Immunohistochemical expression of beta-catenin, BMP4 and TGF-beta in odontomas.

Changes in the expression of nuclear ß-catenin are responsible for tumorigenesis. Beta-catenin acts synergistically with the TGF-ß/BMPs pathway. This interaction leads to greater dentin deposition and may explain the differences between distinct tooth morphologies and hamartomas. The aim of this study was to investigate the role of ß-catenin, BMP4 and TGF-ß in the development of odontomas. This cross-sectional, retrospective, immunohistochemical study evaluated 30 compound odontomas, 30 complex odontomas and 17 tooth germs. The results showed that BMP4 and TGF-ß were more immunoexpressed in the ectomesenchyme of complex odontomas (median = 33.7, p < 0.001; median = 76.4, p = 0.002, respectively). Higher immunoexpression of BMP4 and TGF-ß was also observed in the epithelium of tooth germs (median = 2.0, p < 0.001; median = 120.3, p < 0.001, respectively). TGF-ß and BMP4 showed a positive and significant correlation (p < 0.001). Both TGF-ß and BMP4 were positively correlated with nuclear ß-catenin in ectomesenchyme (p = 0.047 and p = 0.023, respectively). Developing teeth exhibited higher concentrations of the proteins studied in odontogenic epithelium, especially during the bud and cap stages. Higher immunoexpression in odontomas occurred mainly in the ectomesenchyme. We therefore suggest that changes in the ectomesenchyme can lead to the development of odontomas.

Cross-sectional study of sublingual varicosities: systemic exposures.

PURPOSE: Sublingual varicose veins are a common vascular lesion with different names, such as caviar tongue or vascular malformations. This study aimed to investigate whether there is an association between sublingual varicose veins and cardiovascular diseases by observing arterial hypertension, diabetes, thrombosis, and infarction. In addition, to evaluate a series of thrombi that affected the oral cavity and to analyze their clinical aspects and relate them to possible systemic alterations. METHODS: This is a cross-sectional study consisting of a sample of 134 varicosities, 23 vascular malformations, and 4 thrombosis. RESULTS: Lingual varicosities are more frequently observed in women aged 57.4 ± 16.4 years. Hypertension was present in lingual varicosities (n = 73), as well as diabetes (n = 107), reports of thrombosis (n = 41), and infarction (n = 45). Arterial hypertension was decompensated (n = 12). The most frequent underlying diseases were diabetes (p < 0.001), infarction (p = 0.012), and thrombosis (p = 0.004), and the most commonly used drug was losartan. CONCLUSION: It can be inferred from the present study that lingual varicosities are related to cardiovascular diseases and can serve as a parameter to measure their decompensation.

SNAIL1 is involved in the control of the epithelial-mesenchymal transition in oral tongue squamous cell carcinoma.

OBJECTIVE: The aim of the present study was to investigate the role of SNAIL1, E-cadherin, and N-cadherin immunoexpression in oral tongue carcinogenesis. In addition, we evaluated in vitro the impact of silencing of the nuclear transcription factor SNAIL1 on the viability, apoptosis, proliferation, migration, and invasion of SCC-9 and HSC-3 cells. STUDY DESIGN: Immunohistochemical analysis of SNAIL1, E-cadherin, and N-cadherin was carried out in 47 samples representing oral epithelial dysplasia (OED) and 41 oral tongue squamous cell carcinoma (OTSCC). The suppression of SNAIL1 expression was performed using shRNA-expression vectors in HSC-3 and SCC-9 cells to investigate in vitro the impact of SNAIL1 on proliferation, apoptosis, viability, migration, and invasion of SCC-9 and HSC-3 cells. RESULTS: Significant differences were observed in the expression of SNAIL1, E-cadherin, and N-Cadherin between OTSCC and OED. A low membrane expression of E-cadherin was strongly associated with poor overall survival in patients with OTSCC (P < .05), but the association did not withstand the Cox multivariate survival analysis. SNAIL1 silencing played a key role in the suppression of epithelial-mesenchymal transition and inhibited migration and invasion of HSC-3 cells (P < .0001, P < .01, respectively). In SCC-9 cells, SNAIL1 silencing promoted a significant reduction in the proliferation (P < .0001) and invasion (P < .0001). CONCLUSIONS: The epithelial-mesenchymal transition is present in different stages of oral tongue carcinogenesis, and SNAIL1 plays a key role in this process, although the underlying mechanisms still need to be elucidated. Thus, SNAIL1 might be a promising therapeutic target in OTSCC.

