A cross-sectional CBCT assessment of the relative position of one-piece titanium-zirconium mini-implants placed for mandibular overdentures using non-guided surgery.

OBJECTIVE: To assess the relative position of mini-implants to retain a mandibular overdenture, according to the surgical protocol, technical and anatomical factors. METHODS: Mandibular cone-beam computed tomography (CBCT) scans were analyzed for 73 patients who received four one-piece titanium-zirconium mini-implants. Drilling was performed using a 1.6 mm needle drill and a 2.2 mm Pilot Drill, according to the bone density with a surgical stent. Post-insertion CBCT images in DICOM format were analyzed using the E-Vol-DX software with BAR filters. Divergence angle between implants and between implants and the overdenture path of insertion was measured using CliniView 10.2.6 software. RESULTS: Divergence between implants ranged from 0° to 22.3° (mean = 4.2; SD = 3.7) in the lateral and from 0° to 26.2° (mean = 5.3; SD = 4.1) in the frontal projections (p < .001). Only 1 (0.2%) and 3 (0.7%) of the measurements were higher than 20° in the lateral and frontal views, respectively. The mean angulations between the implant and the path of insertion for the overdenture were 9.3° (SD = 7.5) and 4.0° (SD = 2.9) for the lateral and frontal views, respectively (p < .001). Regression analyses showed a significant association between the divergence of implants and the frontal view projection (p < .001), greater distance between the paired implants (p = .017), the flapped surgical protocol (p = .002), higher final insertion torque (p = .011), and deeper preparation with the needle drill (p < .001). CONCLUSIONS: The mini-implants were placed with low divergence angles and satisfactory parallelism. Factors including shorter distances between the implants, higher density bone, and a flapless surgical approach all contributed positively to improved parallelism of the mini-implants.

Validity and reliability of immunochromatographic IgM/IgG rapid tests for COVID-19 salivary diagnosis.

OBJECTIVES: To assess the accuracy of three immunochromatographic rapid tests for salivary detection of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens and the reliability of these tests comparing saliva with plasma samples. MATERIALS AND METHODS: Plasma and saliva samples from 62 patients diagnosed with coronavirus disease 2019 (COVID-19) and 20 healthy volunteers were assayed. IgM/IgG antibody against SARS-COV-2 was detected using three immunochromatographic rapid tests and compared with real-time reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: The tests' overall accuracy for detecting anti-SARS-CoV-2 antibodies ranged from 75.6 to 79.3 for saliva and 86.6-87.8 for plasma tests. The sensitivity of saliva and plasma tests increased with the severity of COVID-19 signs and symptoms. The chance of a positive plasma test in participants with a positive qRT-PCR test was 2.27 greater than a positive saliva test. CONCLUSIONS: Although rapid immunochromatographic tests are more accurate using plasma than saliva, which was expected considering its original use, our findings support the use of saliva as a straightforward supplementary method to assess seroconversion in patients with COVID-19, with important sensitivity and sensibility, especially in severe and critical cases.

Evaluation of PD-L1, PD-L2, PD-1 and cytotoxic immune response in oral lichen planus.

OBJECTIVE: To investigate the expression of programmed death-ligands 1 and 2 (PD-L1, PD-L2), programmed death-1 (PD-1), CD8 and granzyme B (GrB), as well as its correlation with the severity of oral lichen planus (OLP). MATERIALS AND METHODS: In a collaborative study, 33 cases of OLP were evaluated according to the latest criteria proposed by the American Academy of Oral and Maxillofacial Pathology (AAOMP/2016) and were submitted to immunohistochemistry. Positivity was measured semiquantitatively (PD-L1, PD-L2) and quantitatively (PD-1, CD8, GrB). The severity of OLP was assessed according to clinical subtype, symptomatology and response to corticosteroid therapy. RESULTS: Most OLPs were considered to be negative for PD-L1 (66.6%), but high expression of PD-L2 (96.9%) by keratinocytes and immunoinflammatory cells was observed. PD-1+ cell density/mm2 was reduced compared to CD8+ cells. A low cytotoxic immune response (CD8:GrB ratio) was also demonstrated. Interestingly, there were fewer GrB+ cells in the intraepithelial region in reticular OLP compared to erosive/bullous OLP. CONCLUSIONS: PD-L1/PD-1 pathways appear to be compromised in OLP due to low PD-L1 expression in most samples. In contrast, PD-L2 overexpression associated with a possible regulation of the cytotoxic immune response suggests an immune tolerance that may contribute to the chronic profile of OLP.

