Bioinformatic Analysis for Mucoepidermoid and Adenoid Cystic Carcinoma of Therapeutic Targets.

Salivary gland neoplasms are a heterogeneous neoplasm group, including mucoepidermoid carcinoma (MECa), adenoid cystic carcinoma (AdCC), and many others. OBJECTIVE: We aimed to identify new critical genes of MECa and AdCC using bioinformatics analysis. METHODS: Gene expression profile of GSE153283 was analyzed by the GEO2R online tool to use the DAVID software for their subsequent enrichment. Protein-protein interactions (PPI) were visualized using String. Cytoscape with MCODE plugin followed by Kaplan-Meier online for overall survival analysis were performed. RESULTS: 97 upregulated genes were identified for MECa and 86 for AdCC. PPI analysis revealed 22 genes for MECa and 63 for AdCC that were validated by Kaplan-Meier that showed FN1 and SPP1 for MECa, and EGF and ERBB2 for AdCC as more significant candidate genes for each neoplasm. CONCLUSION: With bioinformatics methods, we identify upregulated genes in MECa and AdCC. The resulting candidate genes as possible therapeutic targets were FN1, SPP1, EGF, and ERBB2, and all those genes had been tested as a target in other neoplasm kinds but not salivary gland neoplasm. The bioinformatic evidence is a solid strategy to select them for more extensive research with clinical impact.

Microarray and bioinformatic analysis of conventional ameloblastoma: an observational analysis

Abstract Ameloblastoma is a highly aggressive odontogenic tumor, and its pathogenesis is associated with many participating genes. Objective We aimed to identify and validate new critical genes of conventional ameloblastoma using microarray and bioinformatics analysis. Methodology Gene expression microarray and bioinformatic analysis were performed using CHIP H10KA and DAVID software for enrichment. Protein-protein interactions (PPI) were visualized using STRING-Cytoscape with MCODE plugin, followed by Kaplan-Meier and GEPIA analyses that were used for the candidate's postulation. RT-qPCR and IHC assays were performed to validate the bioinformatic approach. Results 376 upregulated genes were identified. PPI analysis revealed 14 genes that were validated by Kaplan-Meier and GEPIA resulting in PDGFA and IL2RA as candidate genes. The RT-qPCR analysis confirmed their intense expression. Immunohistochemistry analysis showed that PDGFA expression is parenchyma located. Conclusion With bioinformatics methods, we can identify upregulated genes in conventional ameloblastoma, and with RT-qPCR and immunoexpression analysis validate that PDGFA could be a more specific and localized therapeutic target.

Inmunoexpresión de p53 y su relación con el grado de severidad en displasia epitelial oral / Immunoexpression of p53 and its relationship with the degree of severity in oral epithelial dysplasia

Introducción: La displasia epitelial oral (DEO) es la presencia de alteraciones celulares y tisulares, lo que puede significar una etapa anterior al desarrollo del cáncer. Múltiples marcadores han sido considerados para estimar su potencial neoplásico y evolución a carcinoma, incluyendo a la molécula p53, se considera como participe de diversos fenómenos de la homeostasis celular. Objetivo: Determinar la relación entre la inmunoexpresión de p53 DO-7 y PAb 240 con el grado de severidad de la displasia epitelial oral. Material y métodos: Se analizaron nueve muestras de DEO (tres para cada grado de severidad). La inmunoexpresión de p53 tipo silvestre (DO-7) y forma mutada (PAb 240), fue determinada a través de ensayo de inmunohistoquímica por peroxidasa. Se obtuvieron la media y desviación estándar y se realizó la prueba χ2 (p < 0.05). Resultados: La edad media fue de 65.7 ± 11.4 años, la zona anatómica con mayor presencia de DEO es el borde lateral de la lengua. Ocho de nueve muestras fueron positivas para DO-7 y solo dos para PAb 240. Conclusiones: Nuestros resultados indican que, aunque la expresión de p53 DO-7 podría estar relacionada parcialmente con la patogénesis de la displasia epitelial, no todas las displasias presentaron la forma mutada de p53 (PAb 240). Lo cual coincide con el comportamiento biológico incierto de las displasias al poder permanecer sin cambios, involucionar o transformarse

