Clock gene Per2 modulates epidermal tissue repair in vivo.

Wound healing can be influenced by genes that control the circadian cycle, including Per2 and BMAL1, which coordinate the functions of several organs, including the skin. The aim of the study was to evaluate the role of PER2 during experimental skin wound healing. Two groups (control and Per2-KO), consisting of 14 male mice each, were anesthetized by inhalation, and two 6 mm wounds were created on their dorsal skin using a punch biopsy. A silicone ring was sutured around the wound perimeter to restrict contraction. The wound healing process was clinically measured daily (closure index) until complete wound repair. On Day 6, histomorphometric analysis was performed using the length and thickness of the epithelial migration tongue, in addition to counting vessels underlying the lesion by immunofluorescence assay and maturation of collagen fibers through picrosirius staining. Bromodeoxyuridine (BrdU) incorporation and quantification were performed using the subcutaneous injection technique 2 h before euthanasia and through immunohistochemical analysis of the proliferative index. In addition, the qualitative analysis of myofibroblasts and periostin distribution in connective tissue was performed by immunofluorescence. Statistically significant differences were observed in the healing time between the experimental groups (means: 15.5 days for control mice and 13.5 days for Per2-KO; p = 0.001). The accelerated healing observed in the Per2-KO group (p < 0.05) was accompanied by statistical differences in wound diameter and length of the migrating epithelial tongue (p = 0.01) compared to the control group. Regarding BrdU immunoreactivity, higher expression was observed in the intact epithelium of Per2-KO animals (p = 0.01), and this difference compared to control was also present, to a lesser extent, at the wound site (p = 0.03). Immunofluorescence in the connective tissue underlying the wound showed a higher angiogenic potential in the Per2-KO group in the intact tissue area and the wound region (p < 0.01), where increased expression of myofibroblasts was also observed. Qualitative analysis revealed the distribution of periostin protein and collagen fibers in the connective tissue underlying the wound, with greater organization and maturation during the analyzed period. Our research showed that the absence of the Per2 gene positively impacts the healing time of the skin in vivo. This acceleration depends on the increase of epithelial proliferative and angiogenic capacity of cells carrying the Per2 deletion.

Risk factors for oral alterations in intensive care unit patients: A pilot cohort study.

BACKGROUND: Several studies evidenced the presence of oral alterations in ICU patient. However, data about identification of their risk factors in ICU patients is scarce, especially due to the lack of longitudinal prospective studies. Here, we evaluate the risk factors for the development of oral alterations in a group of ICU patients through a prospective longitudinal cohort. METHODS: During May-December 2019, 43 ICU patients in a tertiary hospital in Brazil were evaluated. Medical record reviews and oral examinations of each patient were made by 3 dentists in five distinct moments. RESULTS: Among all patients, 53.5% (n = 23) were female, with a mean age of 59.8 years (±17.4). The incidence of oral alterations was 51.2% (35.6%-66.8%) and among these (n = 22), hyposalivation (n = 9; 40.9%), and lingual biofilm accumulation (n = 9; 40.9%) were the most common. The mean age of the group with oral alterations (66.9 years) was higher compared to the group without alterations (52.3 years). Furthermore, male patients (p = 0.02), older than 60 years (p = 0.004) and treated with mechanical ventilator (p = 0.03) had a higher risk of oral alterations. CONCLUSIONS: Systemic parameters, as age and mechanical ventilator, could influence the oral environment of ICU patients.

AT1 and AT2 Receptor Knockout Changed Osteonectin and Bone Density in Mice in Periodontal Inflammation Experimental Model.

