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INTRODUCTION: Squamous carcinoma is the commonest malignancy of the head and neck region. It is associated with high morbidity and mortality. Epidermal growth factor receptor (EGFR) regulates downstream signaling pathways through its tyrosine kinase (TK) domains that play a role in cell proliferation and survival. EGFR mutations have been found to occur between exons 18 to 21 on chromosome 7. Limited studies are available on EGFR-TK mutations in the head and neck squamous cell carcinoma (HNSCC) globally. This study explores EGFR mutations in 30 HNSCC cases presenting to a tertiary care hospital over a period of two years. MATERIAL AND METHODS: Fresh tumor tissue was collected from the resection specimens of cases of primary HNSCC. Cases with pre-operative therapy were not included. Parameters in the form of patients' age, gender, smoking/tobacco intake, site of the lesion were recorded. Tumor parameters after histopathological examination were recorded in the form of TNM stage, tumor grade. DNA was extracted from fresh tissue of all the cases. EGFR Mutation Analysis Kit assay was used to detect mutations of the EGFR gene. PCR was run and results were analyzed. RESULTS: EGFR Mutations were found in 6.7%of the patients. There was no significant association of the EGFR Mutation with the studied parameters. CONCLUSION: EGFR mutations are present in a subset of patients of HNSCC. Patients having these mutations may benefit from targeted therapy with tyrosine kinase inhibitors.
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Introduction Squamous carcinoma is the commonest malignancy of the head and neck region. It is associated with high morbidity and mortality. Epidermal growth factor receptor (EGFR) regulates downstream signaling pathways through its tyrosine kinase (TK) domains that play a role in cell proliferation and survival. EGFR mutations have been found to occur between exons 18 to 21 on chromosome 7. Limited studies are available on EGFR-TK mutations in the head and neck squamous cell carcinoma (HNSCC) globally. This study explores EGFR mutations in 30 HNSCC cases presenting to a tertiary care hospital over a period of two years. Material and Methods Fresh tumor tissue was collected from the resection specimens of cases of primary HNSCC. Cases with pre-operative therapy were not included. Parameters in the form of patients' age, gender, smoking/tobacco intake, site of the lesion were recorded. Tumor parameters after histopathological examination were recorded in the form of TNM stage, tumor grade. DNA was extracted from fresh tissue of all the cases. EGFR Mutation Analysis Kit assay was used to detect mutations of the EGFR gene. PCR was run and results were analyzed. Results EGFR Mutations were found in 6.7%of the patients. There was no significant association of the EGFR Mutation with the studied parameters. Conclusion EGFR mutations are present in a subset of patients of HNSCC. Patients having these mutations may benefit from targeted therapy with tyrosine kinase inhibitors.
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Humanos , Masculino , Feminino , Genes erbB-1 , Receptores ErbB , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/patologia , Mutação , Proteínas Tirosina QuinasesRESUMO
ABSTRACT Background Glioma, the most common primary malignant brain tumor in adults, is highly aggressive and associated with a poor prognosis. The objectives of this study were to evaluate the association of genetic polymorphisms related to angiogenesis and apoptosis with gliomas, as well as comorbidities, lifestyle, clinical profile, survival and response to treatment (temozolomide [TMZ] and radiotherapy [RT]) in patients with the disease. Methods In a total of 303 individuals, genotypes were performed by real-time PCR, and clinical data, lifestyle and comorbidities were obtained from medical records and questionnaires. The significance level was set at 5%. Results Smoking, alcohol consumption, systemic arterial hypertension, diabetes mellitus and body mass index prevailed among patients, compared to controls (p < 0.05). The heterozygous genotype rs1468727 (T/C) and the homozygous genotype rs2010963 (G/G) (p > 0.05) were observed in both groups. Lifestyle and comorbidities showed independent risk factors for the disease (p < 0.0001, p = 0.0069, p = 0.0394, respectively). Patients with low-grade gliomas had a survival rate of 80.0 ± 1.7% in three years. For the combination of TMZ+RT, survival was 78.7 ± 7.6% in 20 months, compared to TMZ only (21.9 ± 5.1%, p = 0.8711). Conclusions Genetic variants were not associated with gliomas. Specific lifestyle habits and comorbidities stood out as independent risk factors for the disease. Low-grade gliomas showed an increase in patient survival with TMZ+RT treatment.
