Oral health of an indigenous population in northeastern Brazil: a cross-sectional Study of the Fulni-ô ethnic group

ABSTRACT BACKGROUND: There is a lack of studies evaluating the oral health of traditional indigenous communities in Brazil. OBJECTIVES: Thus, the objective of this study was to describe the oral health characteristics of the indigenous Fulni-ô ethnic group in Northeast Brazil. DESIGN AND SETTING: A cross-sectional observational investigation was conducted within the Project on Atherosclerosis among Indigenous Populations. METHODS: This study included participants of both sexes from the Fulni-ô ethnic group. The participants included in this investigation underwent a comprehensive oral health evaluation by a registered and experienced dentist to assess oral health and identify potentially malignant oral lesions. Participants with suspicious lesions were referred for biopsy. Shapiro-Wilk, Mann-Whitney, and Student's t-tests were used, and measures of central tendency and dispersion were described. Statistical significance was 5%. RESULTS: A total of 104 individuals were included in this study. The prevalence of the use of tobacco derivatives was 94.0%, with similarities between sexes. The prevalence of oral changes in this study population was 84.4%. Fifty-one individuals who underwent oral reassessment were referred for oral lesion biopsy. CONCLUSIONS: This study demonstrated a high prevalence of oral alterations in the Fulni-ô population. Histopathological analyses indicated the presence of mild oral epithelial dysplasia in five cases.

Elastin remodeling: Does it play a role in priming the malignant phenotype of oral mucosa?

Background: The extracellular matrix (ECM) is a dynamic tissue that provides nutrition and support to overlying epithelium. During tumorigenesis, the tumor microenvironment (TME) dysregulates the ECM. This is reflected by morphological changes seen in collagen and elastic fibers and is thought to facilitate metastasis. Aim: To study the degradation of elastic fibers in different grades of oral squamous cell carcinoma (OSCC) and in oral epithelial dysplasia (OED) using histochemistry and to correlate it to the TNM stage of OSCC. Materials and Methods: Tumor cores from 38 cases of OSCC (well-differentiated[15], moderately differentiated[14], and poorly differentiated[9]) and 15 incisional biopsies of OED were analyzed. Hematoxylin-eosin and Verhoeff's–Van Gieson (VVG) stains were used. The stained sections were assessed for morphological changes in elastic fibers. Statistical Analysis: Data were analyzed using Statistical Package for Social Sciences (SPSS) version 22 software. Fisher's exact, Kruskal–Wallis, one-way ANOVA, and Turkey post hoc tests were used to establish significance (P ? 0.05). Spearman's correlation test was used to correlate elastin fiber degradation with TNM stage of OSCC. Results: All grades of OSCC showed absence of elastic fibers around the tumor islands. Elastic fiber degradation (fragmented and clumped type fibers) increased proportionately with the grade and TNM stage of OSCC. In OED, A significant reduction in the amount of elastic fibers with increasing grade was noted. Conclusion: A positive correlation was noted between elastin degradation and grade and stage of OSCC. Therefore, it may be implicated in tumor progression of OSCC.

Analysis of 17 cases of Vaterian system adenomyomatous hyperplasia / 中华肝胆外科杂志

Objective:To study the features of adenomyomatous hyperplasia (AH) of the Vaterian system (common bile duct and ampulla of Vater) to help in the diagnosis and management of this disease.Methods:A retrospective analysis on the data of 17 patients who had a postoperative pathological diagnosis of AH of the Vaterian system treated from January 2005 to December 2021 at the First Medical Center of the PLA General Hospital was carried out with 12 males and 5 females, aged (58.4±11.3) years. The clinical presentations, treatment and postoperative pathology of these patients were analyzed. Patients with dysplasia of the tubular mucosal epithelium in the non-cancerous area around the AH under microscopy were included in the AH with dysplasia group ( n=8), and those without dysplasia were included in the control group ( n=9). The clinical characteristics of the two groups were compared. Results:The main clinical symptoms were abdominal pain in 8 patients, jaundice in 7 patients and fever in 2 patients. Preoperative imaging showed 10 cases of occupying lesions and 6 cases of abnormally dilated intrahepatic and extrahepatic bile ducts without obvious lesions or stones or biliary tract injury stenosis. Sixteen patients underwent radical pancreaticoduodenectomy, and 1 patient underwent extrahepatic biliary resection combined with choledochojejunostomy for bile duct obstruction due to biliary stones, 3 patients had combined malignant tumors, 1 patient had a carcinoma of AH origin at the ampulla of Vater, and the other 2 patients had neoplastic lesions in the mucosal epithelium adjacent to the AH (cholangiocarcinoma and ampullary carcinoma, respectively). There were no significant differences in age, gender, bile duct stones, cholangitis, combined carcinoma and liver function indexes between the two groups of patients with AH of the Vaterian system (all P>0.05). Conclusion:Adenomyomatous hyperplasia of the Vaterian system was difficult to distinguish preoperatively from malignant tumors basing on its clinical presentations or imaging findings. Such patients are recommended to be treated surgically.