BACKGROUND: The aim of this study was to evaluate the role of AT1 and AT2 receptors in a periodontal inflammation experimental model. METHODS: Periodontal inflammation was induced by LPS/Porphyromonas gingivalis. Maxillae, femur, and vertebra were scanned using Micro-CT. Maxillae were analyzed histopathologically, immunohistochemically, and by RT-PCR. RESULTS: The vertebra showed decreased BMD in AT1 H compared with WT H (p < 0.05). The femur showed increased Tb.Sp for AT1 H and AT2 H, p < 0.01 and p < 0.05, respectively. The Tb.N was decreased in the vertebra (WT H-AT1 H: p < 0.05; WT H-AT2 H: p < 0.05) and in the femur (WT H-AT1 H: p < 0.01; WT H-AT2 H: p < 0.05). AT1 PD increased linear bone loss (p < 0.05) and decreased osteoblast cells (p < 0.05). RANKL immunostaining was intense for AT1 PD and WT PD (p < 0.001). OPG was intense in the WT H, WT PD, and AT2 PD when compared to AT1 PD (p < 0.001). AT1 PD showed weak immunostaining for osteocalcin compared with WT H, WT PD, and AT2 PD (p < 0.001). AT1 H showed significantly stronger immunostaining for osteonectin in fibroblasts compared to AT2 H (p < 0.01). CONCLUSION: AT1 receptor knockout changed bone density, the quality and number of bone trabeculae, decreased the number of osteoblast cells, and increased osteonectin in fibroblasts.

Multiple Second Primary Oral Squamous Cell Carcinomas in a Nonsmoker and Nondrinker Woman: Case Report and Review of the Literature.

AIM: This manuscript aims to describe an unusual case of multiple second primary squamous cell carcinomas (SCCs) in several sites of the oral mucosa in a nonsmoker and nondrinker woman and to discuss the diagnostic criteria, clinicopathological aspects and outcome of second primary tumor (SPT). BACKGROUND: Patients treated for SCC of the head and neck are at high risk for developing SPT arising from the same dysplastic mucosal feld. Currently, there is no reliable method to predict which of the patients will develop SPT. CASE DESCRIPTION: A 64-year-old nonsmoker and nondrinker woman developed several second primary oral SCCs in 7 years of follow-up, most of them being synchronic, treated by surgery without and with chemotherapy and radiotherapy. CONCLUSION: Patients treated for SCC require a long-term and careful follow-up as the development of SPT contributes with significantly negative impact on the prognosis. CLINICAL SIGNIFICANCE: This report describes the diagnosis and management of a very unusual case of several SPTs affecting different sites of the oral mucosa in the same patient. Moreover, the patient had no apparent risk factors associated with the development of the oral cancer. Therefore, a brief update concerning SPT and its diagnosis and management is also provided.

Alterations in the immunoexpression of galectins-1, -3 and -7 between different grades of oral epithelial dysplasia.

INTRODUCTION: Oral epithelial dysplasia (OED) is a potentially malignant lesion characterized by a combination of cytological and architectural anomalies, which are essential for its diagnosis. Galectins are proteins that participate in cell cycle, adhesion and differentiation, apoptosis, and immune responses, as well as in cancer development and progression. MATERIALS AND METHODS: The aim of this study was to analyze the immunohistochemical expression of galectins-1, -3, and -7 in the OED (21 low risk and 29 high risk) and normal oral mucosa (NOM). The binary grading system was used. RESULTS: Galectin-1 was expressed in the middle/lower third in most OED cases. Nuclear/cytoplasmic staining was observed in most low-risk and high-risk OEDs. All cases of NOM were negative for galectin-1. Galectin-3 was expressed in the middle/lower third in most low-risk cases. Nuclear/cytoplasmic staining was noted in most low-risk and high-risk OEDs. Middle/lower third and in membrane staining was detected in four cases of NOM for galectin-3. Galectin-7 was expressed in the upper/middle third in most of OED cases. Nuclear/cytoplasmic staining predominated in low-risk and high-risk OEDs. Galectin-7 was detected in four cases of NOM, all of them presenting staining in the upper/middle third and in the membrane. CONCLUSION: The differences in the immunoexpression of galactin-1, -3, and -7 between different grades of OEDs suggest the involvement of this protein in the progression of dysplasias.

BMP-2 and Noggin Immunoexpression in Ameloblastomas, Odontogenic Keratocysts, and Dentigerous Cysts.