RESUMO Introdução Glioma, tumor cerebral maligno, é altamente agressivo e associado a mau prognóstico. Os objetivos deste estudo foram avaliar a associação de polimorfismos genéticos relacionados a angiogênese e apoptose em pacientes com glioma, bem como suas comorbidades, hábitos de vida, perfil clínico, sobrevida e resposta ao tratamento (temozolomida [TMZ] e radioterapia [RT]). Métodos 303 indivíduos foram genotipados por PCR em tempo real, e foram coletados dados clínicos, hábitos de vida e comorbidades. Admitiu-se nível de significância para valor p < 0,05. Resultados Tabagismo, elitismo, hipertensão arterial sistêmica, diabetes mellitus e índice de massa corporal prevaleceram entre os pacientes, comprados aos controles (p < 0,05). O genótipo heterozigoto rs1468727 (T/C) e homozigoto rs2010963 (G/G) (p > 0,05) foram observados em ambos os grupos. Tabagismo, elitismo, hipertensão arterial sistêmica, diabetes mellitus e índice de massa corporal apresentaram fatores de risco independentes para a doença (p < 0.0001, p = 0.0069, p = 0.0394, respectivamente). Os pacientes com gliomas de baixo grau apresentaram sobrevida de 80,0 ± 1,7% em três anos. Para a combinação de RT e TMZ, a sobrevida foi de 78,7±7,6% em 20 meses, em comparação com TMZ (21,9 ± 5,1%, p = 0,8711). Conclusões As variantes genéticas não estiveram associadas aos gliomas. Hábitos de vida e comorbidades específicas destacaram-se como fatores de risco independentes para a doença. O tratamento com TMZ + RT mostrou aumento na sobrevida dos pacientes.
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Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Polimorfismo Genético/genética , Neoplasias Encefálicas/genética , Apoptose/genética , Glioma/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Terapia Combinada , Antineoplásicos Alquilantes/administração & dosagem , Dacarbazina/administração & dosagem , Dacarbazina/análogos & derivados , Estimativa de Kaplan-Meier , Reação em Cadeia da Polimerase em Tempo Real , Temozolomida , Genótipo , Glioma/patologia , Glioma/terapia , Estilo de Vida , Neovascularização PatológicaRESUMO
ABSTRACT Objective: to evaluate the expression of the epithelial growth factor receptor (EGFR) by immunohistochemistry, and to verify its association with prognostic factors and survival of patients operated by cholangiocarcinoma. Methods: we verified the immunohistochemical expression of EGFR in 35 surgical specimens of cholangiocarcinoma (CCA). We obtained survival curves with the Kaplan-Meier method. Results: we found significant EGFR expression in ten (28.6%) of the 35 CCAs, eight with score 3 and two with score 2. Advanced stages (III and IV) presented higher EGFR expression (p=0.07). The clinical characteristics that were most associated with positive EGFR expression were female gender (p=0.06) and absence of comorbidities (p=0.06). Overall survival at 12, 24, 36 and 48 months was 100%, 82.5%, 59% and 44.2%, respectively. The survival of EGFR positive patients at 12, 24, 36 and 48 months was 100%, 75%, 50% and 0%, whereas for negative EGFR patients it was 100%, 87.5%, 65.6% and 65.6%, respectively. Conclusion: EGFR expression occurred in 28.6% of the cases studied and was associated with lower survival.