Immunohistochemical evaluation of E-cadherin in oral epithelial dysplasia and squamous cell carcinoma

Aim: To evaluate the expression of E-cadherin (E-cad) in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). Material and Method: Immunohistochemistry was used to detect E-cad expression in 20 cases each of normal oral mucosa, oral epithelial dysplasia and squamous cell carcinoma. Statistical Analysis Used: Inferential statistical methods for statistical analysis used were Chi-square test for comparison of the frequency between different severity of dysplasia and OSCC. Results: Upon assessing the expression of E-cad in OED and OSCC, increase in E-cad immunoreactivity was seen in early lesions. However, the expression of E-cad decreased significantly as the grade of dysplasia increased. Conclusion: We observed a significant decrease in E-cad expression from dysplasia to poorly differentiated squamous cell carcinoma suggesting that loss of expression of E-cad is closely related to carcinoma.

Epidermal Growth Factor Receptor (EGFR) is Overexpressed in Both Dysplasia and Neoplastic Oral Diseases

Introduction: The Epidermal Growth Factor Receptor (EGFR) is a transmembrane cytoplasmic protein; studies indicate that it contributes to the development and progression of potentially malignant lesions to oral squamous cell carcinoma (OSCC). In the present study we determine and characterize the expression of EGFR in samples of oral epithelial dysplasia (OED) and OSCC. Materials and Methods: 54 samples with histopathological diagnosis of OED were selected, 19 of low grade dysplasia (LGD) and 35 of high grade dysplasia (HGD) and a tissue matrix was with 60 samples of OSCC and 9 of normal oral mucosa were used. EGFR detection was performed by immunohistochemical technique. In the photomicrographs, protein expression was deter- mined. Chi square test and Fisher test were used for statistical analysis (P <0.05). Results: 54% of OED and 60% of OSCC showed a significant pattern of high EGFR expression when compared with normal oral mucosa. Discussion: We found a tendency in LGD, HGD and OSCC to over expression of EGFR. Conclusion: There is over expression of EGFR in OED and OSCC, so it could be considered as an early marker of these patholo- gies

Displasia epitelial corneal / Corneal epithelial dysplasia

Las neoplasias intraepiteliales córneo-conjuntival son lesiones premalignas, mal delimitadas, de crecimiento lento y escaso potencial de malignización. Solo el 9 por ciento progresa a carcinoma invasor de células escamosas. Posee varias formas de presentación y tiene múltiples dilataciones vasculares. La displasia epitelial corneal primaria es una forma poco frecuente de neoplasia intraepitelial córnea-epitelial. Se presenta un caso clínico confirmado por estudios anatomopatológicos. En el presente estudio se observó respuesta satisfactoria luego de un mes de tratamiento tópico con 5FU, sin efectos colaterales. El seguimiento durante tres años no ha mostrado signos de recidiva(AU)

Corneal-conjunctival intraepithelial neoplasms are premalignant, poorly demarcated, slow-growing lesions with low malignant potential. Only the 9 percent progresses to invasive squamous cell carcinoma. It appears in several forms and presents multiple vascular dilatations. Primary corneal epithelial dysplasia is a rare form of corneal-epithelial intraepithelial neoplasia. We present a clinical case, confirmed by anatomopathologic studies. In the present study we observed a satisfactory response after one month of topical treatment with 5FU, with no side effects. Follow-up for three years has shown no signs of recurrence(AU)

Parámetros histomorfométricos de la mucosa bucal en pacientes portadores de leucoplasia con displasia epitelial / Histomorphometric Parameters of the Buccal Mucosa in Patients with Leukoplakia and Epithelial Dysplasia

RESUMEN Fundamento la leucoplasia es la lesión potencialmente maligna más frecuente en las membranas mucosas de la boca y se puede presentar con diferentes grados de displasia epitelial. El estudio histológico de esta lesión unido a la medición de parámetros morfométricos y estereológicos, permite la mejor comprensión de procesos tanto fisiológicos como patológicos. Objetivo: caracterizar los parámetros histomorfométricos de la mucosa bucal en pacientes portadores de leucoplasia bucal según grado de displasia epitelial. Método: se realizó un estudio de serie de casos, con el objeto de determinar indicadores morfométricos, de lesiones leucoplásicas de la mucosa oral en biopsias de pacientes atendidos en los Servicios de Anatomía Patológica y Maxilofacial del Hospital General Universitario Dr. Gustavo Aldereguía Lima, de la provincia Cienfuegos. La muestra se obtuvo por muestreo intencionado, la cual quedó constituida por 30 láminas histológicas (biopsias), distribuidas en tres grupos de diez láminas por cada grado de displasia epitelial. La variable de estudio fue la caracterización morfométrica de la leucoplasia de la mucosa oral con displasia. Se aplicó estadística descriptiva e inferencial. Resultados: predominaron tres parámetros en la clasificación de la displasia: alteración de los clavos interpapilares, hiperplasia y pérdida de la polaridad de las células basales. Se constató presencia de ortoparaqueratosis, epitelios hiperplásicos e infiltrado inflamatorio del corion, en más de la mitad de los casos. Hubo significación estadística en las relaciones que se establecieron entre la altura o profundidad de las papilas y la densidad relativa de células según grado de displasia epitelial, al aplicar la estadística inferencial. Conclusiones: predominaron tres parámetros en la clasificación de la displasia. Se constató presencia de ortoparaqueratosis, epitelios hiperplásicos e infiltrado inflamatorio del corion, en más de la mitad de los casos.

