FBXL7 Body Hypomethylation Is Frequent in Tumors from the Digestive and Respiratory Tracts and Is Associated with Risk-Factor Exposure.

Squamous cell carcinoma is the main histological tumor type in the upper aerodigestive tract (UADT), including the esophagus (ESCC) and the head and neck sites, as well as the oral cavity (OCSCC), larynx (LSCC) and oropharynx (OPSCC). These tumors are induced by alcohol and tobacco exposure, with the exception of a subgroup of OPSCC linked to human papillomavirus (HPV) infection. Few genes are frequently mutated in UADT tumors, pointing to other molecular mechanisms being involved during carcinogenesis. The F-box and leucine-rich repeat protein 7 (FBXL7) is a potential tumor-suppressing gene, one that is frequently hypermethylated in pancreatic cancer and where the encoded protein promotes the degradation of AURKA, BIRC5 and c-SRC. Thus, the aim of this study was to evaluate the methylation and expression profile of FBXL7 in the UADT and the gene's association with the clinical, etiological and pathological characteristics of patients, as well as the expression of its degradation targets. Here we show that the FBXL7 gene's body is hypomethylated in the UADT, independently of histology, but not in virus-associated tumors. FBXL7 body methylation and gene expression levels were correlated in the ESCC, LSCC, OCSCC and OPSCC. Immunohistochemistry analysis showed that FBXL7 protein levels are not correlated with the levels of its degradation targets, AURKA and BIRC5, in the UADT. The high discriminatory potential of FBXL7 body hypomethylation between non-tumor and tumor tissues makes it a promising biomarker.

Papiloma escamoso oral: relato de três casos / Oral squamous papilloma: three case reports

Os papilomavírus humanos (HPVs) pertencem à família Papillomaviridae e podem infectar a epiderme e os epitélios da cavidade oral, orofaringe, laringe, árvore brônquica, esôfago, bexiga, ânus e trato genital. Na boca, o HPV está relacionado com o surgimento de lesões verrucosas benignas, sendo a mais frequente o papiloma escamoso oral. Essa lesão apresenta crescimento exofítico, assintomático e normalmente solitário. Dessa forma, o presente estudo teve por objetivo relatar três casos de papiloma escamoso oral com características distintas. Nos três casos foram realizadas biópsias excisionais e os espécimes avaliados por histopatologia. Os pacientes foram acompanhados por um período mínimo de doze meses, sem histórias de recidivas. Acredita-se que o conhecimento das principais características clínicas e histopatológicas dessa lesão auxilie o dentista no processo de diagnóstico e tratamento dessa patologia.

Human papillomaviruses (HPVs) belong to the Papillomaviridae family and can infect the host's epithelial cells, generating lesions. They have more than one hundred subtypes and these can infect the epidermis and epithelium of the oral cavity, oropharynx, larynx, bronchial tree, esophagus, bladder, anus and genital tract. In the mouth, HPV is related to the appearance of benign verrucous lesions, the most frequent the oral squamous papilloma. This lesion reveal exophytic growth, asymptomatic and usually solitary. Thus, the present paper aimed to report three cases of oral squamous papilloma with different characteristics. In the three cases, excisional biopsies were performed and the specimens were evaluated by histopathology. Patients were followed for a minimum period of twelve months, with no recurrences. It is believed that the knowledge of the main clinical and histopathological characteristics of this lesion helps the dentist in the process of diagnosis and treatment of this pathology.

Fenômeno de extravasamento de muco: relato de dois casos clínicos / The mucous retention phenomenom: tho clinical cases report

O fenômeno de extravasamento de muco, também referido como mucocele, é uma lesão comum da mucosa oral resultante da ruptura de um ducto da glândula salivar com extravasamento da mucina. O principal fator etiológico é o trauma local. A localização mais comum é o lábio inferior, mas outros locais podem ser afetados. Existe a necessidade de diagnóstico diferencial uma vez que, pelo aspecto clínico e localização, as mucoceles assemelham-se a outras lesões que afetam a boca. Diante desse cenário, o objetivo deste trabalho foi relatar dois casos clínicos de fenômeno de extravasamento de muco (mucocele), evidenciando suas características clínicas, histopatológicas, tratamento e prognóstico. Acredita-se que o conhecimento das principais características dessa condição patológica possa auxiliar o clínico na adoção dos principais procedimentos na avaliação, conduta e tratamento desses pacientes.