RESUMO Objetivo: avaliar a expressão do receptor do fator de crescimento epitelial (EGFR) por meio de imuno-histoquímica, e verificar sua associação com fatores prognósticos e com a sobrevida dos pacientes operados por colangiocarcinoma. Métodos: a expressão imuno-histoquímica de EGFR foi verificada em 35 peças cirúrgicas de colangiocarcinomas (CCA). Curvas de sobrevida foram obtidas pelo método de Kaplan-Meier. Resultados: expressão significativa de EGFR foi encontrada em dez (28,6%) de 35 CCA, oito com escore 3 e dois com escore 2. Estágios avançados (III e IV) apresentaram maior expressão de EGFR (p=0,07). As características clínicas que mais estiveram associadas com a expressão positiva de EGFR foram o sexo feminino (p=0,06) e ausência de comorbidades (p=0,06). A sobrevida global aos 12, 24, 36 e 48 meses foi de 100%, 82,5%, 59% e 44,2%, respectivamente. A sobrevida de pacientes EGFR positivos aos 12, 24, 36 e 48 meses foi de 100%, 75%, 50% e 0%, enquanto que para EGFR negativos foi de 100%, 87,5%, 65,6% e 65,6%, respectivamente. Conclusão: a expressão do EGFR ocorreu em 28,6% dos casos estudados e esteve associada a menor sobrevida.
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Humanos , Masculino , Feminino , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Receptores ErbB/análise , Prognóstico , Valores de Referência , Coloração e Rotulagem , Imuno-Histoquímica , Distribuição por Sexo , Estimativa de Kaplan-Meier , Pessoa de Meia-IdadeRESUMO
Abstract Purpose: To evaluate the expression of EGFR, KRAS genes, microRNAs-21 and 203 in colon and rectal cancer samples, correlated with their age at diagnosis, histological subtype, value of pretreatment CEA, TNM staging and clinical outcome. Methods: Expression of genes and microRNAs by real time PCR in tumor and non-tumor samples obtained from surgical treatment of 50 patients. Results: An increased expression of microRNAs-21 and 203 in tumor samples in relation to non-tumor samples was found. There was no statistically significant difference between the expression of these genes and microRNAs when compared to age at diagnosis and histological subtype. The EGFR gene showed higher expression in relation to the value of CEA diagnosis. The expression of microRNA-203 was progressively lower in relation to the TNM staging and was higher in the patient group in clinical remission. Conclusions: The therapy of colon and rectum tumors based on microRNAs remains under investigation reserving huge potential for future applications and clinical interventions in conjunction with existing therapies. We expect, based on the exposed data, to stimulate the development of new therapeutic possibilities, making the treatment of these tumors more effective.
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Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/genética , Adenocarcinoma/genética , Expressão Gênica , Proteínas Proto-Oncogênicas p21(ras)/análise , Genes ras , Genes erbB-1 , MicroRNAs/análise , Neoplasias Colorretais/patologia , Neoplasias Colorretais/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/tratamento farmacológico , Antígeno Carcinoembrionário/análise , Biomarcadores Tumorais/análise , Estudos Prospectivos , Fatores Etários , Resultado do Tratamento , Reação em Cadeia da Polimerase em Tempo Real , Estadiamento de NeoplasiasRESUMO
Purpose: To evaluate the expression of EGFR, KRAS genes, microRNAs-21 and 203 in colon and rectal cancer samples, correlated with their age at diagnosis, histological subtype, value of pretreatment CEA, TNM staging and clinical outcome. Methods: Expression of genes and microRNAs by real time PCR in tumor and non-tumor samples obtained from surgical treatment of 50 patients. Results: An increased expression of microRNAs-21 and 203 in tumor samples in relation to non-tumor samples was found. There was no statistically significant difference between the expression of these genes and microRNAs when compared to age at diagnosis and histological subtype. The EGFR gene showed higher expression in relation to the value of CEA diagnosis. The expression of microRNA-203 was progressively lower in relation to the TNM staging and was higher in the patient group in clinical remission. Conclusions: The therapy of colon and rectum tumors based on microRNAs remains under investigation reserving huge potential for future applications and clinical interventions in conjunction with existing therapies. We expect, based on the exposed data, to stimulate the development of new therapeutic possibilities, making the treatment of these tumors more effective.(AU)
