Decreased expression of folate transport proteins in oral cancer.

OBJECTIVES: The purpose of this study was to assess the expression of the 3 major folate transporters-folate receptors (FRs), reduced folate carrier (RFC), and proton-coupled folate transporter (PCFT)-in oral squamous cell carcinoma (OSCC). We hypothesized that patterns of expression of folate transporters would be different in OSCC compared with normal oral epithelium. STUDY DESIGN: We used immunohistochemistry to examine the expression of FR, RFC, and PCFT in 15 primary specimens collected from patients with OSCC, 2 human cadaveric samples of OSCC, and 12 normal human cadaveric oral tissues from a medical gross anatomy laboratory. Possible correlations between the expression of each folate transporter and patients' clinical data were determined. RESULTS: All 3 folate transporters were highly expressed in normal oral epithelium. In contrast, OSCC samples generally demonstrated low expression of FR, RFC, and PCFT, with wide distribution in the invading cancer cells. There were no differences in folate transporter expression between OSCC samples collected from patients and from human cadavers. The lowest expression of FR and PCFT characterized less-differentiated tumors, and the lowest expression of RFC correlated with higher lymph node involvement. CONCLUSIONS: Human oral cancer samples expressed decreased amounts of all 3 major folate transport proteins compared with controls from normal cadaveric oral tissues.

Conditioned fear stress increases bone resorption in apical periodontitislesions in Wistar male rats.

OBJECTIVE: Because the impact of conditioned fear stress on apical bone resorption is unknown, the aim of the current studywas to use a rat model to evaluate the impact of conditioned fear stress on the bone resorption of inflammatory apical periodontitis lesions. METHODS: Twenty-five animals were divided into two groups. They underwent a surgical procedure in the first left lower molar tooth to expose the dental pulp and induce inflammatory apical periodontitis lesions through the retention of contamination (bacterial infection) during a 56-day period. The animals in the case group were stressed daily by using electrical stimuli (1.10 mA), whereas the animals in the control group were absent from the stressful stimuli (shocks). The open field test was performed to validate the stress methodology. The jaws were removed and collected for histological and radiographic analyses. RESULTS: Stressed animals presented increased levels of bone loss and inflammatory cells in the root apex in comparison with the control group (P = 0.0001). However, no radiographic differences were observed between the groups (P > 0.05). CONCLUSIONS: Our results demonstrated that conditioned fear stress could modify a periapical lesion by increasing the size of bone loss there. Conditioned fear stress also increased the total number of inflammatory cells compared with the control group. Studies evaluating the impact of conditioned fear stress on human periapical inflammatory lesions should be encouraged.

Immunoexpression of SOX-2 in oral leukoplakia.

OBJECTIVE: This study was conducted to correlate and compare the immunoexpression of sex-determining region Y-box 2 (SOX-2) in oral leukoplakia (OL) lesions with that in normal buccal mucosa (control). MATERIALS AND METHODS: In this observational study, OL with low-risk (n = 34) and high-risk (n = 33) dysplasia and control samples (n = 25) were subjected to immunohistochemical analysis for SOX-2. In the epithelium, SOX-2 positive and negative cells, as well as semiautomatic segmentation of the immunopositive nuclear area were counted. Statistical tests included chi-square, one-way analysis of variance, Tukey, and Games-Howell. The level of significance was 5%. RESULTS: Groups with OL lesions (low and high-risk) showed higher mean numbers of SOX-2 positive cells (63.47 ± 25.70 and 68.18 ± 21.17) compared to the control group (45.85 ± 27.38) (p = 0.00). Groups with OL lesions (low and high-risk) exhibited higher mean positive nuclear area (0.24 ± 0.47 and 1.09 ± 2.06) compared to the control group (0.00 ± 0.01) (p = 0.01). CONCLUSION: Oral leukoplakia lesions showed a higher expression of SOX-2, suggesting its contribution to the pathogenesis of OL.

Evaluation of HLA-G, HLA-E, and PD-L1 proteins in oral osteosarcomas.