The mucous retention phenomenon, also called as oral mucocele, is a common lesion of the oral mucosa resulting from the rupture of a salivary gland duct. The main etiological factor is local trauma. The most common location is the lower lip, but other locations can be affected. Differential diagnosis is important because mucoceles resemble other oral lesions. Thus, the aim of the present study was to report two cases of mucocele, demonstrating its clinical and histopathological characteristics, treatment and prognosis.. It is believed that knowledge of the main characteristics of this lesions can help the clinician in carrying out the main procedures in the evaluation, conduct and treatment of these patients.

"Dry oral and ocular manifestations and autoantibodies characteristic of primary Sjögren's syndrome in multiple sclerosis".

INTRODUCTION: The relationship between primary Sjögren syndrome (pSS) and demyelinating diseases is still not well understood. These diseases seem to coexist amidst autoimmunity, raising questions about clinical characteristics, relationship with immunomodulatory treatment, and possible common immunological background underlying their pathogenesis. OBJECTIVE: calculate the frequency of dry oral and ocular manifestations and autoantibodies characteristic of primary Sjögren's Syndrome in Multiple Sclerosis. METHODS: 202 patients with multiple sclerosis answered a questionnaire to identify complaints of xerostomia and xerophthalmia, according to diagnostic criteria for primary Sjögren's syndrome; 43 answered positively to at least one question; 27 had comorbidities or used drugs that cause dry symptoms and were excluded; 16 patients were selected for examinations for oral, ocular and serum anti-Ro/SS-A autoantibody evaluation. RESULTS: Eleven (68.75%) patients complained of xerostomia; 14 (87.5%) of xerophthalmia. Sialometry < 0.1 ml/min was observed in three (18.8%); 13 patients underwent minor salivary gland biopsy and histopathological examination: focal score > 1 in three (23.1%). Schirmer test was < 5 mm/5 min in four (25%). Lyssamine green/fluorescein dye score was > 5 in three (18.8%). Anti-Ro/SS-A > 10 UI/mm in two (12.5%). Three (1,49%) patients met current criteria for primary Sjögren's syndrome. CONCLUSIONS: Patients with MS may report xerostomia and/or xerophthalmia even in the absence of comorbidities and use of medications capable of causing these symptoms, which may fulfill the diagnostic criteria for pSS. In this study, the frequency of pSS according to current criteria was within the range observed in the literature with older criteria. But the question remains whether the association between these diseases is fortuitous or whether there is a pathogenic link.

Acquired oral syphilis: A multicenter study of 339 patients from South America.

OBJECTIVE: To report the clinicopathologic features of acquired oral syphilis cases in South American countries. MATERIALS AND METHODS: Clinical data were retrospectively collected from the records of 18 oral diagnostic services in Argentina, Brazil, Chile, Colombia, Venezuela, Uruguay, and Peru. Serologies of nontreponemal and treponemal tests were used for diagnosis. RESULTS: The series comprised 339 cases of acquired oral syphilis. Secondary syphilis ranked as the most common stage (86.7%). Lesions were more frequent among males (58.0%) and young adults with a mean age of 33.3 years. Individuals aged 20-29 years were most affected (35.3%). The most commonly involved sites were the tongue (31.6%), lip/labial commissure (25.1%), and hard/soft palate (20.4%). Clinically, acquired oral syphilis usually presented as mucous patches (28.4%), papules (25.7%), and ulcers (18.1%). Skin manifestations occurred in 67.7% of individuals, while lymphadenopathy and fever were observed in 61.3% and 11.6% of all subjects, respectively. Most patients were treated with the benzathine penicillin G antibiotic. CONCLUSION: This report validates the spread of acquired oral syphilis infection among young adults in South America. Our directives include accessible diagnostic tools for proper disease screening, surveillance, and counselling of affected individuals, especially in low- and middle-income countries.

HPV Infection Leaves a DNA Methylation Signature in Oropharyngeal Cancer Affecting Both Coding Genes and Transposable Elements.