BMP-2 and Noggin are expressed in several tissues and participate in cell differentiation and proliferation during odontogenesis and tumor development. We evaluated the immunohistochemical expression of these proteins in ameloblastomas (AMs), odontogenic keratocysts (OKCs), and dentigerous cysts (DCs). The expression in AM (n.20), OKC (n.20), and DC (n.20) was evaluated by the percentage of positive cells and expression intensity, resulting in a total immunostaining score. Analysis of BMP-2 and Noggin revealed positivity in all cases. The Mann-Whitney test showed a statistically significant difference for Noggin between AM and DC and between OKC/DC. The mean DC scores were always higher than those of the other groups, regardless of the assessment method. Individual analysis of each lesion showed a positive and significant correlation between the percentage of cells positive for BMP-2 and Noggin in DC. We demonstrated the presence of BMP-2 and Noggin in AMs/OKCs/DCs. Marked expression of BMP-2 was observed in OKCs and AMs. There was also a positive correlation between BMP-2 and Noggin in DCs, suggesting a greater role of these markers in the bone formation and remodeling process since DCs are characterized by phases of bone quiescence and healing.

Immunoexpression of HSP27 does not seem to influence the prognosis of oral tongue squamous cell carcinoma.

New methods of early detection and risk assessment have been studied aiming to predict the prognosis of patients and directing a specialized treatment of the oral tongue squamous cell carcinoma (OTSCC). In this context, several molecular biomarkers have been investigated for this purpose, and, among them, the heat shock protein 27 (HSP27) can be named. The study aimed to analyze whether heat shock protein 27 (HSP27) exerts any influence on OTSCC, correlating its immunoexpression with clinicopathological parameters, and patient survival. The sample comprised 55 OTSCC cases and 20 normal oral mucosa specimens. The malignancy grading systems proposed by the WHO in 2005, Brandwein-Gensler et al., and Almangush et al. were applied in a histomorphological study. HSP27 expressions were evaluated through the Immunoreactivity Score System (IRS). Significant values were considered at p <0.05 for all statistical tests. Higher IRS results were observed for normal oral mucosa specimens when compared to OTSCC cases (p <0.001). No significant associations between HSP27 immunostaining, the analyzed clinicopathological parameters and patient survival were observed. The results of the present study indicate lower HSP27 expression in OTSCC cases compared to normal oral mucosa specimens. Thus, HSP27 expression does not seem to influence patient prognosis.

Immunoexpression of proliferation and apoptosis markers in oral vascular anomalies.

The biological behavior of lesions is highly dependent on the imbalance between their proliferative and apoptotic capacity. This study evaluated a correlation between the proliferative and apoptotic rates of different oral vascular anomalies (VAs) by analyzing the immunoexpression of proliferation (Ki-67) and apoptosis (Bcl-2 and Bax) markers in endothelial cells of 20 cases of GLUT-1 positive infantile hemangiomas (IHs), 20 cases of pyogenic granulomas (PGs) and 20 cases of vascular malformations (VMs). Immunoexpression analysis of Ki-67, Bcl-2 and Bax revealed a lower median percentage of positive cells in VMs cases compared to IHs and PGs cases (P <0.001). The Wilcoxon signed-rank test showed significantly higher percentages of immunostaining for Bax than for Bcl-2 in IHs (P = 0.048). In the group of PGs, a positive correlation was observed between the immunoexpressions of Ki-67 and Bax (r = 0.476; P = 0.034). Although oral IHs, PGs and VMs present similar clinical and histopathological features, each of these lesions has its etiopathogenic particularities. The results of this study suggest that different biological behaviors of VAs may be related to differences in the proliferative and apoptotic profiles of their endothelial cells.

Assessment of the presence of interleukin 17+ macrophages and Th17 cells in situ in lip and oral tongue cancer.

Increasing clinical evidence indicates that Th17 cells may promote or inhibit tumor progression, however the exact role of these cells in Oral Squamous Cell Carcinoma (OSCCs) pathogenesis and progression remains unclear. Tumor associated macrophages are highly plastic phenotype cells which can differentiate as M1 or M2. The mechanism and cellular phenotype of IL-17 expressing macrophages are unknown. 40 cases of lip and 28 of tongue SCCs were submitted to immunohistochemical analysis, and histologically graded. In tongue cases TNM was analyzed. The number of IL-17+ T cells was higher in lip SCC (p = 0.028). IL-17+ macrophages was greater in tongue SCC (p = 0.014). There were more IL-17+ macrophages in the high-grade malignancy oral tongue SCCs (p = 0.016), yet there was no significant difference in the numbers of RORγt+ lymphocytes by histopathological or TNM analysis. This study provides evidence concerning IL-17's pleiotropic roles, being possibly dependent on its cellular sources in the tumor microenvironment.

