcinoma of the head and neck region (HNSCC) is the sixth most frequent cancer worldwide. In the USA, 30,000 new cases and 8,000 deaths are reported each year. Differences between normal epithelium and cancer cells from the upper aerodigestive tract arise from alterations in expression of specific genes controlling proliferation and immortalization. The protein products of these genes include growth factor receptors, cell cycle regulators, and tumor suppressors which affect a variety of intracellular signaling pathways. To determine how altered expression of these gene products contribute to HNSCC progression, we examined expression of epidermal growth factor receptor (EGFR), cyclins, p16INK4A, c-myc, proliferating cell nuclear antigen (PCNA), and telomerase in archival pathology specimens by immunohistochemistry. A substantial majority of HNSCC tumors showed loss of p16INK4A expression and dramatic overexpression of EGFR. Overexpression of this receptor correlated with increased cyclin A levels and high mitotic index. EGFR, cyclins A, -B1, -E, and c-myc overexpression was significantly increased in stage III and IV tumors compared to early stage cancers. hTERT was expressed in all tumors and primarily in the basal layer cells of dysplastic epithelial lesions. Suprabasal expression of hTERT was found in a significantly higher number of HNSCC cases than in dysplastic lesions. These results indicate that overexpression of cell cycle regulatory proteins correlates with advanced tumor stage in HNSCC.

Odontopediatría: enfoque sistématico

El desarrollo de la odontología pediátrica. Epidemiología de la enfermedad dental en el niño. Exploración y diagnóstico del paciente. El niño como paciente dental. Psicología infantil aplicada y tratamiento odontológico. Control del dolor. El desarrollo y sus alteraciones. Caries dental en el niño. Gingivitis y enfermedad periodontal. Odontología preventiva. odontología operatoria, prótesis. Tratamiento pulpar. Ortodoncia preventiva. Patología oral. Cirugía oral menor. Cirugía oral menor. Odontología para niños minusválidos. lesiones traumáticas de los dientes. Equipo dental y sus responsabilidad en el futuro

Odontopediatría: enfoque sistématico

El desarrollo de la odontología pediátrica. Epidemiología de la enfermedad dental en el niño. Exploración y diagnóstico del paciente. El niño como paciente dental. Psicología infantil aplicada y tratamiento odontológico. Control del dolor. El desarrollo y sus alteraciones. Caries dental en el niño. Gingivitis y enfermedad periodontal. Odontología preventiva. odontología operatoria, prótesis. Tratamiento pulpar. Ortodoncia preventiva. Patología oral. Cirugía oral menor. Cirugía oral menor. Odontología para niños minusválidos. lesiones traumáticas de los dientes. Equipo dental y sus responsabilidad en el futuro