Immunohistochemical analysis of neutrophils, interleukin-17, matrix metalloproteinase-9, and neoformed vessels in oral squamous cell carcinoma.

BACKGROUND: Tumor-associated neutrophils (TAN), matrix metalloproteinase-9 (MMP-9), interleukin-17 (IL-17), and angiogenesis have been proposed as prognostic biomarkers of malignant tumors. The purpose of this study was to investigate these inflammatory markers as prognostic factors for oral squamous cell carcinoma (OSCC). METHODS: Specimens of OSCC (n = 30), healthy oral mucosa (negative control, n = 10), oral leukoplakia (n = 10), and apical granuloma with abscess (positive inflammatory controls, n = 10) were immunostained for CD66b (neutrophils), MMP-9, IL-17, and CD105 (neoformed microvessels). Semiquantitative (IL-17) and quantitative (CD66b, IL-17, MMP-9, and CD105) analyses were performed. Clinical information (TNM stage, metastasis, recurrence, and survival) and tumor histological grade were also obtained. RESULTS: Positivity for TAN, MMP-9, IL-17, and CD105 was higher in OSCC than in the negative control (P < 0.05) and oral leukoplakia, but similar to the positive inflammatory control. Coincident high counts of inflammatory markers (CD66b, MMP-9, IL-17, and CD105) were associated with lymph node metastasis of OSCC. Associations between high numbers of neoformed microvessels and advanced clinical stage and a higher degree of malignancy were also demonstrated. CONCLUSIONS: Combined positivity for TAN, MMP-9, IL-17, and CD105 appears to be associated with the metastasis-prone phenotype of OSCC.

Characterization of dendritic cells in lip and oral cavity squamous cell carcinoma.

BACKGROUND: There may be differences in the antitumor immunity induced by dendritic cells (DCs) during the development of squamous cell carcinoma (SCC) located in the lip rather than in the oral cavity. The aim of this study was to evaluate the number of immature and mature DCs in SCC and potentially malignant disorders of the oral cavity and lip. METHODS: Immunohistochemistry was used to identify the number (cells/mm(2) ) of immature (CD1a(+) ) or mature (CD83(+) ) DCs in samples of oral cavity SCC (OCSCC) (n = 39), lip SCC (LSCC) (n = 23), leukoplakia (LK) (n = 21), actinic cheilitis (AC) (n = 13), and normal mucosa of the oral cavity (OC control, n = 12) and the lip (lip control, n = 11). RESULTS: The number of CD1a(+) cells tended to be higher in the OC control samples compared with the LK (P = 0.04) and OCSCC (P = 0.21). Unlike, this cell population was lower in the lip control than in AC or LSCC (P < 0.05). The number of CD83(+) cells was increased in the LSCC samples compared with the AC and lip control (P = 0.0001) and in OCSCC compared with both the LK (P = 0.001) and OC control (P = 0.0001) samples. LSCC showed an elevated number of CD1a(+) and CD83(+) cells compared with OCSCC (P = 0.03). The population of mature DCs was lower than the population of immature DCs in all of the tested groups (P < 0.05). CONCLUSION: There were a greater number of both mature and immature DC populations in the LSCC samples than in the OCSCC, which could contribute to establishing a more effective immune antitumor response for this neoplasm.

Immune response in cervical lymph nodes from patients with primary oral squamous cell carcinoma.