Biological marker for the establishment of periodontal disease: cross-sectional study in the gingival tissue.

BACKGROUND: The present study investigated the expression of COX-2, EMMPRIN, HIF-1α, and GLUT-1 in the gingival tissue to verify if there is a correlation between the immunoexpression of these proteins and the changes caused by the inflamed infiltrate present in the gingival tissues. MATERIAL AND METHODS: A morphological analysis of epithelial changes (hyperplasia, exocytosis, spongiosis, and hydropic degeneration) was performed, as well as a semiquantitative analysis of the immunoexpression of COX-2, EMMPRIN, HIF-1α, and GLUT-1 in the epithelium and connective tissue of 60 specimens of gingival tissue. RESULTS: Epithelial immunoexpression to COX-2 was observed in three cases, while EMMPRIN, HIF-1α, and GLUT-1 were strongly expressed in the basal layer of the epithelium and gradually decreased until the upper layers. In the connective tissue, COX-2 immunoexpression showed a statistically significant association (p < 0.001) with the gingival inflammatory infiltrate. In connective tissue, EMMPRIN and HIF-1α exhibited intense immunopositivity, while GLUT-1 was negative in most cases. CONCLUSION: COX-2 expression may constitute a biological marker of gingival tissues since its epithelial immunoexpression may indicate a greater propensity for the establishment of periodontal disease.

Verruciform xanthoma associated with lichen planus.

Verruciform xanthoma (VX) is a rare benign lesion of unknown etiology, with a rough or papillary aspect, painless, sessile, well-defined, most lesions do not exceed 2 cm in their largest diameter, the degree of keratinization of the surface influences color, varying white to red, affecting mainly the gingiva and alveolar mucosa, and can also be seen in skin and genital. Herein, we present a report a clinical case of oral verruciform xanthoma in the buccal mucosa associated with the lichen planus lesion, as well as the morphological and immunohistochemical characteristics of the lesion. The clinical diagnostic hypothesis of oral lichen planus of the white reticular lesions on the buccal mucosa and on the tongue was confirmed by histopathology before a subepithelial connective tissue exhibiting intense inflammatory infiltrate in a predominantly lymphocytic band. In contrast, the hypothesis of the verrucous lesion in the left buccal mucosa was leukoplakia, with histopathological evidence showing exophytic and digitiform proliferations with parakeratin plugs between the papillary projections. Subepithelial connective tissue was characterized by macrophages with foamy cytoplasm (xanthoma cells). An immunohistochemical examination was performed, showing positivity for CD68, a macrophage marker, in addition to testing by Schiff's periodic acid (PAS) with diastasis, which was detected the presence of lipids inside these macrophages. The patient is free of recurrences of verruciform xanthoma and is being monitored due to the presence of lesions of oral lichen planus.

Biomarkers involved in the proliferation of the odontogenic keratocyst, glandular odontogenic cyst and botryoid odontogenic cyst.

INTRODUCTION: Odontogenic cysts are a heterogeneous group of lesions with varied clinical behavior. OBJECTIVE: To analyze the expression of the epidermal growth factor receptor (EGFR), Cyclin D1, and transcription factor SOX2 in the odontogenic epithelium evaluating the cell cycle control and cystic expansion. METHODS: This was a cross-sectional study including 40 cases, 20 odontogenic keratocysts (OKC), 10 botryoid odontogenic cysts (BOC), and 10 glandular odontogenic cysts (GOC). RESULTS: All cases of OKC, BOC, and GOC were positive for EGFR in all layers of the cyst lining. The highest expression of nuclear Cyclin D1 was observed in the suprabasal layer of OKCs and in the basal and suprabasal layers of GOC and BOC (p < 0.001). In addition, SOX2 was only expressed in the suprabasal layer of OKCs. CONCLUSION: The high expression of EGFR in the cyst membrane suggests that EGF stimulates epithelial proliferation in BOCs, and the high expression of SOX2 in OKCs may be related to the presence of stem cells in the lesion. Cyclin D1 is related to cell cycle disruption in G1-S contributing to stimulates epithelial proliferation of OKCs and GOCs and BOCs.

