Identification of Proteomic Biomarkers in Proliferative Verrucous Leukoplakia through Liquid Chromatography With Tandem Mass Spectrometry.

Proliferative verrucous leukoplakia (PVL) is an oral potentially malignant disorder associated with high risk of malignant transformation. Currently, there is no treatment available, and restrictive follow-up of patients is crucial for a better prognosis. Oral leukoplakia (OL) shares some clinical and microscopic features with PVL but exhibits different clinical manifestations and a lower rate of malignant transformation. This study aimed to investigate the proteomic profile of PVL in tissue and saliva samples to identify potential diagnostic biomarkers with therapeutic implications. Tissue and saliva samples obtained from patients with PVL were compared with those from patients with oral OL and controls. Label-free liquid chromatography with tandem mass spectrometry was employed, followed by qualitative and quantitative analyses, to identify differentially expressed proteins. Potential biomarkers were identified and further validated using immunohistochemistry. Staining intensity scan analyses were performed on tissue samples from patients with PVL, patients with OL, and controls from Brazil, Spain, and Finland. The study revealed differences in the immune system, cell cycle, DNA regulation, apoptosis pathways, and the whole proteome of PVL samples. In addition, liquid chromatography with tandem mass spectrometry analyses showed that calreticulin (CALR), receptor of activated protein C kinase 1 (RACK1), and 14-3-3 Tau-protein (YWHAQ) were highly expressed in PVL samples. Immunohistochemistry validation confirmed increased CARL expression in PVL compared with OL. Conversely, RACK1 and YWHA were highly expressed in oral potentially malignant disorder compared to the control group. Furthermore, significant differences in CALR and RACK1 expression were observed in the OL group when comparing samples with and without oral epithelial dysplasia, unlike the PVL. This research provides insights into the molecular mechanisms underlying these conditions and highlights potential targets for future diagnostic and therapeutic approaches.

Clinical profile of oral mucosa lesions in elderly patients: a 20-year retrospective study / Perfil clínico das lesões da mucosa oral em pacientes idosos: um estudo retrospectivo de 20 anos

Background: Life expectancy has considerably increased resulting in population aging. Studies evaluating the outcomes of aging in oral health are scarce. Objective: Evaluate retrospectively the profile of elderly patients from a public Oral Medicine Center during a period of 20 years. Methods:A qualitative and quantitative retrospective observational study was conducted analyzing medical records from an oral medicine service from January 1994 to December 2014. Results were reported as mean ± standard deviation for quantitative variables and percentages for categorical variables. The Chi-square test and T-student test was applied with significance level of 5%. Results: 2,690 medical records were retrieved, comprising of 61% women and 39% men with an average ageof 68.8 ± 6.79 years. Xerostomia was significantly associated, hypoglycemic usage (p<0.0001), anticoagulantusage (p<0.0001), psychotropic usage (p<0.0001) and analgesics and anti-inflammatory usage (p<0.0001). Forcandidiasis, an association with age, xerostomía (p<0.0001), and use of complete dentures was found(p<0.0001). For oral squamous cell carcinoma and oral leukoplakia the tabacco (p<0.0001) and alcohol consumption (p<0.0001) were significant associated. Conclusion:The elderly population was comprised mostly by women that use a large of drugs which wereassociated with xerostomia development. In addition, tabaco and alcohol consumption were associated withoral leukoplakia and OSCC being these two diseases more frequently in men. Dental care services should aimto prevent and treat these complications as way to improve the elderly's quality of life.

Introdução: A expectativa de vida aumentou consideravelmente, resultando no envelhecimento da população. Estudos avaliando os desfechos do envelhecimento na saúde bucal são escassos. Objetivo: Avaliar retrospectivamente o perfil dos pacientes idosos de um Centro de Medicina Oral público durante um período de 20 anos. Materiais e métodos: Estudo observacional retrospectivo qualitativo e quantitativo, analisando os prontuários de um serviço de medicina bucal no período de janeiro de 1994 a dezembro de 2014. Os resultados foram expressos em média ± desvio padrão para variáveis quantitativas e percentuais para variáveis categóricas. Aplicou-se o teste Qui-quadrado e o teste T-student com nível de significância de 5%. Resultados: Foram recuperados 2.690 prontuários, sendo 61% mulheres e 39% homens com idade média de 68,8 ± 6,79 anos. Xerostomia foi significativamente associada, uso de hipoglicemiantes (p<0,0001), uso de anticoagulantes (p<0,0001), uso de psicotrópicos (p<0,0001) e uso de analgésicos e anti-inflamatórios (p<0,0001). Para candidíase, foi encontrada associação com idade, xerostomia (p<0,0001)e uso de prótese total (p<0,0001). Para carcinoma espinocelular oral e leucoplasia oral, o uso de tabaco (p<0,0001) e consumo de álcool (p<0,0001) estiveram associados significativamente. Conclusão: A população idosa foi composta em sua maioria por mulheres que fazem uso de grande quantidade de medicamentos associados ao desenvolvimento de xerostomia. Além disso, o consumo de tabaco e álcool foram associados com leucoplasia oral e OSCC sendo essas duas doenças mais frequentes em homens. Os serviços odontológicos devem ter como objetivo prevenir e tratar essas complicações como forma de melhorar a qualidade de vida dos idosos.

Intraoral atypical lentiginous melanocytic lesion in a pediatric patient.

We present a rare case of intraoral atypical lentiginous melanocytic lesion affecting a pediatric patient, in which the diagnosis of lentiginous junctional melanocytic nevus with cytologic atypia was favored. The main differential diagnosis is lentiginous melanoma, which is a slowly progressing lesion, affecting mainly older adults, and microscopically presenting lentiginous growth pattern of moderately atypical melanocytes, with focal nesting and pagetoid spread. It is strongly recommended that melanocytic lesions showing features of atypical lentiginous growth pattern should be treated with wide excision; however, the impact of these guidelines on pediatric patients needs to be better defined with the report of further cases.

Immunohistochemical characterization of immune cell infiltration in paediatric and adult Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia commonly affecting children with frequent somatic mutations in MAPK pathway genes including BRAFV600E and MAP2K1. Some studies suggest that LCH cells can recruit and modulate inflammatory cells, which could provide reciprocal survival signals. To characterize the immune profile of infiltrating inflammatory cells, and to clarify their participation in LCH pathogenesis, a detailed immunohistochemical analysis was performed. Fifteen (10 children, 5 adults) LCH cases were assessed through macrophage (CD68 and CD163), mature dendritic cell (mDC; CD83 and CD208), regulatory T cell (Treg; CD4, CD25 and FOXP3) and cytotoxic lymphocyte (CL; CD56, CD57, perforin and granzyme B) immunomarkers. Moreover, lymphocytic and LCH markers were also analysed. All cases were S100, CD1a, CD207 and CD4-positive. Bcl-2 and cyclin D1 expression was observed in 13 of 15 cases. In the immune microenvironment, M2-polarized macrophages and Tregs were the predominant cell populations, followed by significantly (P < .005) smaller levels of mDCs and CLs. Additionally, the number of CD3 + cells was significantly higher than that of CD20 + cells. In the CD3 + cell population, there were a significantly higher number of CD4 + cells than CD8 + cells. While there were no differences when comparing the paediatric and adult populations, FOXP3 + cells were significantly higher in patients with multisystem involvement and treated with chemotherapy, than single-site cases and those without chemotherapy. Our results suggest that M2-polarized macrophages and Treg infiltration can promote LCH development and survival, probably through pro-tumoral, immunosuppressive and/or cytokine-mediated mechanisms. This work highlights the need for further exploration of immune-targeted therapy for LCH.