ABSTRACT Background: leukoplakia is the most frequent potentially malignant lesion in the mucous membranes of the mouth and can present with different degrees of epithelial dysplasia. The histological study of this lesion, together with the measurement of morphometric and stereological parameters, allows a better understanding of both physiological and pathological processes. Objective: to characterize the histomorphometric parameters of the oral mucosa in patients with oral leukoplakia according to the degree of epithelial dysplasia. Method: a case series study was carried out in order to determine morphometric indicators of leukoplastic lesions of the oral mucosa in biopsies of patients treated at the Pathology and Maxillofacial Anatomy services of the Dr. Gustavo Aldereguía Lima General University Hospital, in Cienfuegos province. The sample was obtained by intentional sampling, which was made up of 30 histological slides (biopsies), distributed in three groups of ten slides for each degree of epithelial dysplasia. The study variable was the morphometric characterization of oral mucosal leukoplakia with dysplasia. Descriptive and inferential statistics were applied. Results: three parameters prevailed in the classification of dysplasia: alteration of the interpapillary nails, hyperplasia and loss of polarity of the basal cells. The presence of orthoparakeratosis, hyperplastic epithelia and inflammatory infiltrate of the chorion was confirmed in more than half of the cases. There was statistical significance in the relationships established between the height or depth of the papillae and the relative density of cells according to the degree of epithelial dysplasia, when applying inferential statistics. Conclusions: three parameters predominated in the classification of dysplasia. The presence of orthoparakeratosis, hyperplastic epithelia and inflammatory infiltrate of the chorion was confirmed in more than half of the cases.

Enteropatías congénitas y la implicación diagnóstica en la displasia intestinal o enteropatía en penacho

RESUMEN Introducción: la displasia epitelial intestinal o enteropatía en penacho, es una rara y grave enfermedad debido a mutaciones genéticas, categorizada como enteropatía congénita por defecto del transporte de los enterocitos y su polaridad. Objetivo: Examinar los conocimientos más recientes para la orientación diagnóstica de las enteropatías congénitas en el contexto clínico de las diarreas crónicas intratables del período posnatal y primeros meses de vida. Métodos: Análisis de publicaciones en español e inglés en PubMed, Scimago, ScIELO hasta abril 2021 relacionadas con esta temática. Se usaron los términos diarreas intratables, enteropatías congénitas, displasia epitelial intestinal, enteropatía en penacho y enfermedades para diagnóstico diferencial. Análisis e integración de la información: Se describieron criterios sobre diarreas intratables, enteropatías congénitas; su clasificación. Se revisaron rasgos de la displasia epitelial intestinal y sus manifestaciones de formas clínicas, histopatológicas y mutaciones genéticas, epidemiología, diagnóstico de certeza y diferencial por afecciones debido a defectos congénitos relacionados con el tránsito epitelial y polaridad; tratamiento, pronóstico y actualización sobre trascendencia de las enfermedades raras. Conclusiones: Se revisan los conocimientos más recientes relacionados con enfermedades raras por enteropatías congénitas y en particular sobre la displasia epitelial intestinal o enteropatía en penacho. Se describen sus manifestaciones clínicas, histopatológicas y genéticas. La epidemiología, el tratamiento y sus retos. Se enfatizó en criterios sobre la trascendencia diagnóstica de enfermedades raras relacionadas con enteropatías congénitas.