Modification in CLIC4 Expression is Associated with P53, TGF-ß, TNF-α and Myofibroblasts in Lip Carcinogenesis.

Chloride intracellular channel-4 (CLIC4) is regulated by p53 and tumor necrosis factor-α (TNF-α), it is linked to the increase of transforming growth factor-ß (TGF-ß), and myofibroblastic differentiation in skin carcinogenesis. This study analyzed the immunoexpression of CLIC4, p53, TGF-ß, TNF-α, and α-SMA in 50 actinic cheilitis (AC) and 50 lower lip squamous cell carcinoma (LLSCC). AC and LLSCC immunoexpression were categorized as score 1 (<5% positive cells), 2 (5-50%) or 3 (>50%). For CLIC4, nuclear and cytoplasmic immunostaining of epithelial cells was considered individually. For morphologic analysis, the World Health Organization criteria were used to epithelial dysplasia grade of ACs, and Bryne grading of malignancy system was applied for LLSCC. Higher nuclear CLIC4 (CLIC4n) and TGF-ß were observed in ACs with low-risk of transformation, while cytoplasmic CLIC4 (CLIC4c), p53 and TNF-α were higher in the high-risk cases (p<0.05). In LLSCCs, CLIC4c was higher in cases with lymph node metastasis, advanced clinical stages, and histological high-grade malignancy. p53 expression was higher in high-grade LLSCCs, whereas TGF-ß decreased as the clinical stage and morphological grade progressed (p<0.05). ACs showed an increased expression of CLIC4n and TGF-ß, while CLIC4c and α-SMA were higher in LLSCCs (p<0.0001). Both lesions showed negative correlation between CLIC4n and CLIC4c, while in LLSCCs, negative correlation was also verified between CLIC4c and p53, as well as CLIC4c and TGF-ß (p<0.05). Change of CLIC4 from the nucleus to cytoplasm and alterations in p53, TGF-ß, TNF-α, and α-SMA expression are involved in lip carcinogenesis.

Immune response and evasion mechanisms in lip carcinogenesis: An immunohistochemical study.

OBJECTIVES: Programmed death ligand-1 (PD-L1) and human leukocyte antigen-G (HLA-G) are considered immune checkpoint molecules that inhibit T-cell effectiveness, contributing to tumor immune escape. This study investigated PD-L1, HLA-G, CD8, and granzyme B (GrB) expression at different stages of lip carcinogenesis. DESIGN AND RESULTS: Forty cases of lip squamous cell carcinoma (LSCC), 55 actinic cheilitis (AC), and 10 healthy lip mucosa (HLM) were submitted to immunohistochemistry. Semiquantitative (PD-L1, HLA-G), and quantitative (CD8, GrB) analysis were performed. PD-L1 and HLA-G expression in neoplastic cells/keratinocytes and stroma/connective tissue was significantly higher in LSCC and AC, compared to HLM (p<0.05). PD-L1 was not associated with clinicopathological features of the lesions. HLA-G expression by malignant cells was significantly higher in LSCCs with distant metastasis (p = 0.041).CD8+ and GrB+ cell numbers progressively increased from HLMs to LSCC, with AC exhibiting intermediate numbers (p<0.01). Most LSCCs showed coexistence of PD-L1+ and CD8+ cells (72.5%). PD-L1 was directly correlated to CD8+ and GrB+ lymphocytic infiltration in LSCCs (p<0.05). Low cytotoxic immune response was associated with lymph node metastasis in LSCC (p<0.05). CONCLUSIONS: PD-L1 and HLA-G-mediated immune evasion mechanisms are likely to occur from early pre-malignant to advanced malignant stages of lip carcinogenesis, which might provide a rationale for therapeutic blockade of these pathways. PD-L1 expression in LSCCs was correlated with the cytotoxic markers, suggesting that PD-L1 may appear as an escape mechanism in response to an active antitumor response.