BACKGROUND: Deficient immune response in the cervical lymph nodes of patients with head and neck squamous cell carcinoma may contribute to dissemination of metastatic neoplastic cells. This study evaluates the immune response in cervical lymph nodes from patients with primary oral cavity squamous cell carcinoma (OCSCC). METHODS: The density of immature (CD1a(+)) and mature (CD83(+)) dendritic cells (DCs), cytotoxic T lymphocytes CD8(+) /perforin(+) (CTLs), and Foxp3(+) regulatory T (Tregs) cells in the lymph nodes of patients with OCSCC without cervical lymph node metastases (LN1) (negative) (n = 10) were identified through immunohistochemistry. From patients with cervical lymph node metastases, samples were obtained of lymph nodes both with (LM2) (positive) (n = 10) and without (LN2) (negative) (n = 10) metastases. RESULTS: The results demonstrated that the number of CD1a(+) and Foxp3(+) cells was significantly higher in the LM2 group than in either the LN1 or the LN2 group. In addition, the number of CD8(+) /perforin(+) and CD83(+) cells was significantly lower in the LM2 group than in the other groups. CONCLUSION: The results of this study demonstrate a higher density of immature DCs and Tregs cells and a lower density of mature DCs and activated CTLs in metastatic than in non-metastatic lymph nodes. These findings might indicate an immunosuppressive microenvironment, which could be involved in the spread of neoplastic cells to cervical lymph nodes.

Possible role of ALDH1 and CD44 in lip carcinogenesis.

BACKGROUND: Lip squamous cell carcinoma (LSCC) accounts for 12% of all head and neck cancers. It is caused by chronic exposure to ultraviolet light solar radiation and related to previous actinic cheilitis (AC). This study aimed to investigate the immunostaining of the putative cancer stem cells (CSC) markers ALDH1 and CD44 in AC (n=30) and LSCC (n=20). ALDH1 positivity was found to be statistically higher in LSCC than in AC lesions (p=0.0045), whilst CD44 expression was statistically higher in AC than in LSCC lesions (p=0.0155). ALDH1+ cells in AC lesions were associated with specific clinical features: a younger age (<60 years old), the female gender, white skin, not smoking or consuming alcohol, and a fast evolution, and not associated with the chronic exposure to UV radiation (p<0.0001). CD44 positivity was associated with patients who were male, feoderm, smoked, consumed alcohol, underwent occupational exposure to UV-radiation, and demonstrated lesions with log-time evolution (p<0.0001). ALDH1 + cells were associated with mild dysplasia using a system from the World Health Organization (WHO), and with a low risk of malignant transformation, according to the binary system (p<0.0001). CD44+ cells were also associated with moderated dysplasia, according to the WHO system. In LSCC, ALDH1 + cells were positively associated with patients who were older (≥ 60 years old), smokers, and with those who consumed alcohol (p<0.0001). CD44 + cells in LSCC were associated with older (≥ 60 years old) patients as well, but also with female patients, white skin, non-smokers, and individuals who did not consume alcohol (p<0.0001), all of whom showed distinct patterns in pre- and malignant lesions of both markers. Additionally, in LSCC, both ALDH1 and CD44 staining were associated with smaller tumor sizes (T1/T2; p<0.0001). In summary, although both ALDH1 and CD44 were associated with the presence of dysplasia in AC lesions, the present findings suggest that ALDH1 and CD44 may be activated by different etiopathogenic pathways, predominantly in distinct steps of oral carcinogenesis. CD44 would thus be more significantly related to the potentially malignant lesion, while ALDH1 would be closely linked to malignancy.

Distinct anti-NP, anti-RBD and anti-Spike antibody profiles discriminate death from survival in COVID-19.