Use of topical anti-inflammatory and antineoplastic agents in the treatment of young-aged actinic cheilitis: A systematic review.

INTRODUCTION: Several treatments have been used to reduce inflammation and to reverse epithelial alterations in actinic cheilitis (AC). AIM: A systematic review was conducted to analyze the potential of topical treatments for remission and clinical improvement of AC as well as patient acceptability. METHODS: A systematic review of clinical trials was conducted following the PICO strategy to answer the following question: Are topical anti-inflammatory and antineoplastic agents effective in the treatment of actinic cheilitis? The quality of the studies was assessed by ROB-2, and the certainty of evidence was rated by GRADE guidelines. RESULTS: Eight clinical trials were selected, including four that investigated the use of anti-inflammatory drugs and four use of antineoplastic agents. The use of 3% diclofenac sodium was associated with partial remission of AC, while 5% imiquimod and ingenol mebutate promoted complete remission. Furthermore, 5% fluorouracil was the drug most associated with complications during treatment. Diclofenac sodium (3%) and fludroxycortide showed the best acceptance by the patients, especially in terms of symptom relief and comfort provided. CONCLUSION: The anti-inflammatory and antineoplastic agents analyzed largely provided good clinical outcomes, with evidence of remission of AC lesions, development of few local adverse reactions during treatment, and good patient adherence.

Five-year survival and prognostic factors for oropharyngeal squamous cell carcinoma: retrospective cohort of a cancer center.

INTRODUCTION: Oropharyngeal cancer is characterized by high morbidity and mortality. Prognostic factors for this cancer are therefore useful to predict overall survival and may provide additional therapeutic targets. OBJECTIVE: To evaluate the 5-year overall survival and prognostic factors for oropharyngeal squamous cell carcinoma. METHODS: Retrospective cohort (2008-2018) of a cancer referral center. The population of the study was a hospital-based cohort consisting of patients diagnosed with oropharyngeal cancer who underwent surgery and/or adjuvant therapy (radio- and/or chemotherapy). RESULTS: A total of 253 patients with oropharyngeal squamous cell carcinoma were analyzed. The mean age was 59.8 ± 11.9 years and there was a male predominance (81.8%). Smoking and alcohol consumption were found in 88.0% and 84.2% of the sample, respectively. The combination of radiotherapy and chemotherapy was the treatment modality in 42.7% of the sample, followed by surgery combined with radio- and chemotherapy in 15.8%. There were 143 deaths (events), the mean survival was 11.55 ± 9.69 months, and the 5-year overall survival rate was 1.1%. Overall survival was lower for clinical stage III/IV (p < 0.001), HPV p16-negative status (p = 0.019), and an interval > 4 weeks between diagnosis and the beginning of treatment (p < 0.007). CONCLUSION: Among the prognostic factors analyzed in this cohort, p16-negative status as a poor prognostic indicator and tumor stage III/IV and an interval longer than 4 weeks between diagnosis and the beginning of treatment were significantly associated with lower overall survival.

Analysis of Protein Immunoexpression and Its Interrelationship in the Pathogenesis of Odontomas and Ameloblastic Fibro-Odontomas: A Systematic Review.

Odontomas and ameloblastic fibro-odontomas (AFOs) are the result of a developmental anomaly of odontogenic tissues. A literature review of proteins immunoexpressed in odontomas and AFOs was conducted in order to determine which proteins are involved in the pathogenesis of these lesions. AFO was changed to early odontoma in the 2017 WHO classification and will also be discussed in this article. A literature search was performed in the following electronic databases: PubMed/MEDLINE, Web of Science, Scopus, EMBASE, Lilacs, Cochrane Collaboration Library, and Science Direct. The research question was developed according to the population, intervention, comparison, and outcome (PICO) framework: Which proteins are related to the differentiation of odontomas and what is their interrelationship with AFOs? Thirty articles met all inclusion criteria and were selected for this systematic review, totaling 355 cases of odontomas and 43 cases of AFO. Similar immunoexpression was observed in odontomas and AFOs. Immunoexpression of proteins involved in cell differentiation was higher in compound odontomas than in complex odontomas. Proteins involved in histodifferentiation and enamel formation were more frequent in odontomas. The immunoexpression of enamel matrix proteins differs between odontomas and tooth germs, with their persistence being related to the development of odontomas. Compound odontomas exhibit the highest immunoexpression of proteins involved in cellular histodifferentiation and the Wnt/beta-catenin pathway is involved in tumor formation.