OBJECTIVE: The aim of this study was to investigate the expression of human leukocyte antigens (HLAs) G and E and programmed death-ligand 1 (PD-L1) in oral osteosarcoma (OO) (n = 13). The relationship between the expression of these molecules and histologic grading and metastasis was also evaluated. STUDY DESIGN: HLA-G, HLA-E, and PD-L1 were identified by immunohistochemistry. Samples of normal bone tissue (n = 6) were used as controls. The sections were evaluated using a semiquantitative scoring system with an immunoreactive score, where a score of 0 was considered absent, ≤2 was low, and >2 was high expression. RESULTS: We identified high expression of HLA-G, HLA-E, and PD-L1 by malignant osteoblastic cells in 69.2% of OO cases, which was statistically higher than that in controls (P < .05). Overexpression of these proteins was identified in 8 of 11 samples of high-grade and 1 of 2 samples of low-grade OO. Additionally, 66.6% of patients with metastases (n = 4) and 71.4% of patients without metastases (n = 5) had high expression of HLA-G, HLA-E, and PD-L1 in tumor samples (P > .05). CONCLUSION: OO had high expression of HLA-G, HLA-E, and PD-L1 irrespective of clinicopathologic parameters, including histologic grading and metastasis.

The relation between FoxP3⁺ regulatory T cells and fungal density in oral paracoccidioidomycosis: a preliminary study.

Regulatory T (Treg) cells may play an important role in the pathogenesis of paracoccidioidomycosis (PCM), but data on the role of Treg cells in the context of oral PCM are still scarce. The objectives of this study were to investigate the density of FoxP3(+) T regulatory cells in oral PCM and to correlate the results with the density of Paracoccidioides brasiliensis in the lesions. Cases of chronic oral PCM seen between 2000 and 2008 were included in this study. The diagnosis of all lesions was confirmed with histopathological examination and Grocott-Gomori staining. The quantitative analysis of the viable fungi was conducted in all cases with Grocott-stained slides. Treg cells were identified using antibodies against FoxP3. Pearson correlation coefficient was used to test the correlation between the density of fungi and Treg cells. Results were considered significant when P < 0.05. A total of 11 cases of oral PCM were obtained. There was a positive correlation between fungal density and FoxP3(+) Treg cells density in oral lesions, however, without statistical significance. A positive relation between Treg cells and fungal density was seen in oral PCM. Further studies are required to further elucidate the role of these cells in the pathogenesis of oral PCM, as well the clinical significance of these findings.

Spontaneous remission of a squamous cell carcinoma of the floor of the mouth.

Spontaneous remission is a rare, but well recognized event in oncology. Certain tumours, such as melanomas, hypernephromas and neuroblastomas, are known for showing spontaneous regression. Similarly, spontaneous regression of oral lymphomas, as well as oropharyngeal and recurrent tongue carcinomas, has been reported. Here, we present a novel case of a patient with a primary squamous cell carcinoma on the floor of the mouth whose tumour regressed spontaneously in three months, without any treatment. We also review of the literature on the spontaneous remission of oral cancer and discuss possible mechanisms for this phenomenon.

Clinical management of suppurative osteomyelitis, bisphosphonate-related osteonecrosis, and osteoradionecrosis: report of three cases and review of the literature.

In the past, osteomyelitis was frequent and characterized by a prolonged course, treatment response uncertainty, and occasional disfigurement. Today, the disease is less common; it is believed that the decline in prevalence may be attributed to increased availability of antibiotics and improvement of overall health patterns. Currently, more common osteomyelitis variants are seen, namely, osteoradionecrosis (ORN) and bisphosphonate-related osteonecrosis of the jaws (BRONJ). Osteomyelitis, ORN, and BRONJ can present with similar symptoms, signs, and radiographic findings. However, each condition is a separate entity, with different treatment approaches. Thus, accurate diagnosis is essential for adequate management and improved patient prognosis. The aim of this paper is to report three cases of inflammatory lesions of the jaws-osteomyelitis, ORN, and BRONJ-and to discuss their etiology, clinical aspects, radiographic findings, histopathological features, treatment options, and preventive measures.

Th1 and Th2-like protein balance in human inflammatory radicular cysts and periapical granulomas.

INTRODUCTION: Chronic dental periapical lesions result from chronic inflammation of periapical tissues caused by continuous antigenic stimulation from infected root canals. Recent findings have suggested that T helper (Th) 1 and Th2-like cytokines are important in the pathogenesis of chronic periapical inflammatory diseases. However, the mechanisms regulating these immunoinflammatory pathways have not been fully elucidated. Thus, the aim of this study was to evaluate interleukin (IL)-4, IL-12, and interferon γ (IFN-γ) protein levels in human radicular cysts and periapical granulomas. METHODS: Archived samples of cysts (n = 52) and granulomas (n = 27) were sectioned and submitted to immunohistochemistry to evaluate the tissue expression of IL-4, IL-12, and IFN-γ. The data were analyzed using the Mann-Whitney U test (P < .05). RESULTS: An increased expression of IFN-γ was observed in radicular cysts. IL-4 expression was stronger in periapical granulomas than in radicular cysts. IL-12 was not detected in any of the samples. CONCLUSIONS: Our study showed that IFN-γ protein levels are increased in radicular cysts, whereas IL-4 expression is stronger in samples of periapical granulomas. Further studies are necessary to elucidate the signaling pathways mediated by these cytokines and to facilitate the development of more effective periapical disease management strategies.

