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Objective: Guided Bone Regeneration (GBR) is a dental surgical procedure that uses barrier membranes to prevent soft tissue invasion and conduct new bone growth. This study aimed to define a Prognosis Recovery score (PR score) to objectively classify post-surgery responders from non-responder patients who underwent GBR using Cone Beam Computed Tomography (CBCT). Methods: This prospective-observational-longitudinal-cohort study recruited 250 individuals who were assigned to: Conventional-Apical-Surgery (CAS, n = 39), Apical-Surgery using human fascia lata Membrane placement (ASM, n = 42), and Apical-Surgery using human fascia lata Membrane placement and lyophilized allograft Bone powder (ASMB, n = 39); and Apical-Surgery using collagen membrane Porcine origin and Bovine Bone-matrix (ASPBB, n = 130), an independent external validation cohort. Surgery was performed, and evolution was monitored by CBCTs at 0, 6-, 12-, 18-, and 24 months post-surgery. Results: Normalized lesion volumes were calculated, and non-linear time evolution morphology curves were characterized. The three-time evolution bone growth patterns were: a linear tendency (PR0), "S'' shaped log-logistic (PR1), and "C" cellular growth (PR2). The treatment success rates were PR2-46 %, PR2-88 %, and PR2-95 %/PR1-5% for CAS, ASM, and ASMB groups. The xenograft ASPBB counterpart achieved PR2-92 % and PR1-8%. The score PR had a sensitivity, specificity, and accuracy of 100 %. Conclusions: Patients' treatment success can be quantitatively, objectively, and precisely predicted with the Prognosis Recovery score (using only two CBCTs), according to their biological response to allograft or xenograft materials (time-evolution bone growth curves), reducing cost and radiation exposure. Clinical significance: Through digital imaging and bioinformatic analysis of bone regeneration observed in CBCTs, we defined a Prognosis Recovery (PR) score using only two CBCT volume assessments (0 and 6 months). The PR score allowed us to define three time-evolution curves depending on the biomaterials used and to classify patients in a quantitative, objective, and accurate way.
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The Human Papillomavirus (HPV) test is a crucial technology for cervical cancer prevention because it enables programs to identify women with high-risk HPV infection who are at risk of developing cervical cancer. Current U.S. Preventive Services Task Force recommendations include cervical cancer screening every three years with cervical cytology alone or every five years with either high-risk HPV testing alone or high-risk HPV testing combined with cytology (co-testing). In Argentina, 7,548 new cervical cancer cases are diagnosed each year with 3,932 deaths attributed to this cause. Our study aims to show the clinical implementation of a cervical cancer screening program by concurrent HPV testing and cervical cytology (co-testing); and to evaluate the possible cervical cancer screening scenarios for Latin America, focusing on their performance and average cost. A cervical cancer screening five year program via co-testing algorithm (Hybrid-2-Capture/cytology) was performed on women aged 30-65 years old at a university hospital. Statistical analysis included a multinomial logistic regression, and two cancer screening classification alternatives were tested (cytology-reflex and HPV-reflex). A total of 2,273 women were included, 91.11% of the participants were double-negative, 2.55% double-positive, 5.90% positive-Hybrid-2-Capture-/negative-cytology, and 0.44% negative-Hybrid-2-Capture/positive-cytology. A thorough follow-up was performed in the positive-Hybrid-2-Capture group. Despite our efforts, 21 (10.93%) were lost, mainly because of changes on their health insurance coverage which excluded them from our screening algorithm. Of the 171 women with positive-Hybrid-2-Capture results and follow-up, 68 (39.77%) cleared the virus infection, 64 (37.43%) showed viral persistence, and 39 (22.81%) were adequately treated after detection via colposcopy/biopsy of histological HSIL (High-Grade Squamous Intraepithelial Lesion). The prevalence of high-risk HPV in this population was 192 women (8.45%), with HSIL histology detection rates of 17 per 1,000 screened women. A multinomial logistic regression analysis was performed over the women with positive-Hybrid-2-Capture considering the follow up (clearance, persistence and HSIL) as dependent variable, and the cytology test results (positive- or negative-cytology and Atypical Squamous Cells of Undetermined Significance, ASC-US) as independent variable. The model supported a direct association between cytology test results and follow up: negative-cytology/clearance, ASC-US/persistence, and positive-cytology/HSIL with the following probabilities of occurrence for these pairs 0.5, 0.647 and 0.647, respectively. Cytology could be considered a prognostic-factor in women with a positive-Hybrid-2-Capture. These findings suggest that the introduction of co-testing could diminish the burden of cervical cancer in low-and middle-income-countries, acting as a tool against inequity in healthcare.
Assuntos
Infecções por Papillomavirus , Lesões Intraepiteliais Escamosas , Neoplasias do Colo do Útero , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Detecção Precoce de Câncer , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Hospitais UniversitáriosRESUMO
Metastases derived from primary tumours distant to the oral and maxillofacial region account for only 1% of all malignancies at that location, usually with a poor prognosis. In women, the primary tumours that most frequently metastasise to the oral cavity are breast adenocarcinomas affecting the jawbones and soft tissues (41% and 24%, respectively), followed by adrenal glands and female genital organs to the jawbones (8%), and female genital organs to the soft tissues (15%). Metastatic tumours of the mouth are a challenging diagnosis because of their exceptional occurrence. We report on the case of an 83-year-old woman who consulted for a bleeding ulcerated tumour on the floor of the mouth. A biopsy-confirmed metastasis of an adenocarcinoma of Müllerian origin. The oral lesion was the first sign of undetected cancer. The patient agreed to surgical resection and was further referred to palliative care for her symptoms.