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Feminino , Gravidez , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias do Colo/genética , Neoplasias Retais/genética , Expressão Gênica , MicroRNAs/análise , Genes erbB-1/genética , Evolução ClínicaRESUMO
OBJECTIVE: Sixteen percent of US population is Hispanic, mostly Mexican. Recently, two independent American reports demonstrated a higher overall survival (OS) in Hispanic populations compared with non-Hispanic-white populations (NHW) with non-small-cell lung cancer (NSCLC), even when most Hispanic patients are diagnosed at advanced disease stages and have lower income status. We analyzed the clinical, pathological, and molecular characteristics as well as outcomes in a cohort of NSCLC Hispanic patients from the National Cancer Institute of Mexico that could explain this "Hispanic Paradox". MATERIAL AND METHODS: A cohort of 1260 consecutive NSCLC patients treated at the National Cancer Institute of Mexico from 2007 to 2014 was analyzed. Their clinical-pathological characteristics, the presence of EGFR and KRAS mutations and the prognosis were evaluated. RESULTS: Patients presented with disease stages II, IIIa, IIIb and IV at rates of 0.6, 4.8, 18.4 and 76.3%, respectively. NSCLC was associated with smoking in only 56.5% of the patients (76.7% of male vs. 33.0% of female patients). Wood smoke exposure (WSE) was associated with 37.2% of the cases (27.3% in men vs. 48.8% in women). The frequency of EGFR mutations was 27.0% (18.5% in males vs. 36.9% in females, p<0.001) and the frequency for KRAS mutations was 10.5% (10.3% men vs. 10.1% in women p=0.939). The median OS for all patients was 23.0 [95% CI 19.4-26.2], whereas for patients at stage IV, it was 18.5 months [95% CI 15.2-21.8]. The independent factors associated with the OS were the ECOG, disease stage, EGFR and KRAS mutation status. CONCLUSION: The high frequency of EGFR mutations and low frequency of KRAS mutations in Hispanic populations and different prevalence in lung cancer-related-developing risk factors compared with Caucasian populations, such as the lower frequency of smoking exposure and higher WSE, particularly in women, might explain the prognosis differences between foreign-born-Hispanics, US-born-Hispanics and NHWs.
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Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Receptores ErbB/genética , Feminino , Hispânico ou Latino , Humanos , Masculino , México , Pessoa de Meia-Idade , Prognóstico , Fumaça/efeitos adversos , Fumar/efeitos adversos , Adulto Jovem , Proteínas ras/genéticaRESUMO
ABSTRACT Objective: To report the demographic data and clinical outcomes of non-small-cell lung cancer patients exposed to erlotinib in any line of treatment. Methods: This was a retrospective cohort study of nonsmall-cell lung cancer patients from a reference general hospital and a private oncology clinic, who received erlotinib from 2005 to 2011. Statistical analysis was performed and we evaluated demographic data and response to treatment, by correlating the results of this first cohort published in Brazil with results of current literature. Results: A total of 44 patients were included; 65.9% were diagnosed with adenocarcinoma, and 63.6% had metastatic disease. The mean age was 63.3 years. The median follow-up was 47.9 months. Epidermal growth factor receptor mutation screening was performed in 22.7% of patients (n=10), with mutation present in 30% of patients. The median overall survival was 46.3 months, and there was a higher probability of survival at 60 months for females compared to males (29.4% versus 15.8%; p=0.042). The other variables did not present significant statistical difference. Conclusion: We collected the largest cohort of patients with non-small-cell lung cancer who have used erlotinib in Brazil to date, and demonstrated that outcomes of patients treated at our clinic during the study period were consistent with the results of current literature in similar patients. .