HPV oncoproteins can modulate DNMT1 expression and activity, and previous studies have reported both gene-specific and global DNA methylation alterations according to HPV status in head and neck cancer. However, validation of these findings and a more detailed analysis of the transposable elements (TEs) are still missing. Here we performed pyrosequencing to evaluate a 5-CpG methylation signature and Line1 methylation in an oropharyngeal squamous cell carcinoma (OPSCC) cohort. We further evaluated the methylation levels of the TEs, their correlation with gene expression and their impact on overall survival (OS) using the TCGA cohort. In our dataset, the 5-CpG signature distinguished HPV-positive and HPV-negative OPSCC with 66.67% sensitivity and 84.33% specificity. Line1 methylation levels were higher in HPV-positive cases. In the TCGA cohort, Line1, Alu and long terminal repeats (LTRs) showed hypermethylation in a frequency of 60.5%, 58.9% and 92.3%, respectively. ZNF541 and CCNL1 higher expression was observed in HPV-positive OPSCC, correlated with lower methylation levels of promoter-associated Alu and LTR, respectively, and independently associated with better OS. Based on our findings, we may conclude that a 5-CpG methylation signature can discriminate OPSCC according to HPV status with high accuracy and TEs are differentially methylated and may regulate gene expression in HPV-positive OPSCC.

Fibrolipoma em cavidade oral: relato de caso / Fibrolipoma of the oral cavity: case report

Fibrolipoma is a benign neoplasm characterized by the presence of mature adipose cells separated by broad bands of dense fibrous connective tissue. This pathology is a microscopic variant of lipoma and can affect any part of the body. However, its occurrence in the oral cavity is uncommon. It is usually a smooth-surface lesion, asymptomatic, slow-growing, pedicled, asymptomatic, yellowish or pinkish color when deeper, soft on palpation, occurring mainly in the jugal mucosa. Thus, the aim of this paper is to describe the main clinical, histopathological and treatment characteristics of a clinical case of fibrolipoma. A 67-year-old female patient, leukoderma, had a normochromic, asymptomatic, firm palpation nodule, fibrous consistency, and smooth surface, with a time course of approximately two years, located in the left jugal mucosa. The diagnostic hypotheses were lipoma, fibroma, mucus extravasation phenomenon and giant cell fibroma. The patient underwent excisional biopsy and histopathological examination revealed the definitive diagnosis of fibrolipoma. The patient is in preservation, with no sign of relapse. It is concluded that, although fibrolipoma is a benign lesion, its growth can reach large dimensions, reinforcing the need for surgical excision. It should also emphasize the importance of histopathological examination to differentiate histopathological variations of lipoma.

O fibrolipoma é uma neoplasia benigna, caracterizada pela presença de células adiposas maduras, separadas por largas bandas de tecido conjuntivo fibroso denso. Esta patologia é uma variante microscópica do lipoma e pode acometer qualquer parte do corpo, no entanto, sua ocorrência em cavidade oral é infrequente. Em geral, é uma lesão de superfície lisa, base séssil ou pediculada, assintomática, de crescimento lento, coloração amarelada ou rósea quando mais profunda, mole a palpação, ocorrendo principalmente na mucosa jugal. Assim, o objetivo deste trabalho é descrever as principais características clínicas, histopatológicas e tratamento de um caso clínico de fibrolipoma. Paciente do sexo feminino, 67 anos, leucoderma, apresentava um nódulo pediculado de cor normocrômica, assintomático, firme a palpação, consistência fibrosa e superfície lisa, com tempo de evoluçã de aproximadamente dois anos, localizado em mucosa jugal esquerda. As hipóteses de diagnóstico foram de lipoma, fibroma, fenômeno de extravasamento de muco e fibroma de células gigantes. A paciente foi submetida a biópsia excisional e o exame histopatológico revelou o diagnóstico definitivo de fibrolipoma. O paciente encontra-se em proservação, sem sinal de recidiva. Conclui-se que, apesar de o fibrolipoma ser uma lesão benigna, o seu crescimento pode alcançar grandes dimensões, reforçando a necessidade de excisão cirúrgica. Deve também ressaltar a importância do exame histopatológico para diferenciar as variações histopalógicas

How pathological criteria can impact prognosis of tongue and floor of the mouth squamous cell carcinoma.