Assuntos
Adenocarcinoma , Neoplasias da Mama , Adenocarcinoma/diagnóstico , Idoso de 80 Anos ou mais , Feminino , Humanos , Soalho Bucal , Cuidados PaliativosRESUMO
Small cell lung cancer (SCLC) is a highly proliferative lung cancer that is not amenable to surgery in most cases due to the high metastatic potential. Precision medicine has not yet improved patients' survival due to the lack of actionable mutations. Intra- and intertumoral heterogeneity allow the neoplasms to adapt to various microenvironments and treatments. Further studying this heterogeneous cancer might yield the discovery of actionable mutations. First-line SCLC treatment has added immunotherapy to its armamentarium. There has been renewed interest in SCLC, and numerous clinical trials are underway with novel therapeutic approaches. Understanding the molecular and genetic landscape of this heterogeneous and lethal disease will pave the way for novel drug development.
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Lung cancer is the leading cause of cancer-related death worldwide. Recent advances in the management of non-small cell carcinoma are focused on the discovery of targeted therapies and novel immunotherapy strategies for patients with advanced disease. Treatment with anti PD-(L)1 immune checkpoint inhibitors requires the development of predictive biomarkers to select those patients that can most benefit from these therapies. Several immunohistochemical biomarkers have been developed in different technological platforms. However, the most useful and accessible for the daily clinical practice need to be selected. The objective of this study was to compare PD-L1 expression by automated immunohistochemistry in lung adenocarcinoma (ADC) FFPE samples with clones 28-8 and SP263 performed with the BenchMark GX automated staining instrument. To further determine interobserver agreement between two pathologists, and to correlate the results with histologic and pathology variables. FFPE tissue from 40 samples obtained from patients with lung ADC were reviewed retrospectively. Among all studied specimens, 53% of samples presented <1% of positive tumor cells with the 28-8 clone and 50% had <1% of PD-L1 expression in tumor cells with the SP263 clone; PD-L1 expression between ≥1 and <5% was observed in 18% and 24%; ≥5 and <50% PD-L1 expression in 18% and 21%; and ≥50% PD-L1 expression in 11% and 5% of samples, respectively. Similar results between antibodies were observed in 84% of cases for each of the four PD-L1 cutoff groups (Pearson's score 0.90, p < 0.00001). The interobserver degree of agreement calculated with Kappa was 0.75 (95%CI: 0.57-0.93), z = 7.08; p < 0.001. Lepidic, acinar and mucinous patterns had predominantly <1% PD-L1 expression, and the solid pattern subtype had high levels of PD-L1 staining using both clones. PD-L1 expression in less than 1% of tumor cells was similar in stages I/II compared to III/IV. No significant differences were observed in PD-L1 staining and quantification pattern between IHC antibodies 28-8 and SP263.
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Malignant melanoma (MM) is the more aggressive form of skin cancer with a mortality rate in Argentina 1997-2001 = 1.1/100 000 in men and 0.6 in women. BRAF proto-oncogene is focus of intense research; its mutation is one of the main tumor promoters and occurs in approximately 50% of MM. Several drugs with clinical activity on BRAF mutations have been approved. The aim of the study is to evaluate the mutational status of BRAF (exon 15) in cutaneous MM biopsies and its relationship with histopathological characteristics. We carried out an observational, retrospective study of samples fixed in formaldehyde and paraffin embedded; reviewing age, sex, diagnosis, histopathological data, tumor size and percentage, viability for molecular analysis and melanin presence. We evaluated BRAF mutations with PCR/Sanger sequencing. For statistics we used Student's t test, Chi square, Wilcoxon and Fisher's exact test. We were able to purify and sequence 76% (38/49) samples, 13/38 (34%) from women and 25/38 (66%) from men, the median age being 70 years. Most frequent location: thorax 14/35 (40%). Histological type: Superficial spreading 18/38 (47%). Clark's levels, 11/38 (29%): I-II and 27/38 (71%): III, IV and V. Breslow's median: 1.6 mm. Radial growth phase 11/38 (29%) and 27/38 (71%) vertical. Presented mutations 16/38 (42%). As reported by other authors, no association was found between the mutational state of exon 15 and clinical or histopathological parameters.