ABSTRACT Introduction: Intestinal epithelial dysplasia or plume enteropathy is a rare and serious disease due to genetic mutations, categorized as congenital enteropathy due to the defect of enterocyte transport and their polarity. Objective: Examine the most recent knowledge on the diagnostic orientation of congenital enteropathies in the clinical context of intractable chronic diarrhea of the postnatal period and first months of life. Methods: Analysis of publications in Spanish and English in PubMed, Scimago, ScIELO until April 2021 related to this topic. The terms intractable diarrhea, congenital enteropathies, intestinal epithelial dysplasia, plume enteropathy and diseases were used for differential diagnosis. Analysis and integration of information: Criteria on intractable diarrhea, and congenital enteropathies were described; and their classification. Features of intestinal epithelial dysplasia and its manifestations of clinical, histopathological forms and genetic mutations, epidemiology, diagnosis of certainty and differential for conditions due to congenital defects related to epithelial transit and polarity were reviewed; treatment, prognosis and update on the importance of rare diseases. Conclusions: The most recent knowledge related to rare diseases due to congenital enteropathies and in particular about intestinal epithelial dysplasia or plume enteropathy is reviewed. Its clinical, histopathological and genetic manifestations are described, epidemiology, treatment and its challenges. Emphasis was placed on criteria on the diagnostic significance of rare diseases related to congenital enteropathies.

Identificación y evaluación de lesiones gástricas premalignas asociadas a la infección por Helicobacter pylori / Identification and evaluation of premalignant gastric lesions associated with Helicobacter pylori infection

Introducción: La infección por Helicobacter pylori es la causa principal de enfermedades gastroduodenales (gastritis crónica, úlceras pépticas y cáncer gástrico). En Guatemala existen pocos estudios sobre la prevalencia de H. pylori y su relación con enfermedades gastrointestinales, particularmente con cáncer. Objetivos: Identificar la presencia de lesiones premalignas (atrofia gástrica, metaplasia intestinal y displasia) y su relación con la infección por H. pylori en pacientes de consulta externa en unidades de gastroenterología de dos hospitales nacionales de la ciudad de Guatemala. Métodos: El diagnóstico histopatológico y bacteriológico se realizó por medio de las tinciones de H & E y Giemsa, cultivo e identificación bioquímica, detección de anticuerpos específicos mediante la prueba ELISA, diagnóstico molecular por la amplificación del gen glmM y genotipificación por PCR para identificar los genes VacA y CagA. Se analizaron datos clínico-epidemiológicos de los pacientes, la prevalencia de la infección por H. pylori y la genotipificación de la bacteria. Resultados: En 293 de los pacientes estudiados (83 por ciento) se encontró algún tipo de lesión premaligna; las más frecuentes fueron la atrofia gástrica (70 por ciento), metaplasia intestinal (11 por ciento) y displasia gástrica (2 por ciento). El 17 por ciento de los pacientes no presentó lesiones premalignas. Se halló una prevalencia de infección por H. pylori del 58 por ciento, y el gen cagA se detectó en 118 (57 por ciento) de los pacientes infectados. Conclusiones: La mayoría de los pacientes presentó atrofia gástrica (70 por ciento) y el 43,5 por ciento estaba infectado por H. pylori, principalmente con cepas CagA positivo. Este hecho confirma la importancia del estudio de H. pylori y su relación con cáncer gástrico(AU)

Introduction: Helicobacter pylori infection is the main cause of gastroduodenal diseases (chronic gastritis, peptic ulcer and gastric cancer). In Guatemala few studies have been carried out on the prevalence of H. pylori and its relationship with gastrointestinal diseases, particularly with cancer. Objective: To identify the presence of premalignant lesions (gastric atrophy, intestinal metaplasia and dysplasia) and their relationship with H. pylori infection in outpatients in gastroenterology units in two national hospitals in Guatemala City. Methods: Histopathological and bacteriological diagnostic testings were performed by H & E and Giemsa stain, culture and biochemical identification, detection of specific antibodies by ELISA, molecular diagnosis by glmM gene amplification, and genotypification by PCR to identify vacA and cagA genes. Clinical and epidemiological data from patients, prevalence of H. pylori infection, and bacterium genotypification were analyzed. Results: Among the studied patients, 293 (83 percent) presented some type of premalignant lesion. The most prevalent were gastric atrophy (70 percent), intestinal metaplasia (11 percent), and gastric dysplasia (2 percent). Seventeen percent of the patients did not have any premalignant lesions. The prevalence of H. pylori infection was 58 percent, and cagA gene was identified in 118 (57 percent) of the infected patients. Conclusions: The majority of the patients presented gastric atrophy (70 percent), and 43.5 percent were infected by H. pylori, mainly with positive cagA strains. This finding confirms the importance of studying H. pylori and its relationship with gastric cancer(AU)