Immunohistochemical analysis of lymphatic vessel density and mast cells in oral tongue squamous cell carcinoma.

The aim of this study was to analyze lymphangiogenesis and the presence of mast cells in oral tongue squamous cell carcinoma (OTSCC), correlating the findings with clinicopathological parameters (clinical stage, tumor size, nodal metastasis, histological grade of malignancy, local recurrence, and clinical outcome). Fifty-six cases of primary OTSCC were selected. Lymphatic vessels and mast cells were identified by immunostaining with anti-podoplanin (D2-40) and anti-tryptase antibody, respectively. Lymphatic vessel density (LVD) and mast cell density (MCD) were determined in the intratumoral and peritumoral areas. Intratumoral LVD was higher in advanced clinical stages (III/IV) when compared to early-stage (p = 0.017) and in metastatic cases compared to non-metastatic tumors (p = 0.013). Peritumoral LVD and intratumoral or peritumoral MCD did not differ significantly according to the clinicopathological parameters of OTSCCs (p > 0.05). No significant correlations between LVD and MCD were observed at the intratumoral (r = -0.014; p = 0.918) or peritumoral level (r = 0.156; p = 0.251). Our findings suggest that intratumoral lymphatic vessels, compared to peritumoral lymphatic vessels, appear to be more related to the progression of OTSCC. MCD alone does not seem to be determinant for lymphangiogenesis or for the biological behavior of OTSCC, indicating multiple pro- and antitumor effects of these inflammatory cells.

Recurrent aphthous ulceration: an epidemiological study of etiological factors, treatment and differential diagnosis.

BACKGROUND: Recurrent aphthous ulcerations are common benign ulcerated lesions on the mouth, whose etiology is poorly understood, with controversial treatment and difficult to control in clinical practice. OBJECTIVE: To evaluate the cases of recurrent aphthous ulcerations with a focus on treatment, diagnosis and etiology. METHODS: This is a retrospective study of the cases of the Oral Diagnosis service of the Rio Grande do Norte Federal University in Natal/RN. Data such as sex, age, race, location, smoking habits, types of treatment, relapsing episodes, laboratory test results and clinical characteristics were collected. The associations between the variables were analyzed using the Pearson Chi-square test (p <0.05). RESULTS: A total of 4895 patients were seen in the service over a period of 11 years. Of these, 161 (3.3%) had complaints of oral aphthous ulcerations, of which 76 (47.2%) were diagnosed as suffering from recurrent aphthous ulcerations and 68 (42.2%) with clinical information necessary for evaluation. The tongue was the most affected anatomical region, with 27 individuals (39.7%), followed by the buccal mucosa, with 22 cases (32.3%). STUDY LIMITATIONS: Retrospective study with data from medical records. CONCLUSION: Dental surgeons, dermatologists and otorhinolaryngologists are the main responsible for the first contact with patients with this disease and should be attentive to the clinical aspects and treat each patient in an individualized way, since the therapy is palliative, its diagnosis is by exclusion and its etiology is unknown.

Immunoexpression of HSP27 does not seem to influence the prognosis of oral tongue squamous cell carcinoma

Abstract New methods of early detection and risk assessment have been studied aiming to predict the prognosis of patients and directing a specialized treatment of the oral tongue squamous cell carcinoma (OTSCC). In this context, several molecular biomarkers have been investigated for this purpose, and, among them, the heat shock protein 27 (HSP27) can be named. The study aimed to analyze whether heat shock protein 27 (HSP27) exerts any influence on OTSCC, correlating its immunoexpression with clinicopathological parameters, and patient survival. The sample comprised 55 OTSCC cases and 20 normal oral mucosa specimens. The malignancy grading systems proposed by the WHO in 2005, Brandwein-Gensler et al., and Almangush et al. were applied in a histomorphological study. HSP27 expressions were evaluated through the Immunoreactivity Score System (IRS). Significant values were considered at p <0.05 for all statistical tests. Higher IRS results were observed for normal oral mucosa specimens when compared to OTSCC cases (p <0.001). No significant associations between HSP27 immunostaining, the analyzed clinicopathological parameters and patient survival were observed. The results of the present study indicate lower HSP27 expression in OTSCC cases compared to normal oral mucosa specimens. Thus, HSP27 expression does not seem to influence patient prognosis.