El melanoma maligno es la forma más agresiva de cáncer de piel, con una tasa de mortalidad en Argentina 1997-2001 = 1.1/100 000 en varones y 0.6 en mujeres. El proto-oncogén BRAF es foco de intensa investigación, su mutación es uno de los principales promotores tumorales y pueden presentarse en 50% de los melanomas. Se han aprobado varios fármacos con actividad clínica sobre las mutaciones BRAF. El objetivo del trabajo es evaluar el estado mutacional de BRAF (exón 15) en biopsias con melanoma maligno cutáneo y su relación con las características histopatológicas. Realizamos un estudio observacional, retrospectivo, de muestras fijadas en formol e incluidas en parafina. Revisamos edad, sexo, diagnóstico y datos histopatológicos, tamaño y porcentaje tumoral, viabilidad para análisis molecular y presencia de melanina. Evaluamos mutaciones de BRAF con PCR/secuenciación Sanger. Utilizamos test de Student, Chi cuadrado, Wilcoxon y prueba exacta de Fisher. De 49 casos se pudo purificar y secuenciar el 76% (38/49), 13/38 (34%) mujeres y 25/38 (66%) varones, edad mediana 70 años. Localización más frecuente: tórax con 14/35 (40%). Tipo histológico: extensivo superficial 18/38 (47%). Niveles de Clark, 11/38 (29%): I-II y 27/38 (71%): III, IV y V. Mediana del Breslow: 1.6 mm. Fase de crecimiento radial 11/38 (29%) y 27/38 (71%) vertical. Presentaron mutaciones 16/38 (42%). Como lo informado por otros autores, no se encontró asociación entre el estado mutacional del exón 15 y los parámetros clínicos o histopatológicos.
Assuntos
Melanoma/genética , Mutação/genética , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Proto-Oncogene Mas , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Melanoma Maligno CutâneoRESUMO
El melanoma maligno es la forma más agresiva de cáncer de piel, con una tasa de mortalidad en Argentina 1997-2001 = 1.1/100 000 en varones y 0.6 en mujeres. El proto-oncogén BRAF es foco de intensa investigación, su mutación es uno de los principales promotores tumorales y pueden presentarse en 50% de los melanomas. Se han aprobado varios fármacos con actividad clínica sobre las mutaciones BRAF. El objetivo del trabajo es evaluar el estado mutacional de BRAF (exón 15) en biopsias con melanoma maligno cutáneo y su relación con las características histopatológicas. Realizamos un estudio observacional, retrospectivo, de muestras fijadas en formol e incluidas en parafina. Revisamos edad, sexo, diagnóstico y datos histopatológicos, tamaño y porcentaje tumoral, viabilidad para análisis molecular y presencia de melanina. Evaluamos mutaciones de BRAF con PCR/secuenciación Sanger. Utilizamos test de Student, Chi cuadrado, Wilcoxon y prueba exacta de Fisher. De 49 casos se pudo purificar y secuenciar el 76% (38/49), 13/38 (34%) mujeres y 25/38 (66%) varones, edad mediana 70 años. Localización más frecuente: tórax con 14/35 (40%). Tipo histológico: extensivo superficial 18/38 (47%). Niveles de Clark, 11/38 (29%): I-II y 27/38 (71%): III, IV y V. Mediana del Breslow: 1.6 mm. Fase de crecimiento radial 11/38 (29%) y 27/38 (71%) vertical. Presentaron mutaciones 16/38 (42%). Como lo informado por otros autores, no se encontró asociación entre el estado mutacional del exón 15 y los parámetros clínicos o histopatológicos.
Malignant melanoma (MM) is the more aggressive form of skin cancer with a mortality rate in Argentina 1997-2001 = 1.1/100 000 in men and 0.6 in women. BRAF proto-oncogene is focus of intense research; its mutation is one of the main tumor promoters and occurs in approximately 50% of MM. Several drugs with clinical activity on BRAF mutations have been approved. The aim of the study is to evaluate the mutational status of BRAF (exon 15) in cutaneous MM biopsies and its relationship with histopathological characteristics. We carried out an observational, retrospective study of samples fixed in formaldehyde and paraffin embedded; reviewing age, sex, diagnosis, histopathological data, tumor size and percentage, viability for molecular analysis and melanin presence. We evaluated BRAF mutations with PCR/Sanger sequencing. For statistics we used Student's t test, Chi square, Wilcoxon and Fisher's exact test. We were able to purify and sequence 76% (38/49) samples, 13/38 (34%) from women and 25/38 (66%) from men, the median age being 70 years. Most frequent location: thorax 14/35 (40%). Histological type: Superficial spreading 18/38 (47%). Clark´s levels, 11/38 (29%): I-II and 27/38 (71%): III, IV and V. Breslow´s median: 1.6 mm. Radial growth phase 11/38 (29%) and 27/38 (71%) vertical. Presented mutations 16/38 (42%). As reported by other authors, no association was found between the mutational state of exon 15 and clinical or histopathological parameters.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias Cutâneas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Melanoma/genética , Mutação/genética , Neoplasias Cutâneas/patologia , Análise Mutacional de DNA , Estudos Retrospectivos , Reação em Cadeia da Polimerase em Tempo Real , Melanoma/patologiaRESUMO
The prevalence of relevant oncogenic drivers in lung adenocarcinoma varies in our region and data on clinical outcomes is scarce. The objective of the study was to describe the prevalence of KRAS, BRAF and EGFR mutations and ALK translocations in patients with advanced lung adenocarcinoma, and to depict the clinical outcome according to treatment strategies. Patients with adequate tumor biopsy sampling were included. KRAS, BRAF and EGFR mutations were studied by Sanger sequencing. ALK translocations were studied by fluorescent in situ hybridization (FISH) and immunohistochemistry (IH) with antibodies against ALK with clones D5F3 and 5A4. Informed consent was signed by 118 patients and 84 (72%) with complete molecular analysis were included. KRAS mutations were detected in 16 samples (19%), EGFR in 11 (13%), 9 of them conferring sensitivity to EGFR inhibitors, and BRAF mutations in 1 (1%). ALK translocations were detected in 3 samples (4%). Median follow-up was 42.4 [interquartile range (IQR): 27.0-64.2] months. Globally, median overall survival was 10.3 [IQR: 5.6-20.2] months. Median survival was 10.8 [IQR: 6.0-20.3] months in the group of patients without detectable molecular alteration, 9.6 [IQR: 3.7-16.1] months in KRAS mutant population (HR: 1.08; p = 0.82) and 32.5 [IQR: 19.6-38.4] months in patients with ALK translocations or sensitizing EGFR mutated tumors treated with tyrosine kinase inhibitors (HR: 0.27; p = 0.03). In conclusion, the prevalence of molecular alterations and outcomes in our population is similar to that reported in other studies in Western countries.