Differential expression profile of circRNAs in oral leukoplakia / 口腔疾病防治

Objective@#To investigate the differences and clinical significance of circRNA expression profiles in oral leukoplakia (OLK) tissues and normal oral mucosal (NOM) tissues.@*Methods@# High-throughput sequencing was used to detect differentially expressed circRNAs in 6 pairs of OLK and NOM tissues, and qRT-PCR was used to verify the expression of 10 circRNAs screened in 6 pairs of OLK and NOM tissues. The ring formation of circRNA was verified by RNase R digestion and Sanger sequencing, and the target circHLA-C was further verified by qRT-PCR in 20 pairs of OLK and NOM tissues. CircHLA-C was visualized using the UCSC genome browser (genome.ucsc.edu). The function of differentially expressed circRNAs was analyzed by GO and KEGG enrichment analyses. TargetScan and miRanda predicted the downstream miRNAs and mRNAs of the target circRNAs, and a ceRNA network related to the identified circRNAs was constructed in Cytoscape.@* Results@#Sequencing analysis showed that 366 circRNAs were significantly differentially expressed in OLK tissues, including 65 upregulated and 301 downregulated circRNAs. After qRT-PCR verification, 7 of the 10 screened circRNAs were expressed consistent with the sequencing results. The upregulated circHLA-C was confirmed to be a real circRNA with back-splice junction sites by RNase R digestion and Sanger sequencing. Correlation analysis showed a positive correlation between circHLA-C and the degree of OLK dysplasia. ROC curve analysis suggested that circHLA-C had potential value in diagnosing OLK with high accuracy and specificity.@*Conclusion@#CircRNA was significantly abnormally expressed in OLK tissues, and the upregulation of circHLA-C may be related to the degree of OLK dysplasia, providing guiding value for the diagnosis of OLK in the future.

Observer variability in the grading of oral epithelial dysplasia

Background: Various grading systems have been suggested in the literature by different authors to determine the severity of dysplastic features. Histopathological grading is subjective with low reproductivity and lacks sensitivity. Aim: To determine the inter observer and intra observer variability in diagnosing oral epithelial dysplasia using different grading systems. Materials and methods: Three oral pathologists from the Department the Oral pathology, GDC Srinagar observed the same 30 consecutive sections of oral epithelial dysplasia. Each reviewing pathologist asked to grade each case on the basis of WHO (2005) and binary grading system (2006) at different time intervals and was repeated twice. Results: The inter observer variability ranged from poor to slight in WHO system and slight to fair in binary system whereas the intra observer variability ranged from slight to fair in WHO system and fair in the binary system. Conclusion: Grading of oral epithelial dysplasia is subjective and has been shown not to be highly reproducible. The binary grading system verified to have better inter observer and intra observer agreement in the present study than the WHO grading system.

Queilitis actínica: Reporte de tres casos y revisión de literatura / Actinic Cheilitis: Report of Three Cases and Review of Literature

RESUMEN La queilitis actínica (QA) es un desorden potencialmente maligno del labio inducido por la exposición crónica a la luz ultravioleta, que afecta principalmente al bermellón del labio inferior de personas adultas y de piel clara. Si no es tratada en forma oportuna puede transformarse en un carcinoma de células escamosas del labio. Histológicamente la QA presenta una serie de alteraciones a nivel epitelial que van desde hiperplasia a displasia; en el tejido conectivo se presentan distintos grados de elastosis actínica acompañada por infiltrado inflamatorio. El objetivo de este trabajo es presentar tres casos de pacientes con QA y analizar sus características clínicas e histopatológicas.

ABSTRACT Actinic cheilitis (AC) is a potentially malignant lip disorder induced by chronic exposure to ultraviolet light, which mainly affects the vermilion of the lower lip of adults and fair skin. If it is not treated in a timely manner it can become a squamous cell carcinoma of the lip. Histologically, AC presents a series of alterations at the epithelial level ranging from hyperplasia to dysplasia; Connective tissue presents different degrees of actinic elastosis accompanied by inflammatory infiltrate. The objective of this work is to present three cases of patients with AC and analyze their clinical and histopathological characteristics.

Extremely Well-Differentiated Papillary Thyroid Carcinoma Resembling Adenomatous Hyperplasia Can Metastasize to the Skull: A Case Report

We describe herein histologic, immunohistochemical, and molecular findings and clinical manifestations of a rare case of an extremely well differentiated papillary thyroid carcinoma (EWD-PTC). Similarly, it is also difficult to diagnose follicular variant papillary thyroid carcinoma (FVPTC), whose diagnosis is still met with controversy. A recently reported entity of well-differentiated tumor of uncertain malignant potential (WDT-UMP) is added to the diagnostic spectrum harboring EWD-PTC and FVPTC. We report this case, because EWD-PTC is different from FVPTC in its papillary architecture, and also from WDT-UMP in its recurrence and metastatic pattern. These morphologically deceptive entities harbored diagnostic difficulties in the past because the diagnosis depended solely on histology. However, they are now diagnosed with more certainty by virtue of immunohistochemical and molecular studies. We experienced a case of EWD-PTC, which had been diagnosed as adenomatous hyperplasia 20 years ago and manifested recurrence with lymph node (LN) metastasis 7 years later. After another 7 years of follow-up, a new thyroid lesion had developed, diagnosed as FVPTC, with LN metastasis of EWD-PTC. One year later, the patient developed metastatic FVPTC in the skull. Immunohistochemically, the EWD-PTC was focally positive for CK19, negative for galectin-3, and focally negative for CD56. Molecular studies revealed BRAF-positivity and K-RAS negativity. The FVPTC in the left thyroid showed both BRAF and K-RAS negativity. In conclusion, EWD-PTC and FVPTC share similar histologic features, but they are different tumors with different molecular biologic and clinical manifestations. A large cohort of EWD-PTC should be included in further study.