RESUMO Objetivo: Relatar as características demográficas e a evolução de pacientes com neoplasia de pulmão de não pequenas células que receberam erlotinibe em qualquer linha de tratamento. Métodos: Coletamos retrospectivamente dados de pacientes portadores de neoplasia de pulmão de não pequenas células que receberam erlotinibe em qualquer linha de tratamento em um hospital geral de referência e em uma clínica particular de oncologia em São Paulo, no período de 2005 a 2011. Foi realizada a análise estatística e foram avaliados aspectos demográficos e resposta ao tratamento estabelecido, correlacionando os resultados dessa primeira coorte publicada no Brasil com resultados da literatura vigente. Resultados: Foram avaliados 44 pacientes, dos quais 65,9% eram portadores de adenocarcinoma e 63,6% tinham doença metastática. A média de idade foi de 63,3 anos. O seguimento mediano foi de 47,9 meses. A pesquisa de mutação do receptor do fator de crescimento epidérmico foi realizada em 22,7% dos pacientes (n=10), resultando positiva em 30% dos avaliados. A sobrevida global mediana foi de 46,3 meses, e observou-se uma probabilidade maior de sobrevida em 60 meses para o grupo feminino, quando comparado ao grupo masculino (29,4% versus 15,8%; p=0,042). As demais variáveis não apresentaram diferença estatística significativa. Conclusão: Coletamos a maior sequência de pacientes com neoplasia de pulmão de não pequenas células que fizeram uso de erlotinibe no Brasil até a data vigente e demonstramos que a evolução dos pacientes tratados no período avaliado teve resultados concordantes com os da literatura vigente em pacientes semelhantes. .
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Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Brasil , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Cloridrato de Erlotinib , Seguimentos , Hospitais Gerais , Hospitais com Fins Lucrativos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Mutação/genética , Estudos Retrospectivos , Receptores ErbB/genética , Distribuição por Sexo , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Lung cancer often exhibits molecular changes, such as the overexpression of the ErbB1 gene that encodes epidermal growth factor receptor (EGFR). ErbB1 amplification and mutation are associated with tumor aggressiveness and low response to therapy. The aim of the present study was to design a schedule to synchronize the cell cycle of A549 cell line (a non-small cell lung cancer) and to analyze the possible association between the micronuclei (MNs) and the extrusion of ErbB1 gene extra-copies. After double blocking, by the process of fetal bovine serum deprivation and vincristine treatment, MNs formation was monitored with 5-bromo-2-deoxyuridine (BrdU) incorporation, which is an S-phase marker. Statistical analyses allowed us to infer that MNs may arise both in mitosis as well as in interphase. The MNs were able to replicate their DNA and this process seemed to be non-synchronous with the main cell nuclei. The presence of ErbB1 gene in the MNs was evaluated by fluorescent in situ hybridization (FISH). ErbB1 sequences were detected in the MNs, but a relation between the MNs formation and extrusion of amplified ErbB1could not be established. The present study sought to elucidate the meaning of MNs formation and its association with the elimination of oncogenes or other amplified sequences from the tumor cells.
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Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Alzheimer , Apolipoproteínas E/genética , Encéfalo/patologia , Proteínas de Transferência de Ésteres de Colesterol/genética , Polimorfismo Genético/genética , Distribuição por Idade , Atrofia , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Seguimentos , Genótipo , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Imageamento por Ressonância Magnética , Fatores de RiscoRESUMO
INTRODUÇÃO e OBJETIVOS: Os astrocitomas anaplásicos (AAs) são gliomas classificados como grau III pela OMS, constituindo um grupo intermediário de agressividade e uma zona cinzenta na atuação clínica e interpretação histológica. Além disso, o material obtido nas neurocirurgias muitas vezes é pouco representativo, seja por amostras exíguas, seja por amostragem da periferia da lesão. Metodologias como imuno-histoquímica, hibridização in situ e/ou sequenciamento tem sido amplamente utilizadas para analisar a expressão e a validação de marcadores biológicos de agressividade, reclassificar as entidades e avaliar as vias de tumorigênese, com o intuito também de direcionar a terapêutica. Nos gliomas, algumas alterações moleculares têm sido pesquisadas, como em IDH1, alfa-internexina (INA), EGFR, MGMT e nos cromossomos 1p/19q, sem