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Adenocarcinoma/genética , Adenocarcinoma/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Adenocarcinoma/mortalidade , Idoso , Quinase do Linfoma Anaplásico/genética , Argentina/epidemiologia , Biópsia , Feminino , Genes erbB-1/genética , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transporte Proteico/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Estatísticas não ParamétricasRESUMO
The prevalence of relevant oncogenic drivers in lung adenocarcinoma varies in our region and data on clinical outcomes is scarce. The objective of the study was to describe the prevalence of KRAS, BRAF and EGFR mutations and ALK translocations in patients with advanced lung adenocarcinoma, and to depict the clinical outcome according to treatment strategies. Patients with adequate tumor biopsy sampling were included. KRAS, BRAF and EGFR mutations were studied by Sanger sequencing. ALK translocations were studied by fluorescent in situ hybridization (FISH) and immunohistochemistry (IH) with antibodies against ALK with clones D5F3 and 5A4. Informed consent was signed by 118 patients and 84 (72%) with complete molecular analysis were included. KRAS mutations were detected in 16 samples (19%), EGFR in 11 (13%), 9 of them conferring sensitivity to EGFR inhibitors, and BRAF mutations in 1 (1%). ALK translocations were detected in 3 samples (4%). Median follow-up was 42.4 [interquartile range (IQR): 27.0-64.2] months. Globally, median overall survival was 10.3 [IQR: 5.6-20.2] months. Median survival was 10.8 [IQR: 6.0-20.3] months in the group of patients without detectable molecular alteration, 9.6 [IQR: 3.7-16.1] months in KRAS mutant population (HR: 1.08; p = 0.82) and 32.5 [IQR: 19.6-38.4] months in patients with ALK translocations or sensitizing EGFR mutated tumors treated with tyrosine kinase inhibitors (HR: 0.27; p = 0.03). In conclusion, the prevalence of molecular alterations and outcomes in our population is similar to that reported in other studies in Western countries.
La prevalencia de alteraciones en oncogenes en adenocarcinoma de pulmón varía en nuestra región. El objetivo fue describir la prevalencia de mutaciones en KRAS, BRAF y EGFR y las translocaciones de ALK en pacientes con adenocarcinoma de pulmón y estudiar la supervivencia de acuerdo a subtipos moleculares. Se incluyeron pacientes con biopsias adecuadas para el estudio. Se evaluó el estado mutacional de KRAS, BRAF y EGFR por secuenciación con la técnica de Sanger. Las translocaciones de ALK se estudiaron por hibridación in situ por fluorescencia (FISH) e inmunohistoquimica (IHQ) contra ALK (clones D5F3 y 5A4). De 118 pacientes evaluados, se incluyeron 84 (72%) con análisis molecular completo. Se detectaron mutaciones de KRAS en 16 muestras (19%), EGFR en 11 (13%), y BRAF en 1 muestra (1%). Se detectaron rearreglos de ALK en 3 muestras (4%). La mediana de seguimiento de los pacientes fue de 42.4 [rango intercuatilo (RIC): 27.0-64.2] meses. Globalmente, la mediana de supervivencia en la población fue 10.3 [RIC: 5.6-20.2] meses y fue de 10.8 [RIC: 6.0 20.3] meses en pacientes sin alteraciones moleculares detectables. La mediana de supervivencia de los pacientes con mutación en KRAS fue de 9.6 [RIC: 3.7-16.1] meses (HR: 1.08; p = 0.82) y 32.5 [RIC: 19.6-38.4] meses en el grupo con rearreglos de ALK o mutaciones en EGFR tratados con inhibidores de tirosina quinasa (HR: 0.27; p = 0.03). En conclusión, la prevalencia de alteraciones moleculares en nuestra población fue similar a otros países occidentales.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adenocarcinoma/genética , Adenocarcinoma/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Argentina/epidemiologia , Biópsia , Imuno-Histoquímica , Adenocarcinoma/mortalidade , Estudos Prospectivos , Hibridização in Situ Fluorescente , Estatísticas não Paramétricas , Genes erbB-1/genética , Proteínas Proto-Oncogênicas B-raf/genética , Estimativa de Kaplan-Meier , Quinase do Linfoma Anaplásico/genética , Neoplasias Pulmonares/mortalidadeRESUMO
Lung carcinoma is the main cause of cancer death worldwide. Adenocarcinoma molecular biomarkers have been discovered, and targeted therapies have been developed with encouraging results. The epidermal growth factor receptor gene is one of these biomarkers. Exons 18 to 21 should be studied in patients with advanced adenocarcinoma, who are candidates for treatment with tyrosine kinase inhibitors. The objective was to compare the performance of the determination in large and small samples in daily practice conditions, trying to adjust to published consensus guidelines. A retrospective observational study of 141 cases was carried out, with exons 19 and 21 sequencing. Sample size (small vs. large), including number of satisfactory polymerase chain reaction (PCR), sequencing, deletions, and mutations, were evaluated. In small biopsies, sample type, fragment number, and percentage of tumor per sample were analyzed. The results shown 114/141 (80.8) cases that met selection criteria; 60/114 (53%) were large (surgical) and 54/114 (47%) were small samples (19/54 endoscopic, 17/54 fine needle aspiration clots, 4/54 lymph nodes, 14/54 core and other). All large samples were satisfactory PCR, 56/60 (93%) satisfactory sequencing, and 12/56 (21%) had deletions in exon 19. Small samples were satisfactory PCRs in 50/54 (93%) cases, and satisfactory sequencing in 35/50 (65%), 8/35 (23%) showed alterations in exon 19, and 1/35 (3%) in exon 21. In conclusion, the proportion of samples unfit for the study of the epidermal growth factor receptor gene mutational status increased from 7% in large samples to 35% in small ones. Nineteen small samples were inconclusive, with cell blocks predominating, 10/19 (53%).