Introduction: Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces rapid production of IgM, IgA, and IgG antibodies directed to multiple viral antigens that may have impact diverse clinical outcomes. Methods: We evaluated IgM, IgA, and IgG antibodies directed to the nucleocapsid (NP), IgA and IgG to the Spike protein and to the receptor-binding domain (RBD), and the presence of neutralizing antibodies (nAb), in a cohort of unvaccinated SARS-CoV-2 infected individuals, in the first 30 days of post-symptom onset (PSO) (T1). Results: This study included 193 coronavirus disease 2019 (COVID-19) participants classified as mild, moderate, severe, critical, and fatal and 27 uninfected controls. In T1, we identified differential antibody profiles associated with distinct clinical presentation. The mild group presented lower levels of anti-NP IgG, and IgA (vs moderate and severe), anti-NP IgM (vs severe, critical and fatal), anti-Spike IgA (vs severe and fatal), and anti-RBD IgG (vs severe). The moderate group presented higher levels of anti-RBD IgA, comparing with severe group. The severe group presented higher levels of anti-NP IgA (vs mild and fatal) and anti-RBD IgG (vs mild and moderate). The fatal group presented higher levels of anti-NP IgM and anti-Spike IgA (vs mild), but lower levels of anti-NP IgA (vs severe). The levels of nAb was lower just in mild group compared to severe, critical, and fatal groups, moreover, no difference was observed among the more severe groups. In addition, we studied 82 convalescent individuals, between 31 days to 6 months (T2) or more than 6 months (T3), PSO, those: 12 mild, 26 moderate, and 46 severe plus critical. The longitudinal analyzes, for the severe plus critical group showed lower levels of anti-NP IgG, IgA and IgM, anti-Spike IgA in relation T3. The follow-up in the fatal group, reveals that the levels of anti-spike IgG increased, while anti-NP IgM levels was decreased along the time in severe/critical and fatal as well as anti-NP IgG and IgA in several/critical groups. Discussion: In summary, the anti-NP IgA and IgG lower levels and the higher levels of anti-RBD and anti-Spike IgA in fatal compared to survival group of individuals admitted to the intensive care unit (ICU). Collectively, our data discriminate death from survival, suggesting that anti-RBD IgA and anti-Spike IgA may play some deleterious effect, in contrast with the potentially protective effect of anti-NP IgA and IgG in the survival group.

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.

Poor oral health status and adverse COVID-19 outcomes: A preliminary study in hospitalized patients.

BACKGROUND: Most of the common risk factors for severe outcomes of coronavirus disease 2019 (COVID-19) are correlated with poor oral health, tooth loss, and periodontitis. This has pointed to a possible relationship between oral and systemic health in COVID-19 patients. Hence, this study aimed to assess the dental and periodontal status of hospitalized COVID-19 patients and their associations with the incidence of adverse COVID-19 outcomes. METHODS: We included 128 hospital patients aged between 20 and 97 years and with diagnoses of COVID-19 in this prospective observational study. Dental and periodontal status was assessed using in-hospital clinical examinations, including the Decayed, Missing, and Filled Teeth index, periodontal status, and tooth loss patterns (Eichner index). Associations between oral health measures, the severity of COVID-19 symptoms, and hospitalization endpoints were tested using chi-square test and incidence rate ratio (IRR) estimation using a generalized linear model with log-Poisson regression. The regression models used a block-wise selection of predictors for oral health-related variables, comorbidities, and patients' ages. RESULTS: Overall, poor oral health conditions were highly prevalent and associated with critical COVID-19 symptoms, higher risk for admission in the intensive care unit (ICU), and death. Periodontitis was significantly associated with ICU admission (IRR = 1.44; 95% confidence interval [95%CI] = 1.07-1.95; P = 0.017), critical symptoms (IRR = 2.56; 95%CI = 1.44-4.55; P = 0.001), and risk of death (IRR = 2.05; 95%CI = 1.12-3.76; P = 0.020) when adjusted for age and comorbidities. The Eichner index (classes B and C) was associated with ICU admission. CONCLUSION: There was a positive association between deleterious oral health-related conditions, especially periodontitis, and severe COVID-19 outcomes in hospitalized COVID-19 patients.

Distinct expression of perforin and granzyme B in lip and oral cavity squamous cell carcinoma.

BACKGROUND: Perforin and granzyme B (GB) are the main constituents of cytotoxic T-lymphocyte granules, and they have important roles in preventing the initiation and progression of cancer. METHODS: The aim of this study was to compare the expression of CD8(+) /perforin(+) double-staining and GB(+) cells, by immunohistochemistry, in primary oral cavity squamous cell carcinoma (OCSCC), lip squamous cell carcinoma (LSCC), non-dysplastic leukoplakia (LK), dysplastic LK, actinic cheilitis (AC), oral lichen planus (LP) and normal oral mucosa. RESULTS: Our results showed a higher expression of CD8(+) /perforin(+) and GB(+) cells in LSCC when compared with the samples of OCSCC, non-dysplastic and dysplastic LK, AC, oral LP and normal oral mucosa. In addition, increased CD8(+) /perforin(+) and GB(+) cell numbers were observed in all pre-malignant lesions (non-dysplastic LK, dysplastic LK, AC) when compared with the control. CONCLUSIONS: Perforin and GB proteins may contribute to antitumoural immunity, leading to the direct killing of tumour cells; however, it seems to occur more effectively in LSCC than OCSCC.