Introduction: Oral epithelial dysplasia (OED) is the presence of cellular and tissue alterations, which may mean a stage prior to the development of cancer. Multiple markers have been considered to estimate its pathogenic potential and evolution to neoplasms, including the p53 molecule, considered as participating in various phenomena of cellular homeostasis. Objective: To determine the relationship between the immunoexpression of p53 DO-7 and PAb 240 with the degree of severity of oral epithelial dysplasia. Material and methods: Nine OED samples were analyzed (three for each degree of severity). The immunoexpression of wild-type p53 (DO-7) and mutated form (PAb 240) was determined through a peroxidase immunohistochemical assay. The mean and standard deviation were obtained, and χ2 test (p < 0.05) were performed. Results: The mean age was 65.7 ± 11.4 years, with a greater presence of OED in the anatomical area of the lateral side of the tongue. Eight out of nine samples were positive for DO-7 and only two for PAb 240. Conclusions: Our results indicate that, although the expression of p53 DO-7 could be partially related to the pathogenesis of epithelial dysplasia, not all dysplasias presented the mutated form of p53 (PAb 240), which coincides that not all dysplasias have a potential for malignant transformation and that could be related to other oncogenic mechanisms (AU)

Epstein-Barr virus-positive ulcer in the oral cavity.

Epstein-Barr virus-positive ulcer (EBV + U) is a recently reported B cell lymphoproliferative disorder in the oral cavity, oropharynx, gastrointestinal tract and skin, principally in immunosuppressed patients. A 53-year-old female patient with rheumatoid arthritis treated with methotrexate, presenting ulcers of unknown duration on the dorsum and the lateral left border of the tongue. Excisional biopsy, histopathological analysis and histochemical stains for syphilis (Warthin-Starry), mycotic diseases (Grocott silver methenamine), tuberculosis (Ziehl-Neelsen), immunohistochemistry tests for herpesvirus type 8 (CMV), EBV (LMP-1) and DNA extraction for polymerase chain reaction (PCR) assay to CMV, EBV and herpes simplex virus-1 were performed. Posterior to PCR assay, the final diagnosis was EBV + U in the oral cavity. Acyclovir® was prescribed, showing clinical improvement. A case of EBV + U with clinical characteristics similar to other lesions or conditions has been reported. Special assays are necessary for an accurate diagnosis and treatment.

Análisis de microdensidad vascular y factores de crecimiento en carcinoma oral de células escamosas / Analysis of vascular microdensity and growth factors in oral squamous cell carcinoma

Introducción: El carcinoma oral de células escamosas (COCE) es una neoplasia epitelial maligna que se presenta frecuentemente entre la quinta y sexta década de la vida. Su compleja patogénesis incluye el proceso de angiogénesis y la regulación del microambiente tumoral como mecanismos de progresión tumoral. Objetivo: Determinar la relación entre las variables clínicas e histológicas del COCE con la inmunoexpresión de VEGF, FGF-1, FGFR-1, TGFB-1, TGFBR-II y CD105. Material y métodos: Nueve casos de COCE; tres bien (BD), tres moderado (MD) y tres pobremente diferenciados (PD) obtenidos del Departamento de Patología y Medicina Bucal, División de Estudios de Postgrado e Investigación. Se aplicó la técnica de inmunohistoquímica por peroxidasa para identificar la expresión de VEGF, FGF-1, FGFR- 1, TGFB-1, TGFBR-II y CD105. El análisis de inmunoexpresión se realizó con el programa ImageJ. Se aplicó la prueba de Kruskal-Wallis y correlación de Spearman (p < 0.05). Resultados: La inmunoexpresión de VEGF fue mayor en los COCE PD, FGFR-1 fue positivo en los BD, mientras que FGF, TGFB-1 y TGFBR-II fueron negativos. El análisis de microdensidad vascular (MVD) indicó mayor número de vasos CD105 positivos en los carcinomas BD, seguidos de los PD y MD. Conclusión: Considerando los resultados obtenidos podemos concluir que la angiogénesis es un fenómeno constante independiente del grado de diferenciación que durante el proceso de transformación de una neoplasia requerirá la formación de vasos sanguíneos y que este proceso puede ser modulado por factores de crecimiento tales como los analizados en este trabajo (AU)