Resumo Novos métodos de detecção precoce e avaliação de risco estão sendo estudados com o intuito de predizer o prognóstico dos pacientes e direcionar um tratamento diferenciado. Neste contexto, vários biomarcadores moleculares têm sido investigados com esta finalidade, dentre eles a heat shock protein 27 (HSP27). Esta pesquisa objetivou analisar se a HSP27 exerce alguma influência nos carcinomas de células escamosas de língua oral (CCELO), correlacionando a sua imunoexpressão com parâmetros clinicopatológicos e com a sobrevida dos pacientes. A amostra foi constituída por 55 casos de CCELO e 20 espécimes de mucosa oral normal. Os sistemas de gradação de malignidade propostos pela OMS em 2005, Brandwein-Gensler et al. e Almangush et al. foram aplicados em um estudo histomorfológico. A expressão da HSP27 foi avaliada através do Sistema de Escore de Imunorreatividade (IRS). Para todos os testes estatísticos foram considerados valores significativos com p<0,05. Foi observado um maior IRS para a mucosa oral normal quando comparado aos casos de CCELO (p<0,001). Não foram encontradas associações significativas entre a imunomarcação da HSP27 com os parâmetros clinicopatológicos analisados e com a sobrevida dos pacientes. Os resultados do presente estudo indicam uma menor expressão da HSP27 nos casos de CCELO quando comparados aos espécimes de mucosa oral normal. Assim, a expressão da HSP27 parece não influenciar o prognóstico dos pacientes.

Solitary fibrous tumor: Two cases report with a focus on the differential diagnosis / Tumor Fibroso Solitário: Relato de dois casos com foco no diagnóstico diferencial

Solitary fibrous tumor (SFT) is a neoplasm of fibroblastic/myofibroblastic origin with intermediate biological behavior. We report here two cases of SFT affecting an unusual anatomical site in 58-year-old and 40-year-old female patients and discuss the differential diagnosis of this lesion. In case 01, the lesion showed the clinical appearance of an asymptomatic "blister" with normal color, rubbery consistency, measuring 0.3 cm, and affected the lower lip; while in case 02, a symptomatic red nodular lesion with a soft consistency and measuring 0.5 cm affected the floor of the mouth. Excisional biopsies were performed. Microscopically, two well-delimited benign neoplasms were observed, exhibiting the proliferation of ovoid to spindle-shaped mesenchymal cells, vascular spaces with staghorn arrangement, and the absence of mitosis figures. Immunohistochemistry was performed in case 01 to assist in the diagnosis. Weak and diffuse immunostaining was observed for α-SMA and intense and diffuse immunopositivity for Bcl-2 and CD34. Based on histopathological and immunohistochemical features, a diagnosis of SFT was rendered in both cases. The low occurrence and nonspecific clinical features of oral SFT may make its clinical diagnosis difficult. Also, morphological and immunohistochemical are essential for differential diagnosis with other mesenchymal neoplasms.(AU)

O tumor fibroso solitário (TFS) é uma neoplasia de origem fibroblástica/miofibroblastica com comportamento biológico intermediário. Nesse artigo relatamos dois casos de TFS afetando sítios anatômicos incomuns em pacientes do sexo feminino de 58 anos e 40 anos e discutir os seus diagnósticos. No caso 01 clinicamente a lesão apresentou um aspecto de "bolha" assintomática, coloração normal da mucosa, consistência borrachoide medindo 0,3 cm, em região de lábio inferior, enquanto que no caso 02, como uma lesão sintomática, vermelha, nodular com consistência mole e medindo 0,5 cm afetando o assoalho bucal. As biópsias excecionais foram realizadas. Microscopicamente, observamos duas lesões neoplásicas bem delimitadas exibindo uma proliferação de células mesenquimais variando de ovoides a fusiformes, vasos sanguíneos em formato de "chifre de veado", com ausência de figuras de mitoses. No caso 01 foi realizado análise imuno-histoquímica para auxiliar no diagnóstico. Foi observado uma marcação fraca e difusa de α-SMA e uma intensa e difusa imunopositividade para o Bcl-2 e CD34.Baseado nos achados histopatológicos e imuno-histoquímicos o diagnóstico de TFS foi estabelecido em ambos os casos. A baixa ocorrência e os achados clínicos inespecíficos do TFS oral podem dificultar o diagnóstico clínico. Além disso, as análises morfológicas e imuno-histoquimicas são essenciais para realização do diagnóstico diferencial com outras neoplasias mesenquimais.(AU)_