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Carcinoma Pulmonar de Células não Pequenas/genética , Éxons , Neoplasias Pulmonares/genética , Mutação , Proteínas de Neoplasias/genética , Análise de Sequência de DNA , Adulto , Idoso , Biópsia por Agulha Fina , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Reação em Cadeia da Polimerase , Estudos RetrospectivosRESUMO
Antecedentes: el cáncer de la vía aerodigestiva superior (CVADS), al que con frecuencia se lo engloba como cáncer de cabeza y cuello, tiene una incidencia aproximada de 30 nuevos casos cada 100.000 habitantes por año, habiendo presentado un aumento significativo en la última década. Los principales factores de riesgo para el CVADS siguen siendo la exposición al tabaco y el alcohol, pero el virus del papiloma humano (VPH) se ha encontrado asociado en la etiología del 20 al 25% de los CVADS, principalmente los ubicados en la región de la orofaringe. El virus tiene dos oncoproteínas, E6 y E7. E6 tiene la propiedad de unirse a la proteína celular p53, que regula la transcripción de la p21 e inhibe las quinasas ciclindependientes, las cuales son esenciales para la progresión del ciclo celular a la fase S, haciendo que la célula se replique descontroladamente...
Background: cancer of the upper aerodigestive tract (cuadt) that often encompasses it as cancer of the head and neck, has an incidence of 30 new cases per 100,000 population per year, having presented a significant increase in the last decade. The main risk factors for CUADT remain exposure to tabaco and alcohol, but the human papillomavirus (HPV) has been found associated in the etiology of 20 to 25% of CUADT, mainly those located in the region oropharynx. The virus has two oncoproteins E6 and E7. E6 has the property of binding to cellular p53 protein that regulates transcription of p21, which inhibits cyclin dependent-kinases which are essential for cell cycle progression to S phase causing the cell to replicate uncontrollably...
Antecedentes: o câncer do trato aerodigestivo superior, que é frequentemente englobado no câncer de cabeça e pescoço, tem uma incidência aproximada de 30 casos novos cada 100.000 habitantes por ano, com um incremento significativo na última dé- cada. Os principais fatores de risco para o câncer de cabeça e de pescoço continuam sendo a exposição ao tabaco e ao álcool, mas o vírus do papiloma humano (VPH) é associado na etiologia de 20% até 25% dos casos de câncer do trato aerodigestivo superior, principalmente nos localizados na região da orofaringe. O vírus contém duas oncoproteínas E6 e E7. A E6 tem a propriedade de se unir à proteí- na celular p53, a qual regula a transcrição da p21, a qual inibe as quinases dependentes de ciclina que são essenciais para a progressão do ciclo celular à fase S, fazendo com que a célula se replique descontroladamente...
Assuntos
Masculino , Feminino , Humanos , Infecções por Papillomavirus/classificação , Infecções por Papillomavirus/epidemiologia , Biópsia , Incidência , Vacinas contra Papillomavirus , Infecções por Papillomavirus/diagnóstico , Infecções Respiratórias , Neoplasias do Sistema RespiratórioRESUMO
Helicobacter pylori (H. pylori) has been found in the oral cavity and stomach, and its infection is one of the most frequent worldwide. We reviewed the literature and conducted a Topic Highlight, which identified studies reporting an association between H. pylori-infection in the oral cavity and H. pylori-positive stomach bacterium. This work was designed to determine whether H. pylori is the etiologic agent in periodontal disease, recurrent aphthous stomatitis (RAS), squamous cell carcinoma, burning and halitosis. Record selection focused on the highest quality studies and meta-analyses. We selected 48 articles reporting on the association between saliva and plaque and H. pylori-infection. In order to assess periodontal disease data, we included 12 clinical trials and 1 meta-analysis. We evaluated 13 published articles that addressed the potential association with RAS, and 6 with squamous cell carcinoma. Fourteen publications focused on our questions on burning and halitosis. There is a close relation between H. pylori infection in the oral cavity and the stomach. The mouth is the first extra-gastric reservoir. Regarding the role of H. pylori in the etiology of squamous cell carcinoma, no evidence is still available.