Apoptosis in oral epithelial dysplastic lesions and oral squamous cell carcinoma: A prognostic marker.

Background: Apoptotic index (AI) using light microscopy as an indirect measure to assess the significance of apoptosis as a proliferative marker in dysplastic lesions and malignant epithelial lesions of the oral cavity. Aims: (1) To quantify the apoptotic bodies/cells in oral epithelial dysplastic (OED) lesions and oral squamous cell carcinoma (OSCC). (2) To measure AI in OED and OSCC. (3) To compare AI in OED and OSCC. Settings and Design: The proposed laboratory‑based retrospective study involved the use of hematoxylin and eosin (H and E)‑stained slides of previously diagnosed OED lesions and OSCC from institutional archives. Materials and Methods: This study constituted 50 cases, each of H and E‑stained slides of previously diagnosed cases of OED and OSCC. AI was calculated as the number of apoptotic bodies/cells expressed as a percentage of the total number of nonapoptotic tumor/dysplastic cells counted in each case. Statistical Analysis Used: Nonparametric tests such as Kruskal–Wallis test and Mann–Whitney test were used. Results: There was a statistically significant increase in AI from OED to OSCC (P = 0.000). Conclusions: Further studies need to be undertaken to detect and understand the apoptotic mechanisms in the progression from OED to OSCC.

p53 and p16 in oral epithelial dysplasia and oral squamous cell carcinoma: A study of 208 cases.

Background: The use of p16 and p53 as biomarkers of malignant transformation of oral epithelial dysplasia (OED) and biological behavior of oral squamous cell carcinoma (OSCC) is controversial. Aim: To determine the immunoexpression of p16 and p53 in OED and OSCC and to establish their possible relation to histopathological grading of OED/OSCC. Materials and Methods: Ninety‑six OEDs (40 mild, 36 moderate, and 20 severe dysplasia); and 112 OSCCs (64 well‑differentiated, 38 moderately differentiated, and 10 poorly differentiated) coming from archives of four centers of oral pathology were included. Histological slides from all cases were processed with immunohistochemical technique using anti‑p53 and anti‑p16 antibodies. The intensity of the immunoreactivity were classified using the ImageLab®MCM systemas follows: <60 mild, >60–<90 moderate, and >90 strong. Forstatistical purposesa χ2 test (P < 0.05) was performed. Results: Severe dysplasia show highest relative frequency of p16‑positive (35.5%), whereas p53 is associated with mild dysplasia (P = 0.04). Moderately differentiated OSCC had larger relative frequency of p16‑positive and p53‑positive cases (47.3% both circumstances) (P > 0.05). Statistical association of p16‑positive and p53‑positive cells to basal stratum of OED (P = 0.0008; P = 0.0000, respectively) and p16‑positive cells and p53‑positive cells to perivascular zone of OSCC (P = 0.001; P = 0.0000, respectively) was found. Conclusions: p16 and p53 could be not specific enough to identify patients suffering OED with high risk to malignancy; however, the evaluation of the presence of p16 and p53 in the tumoral invasive front of OSCC could contribute to establish the tumor progression.

Oral lichen planus: clinical profile and determination of oral epithelial dysplasia / Liquen plano oral: perfil clínico y determinación de la displasia epitelial oral

Oral lichen planus (OLP) is the most common noninfectious oral disease and is considered a potentially malignant disorders (OPMDs). The etiology and pathogenesis of OLP are not completely understood and the malignant transformation remains under discussion. The aim was to asses the cytological and histological features of OLP, and establish relationship between clinical and microscopic profiles. A total of 10 patients diagnosed with OLP were investigated. Slides were prepared and stained with Hematoxylin­Eosin to identify 8 histological features and 8 cytological alterations. Finally, oral epithelial dysplasia degree was determined. Hyperplasia and loss of polarity of basal cells were detected in 90 % of cases. Anisonucleosis, nuclear pleomorphism and hyperchromasia affected 100 % of the sample. Six cases were classified as mild-grade OED, with no cases of severe-grade. Microscopic alterations were higher in women (P <0.0001) and moderate-grade OED was diagnosed only in this group (P <0.0014). The findings demonstrated that microscopic and clinical data association should be analyzed to a better understand of disease behavior. OED was absence only in one case, so the periodic follow-up of patients diagnosed with OLP is mandatory to avoid the malignant transformation.