The stromal immunoexpression of CLIC4 may be related to the difference in the biological behavior between oral squamous cell carcinoma and oral verrucous carcinoma

Background: Oral squamous cell carcinoma (OSCC) has high morbidity and mortality rates while oral verrucous carcinoma (OVC), an uncommon variant of OSCC, exhibits a distinct biological behavior. CLIC4 protein plays a role in the cell cycle and apoptosis regulation and participates in the myofibroblasts transdifferentiation process, which are the main cells of the tumor stroma. This study analyzed the immunoexpression of CLIC4 and α-SMA in 20 OSCC cases and 15 OVC cases. Material and methods: A semiquantitative analysis of CLIC4 and α-SMA immunoexpression was performed in the parenchyma and stroma. Nuclear and cytoplasmic reactivity was analyzed separately for the CLIC4 immunostaining. The data were submitted to Pearson's chi-square and Spearman's correlation tests (p ≤ 0.05). Results: In the CLIC4 analysis, there was a significant difference in the immunoexpression of this protein between OSCC and OVC stroma (p < 0.001). It was observed a higher expression of α-SMA in the OSCC stroma. There was a positive and significant correlation between CLIC4 and α-SMA immunoexpression in the OVC stroma (r = 0,612; p = 0,015). Conclusions: The decrease or absence of nuclear CLIC4 immunoexpression in the neoplastic epithelial cells and the increase of its expression in the stroma may influence the difference in biological behavior between OSCC and OVC. (AU)

Correlation of clinical, histological, and cytokeratin profiles of squamous cell carcinoma of the oral tongue with prognosis.

The aim of the present study was to clinically, morphologically, and immunohistochemically correlate the expression of cytokeratins (CKs) 7, 10, 13, 14, 16, and 19 in 30 cases of tongue squamous cell carcinoma (SCC) with disease outcome, metastases, clinical stage (tumor, node, metastasis [TNM]), and histological grade of malignancy proposed by Bryne. Statistical analysis (chi2 test) showed that only histological grading was not significantly correlated with the clinical variables. CK expression varied in the samples analyzed. CK 10 expression was significantly correlated with the presence of metastases, and the expression of CK 16 was related to disease outcome and also to TNM stages III and IV. These results indicate that metastases and TNM are effective prognostic indicators. The histological grading proposed by Bryne did not reflect the biological behavior of the tongue SCC cases studied. Analysis of some intermediate CK filaments can reflect the biological behavior and aggressiveness of some tongue SCCs.

Florid cemento-osseous dysplasia and peripheral giant cell granuloma in a patient with neurofibromatosis 1.

We report a 35-year-old mulatto female patient with neurofibromatosis Type 1 who presented with facial asymmetry. The patient had two lesions: florid cemento-osseous dysplasia associated with peripheral giant cell granuloma. She was referred for surgical treatment of the peripheral giant cell granuloma and the florid cemento-osseous dysplasia was treated conservatively by a multidisciplinary team. So far, no changes have been observed in the patient's clinical status. We observed no recurrence of peripheral giant cell granuloma. To the best of our knowledge, the present case is the first report of a patient with neurofibromatosis Type 1 associated with a giant cell lesion and florid cemento-osseous dysplasia.

Analysis of CD57+ natural killer cells and CD8+ T lymphocytes in periapical granulomas and radicular cysts.