Effects of Curcuma as an adjunct therapy on periodontal disease: A systematic review and meta-analysis.

BACKGROUND: Periodontal disease (PD) is the second most prevalent buccal infectious condition in adults. Owing to its multifactorial etiology, treatment and maintenance are challenging. Scaling and root planing, associated with adequate plaque control, are considered the gold standard treatments for this disease. However, the instrumentation techniques can fail to completely eliminate calculus, particularly in higher grade and progression rated PD cases, and the continuing efficient removal of the biofilm by the patient can limit the long-term response of this treatment. Anti-infective herbal products, such as Curcuma, have been added as adjuvant therapy to prolong periodontal treatment outcomes. OBJECTIVE: This systematic review aimed to summarize and evaluate whether Curcuma can contribute to PD treatment when applied as an adjunct to the standard scaling and root planing therapy. DATA SOURCES: We searched databases using specific keywords and Boolean operators and systematically conducted the extraction and analysis according to the PROSPERO (CRD42019145691) database. The main eligibility criteria were randomized clinical trials in humans published in the English language. RESULTS: Twelve studies were included in the review and 11 in the meta-analysis. Quantitative analysis of different clinical parameters was described. In comparison with the control group, Curcuma was associated with a reduction in pocket depth after 90 days of treatment (mean deviation: 0.48; 95% confidence interval: 0.89-0.08). CONCLUSION: This systematic review and meta-analysis indicated that Curcuma is an effective product when applied as adjunct therapy for PD treatment. This improved the clinical and microbiological parameters.

Differential diagnoses of solitary and multiple pigmented lesions of the oral mucosa: Evaluation of 905 specimens submitted to histopathological examination.

BACKGROUND: The aim was to analyze the frequency, clinical and demographic features of solitary and multiple/diffuse oral pigmented lesions submitted to histopathological examination, and to summarize the features that guide the clinical differential diagnosis. METHODS: Clinical and demographic data were retrieved from biopsy records and descriptive statistics were performed. RESULTS: Nine hundred and five (0.51%) oral pigmented lesions were retrieved among 177 356 specimens, being 95.9% solitary and 4.1% multiple/diffuse lesions. Regardless the overlapping clinical presentation, age, site, association with amalgam restoration, and a nodular appearance may help in the clinical differential diagnosis of solitary oral pigmentations. Patient's habits, site, and systemic signs and symptoms are helpful in the clinical differential diagnosis of multiple/diffuse lesions. CONCLUSIONS: Oral pigmented lesions are a rare diagnosis in oral pathology and solitary lesions are more commonly submitted to biopsy. Some key features help in the differential diagnosis, though biopsy can be warranted in doubtful cases.

T-Cell/Histiocyte-Rich Large B-Cell Lymphoma: Report of the First Case in the Mandible.

T-cell/histiocyte-rich large B-cell lymphoma (THRBCL) is an uncommon subtype of non-Hodgkin's lymphoma. It is a predominant nodal neoplasm; however, extranodal sites, such as the spleen, liver and bone marrow, can be involved at diagnosis. However, only one case of primary THRLBCL in the jaws have been reported. We herein describe a 29-year-old female patient who presented with a swelling of the right mandible that had grown rapidly over the previous 2 months. Periapical and panoramic radiographs showed a multilocular osteolytic lesion located in the mandibular periapical region of the canine and premolar teeth and molar region. Preoperative examination and incisional biopsy were performed. Immunohistochemistry was applied to confirm the diagnosis of THRBCL in the jaw. The treatment consisted of CHOP therapy and radiotherapy. After complete tumor remission following initial treatment, additional sites of the disease appeared in the lung, abdomen and long bones. The patient died within 2 months. THRLBCL is an uncommon and aggressive malignant neoplasm that can involve the jaws, mimicking a periapical disease.