Recurrence-free survival and prognostic factors of odontogenic keratocyst: a single-center retrospective cohort.

PURPOSE: The aim of the present study was to evaluate the 5-year recurrence-free survival and prognostic factors of odontogenic keratocyst (OKC) from a single-center retrospective cohort in the northeastern region of Brazil. METHODS: Forty cases of OKC comprised the study population. In the cohort analyzed, 18 (45%) cases were recurrent OKCs and 22 (55%) were non-recurrent OKCs. Recurrence-free survival was defined as the period from the release of the histopathological report to the occurrence of relapse or last visit to the service. RESULTS: Comparison of the clinicopathological variables between primary and recurrent OKC lesions revealed no differences in the frequency of epithelial thickness, presence of satellite cysts and cystic spaces, presence of an inflammatory infiltrate, locularity, and lesion borders. The frequency of symptoms was practically the same even after recurrence. Satellite cysts were more frequent in the group of recurrent lesions (n = 9, p = 0.002) and the presence of an inflammatory infiltrate was also significantly associated with recurrent lesions (n = 15, p = 0.006). Previous decompression or marsupialization was associated with recurrence of the lesion (p = 0.010). CONCLUSIONS: In conclusion, the most significant prognostic factors were previous decompression or marsupialization, as well as, morphological parameters associated with the recurrence cases were the presence of an inflammatory infiltrate and satellites cysts. The risk of recurrence is low but continues due to the particularities of epithelial proliferation in OKC.

Clinicopathologic Analysis of Oral and Maxillofacial Solitary Fibrous Tumor.

OBJECTIVES: The aim of this systematic review was to provide an overview of the oral and maxillofacial solitary fibrous tumor (SFT) in order to determine its clinicopathologic characteristics and biological behavior. METHODS: We conducted a systematic review in May 2019 in multiple databases. Cases diagnosed as SFT in the oral cavity and maxillofacial complex were included. RESULTS: Seventy-three published articles were included in our systematic review, corresponding to a total of 154 cases. SFT showed a slight female predilection (53.2%), and the cheek mucosa/cheek, tongue, and palate were the most affected anatomical sites. The mean size of SFT in the oral cavity and maxillofacial region at diagnosis was 1.4 cm. Histologic features of malignancy by morphologic analysis (P < .001) were significantly associated with a larger tumor size. Surgical excision was the most frequent therapeutic modality. Recurrence and metastasis were uncommon findings in our sample. CONCLUSIONS: Histologic features of malignancy can be important parameters of tumor behavior. Adequate surgical treatment and long-term follow-up are required for these cases.

Surgical osteoplasty and soft tissue excision as treatment for facial deformities in patients with renal osteodystrophy: three case reports.

BACKGROUND: Renal osteodystrophy (ROD) may occur in patients presenting chronic kidney disease (CKD), leading to laboratory test alterations and changes in bone turnover with extra-skeletal calcifications. Treatment involves the medical management of secondary hyperparathyroidism, potential total parathyroidectomy, and surgical interventions concerning calcifications if causing facial deformities with esthetic and functional repercussions. In this context, the aim of the present study is to describe three cases of facial deformities caused by ROD treated through cosmetic-functional surgeries. CASE PRESENTATION: All patients underwent osteoplasty and soft tissue excision for several purposes, including speech difficulties, chewing difficulties, airway obstructions, malocclusion, and facial disharmony. Most patients were male (n = 2, 66.7%) with a mean age of 30.0 years old. Patients underwent a mean hemodialysis time of 9 years, and the maximum mean parathyroid hormone (PTH) level was of 2384.5 pg/ml. CONCLUSIONS: Long hemodialysis periods and elevated PTH levels were the probable factors for the development of facial deformities in this group of patients. The main complications associated to the surgical management of facial deformities in ROD patients are directly related to end-stage renal disease, with increased risks for hemorrhage and systemic drug accumulation.