Introduction: Oral squamous cell carcinoma (OSCC) is a malignant epithelial neoplasm that frequently occurs between the fifth and sixth decade of life. Its complex pathogenesis includes the angiogenesis process and the regulation of the tumor microenvironment as mechanisms of tumor progression. Objective: To determine the relationship between the clinical and histological variables of OSCC with the immunoexpression of VEGF, FGF-1, FGFR-1, TGFB- 1, TGFBR-II and CD105. Material and methods: Nine cases of OSCC; three well (WD), three moderate (MD) and three poorly differentiated (PD) obtained from the Oral Medicine and Pathology Department, Division of Graduate Studies and Research. The peroxidase immunohistochemistry technique was performed to identify the expression of VEGF, FGF-1, FGFR-1, TGFB-1, TGFBR-II and CD105. The immunoexpression analysis was performed with the ImageJ software. The Kruskal-Wallis and Spearman correlation test were performed (p < 0.05). Results: VEGF immunoexpression was higher in PD OSCC, while FGFR-1 was predominantly positive in WD; FGF, TGFB-1 and TGFBR-II were negative. Vascular microdensity analysis (MVD) indicated a greater number of CD105 positive vessels in WD carcinomas, followed by PD and MD. Conclusion: Considering the results obtained, we can conclude that angiogenesis is a constant phenomenon independent of the degree of differentiation; that during the transformation process of a neoplasm it will require the formation of blood vessels and that this process can be modulated by growth factors such as those analyzed in this work (AU)

Terapia láser de baja frecuencia en el manejo del dolor en pacientes con osteonecrosis mandibular / Low level laser therapy in the management of pain in patients with osteonecrosis of the jaw

La terapia láser de baja frecuencia (TLBF) o fotobioestimulación es aquella que cuya luz provoca la regeneración y remodelación ósea, la restauración de la función neural, la disminución del dolor y la modulación del sistema inmune; esta terapia es un coadyuvante junto a la terapia conservadora y/o quirúrgica. Se considera un estándar de oro para el manejo del dolor en la osteonecrosis en aquellos pacientes que consumen o han consumido bifosfonatos como terapia para inhibir la resorción ósea. La Sociedad Americana de Investigación de Hueso y Minerales (SAIHM) definió la osteonecrosis mandibular como «un área de hueso expuesto en la región maxilofacial que no cicatriza dentro de las ocho semanas posteriores a la identificación, en un paciente que está recibiendo o ha estado expuesto a bifosfonatos y que no ha recibido radioterapia en la región craneofacial¼. En este reporte presentamos dos casos de pacientes con osteonecrosis mandibular relacionada a bifosfonatos tratados con TLBF. Se evaluó el dolor antes y después de la terapia con la escala visual análoga (EVA). Ambos casos tuvieron disminución del dolor al 100%. Se presentan los métodos de diagnóstico clínico y radiográfico, el tratamiento elegido y los resultados obtenidos (AU)

Low level laser therapy (LLLT) or photobiostimulation is one whose light causes bone regeneration and remodeling, restoration of neural function, reduction of pain, and modulation of the immune system; this therapy is an adjuvant together with conservative and / or surgical therapy. It is considered a gold standard for pain management in osteonecrosis in those patients who consume or have used bisphosphonates as antiresorptive therapy. The American Society for Bone and Mineral Research (ASBMR) defined osteonecrosis of the jaw as «an area of exposed bone in the maxillofacial region that does not heal within eight weeks after identification by a health care provider, in a patient who was receiving or had been exposed to a BP and who has not received radiation therapy to the craniofacial region¼. In this report we present two cases of patients with mandibular osteonecrosis related to bisphosphonates treated with LLLT. Pain before and after visual analogue scale (VAS) was evaluated. Both cases had pain reduction at 100%. The methods of clinical and radiographic diagnosis, the treatment chosen and the results obtained are presented (AU)

Prevalence and distribution of odontogenic cysts in a Mexican sample. A 753 cases study.

BACKGROUND: Odontogenic cysts (OC) are the most frequent lesions of the jaws and their constant epidemiological update is necessary and indispensable. Therefore the principal objective of this report was To determine prevalence and clinical-demographical characteristics of OC in a Mexican sample. MATERIAL AND METHODS: 753 cases of OC coming from the archive of a head and neck histopathological teaching service, from January 2000 to December 2013, were included. OC cases were re-assessed according 2005 WHO classification. Chi square test was used to establish possible associations (p<0.05IC95%). RESULTS: From 753 OC, 369 were female and 384 male; 52.9% of them were in their 2nd- 4th decade of life. The most common location (41%) was the mandibular posterior area. Radicular cysts were more frequent in maxillary anterior zone of females (p 0.0002) at their fourth decade of life. Dentigerous cysts were more frequent in the mandibular posterior zone of males (p 0.0000) in their second decade of life. Six cases of periodontal lateral cyst; 4 cases of paradental cysts; 4 eruption cysts and 4 cases of adult gingival cyst, as well were identified. CONCLUSIONS: Radicular cyst and dentigerous cyst are the most prevalent odontogenic cyst in this Mexican sample. Due to their etiology, dental pulpar necrosis and impacted teeth, radicular cyst and dentigerous cyst could be prevenible. Therefore, it is necessary to establish preventive strategies to diminish dental decay and programs of prophylactic extractions of impacted teeth, to in consequence decrease the prevalence of odontogenic cysts. Key words:Cyst, dentigerous cyst, mexican, odontogenic cyst, radicular cyst.