El liquen plano oral (LPO) es la enfermedad no infecciosa más común y se considera un trastorno potencialmente maligno. La etiología y la patogénesis del LPO no se conoce y la transformación maligna sigue siendo objeto de debate. El objetivo de este estudio fue evaluar las características citológicas e histológicas del LPO y establecer la relación entre los perfiles clínicos y microscópicos. Un total de 10 pacientes diagnosticados con LPO fueron investigados. Secciones histológicas se prepararon y tiñeron con hematoxilina-eosina para identificar 8 características histológicas y 8 alteraciones citológicas. Finalmente, se determinó el grado de displasia epitelial. La hiperplasia y la pérdida de la polaridad de las células basales se detectaron en el 90 % de los casos. Anisonucleosis, pleomorfismo nuclear e hipercromasia afectaron al 100 % de las muestras. Seis casos fueron clasificados como displasia epitelial oral (DEO) de grado leve y no se reportaron casos de grado severo. Las alteraciones microscópicas fueron mayores en las mujeres (p <0,0001) y DEO de grado moderado fue diagnosticado sólo en este grupo (p <0,0014). Los resultados demostraron que la asociación de datos microscópicos y clínicos deben ser analizados para una mejor comprensión del comportamiento de la enfermedad. La DEO estuvo ausente sólo en un caso, por lo que el seguimiento periódico de los pacientes diagnosticados con LPO es necesario para evitar la transformación maligna.

Avaliação da expressão de ß-catenina e ciclina D1 como biomarcadores preditivos para o câncer de lábio / Evaluation of ß-catenin and cyclin D1 expression as predictive biomarkers for lip cancer

Um dos objetivos da pesquisa científica, atualmente, é encontrar biomarcadores que possam auxiliar na definição da probabilidade de progressão das lesões orais displásicas, e ainda sejam capazes de identificar os principais agentes moleculares envolvidos na carcinogênese de um determinado tipo de tumor. Assim, o objetivo deste estudo foi investigar a expressão de ß-catenina, ciclina D1 e Ki-67 em 15 espécimes de epitélio oral normal, 45 queilites actínicas displásicas e em 30 carcinomas espinocelulares de lábio. Essa amostra foi constituída por pacientes tratados na Faculdade de Medicina de Botucatu (Brasil) e no Hospital Clínico San Cecílio de Granada (Espanha). O grau de displasia epitelial e de diferenciação tumoral foi classificado com base nos critérios definidos pela Organização Mundial da Saúde. A avaliação dos biomarcadores foi realizada por meio da técnica imunohistoquímica, dividindo a espessura do epitélio em quatro compartimentos (basal, suprabasal, terço médio e terço superior) para o grupo controle e para as queilites actínicas e em três compartimentos (basal, suprabasal e região interna) para o grupo dos carcinomas espinocelulares de lábio. Para a comparação da média de expressão de cada marcador, nas diferentes localizações do epitélio foi utilizado o teste estatístico de Kruskal-Wallis. Para a correlação da expressão dos três marcadores entre os grupos foi utilizada a correlação de Spearman, com nível de significância de 5%. Os resultados demonstraram uma perda discreta da expressão membranosa de ß-catenina na camada basal das queilites actínicas com displasia epitelial intensa (Cis) e nos carcinomas espinocelulares de lábio, assim como uma expressão citoplasmática e nuclear, discreta e diretamente proporcional à desorganização epitelial nas camadas basal e suprabasal das queilites actínicas e carcinomas espinocelulares de lábio. Notou-se também um aumento da expressão de ciclina D1 e Ki-67 na camada basal à medida que aumentava a desorganização epitelial. Houve uma associação estatisticamente significativa da expressão de ciclina D1 e Ki-67 na camada suprabasal do grupo controle (p=0,030) e das queilites actínicas (p=0,001) e ainda na região interna dos carcinomas espinocelulares de lábio (p=0,000). Não houve correlação significativa entre as expressões nucleares de ß-catenina e de ciclina D1. Nossos resultados reforçam que a ß-catenina, a ciclina D1 e o Ki-67, podem ser utilizados como biomarcadores preditivos para o câncer de lábio. Além disso, sugerem que a ß-catenina e a ciclina D1 participam da carcinogênese labial, em eventos independentes da via de sinalização/Wnt.(AU)