Assuntos
Gastrite/microbiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Doenças da Boca/microbiologia , Boca/microbiologia , Estômago/microbiologia , Placa Dentária/microbiologia , Gastrite/diagnóstico , Gastrite/epidemiologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/isolamento & purificação , Humanos , Doenças da Boca/diagnóstico , Doenças da Boca/epidemiologia , Prognóstico , Fatores de Risco , Saliva/microbiologiaRESUMO
Colorectal cancer is the third most frequent cancer in men and the second most frequent in women, with a worldwide incidence of approximately 1.2 million new cases per year. Our primary objective was to study the relationship between clinical and histological features of individuals with colorectal cancer and the mutational status of codons 12 and 13 of the KRAS gene (7 validated mutations), in order to find a histopathological marker to mutated tumors. The secondary objective was to determine how many patients had additional mutations in codons 15 and 61 of the KRAS gene, and codon 600 of the BRAF gene, which could modify the tumor phenotype. Sixty individuals with colorectal cancer (30 wild-type subjects and 30 with validated mutations in codons 12 and 13 of the KRAS gene) were selected. Exons 2 and 3 of the KRAS gene, and exon 15 of the BRAF gene were amplified and sequenced. The data collected were reviewed by a descriptive, univariate and/or multivariate analysis, as appropriate. In conclusion, no relation was found between clinical and histological features of individuals with colorectal cancer and their mutational status for codons 12 and 13 of the KRAS gene. This suggests that those easily available data do not allow predicting the response to anti-EGFR therapy. In patients with advanced colorectal adenocarcinomas and KRAS wild-type status, further study of codon 600 of the BRAF gene could be required.
Assuntos
Adenocarcinoma/genética , Códon/genética , Neoplasias Colorretais/genética , Genes ras/genética , Mutação/genética , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Polimorfismo Genético , Valor Preditivo dos TestesRESUMO
El cáncer colorrectal es el tercer cáncer más frecuente en hombres y el segundo más frecuente en mujeres, con una incidencia mundial aproximada de 1.2 millones de casos nuevos por año. Nuestro objetivo primario fue estudiar la relación existente entre las características clínico-histológicas en individuos con cáncer colorrectal y el estado mutacional de los codones 12 y 13 del gen KRAS (7 mutaciones validadas), con el fin de hallar un marcador histopatológico para los tumores mutados. El objetivo secundario fue determinar cuántos pacientes tenían mutaciones adicionales en los codones 15 y 61 del gen KRAS y 600 del gen BRAF que podrían modificar el fenotipo tumoral. Fueron seleccionados 60 individuos con cáncer colorrectal (30 wild-type y 30 con mutaciones validadas en los codones 12 y 13 del gen KRAS). Se amplificaron y secuenciaron del gen KRAS los exones 2 y 3, y del gen BRAF el exón 15. La información recolectada se examinó mediante un análisis descriptivo, análisis univariado y/o análisis multivariado, según correspondiese. En conclusión, no se encontró relación entre las características clínico-histológicas de los tumores de individuos con diagnóstico de cáncer colorrectal y el estado mutacional de los codones 12 y 13 del gen KRAS. No hallamos un marcador histopatológico para los tumores mutados. En pacientes con adenocarcinomas colorrectales avanzados y KRAS wild-type resulta de interés considerar el estudio del codón 600 del gen BRAF.(AU)
Colorectal cancer is the third most frequent cancer in men and the second most frequent in women, with a worldwide incidence of approximately 1.2 million new cases per year. Our primary objective was to study the relationship between clinical and histological features of individuals with colorectal cancer and the mutational status of codons 12 and 13 of the KRAS gene (7 validated mutations), in order to find a histopathological marker to mutated tumors. The secondary objective was to determine how many patients had additional mutations in codons 15 and 61 of the KRAS gene, and codon 600 of the BRAF gene, which could modify the tumor phenotype. Sixty individuals with colorectal cancer (30 wild-type subjects and 30 with validated mutations in codons 12 and 13 of the KRAS gene) were selected. Exons 2 and 3 of the KRAS gene, and exon 15 of the BRAF gene were amplified and sequenced. The data collected were reviewed by a descriptive, univariate and/or multivariate analysis, as appropriate. In conclusion, no relation was found between clinical and histological features of individuals with colorectal cancer and their mutational status for codons 12 and 13 of the KRAS gene. This suggests that those easily available data do not allow predicting the response to anti-EGFR therapy. In patients with advanced colorectal adenocarcinomas and KRAS wild-type status, further study of codon 600 of the BRAF gene could be required.(AU)