P53 and bcl-2 immunoexpression in patients with oral lichen planus and oral squamous cell carcinoma.

OBJECTIVE: The aim of this study was to determine by immunohistochemistry the presence and significance of p53 and bcl-2 proteins in oral lichen planus (OLP) and oral squamous cell carcinoma (OSCC). STUDY DESIGN: We used 21 cases diagnosed as OLP 16 diagnosed as OSCC and four normal gingival biopsies taken from healthy patients were used as controls. Slides were processed for immunohistochemistry using anti-p53 and anti-bcl-2 monoclonal antibodies. RESULTS: We found p53 immunoexpression in 71.4% OLP cases and 68.7% OSCC cases, with no immunoexpression in control cases. Bcl-2 was negative for all OLP and OSCC cases, and mild positivity was observed in normal tissue. We found significant correlation among p53 expression and OSCC malignancy. CONCLUSIONS: Our results suggest that TP53 system mainly promotes a hyperproliferative state by cell cycle arrest of the OLP epithelial cells for repairing damaged DNA nor apoptosis and that anti-apoptotic action of bcl-2 is not important in this disease.

Estandarización en la observación y clasificación de lesiones epiteliales premalignas y malignas / Standardization in the observation and classification of premalignant and malignant epithelial lesions

Los criterios histológicos para determinar el grado de displasia, la clasificación de Broders y el frente de invasión tumoral (FIT) son parámetros subjetivos no cuantificables que pueden indicar el grado de evolución de displasias y carcinomas. Un factor importante a considerar durante la valoración histológica, es la variabilidad del diagnóstico entre patólogos. El objetivo es estandarizar los criterios y determinar la variabilidad intra e inter observador en el diagnóstico de displasias y COCE. Se seleccionaron y estandarizaron los criterios morfológicos para el diagnóstico y se revisaron los casos seleccionados aleatoriamente por tres patólogos bucales (30 displasias y 30 carcinomas) del Laboratorio de Patología Clínica y Experimental de la DEPeI de la FO, UNAM. Cada patólogo analizó y registró los parámetros establecidos para displasia, COCE y FIT en 2 ocasiones. Se aplicó el test Kappa para valorar la concordancia intra e inter observador. El Observador 1 v/s el 2 obtuvo una concordancia para COCE de 0,75 y en displasias de 0,60 e intraobservador de 0,90. El observador 2 v/s el 3 presentó una concordancia para COCE de 0,75 y en displasias de 0,59 e intraobservador de 0,91. El Observador 3 Vs el 1 tuvo una concordancia para COCE de 0,77, y en displasias de 0,59 e intraobservador de 0,92. La concordancia intraobservador e interobservador en COCE fue de buena a excelente, pero en displasias fue aceptable confirmando que su evaluación presenta mayor grado de dificultad. Con una adecuada estandarización se puede obtener una buena concordancia entre patólogos.

In the histological criteria for determining the degree of dysplasia, the Broders classification and the front of tumor invasion (FTI) are unquantifiable subjective parameters that may indicate the degree of development of carcinomas. An important factor to consider during the histological evaluation is the variability in the diagnosis of pathologists. The objective to standardize criteria and determine the intra and inter-observer variability in the diagnosis of dysplasias and OSCC. We selected and standardized morphological criteria for the diagnosis, and the cases were reviewed randomly by three oral pathologists (30 dysplasias and 30 carcinomas) from the Laboratory of Clinical and Experimental Pathology of the FO DEPeI, UNAM. Each pathologist analyzed and recorded the parameters for dysplasia and OSCC FIT on two occasions. Kappa test was applied to assess intra and inter-observer agreement. Observer 1 v/s 2 match for OSCC was 0.75, 0.60 for dysplasias and intra observer 0.90. Observer 2 v/s 3 presented a concordance of 0.75 for OSCC, 0.59 for dysplasias and intra-observer 0.91. Observer 3 v/s observer 1 for OSCC was 0.77, 0.59 for dysplasias and intra-observer 0.92. Intra observer and inter-observer concordance in OSCC were good or excellent, but in dysplasia was acceptable, confirming that its assessment showed the greatest difficulty with proper standardization we can obtain a better consensus between pathologists.