One of the goals of scientific research today is to find predictive biomarkers that can help define the probability of progression of dysplastic oral lesions, and are still able to identify key molecular agents involved in the carcinogenesis of a particular type of tumor. The objective of this study was to investigate ß-catenin, cyclin D1 and Ki-67 expression in 15 specimens of normal oral epithelium, 45 dysplastic actinic cheilitis and 30 squamous cell carcinoma of the lip. This sample consisted of patients treated at the Botucatu Medicine School (Brazil) and the Clinical Hospital San Cecilio of Granada (Spain). The degree of epithelial dysplasia and tumor differentiation was classified based on the criteria defined by the World Health Organization. The evaluation of biomarkers was performed by immunohistochemical technique, dividing the thickness of the epithelium into four compartments (basal, suprabasal, middle third and upper third) for the control group and actinic cheilitis and three compartments (basal, suprabasal and inner region) to the group of squamous cell carcinoma of the lip. For comparing the average expression of each marker in different locations of the epithelium we used the statistical test of Kruskal-Wallis. For the correlation of the three markers expression between the groups was used Spearman, with 5% significance level. The results showed a slight loss of membranous expression of ß-catenin in the basal layer of actinic cheilitis with severe epithelial dysplasia (Cis) and squamous cell carcinoma of the lip, and a cytoplasmic and nuclear expression, slight and directly proportional to the epithelial disorganization in layers basal and suprabasal of actinic cheilitis and squamous cell carcinoma of the lip. It was also noted an increase in expression of cyclin D1 and Ki-67 in the basal layer as increased epithelial disorganization. There was a statistically significant association of cyclin expression D1 and Ki-67 in the suprabasal layer of the control group (p=0.030) and actinic cheilitis (p=0.001) and also in the inner region of squamous cell carcinoma of the lip (p=0.000). There was no significant correlation between the nuclear expression of ß-catenin and cyclin D1. Our results emphasize that ß-catenin, cyclin D1 and Ki-67 can be used as predictive biomarkers for lip cancer. Moreover, they suggest that ß-catenin and cyclin D1 acts on the lip carcinogenesis, in independent events signaling pathway/Wnt.(AU)

Randomized double-blind clinical trial of Moluodan () for the treatment of chronic atrophic gastritis with dysplasia / 中国结合医学杂志

<p><b>OBJECTIVE</b>To assess the efficacy and safety of Moluodan () in treating dysplasia in chronic atrophic gastritis (CAG) patients.</p><p><b>METHODS</b>This was a multi-centered, double-blind, randomized controlled trial. The total of 196 subjects were assigned to receive either Moluodan or folic acid in a 2:1 ratio by blocked randomization. Mucosa marking targeting biopsy (MTB) was used to insure the accuracy and consistency between baseline and after 6-month treatment. Primary outcomes were histological score, response rate of pathological lesions and dysplasia disappearance rate. Secondary endpoints included gastroscopic findings, clinical symptom and patient reported outcome (PRO) instrument.</p><p><b>RESULTS</b>Dysplasia score decreased in Moluodan group (P =0.002), significance was found between groups (P =0.045). Dysplasia disappearance rates were 24.6% and 15.2% in Moluodan and folic acid groups respectively, no significant differences were found (P =0.127). The response rate of atrophy and intestinal metaplasia were 34.6% and 23.0% in Moluodan group, 24.3% and 13.6% in folic acid group. Moluodan could improve erythema (P =0.044), and bile reflux (P =0.059), no significance between groups. Moluodan was better than folic acid in improving epigastric pain, epigastric suffocation, belching and decreased appetite (P <0.05), with symptom disappearance rates of 37% to 83%.</p><p><b>CONCLUSIONS</b>Moluodan improved dysplasia score in histopathology, and erythema and bile reflux score in endoscopy, and superior to folic acid in improving epigastric pain, epigastric suffocation, belching and decreased appetite. [ChiCTR-TRC-00000169].</p>

Immunohistochemical expression of Bcl‑2 in oral epithelial dysplasia and oral squamous cell carcinoma.

BACKGROUND: The B cell lymphoma‑2 gene is a proto‑oncogene whose protein product inhibits apoptosis. Its role is associated with keeping cells alive, but not by stimulating them to proliferation, as other proto‑oncogenes do. Increased expression of protein product of Bcl‑2 gene appears in the early phase of carcinogenesis leading to apoptosis impairment and in consequence to the progression of neoplastic changes. OBJECTIVE: To evaluate and compare the expression of Bcl‑2 protein in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Sixty cases of formalin‑fixed paraffin‑embedded archival specimens comprising of 30 cases of leukoplakia with oral epithelial dysplasia and 30 cases of OSCC were taken for immunohistochemical analysis using monoclonal antibody against anti‑human Bcl‑2 oncoprotein. RESULTS: Immunostaining for Bcl‑2 protein was identified in basal and parabasal layers as granular cytoplasmic staining in oral epithelial dysplasia. In OSCC, Bcl‑2 immunoreactivity was most prominent in the peripheral cells of the infiltrating tumor islands which diminished toward the center in well‑differentiated and moderately differentiated OSCC, whereas stronger and more diffuse expression of Bcl‑2 oncoprotein was seen in poorly differentiated OSCC. Overall positivity of 26.7% (8/30) was observed in oral epithelial dysplasia and 30% (9/30) in OSCC in this study. INTERPRETATION AND CONCLUSION: Altered expression of Bcl‑2 oncoprotein may be an early molecular event which leads to prolonged cell survival, increased chances of accumulation of genetic alterations, and subsequent increase in malignant transformation potential.