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma/genética , Códon/genética , Neoplasias Colorretais/genética , Genes ras/genética , Mutação/genética , Adenocarcinoma/patologia , Neoplasias Colorretais/patologia , Marcadores Genéticos , Predisposição Genética para Doença , Análise Multivariada , Polimorfismo Genético , Valor Preditivo dos TestesRESUMO
El cáncer colorrectal es el tercer cáncer más frecuente en hombres y el segundo más frecuente en mujeres, con una incidencia mundial aproximada de 1.2 millones de casos nuevos por año. Nuestro objetivo primario fue estudiar la relación existente entre las características clínico-histológicas en individuos con cáncer colorrectal y el estado mutacional de los codones 12 y 13 del gen KRAS (7 mutaciones validadas), con el fin de hallar un marcador histopatológico para los tumores mutados. El objetivo secundario fue determinar cuántos pacientes tenían mutaciones adicionales en los codones 15 y 61 del gen KRAS y 600 del gen BRAF que podrían modificar el fenotipo tumoral. Fueron seleccionados 60 individuos con cáncer colorrectal (30 wild-type y 30 con mutaciones validadas en los codones 12 y 13 del gen KRAS). Se amplificaron y secuenciaron del gen KRAS los exones 2 y 3, y del gen BRAF el exón 15. La información recolectada se examinó mediante un análisis descriptivo, análisis univariado y/o análisis multivariado, según correspondiese. En conclusión, no se encontró relación entre las características clínico-histológicas de los tumores de individuos con diagnóstico de cáncer colorrectal y el estado mutacional de los codones 12 y 13 del gen KRAS. No hallamos un marcador histopatológico para los tumores mutados. En pacientes con adenocarcinomas colorrectales avanzados y KRAS wild-type resulta de interés considerar el estudio del codón 600 del gen BRAF.
Colorectal cancer is the third most frequent cancer in men and the second most frequent in women, with a worldwide incidence of approximately 1.2 million new cases per year. Our primary objective was to study the relationship between clinical and histological features of individuals with colorectal cancer and the mutational status of codons 12 and 13 of the KRAS gene (7 validated mutations), in order to find a histopathological marker to mutated tumors. The secondary objective was to determine how many patients had additional mutations in codons 15 and 61 of the KRAS gene, and codon 600 of the BRAF gene, which could modify the tumor phenotype. Sixty individuals with colorectal cancer (30 wild-type subjects and 30 with validated mutations in codons 12 and 13 of the KRAS gene) were selected. Exons 2 and 3 of the KRAS gene, and exon 15 of the BRAF gene were amplified and sequenced. The data collected were reviewed by a descriptive, univariate and/or multivariate analysis, as appropriate. In conclusion, no relation was found between clinical and histological features of individuals with colorectal cancer and their mutational status for codons 12 and 13 of the KRAS gene. This suggests that those easily available data do not allow predicting the response to anti-EGFR therapy. In patients with advanced colorectal adenocarcinomas and KRAS wild-type status, further study of codon 600 of the BRAF gene could be required.
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma/genética , Códon/genética , Neoplasias Colorretais/genética , Genes ras/genética , Mutação/genética , Adenocarcinoma/patologia , Neoplasias Colorretais/patologia , Marcadores Genéticos , Predisposição Genética para Doença , Análise Multivariada , Polimorfismo Genético , Valor Preditivo dos TestesRESUMO
Objetivo: Estimar el riesgo del potencial de malignización del liquen plano bucal analizando la expresión de la proteína p53. Materiales y metodos: Se realizó un diseño de cohorte de sujetos con diagnostico histopatológico de liquen. El desenlace fue el desarrollo de cáncer si/no. El total de individuos que cumplió con los criterios de inclusión/exclusión fue de 58. A los 58 sujetos se les realizó la determinación de p53. Resultados: Cuarenta y nueve individuos mostraron una expresión de p53 menor al 5% con una P>0,05% intrasujeto no transformado. En los 9 individuos transformados se observaron diferencias significativas entre la determinación pre y post de la proteína p53. El Riesgo Relativo fue de 188 con una significación estadística de P< 0,01. Conclusion: La expresión de la proteína p53 en los individuos con liquen apoya la hipótesis que niveles superiores al 5%constituye un factor de incremento del riesgo en la transformación maligna de esta patología. Nuestros hallazgos deberían ser corroborados en el futuro con mayor número de individuos. La determinación de la p53 mediante IHQ en individuos con liquen plano bucal podría modificar el seguimiento clínico de estos individuos. Esto permitiría un diagnóstico precoz de cualquier alteración que pueda indicar un posible cambio hacia la malignización.