other: Pathological parameters have been indicated as tumor prognostic factors in oral carcinoma. OBJECTIVE: The objective of this study was to investigate the impact of pathological parameters on prognosis of patients affected only by tongue and/or floor of the mouth squamous cell carcinoma (SCC). METHODOLOGY: In total, 380 patients treated in the Brazilian National Cancer Institute (INCA) from 1999 to 2006 were included. These patients underwent radical resection followed by neck dissection. The clinical and pathological characteristics were recorded. The Kaplan-Meier method and Cox proportional hazards model were used in survival analysis. Overall survival (OS), cancer-specific survival (CSS) and disease-free interval (DFI) were estimated. Cox residuals were evaluated using the R software version 3.5.2. Worst OS, CSS and DFI were observed in patients with tumors in advanced pathological stages (p<0.001), with the presence of perineural invasion (p<0.001) and vascular invasion (p=0.005). RESULTS: Advanced pathological stage and the presence of a poorly differentiated tumor were independent prognostic factors for OS and CSS. However, advanced pathological stage and perineural invasion were independent predictors of a shorter OS, DFI and CSS. CONCLUSION: Pathological stage and perineural invasion were the most significant pathological variables in survival analysis in tongue and/or floor of the mouth SCC.

How pathological criteria can impact prognosis of tongue and floor of the mouth squamous cell carcinoma

Abstract Pathological parameters have been indicated as tumor prognostic factors in oral carcinoma. Objective: The objective of this study was to investigate the impact of pathological parameters on prognosis of patients affected only by tongue and/or floor of the mouth squamous cell carcinoma (SCC). Methodology: In total, 380 patients treated in the Brazilian National Cancer Institute (INCA) from 1999 to 2006 were included. These patients underwent radical resection followed by neck dissection. The clinical and pathological characteristics were recorded. The Kaplan-Meier method and Cox proportional hazards model were used in survival analysis. Overall survival (OS), cancer-specific survival (CSS) and disease-free interval (DFI) were estimated. Cox residuals were evaluated using the R software version 3.5.2. Worst OS, CSS and DFI were observed in patients with tumors in advanced pathological stages (p<0.001), with the presence of perineural invasion (p<0.001) and vascular invasion (p=0.005). Results: Advanced pathological stage and the presence of a poorly differentiated tumor were independent prognostic factors for OS and CSS. However, advanced pathological stage and perineural invasion were independent predictors of a shorter OS, DFI and CSS. Conclusion: Pathological stage and perineural invasion were the most significant pathological variables in survival analysis in tongue and/or floor of the mouth SCC.

Lower lip squamous cell carcinoma in patients with photosensitive disorders: Analysis of cases treated at the Brazilian National Cancer Institute (INCA) from 1999 to 2012

Background: Lower lip squamous cell carcinoma (LLSCC) is a common malignancy of the head and neck, being mainly a consequence of a chronic exposure to ultraviolet (UV) light solar radiation. Here, we evaluated the clinicopathological profile of patients with photosensitive disorders (xeroderma pigmentosum, lupus erythematosus and albinism) that developed LLSCC. Material and Methods: Data from patients who had a diagnosed LLSCC with a prior xeroderma pigmentosum, lupus erythematosus or albinism diagnosis that were treated at INCA from 1999 to 2012 were collected from patients' medical records (n=16). The control group was composed of 68 patients with LLSCC without a medical history of photosensitivity. The clinicopathological data of this study population were collected and the association between these variables was analyzed by Fisher's exact test. Survival curves were constructed using the Kaplan-Meier method and compared by log-rank test. All statistical analyses were performed using SPSS statistics package. Results: The mean age of patients in the photosensitive and non-photosensitive groups was 42 years and 67 years, respectively (p<0.0001). A previous history of malignant diseases was more common in the photosensitive group (p=0.001). In both groups, most tumors showed a pathological stage I/II disease. Overall and cancer-specific survival were not statistically different. However, disease-free interval showed a significant difference (p=0.01) between the photosensitive and non-photosensitive patients. Conclusions: Photosensitive patients presented LLSCC at earlier age but it usually was not the primary tumor in these patients. Furthermore, a more aggressive pathological behavior was not seen when compared with tumors from non-photosensitive patients. The disease-free interval was lower in photosensitive patients, as expected (AU)

No disponible