Possible role of ALDH1 and CD44 in lip carcinogenesis

Abstract Lip squamous cell carcinoma (LSCC) accounts for 12% of all head and neck cancers. It is caused by chronic exposure to ultraviolet light solar radiation and related to previous actinic cheilitis (AC). This study aimed to investigate the immunostaining of the putative cancer stem cells (CSC) markers ALDH1 and CD44 in AC (n=30) and LSCC (n=20). ALDH1 positivity was found to be statistically higher in LSCC than in AC lesions (p=0.0045), whilst CD44 expression was statistically higher in AC than in LSCC lesions (p=0.0155). ALDH1+ cells in AC lesions were associated with specific clinical features: a younger age (<60 years old), the female gender, white skin, not smoking or consuming alcohol, and a fast evolution, and not associated with the chronic exposure to UV radiation (p<0.0001). CD44 positivity was associated with patients who were male, feoderm, smoked, consumed alcohol, underwent occupational exposure to UV-radiation, and demonstrated lesions with log-time evolution (p<0.0001). ALDH1 + cells were associated with mild dysplasia using a system from the World Health Organization (WHO), and with a low risk of malignant transformation, according to the binary system (p<0.0001). CD44+ cells were also associated with moderated dysplasia, according to the WHO system. In LSCC, ALDH1 + cells were positively associated with patients who were older (≥ 60 years old), smokers, and with those who consumed alcohol (p<0.0001). CD44 + cells in LSCC were associated with older (≥ 60 years old) patients as well, but also with female patients, white skin, non-smokers, and individuals who did not consume alcohol (p<0.0001), all of whom showed distinct patterns in pre- and malignant lesions of both markers. Additionally, in LSCC, both ALDH1 and CD44 staining were associated with smaller tumor sizes (T1/T2; p<0.0001). In summary, although both ALDH1 and CD44 were associated with the presence of dysplasia in AC lesions, the present findings suggest that ALDH1 and CD44 may be activated by different etiopathogenic pathways, predominantly in distinct steps of oral carcinogenesis. CD44 would thus be more significantly related to the potentially malignant lesion, while ALDH1 would be closely linked to malignancy.

Subcellular localization and expression of E-cadherin and SNAIL are relevant since early stages of oral carcinogenesis.

The biological process of epithelial-to-mesenchymal transition (EMT) has been studied in oral squamous cell carcinoma (OSCC) metastasis, but it is rarely evaluated at several stages of oral carcinogenesis. This study aimed to analyze the presence of SNAIL and E-cadherin proteins, markers of EMT, in the development and progression of OSCC, evaluating excised specimens of potentially malignant lesions (oral leukoplakia with and without dysplasia-OL and OLD, respectively), tumor tissues (OSCC), metastatic lymph nodes (LN), and normal oral mucosa (NOM) by immunohistochemistry, considering subcellular localization. Additionally, SNAIL and E-cadherin transcripts were evaluated in vitro by qPCR, using SCC-9 cell line in comparison to human keratinocytes (HPEC). There was a significant increase in nuclear expression of SNAIL from NOM to OLD followed by a noticeable decrease in nuclear expression accompanied by increased cytoplasmic expression in OSCC (p<0.05). The E-cadherin cytoplasmic expression was remarkable and statistically significant higher in OSCC and LN, both compared to NOM (p< 0.0001), OL (p<0.01) and OLD (p< 0.0001 and p<0.001, respectively). In vitro, E-cadherin and SNAIL transcripts were lower in SCC-9 compared to HPEC cells, although only the decrease of E-cadherin was statistically significant (p<0.05). Regarding the association of E-cadherin and SNAIL expression with the clinical findings, the analysis revealed an association between the cytoplasmic expression of SNAIL and the invasion pattern (p=0.05) in OSCC. The increased nuclear SNAIL expression may be characteristic of OLD, and the presence of E-cadherin in cell cytoplasm a marker of transformation to malignancy of potentially malignant oral leukoplakias into OSCC.

Decrease in mast cells in oral squamous cell carcinoma: possible failure in the migration of these cells.