[Hospital discharges for oral cancer in the Mexican Institute of Social Security, 1991-2000]. / Egresos hospitalarios por cáncer bucal en el IMSS (1991-2000).

A descriptive study based on the secondary analysis of the Unique System of Information database, Subsystem 13 of Hospital discharges to oral cancer of the Mexican Institute of Social Security (IMSS) during the decade from 1991 to 2000, it was considered all the registrations for oral cancer according to the International Classification of Diseases ICD-9. During that time, 8,800 hospital discharges were registered for oral cancer, out of which 64.6% (n = 5682) were men. The men: women ratio showed 1.8 men per admitted woman for oral cancer. The mortality gross rate for oral cancer was of 50.4 for each 100,000 hospital discharges with a significantly descendent trend. Hospital discharges rate by age group was specifically concentrated in population to 35 years-old or more, registering themselves the greater rates as of the 55 years-old. The hospital average stay was of 5.1 days. According to the topography of the oral cavity, we found that the tongue (25.1%), principal salivary glands (24.0%) and tonsil-oropharynx (14.2%) were the main places where this pathology presented. During the above decade, the oral cancer hospital discharges registered in the IMSS didn't show an increasing pattern.

Regiones de organizadores nucleolares en células de descamación de la mucosa bucal en fumadores crónicos / Nucleolar organizer regions in desquamative cells of the oral mucosa in chronic smokers

La citología exfoliativa es un método diagnóstico de ejecución rápida, simple y no invasiva utilizada en patología bucal. El objetivo fue cuantificar el número de regiones de organizadores nucleolares (NORs) teñidos con plata coloidal (AgNORs) como indicador de proliferación celular en células de descamación de la mucosa de pacientes fumadores crónicos. Los NORs se localizan dentro del núcleo en número de 1 o 2, nosotros encontramos que variaron en tamaño y número. El promedio fue de 3 a 7.5 por célula en la mucosa yugal y de 2.1 a 4.3 en la lengua, el promedio de AgNORs por núcleo en las células de la mucosa yugal fue estadisticamente mayor en comparación al promedio de ellos en las células de descamación de la lengua. El análisis de las relaciones de Pearson mostró un margen de error de .20 por ciento de acuerdo a los promedios del número de AgNORs por célula

Efecto del piroxicam sobre la microflora local en el complejo pulpoperiapical posterior a la exposición pulpar / Effect of piroxicam on local microflora on the pulp-periapical complex, after pulp exposure

El objetivo de este reporte fue determinar el efecto del piroxicam (antiinflamatorio no esteroide) sobre las bacterias en el complejo pulpoperiapical, cuando se administra para inhibir el desarrollo de lesiones periapicales experimentales. A 12 ratas cepa long Evans se les provocó exposición pulpar previo a la administración de piroxicam, administrando el medicamento cada 24 horas durante 15 días. Se encontró que el porcentaje de bacterias decrece de la cámara pulpar hacia el periápice observándolos escasos en la lesión periapical en ambos grupos, sin embargo se encuentran incrementados con respecto a porcentajes en el grupo al cual se le administró el piroxicam, lo que sugiere que si bien el piroxicam disminuye el desarrollo de lesiones periapicales, favorece el desarrollo de bacterias incrementando su número en el complejo pulpoperiapical

Detección de células cebadas y basófilos en lesiones periapicales experimentales tratadas con piroxicam / Detection of mast cells and basophils in experimental periapical lesions treated with piroxicam

En este estudio, se reportó la respuesta del tejido periapical ante la exposición prolongada del tejido pulpar y el efecto de la administración de un antiinflamatorio no esteroide (piroxicam), sobre dos tipos celulares involucrados en la respuesta inflamatoria e inmunológica local como son las células cebadas y los basófilos, utilizando ratas Long Evans a las cuales se les provocó exposición pulpar previo a la administración del piroxicam. Los hallazgos fueron: en el área de los abscesos en el grupo experimental, a los 8 días las células cebadas se encontraron en un porcentaje del 50.0 disminuyendo a 16.6 por ciento a los 15 días, mientras que en el grupo control a los 8 días se presentaron en 11.1 por ciento, aumentando a 22.2 por ciento a los 15 días en el total de los animales. Con respecto a los basófilos en la misma zona se observó en el grupo control a los 8 días un porcentaje de 61.1 disminuyendo a 33.3 por ciento a los 15 días, siendo lo contrario en el grupo experimental, donde de 16.6 por ciento aumentó a 33.3 por ciento en el transcurso del tratamiento; la degranulación fue raramente observada en ambos tipos celulares probablemente por efecto del antiinflamatorio en estudio