The aim of this study was to compare the number of CD57+ natural killer (NK) cells and CD8+ T lymphocytes between periapical granulomas (PGs) and radicular cysts (RCs). Twenty-fives cases of PGs and 25 of RCs were submitted to histological analysis and immunohistochemistry using anti-CD57 and anti-CD8 biomarkers. Positive cells were counted in 10 fields (400× magnification) and the median value was calculated for each case. Statistical tests were used to evaluate differences in the number of CD57+ NK cells and CD8+ T lymphocytes according to type of lesion, intensity of the infiltrate and thickness of the lining epithelium. The number of CD57+ NK cells and CD8+ T lymphocytes was higher in PGs than in RCs (p = 0.129 and p = 0.541, respectively). Comparison of the number of CD57+ NK cells in atrophic and hyperplastic epithelium revealed a larger number of cells in the atrophic epithelium (p = 0.042). A larger number of CD57+ NK cells and CD8+ T lymphocytes were observed in grade III infiltrates compared to grade I/II (p = 0.145 and p = 0.725, respectively). CD8+ T lymphocytes were more prevalent than CD57+ NK cells in most cases when PGs and RCs were analyzed separately or in combination (p < 0.0001). CD57+ NK cells and CD8+ T lymphocytes play a key role in antiviral defense and the presence of these cells supports evidence suggesting the participation of these microorganisms in the pathogenesis of PGs and RCs. The response mediated by CD8+ T lymphocytes was more frequent, indicating greater participation of the adaptive immunity in these chronic lesions.

Immunoexpression of proliferation and apoptosis markers in oral vascular anomalies

Abstract The biological behavior of lesions is highly dependent on the imbalance between their proliferative and apoptotic capacity. This study evaluated a correlation between the proliferative and apoptotic rates of different oral vascular anomalies (VAs) by analyzing the immunoexpression of proliferation (Ki-67) and apoptosis (Bcl-2 and Bax) markers in endothelial cells of 20 cases of GLUT-1 positive infantile hemangiomas (IHs), 20 cases of pyogenic granulomas (PGs) and 20 cases of vascular malformations (VMs). Immunoexpression analysis of Ki-67, Bcl-2 and Bax revealed a lower median percentage of positive cells in VMs cases compared to IHs and PGs cases (P <0.001). The Wilcoxon signed‐rank test showed significantly higher percentages of immunostaining for Bax than for Bcl‐2 in IHs (P = 0.048). In the group of PGs, a positive correlation was observed between the immunoexpressions of Ki-67 and Bax (r = 0.476; P = 0.034). Although oral IHs, PGs and VMs present similar clinical and histopathological features, each of these lesions has its etiopathogenic particularities. The results of this study suggest that different biological behaviors of VAs may be related to differences in the proliferative and apoptotic profiles of their endothelial cells.

Resumo O comportamento biológico das lesões é altamente dependente do desequilíbrio entre sua capacidade proliferativa e apoptótica. Neste estudo, avaliou-se se existe correlação entre as taxas proliferativas e apoptóticas de diferentes anomalias vasculares orais (AVs) analisando a imunoexpressão de marcadores de proliferação (Ki-67) e apoptose (Bcl-2 e Bax) em células endoteliais de 20 casos de hemangiomas infantis GLUT-1 positivos (HIs), 20 casos de granulomas piogênicos (GPs) e 20 casos de malformações vasculares (MVs). A análise de imunoexpressão de Ki-67, Bcl-2 e Bax revelou uma porcentagem mediana menor de células positivas nos casos de MVs em comparação aos casos de HIs e GPs (P <0,001). O teste de Wilcoxon mostrou porcentagens significativamente maiores de imunocoloração para Bax do que para Bcl-2 em HIs (P = 0,048). No grupo dos GPs, foi observada correlação positiva entre as imunoexpressões de Ki-67 e Bax (r = 0,476; P = 0,034). Embora HIs, GPs e MVs orais apresentem características clínicas e histopatológicas muito semelhantes, cada uma dessas lesões tem suas particularidades etiopatogênicas. Os resultados deste estudo sugerem que diferentes comportamentos biológicos dos AVs podem estar relacionados a diferenças nos perfis proliferativo e apoptótico de suas células endoteliais.