It is becoming accepted that multiple cell types in stromal microenvironment are involved in tumorigenesis. In this setting, mast cells (MC) display a diversity of roles that may contribute to the defense against tumors or tumor progression. Thus, the aim of this study was to evaluate density and migration of MCs in OSCC (oral squamous cell carcinoma) and pre-malignant oral hyperkeratosis (leukoplakia) as well as their relationship with clinical and microscopic parameters. The tryptase and c-kit expression was analyzed in 38 cases of OSCC, 26 cases of leukoplakia, and 12 cases of clinically healthy oral mucosa (control) by means of immunohistochemistry. The tryptase(+) cell numbers were decreased in OSCC (P=0.0003) and leukoplakia (P=0.03) compared with control. Similar numbers of tryptase(+) cells were observed in leukoplakia and OSCC (P=0.31). The density of c-kit(+) MCs was also significantly lower in OSCC and leukoplakia in relation to control resulting in a reduced c-kit(+)/tryptase(+) relationship in OSCC (19%) in comparison with leukoplakia (59%) and control (63%). No correlation was observed between MC populations with clinical and microscopic characteristics of OSCC. Our findings suggest that the decrease in MC numbers in pre-malignant and malignant oral lesions may be related to the migration failure of these cells, possibly reflecting an important modification in the microenvironment during tumor initiation and progression.

Overexpression of immunomodulatory mediators in oral precancerous lesions.

Human leukocyte antigen (HLA) G and E, programmed cell death 1 ligand 1 (PD-L1), IL-10 and TGF-ß are proteins involved in failure of the antitumor immune response. We investigated the expression of these immunomodulatory mediators in oral precancerous lesions (oral leukoplakia-OL; n=80) and whether these molecules were related to the risk of malignant transformation. Samples of normal mucosa (n=20) and oral squamous cells carcinoma (OSCC, n=20) were included as controls. Tissue and saliva samples were analyzed by immunohistochemistry and ELISA respectively. Fifteen OL samples showed severe dysplasia (18.7%) and 40 samples (50%) presented combined high Ki-67/p53. Irrespective of the degree of epithelial dysplasia and the proliferation/apoptosis index of OL, the expression of HLA-G, -E, PD-L1, IL-10, TGF-ß2 and -ß3 was higher to control (P<0.05) and similar to OSCC (P>0.05). The number of granzyme B+ cells in OL was similar to control (P=0.28) and lower compared to OSCC (P<0.01). Salivary concentrations of sHLA-G, IL-10 and TGF-ß did not allow for a distinction between OL and healthy individuals. Overexpression of immunosuppressive mediators in the OL reflects the immune evasion potential of this lesion, which is apparently independent of at cytological and proliferation/apoptosis status.

A multicenter study of malignant oral and maxillofacial lesions in children and adolescents.

OBJECTIVES: To investigate the frequency of malignant oral and maxillofacial lesions among children and adolescents from representative geographic regions of Brazil. MATERIALS AND METHODS: A retrospective study was conducted on biopsies obtained from 1990 to 2016 at six Brazilian oral and maxillofacial pathology referral centers. A total of 85,105 biopsy specimens from children and adolescents were analyzed. Gender, age, anatomical location, symptomatology and histopathological diagnosis were evaluated. Data were analyzed using descriptive statistical methods. RESULTS: Fifty-eight (0.06%) malignant oral and maxillofacial lesions were diagnosed in children (19%) and adolescents (81%). The lesions were more frequent among females (60.3%) and adolescents. The most prevalent lesions were mucoepidermoid carcinomas (22.4%), osteosarcomas (13.8%), squamous cell carcinomas (12.1%), and Burkitt's lymphomas (12.1%). The most commonly affected sites were the palate (19%), mandible (13.8%), and maxilla (13.8%). Almost half the patients were asymptomatic. CONCLUSION: Pediatric oral and maxillofacial malignant lesions were infrequent and showed wide diversity, with a prevalence of mucoepidermoid carcinomas. Analysis of malignant lesions in children and adolescents helps pediatric dentists and oncologists to obtain a better understanding of such lesions and to reduce the time for diagnosis, with a consequent improvement of prognosis.