Periodontal care in patients undergoing radiotherapy for head and neck cancer.

PURPOSE: The aim of this study was to evaluate periodontal changes after periodontal treatment and control in patients with malignant tumors of the upper aerodigestive tract who were submitted to radiotherapy with or without chemotherapy. METHODS: We included all patients attending the Oncology Clinic of the Federal University of Minas Gerais, School of Dentistry. Clinical periodontal parameters obtained by a single calibrated examiner were evaluated at baseline, 10 days after radiotherapy, and 180 days after radiotherapy. Patients were grouped into healthy or periodontally diseased individuals. All patients received oral hygiene instructions, and the diseased patients received periodontal therapy at baseline. Comparisons between the groups were performed via the McNemar and Wilcoxon tests using SPSS v. 17.0. RESULTS: A total of 28 patients were examined at baseline, of which 27 were examined 10 days after radiotherapy and 25 were examined 180 days after radiotherapy. The prevalence of periodontal disease at baseline was 67.9 % and did not decrease over time (p = 1.0). There was a significant reduction in probing depth (PD), plaque index (PI), and bleeding on probing between baseline and follow-up, which was not observed in the attachment level (AL). CONCLUSIONS: Periodontal therapy was effective in reducing PI and improving periodontal status, as evidenced by the decreases in PD and the maintenance of AL.

Midkine expression in oral squamous cell carcinoma and leukoplakia.

BACKGROUND: Midkine (MK), a 13-kDa heparin-binding growth factor, is overexpressed in various human cancers. However, its role in the development and progression of oral cavity squamous cell carcinoma (OCSCC) is still unclear. Thus, the aim of this study was to evaluate the expression of MK in samples of OCSCC, leukoplakia, and healthy oral mucosa (control). METHODS: Surgically excised specimens from patients with primary OCSCC (n = 28) were immunostained for MK, Ki-67, PCNA, p53, bcl-2, Bax, and CD31. Besides this, MK expression was also investigated in leukoplakia and normal oral mucosa. The relationship of MK(+) cells with clinical parameters (tumor location, tumor size, lymph node metastasis, and survival) and microscopic parameters (WHO histological grading, intensity of inflammation, proliferation index, apoptosis, and angiogenesis) was also evaluated. RESULTS: The results showed that MK expression was increased in OCSCC in relation to leukoplakia and normal mucosa. Furthermore, MK expression was increased in late-stage tumors (T3/T4) compared with early-stage lesions (T1/T2). MK-positive lesions also showed increased expression of the anti-apoptotic protein bcl-2. CONCLUSION: OCSCC, particularly late-stage tumors, exhibits increased MK expression, which may be involved in tumor progression via upregulation of anti-apoptotic genes, as shown by the augmented bcl-2 positivity in MK-positive tumors.

Sequential supernumerary teeth in nonsyndromic patients: report of 3 cases.

Supernumerary tooth/teeth (ST) are a well recognized clinical phenomenon defined as teeth that are additional to the normal complement. The purpose of this report was to describe 3 patients who developed multiple sequential ST. All patients were boys between 8 and 12 years old without significant medical history. In 2 cases, the ST were discovered while investigating the nonexfoliation of primary teeth, whereas in the other they were an occasional finding on a radiograph taken for orthodontic purposes. All patients were kept under close follow-up ofter treatment. The 3 patients collectively developed a total of 17 ST with 9 found in a single patient, over a 5-year period. This article demonstrates the importance of clinical and radiographic follow-up of ST patients, regardless of age, family history, or systemic condition.

A survey of 460 supernumerary teeth in Brazilian children and adolescents.