Objective: To determine the risk for potential malignant transformation of oral lichen planus by analyzing protein p53 expression. Materials and methods: Cohort study of subjects with a histopathologic diagnosis of lichen. The study analyzed whether or not subjects developed cancer. A total of 58 subjects fulfilled the inclusion/exclusion criteria, and were analyzed for p53. Results: Fortynine(49) subjects showed a p53 expression <5%, with a p>0.05 among subjects undergoing no transformation. In the 9 subjects undergoing malignant transformation, significant differences were observed between pre and post p53 expression. The relative risk was 188, with a statistical significance of p< 0.01. Conclusions: Protein p53 expression in subjects with lichen supports the hypothesis that levels >5% are associated with an increased risk of malignant transformation of this condition. Should our findings be proved in a larger series in the future, the clinical follow-up of these subjects could be modified. This would allow an early diagnosis of any disorder indicative of a potential malignant transformation.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Imuno-Histoquímica/métodos , Líquen Plano Bucal/imunologia , /análise , Transformação Celular Neoplásica/imunologia , Distribuição por Idade e Sexo , Protocolos Clínicos , Estudos de Coortes , Fatores de Risco , Interpretação Estatística de DadosRESUMO
Colorectal cancer is the third most frequent cancer in men and the second most frequent in women, with a worldwide incidence of approximately 1.2 million new cases per year. Our primary objective was to study the relationship between clinical and histological features of individuals with colorectal cancer and the mutational status of codons 12 and 13 of the KRAS gene (7 validated mutations), in order to find a histopathological marker to mutated tumors. The secondary objective was to determine how many patients had additional mutations in codons 15 and 61 of the KRAS gene, and codon 600 of the BRAF gene, which could modify the tumor phenotype. Sixty individuals with colorectal cancer (30 wild-type subjects and 30 with validated mutations in codons 12 and 13 of the KRAS gene) were selected. Exons 2 and 3 of the KRAS gene, and exon 15 of the BRAF gene were amplified and sequenced. The data collected were reviewed by a descriptive, univariate and/or multivariate analysis, as appropriate. In conclusion, no relation was found between clinical and histological features of individuals with colorectal cancer and their mutational status for codons 12 and 13 of the KRAS gene. This suggests that those easily available data do not allow predicting the response to anti-EGFR therapy. In patients with advanced colorectal adenocarcinomas and KRAS wild-type status, further study of codon 600 of the BRAF gene could be required.
Assuntos
Adenocarcinoma/genética , Códon/genética , Neoplasias Colorretais/genética , Genes ras/genética , Mutação/genética , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Polimorfismo Genético , Valor Preditivo dos TestesRESUMO
BACKGROUND: After skin cancer, breast cancer is the most common malignancy in women. Tumors of unknown origin account for 5-15% of malignant neoplasms, with 1.5% being breast cancer. An immunohistochemical panel with conventional and newer markers, such as mammaglobin, was selected for the detection of neoplastic cells of breast origin. The specific objectives are: 1) to determine the sensitivity and specificity of the panel, with a special emphasis on the inclusion of the mammaglobin marker, and 2) to compare immunohistochemistry performed on whole tissue sections and on tissue micro-array. METHODS: Twenty-nine metastatic breast tumors were included and assumed as tumors of unknown origin. Other 48 biopsies of diverse tissues were selected and assumed as negative controls. Tissue Micro-Array was performed. Immunohistochemistry for mammaglobin, gross cystic disease fluid protein-15, estrogen receptor, progesterone receptor and cytokeratin 7 was done. RESULTS: Mammaglobin positive staining was observed in 10/29 cases, in 13/29 cases for gross cystic disease fluid protein-15, in 20/29 cases for estrogen receptor, in 9/29 cases for progesterone receptor, and in 25/29 cases for cytokeratin 7. Among the negative controls, mammaglobin was positive in 2/48, and gross cystic disease fluid protein-15 in 4/48. CONCLUSIONS: The inclusion of MAG antibody in the immunohistochemical panel for the detection of tumors of unknown origin contributed to the detection of metastasis of breast cancer. The diagnostic strategy with the highest positive predictive value (88%) included hormone receptors and mammaglobin in serial manner.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/química , Imuno-Histoquímica , Neoplasias Primárias Desconhecidas/química , Biópsia , Neoplasias da Mama/secundário , Proteínas de Transporte/análise , Feminino , Glicoproteínas/análise , Humanos , Queratina-7/análise , Proteínas de Membrana Transportadoras , Neoplasias Primárias Desconhecidas/patologia , Valor Preditivo dos Testes , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Secretoglobinas/análise , Sensibilidade e Especificidade , Análise Serial de TecidosRESUMO
Weanling Sprague-Dawley rats were fed on a choline-deficient diet with hydrogenated vegetable oil and corn oil as lipids develop acute renal failure. Pathogenesis of the latter is controversial and an ischemic mechanism has been proposed. Arachidonic acid derivatives are involved in the regulation of vascular tonus. Vasospasm could be due to an increase in tromboxane A2-mediated vasoconstriction or to a decrease in prostacyclin-induced vasodilatation. Enzymes involved in the synthesis of both compounds are tromboxane A2- and prostacyclin-synthase respectively. The aim of this study was to identify the variable number tandem repeats (VNTR) in the promoter region of prostacyclin synthase gene and verify if there exists a relationship between the occurrence of VNTR in those choline-deficient rats which die because of acute renal failure and those which do not. We verified the presence of the VNTR in the prostacyclin synthase rat gene, but we did not find any difference in the molecular weight of the alleles between experimental and control rats. Renal reparation of the acute kidney injury due to choline deficiency in some rats is not related with differences in VNTR in the promoter region of the prostacyclin synthase gene.