OBJECTIVE: This study aimed to survey the demographic profile of supernumerary teeth (ST) in Brazilian children and adolescents. METHODS: A retrospective analysis was carried out of all nonsyndromic patients with ST attended at the Pediatric Oral Surgery Service of the Universidade Federal de Minas Gerais between 1995 and 2004. Diagnosis of ST was based on clinical and radiographic examination. Chi-squared test was used for statistical analysis. RESULTS: This study included 460 ST found in 305 patients. Radiographic assessment (32.1%) was the main care-seeking reason and also the means through which most (97.6%) permanent ST were identified. Most cases were single (63.0%), conical (44.6%), and unerupted (76.8%) ST. Most teeth were fully developed (41.3%), normally orientated (78.9%), placed in a palatal/lingual-sagittal position (84.1%), adjacent to the crown of permanent teeth (50.2%) (P < 0.001). The most frequent clinical complication was permanent teeth displacement (36.0%). Treatment was surgical removal followed by orthodontics (61.6%). CONCLUSIONS: The demographic profile of ST herein presented will be useful to provide additional epidemiological information. A wide range of factors should be considered when evaluating ST. In addition, it is essential to detect ST as early as possible to avoid complications and to assure successful management. Even after treatment, patients must be followed up.

Primary diffuse large B-cell lymphoma of the oral cavity

Lymphomas arising within the oral cavity account for only 3.5 percent of all oral malignancies. Diffuse large B-cell lymphoma is a non-Hodgkin lymphoma subtype characterized by diffuse proliferation of large neoplastic B lymphoid cells. This paper reports a case of diffuse large B-cell lymphoma affecting the oral cavity of a Brazilian woman, along with its clinical, microscopical, immunohistochemical, and molecular features.

Linfomas correspondem a 3,5 por cento de todos os casos de lesões malignas de boca. O linfoma difuso de grandes células B é um subtipo de linfoma não-Hodgkin caracterizado pela proliferação difusa de células linfóides B. Este artigo relata um caso de linfoma difuso de grandes células B localizado na cavidade bucal de uma mulher brasileira, incluindo os achados clínicos, microscópicos, imuno-histoquímicos e moleculares.

Candida oral colonization and infection in Brazilian patients undergoing head and neck radiotherapy: a pilot study.

OBJECTIVE: The aim of this study was to verify the profile of Candida species responsible for colonizing and infecting the oral cavity of Brazilian patients undergoing radiotherapy (RT). STUDY DESIGN: Saliva samples were collected from 21 patients before, during, and immediately after RT. Each sample was distributed in agar Sabouraud dextrose/chlorophenicol and incubated at 37 degrees C for 18 hours. Emerging colonies were identified biochemically and through the germinative tube test. Patients were examined weekly to identify clinical candidiasis. RESULTS: Candida colonization continuously increased during RT. Infection occurred in 52% of the patients, and baseline colonization was higher in infected patients. A shift toward non-albicans species was observed in both infected and noninfected patients. CONCLUSIONS: RT leads to increased colonization and infection by Candida. The shift toward non-albicans species was unrelated to antifungal therapy. There may be epidemiological differences between infected and noninfected patients.

A randomized phase III prospective trial of bethanechol to prevent radiotherapy-induced salivary gland damage in patients with head and neck cancer.

The aim of this study was to verify whether the use of bethanechol during radiotherapy (RT) for head and neck cancer (HNC) prevents radiation-induced xerostomia and salivary flow reduction. Patients that would begin RT were randomly allocated into bethanechol (group 1) or artificial saliva (group 2). Whole resting saliva (WRS) and whole stimulated saliva (WSS) were collected from all the patients at the following four stages: baseline, during, immediately after, and at least two months after the end of RT. Xerostomia was assessed by a subjective visual analogue scale (VAS), and by asking patients whether they felt dry mouth. Forty-three patients were randomized into this trial. The use of bethanechol during RT for HNC cancer was associated with significantly higher WRS immediately after RT (p=0.03) in comparison to a similar cohort of patients who had not received bethanechol.

Hereditary benign intraepithelial dyskeratosis: a new case?

Hereditary benign intraepithelial dyskeratosis (HBID) is a rare disorder first described in 1960. To date, all but one published case trace their ancestry back to an Indian tribe in North Carolina. Affected patients usually develop asymptomatic ocular and oral lesions. The latter may resemble other dermatologic conditions that affect the oral mucosa, such as white sponge nevus. This report describes a case of a Brazilian patient who showed clinical and histological features of HBID, which appears to be the first reported case in South America. Although genetic analysis could not be carried out, the family history suggests a genetic etiology.

Solitary fibrous tumour of the buccal mucosa: case report and review of the literature.

Solitary fibrous tumours are spindle-cell neoplasms that usually occur in the pleura and peritoneum, and rarely involve the oral mucosa. We report a 30-year-old man with a large solitary fibrous tumour on the buccal mucosa that resembled a salivary gland neoplasm. The lesion was excised and has not recurred.