caracterização precisa nos AAs. O presente estudo pretendeu avaliar tais alterações moleculares em material parafinado e correlacionar com dados clínicos e anátomo-patológicos. MATERIAL E MÉTODOS: Estudamos 22 casos de AA, com diagnóstico histopatológico confirmado por 2 patologistas. Os dados clínicos e demográficos (idade, gênero, localização, KPS ao diagnóstico, dimensão e tratamento utilizado) foram obtidos dos prontuários. A pesquisa de expressão de IDH1, INA e MGMT foi realizada por imuno-histoquímica (IHQ). A determinação do estatus 1p/19q foi realizada por FISH. A pesquisa do gene EGFR e sua expressão proteica foi realizada pelos 2 métodos (IHQ e FISH). RESULTADOS: Os pacientes incluídos neste estudo apresentaram média de idade de 41,7 anos, sendo 14 mulheres e 8 homens. A maioria dos casos era de localização intracerebral. 13 casos foram considerados "de novo" (primários) e 9 provenientes de recidivas de astrocitomas difusos. Terapia adjuvante foi realizada em 20 pacientes, sendo que em 14 pacientes a radio (RT) e a quimioterapia (QT) foram concomitantes, em 3 casos foram tratados exclusivamente com QT e 3 exclusivamente com RT. A positividade para IDH1 (R132H) foi identificado em metade dos casos. A positividade forte e de membrana para EGFR foi identificada em 4 casos. A positividade para MGMT foi identificada em praticamente todos os casos. Não foi observado nenhum caso de codeleção 1p/19q, mas 9 casos apresentaram ganhos de 1p e 7 casos ganhos de 19q. Não foi identificada positividade para INA. Foi observada associação entre ressecção cirúrgica parcial, amplificação e expressão imuno- histoquímica forte e padrão membrana de EGFR, imunonegatividade para IDH1-mutado, ganho de 19q e ausência de terapia adjuvante como fatores associados à redução da taxa de sobrevida global. Assim, status de EGFR, IDH1 e 19q, tipo de cirurgia e tratamento adjuvante parecem ser fatores prognósticos em AAs.
INTRODUCTION and AIMS: Anaplastic astrocytomas (AAs) are classified as grade III gliomas by WHO, constituing an intermediate group of malignancy and a gray zone for clinical management and histological interpretation. In addition, through technical difficulties, the material obtained from neurosurgery is often suboptimal, either by too small samples or by sampling the periphery of the lesion. Immunohistochemistry, in situ hybridization and / or sequencing has been widely used to analyze the biomarkers expression and validation, to predict aggressiveness, reclassify and evaluate tumorigenesis pathways and guide the therapeutics. In gliomas, some molecular alterations have been researched, such as IDH1, alphainternexin (INA), EGFR, MGMT and status 1p / 19q, without precise characterization in AAs. This study aimed to evaluate such molecular changes in paraffin embedded material and correlate with clinical and pathological data. MATERIALS AND METHODS: We studied 22 cases of AA, with histopathological diagnosis confirmed by two pathologists. Clinical and demographic data (age, gender, tumor location, KPS at diagnosis, size and treatment used) were obtained from medical records. IDH1 (R132H), INA and MGMT expression were evaluated by immunohistochemistry (IHC). The determination of the status 1p / 19q was evaluated by FISH. The number of EGFR gene copies and its protein expression were obtained by both methods (IHC and FISH). RESULTS: The patients included in this study had a mean age of 41.7 years, being 14 women and 8 men. Most cases were intracerebral. 13 cases were considered "de novo" (primary) and 9 relapses from diffuse astrocytomas. Adjuvant therapy was performed in 20 patients: 14 had radio (RT) and chemotherapy (CT) simultaneously, 3 were treated exclusively with CT and 3 exclusively with RT. Immunopositivity for IDH1 (R132H) was identified in half of the cases. The strong and membrane pattern positivity of EGFR was identified in 4 cases. The positivity for MGMT was identified in virtually all cases. There were no cases of 1p / 19q codeletion, but 9 cases showed gains of 1p and 7 had 19q gains. None case was positive for INA. Association was observed between partial surgical resection, amplification and strong membrane pattern EGFR imunoexpression, imunonegativity for IDH1-mutated, 19q gain and absence of adjuvant therapy as factors associated with reduced overall survival rate. Thus, status of EGFR, IDH1 and 19q, extension of surgery and adjuvant treatment appear to be prognostic factors in AA.
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Astrocitoma , Imuno-Histoquímica , Glioma , Expressão GênicaRESUMO
INTRODUÇÃO: O estudo da imunoexpressão tecidual do receptor do fator de crescimento epitelial (EGFR) pode contribuir para o entendimento de seu papel no prognóstico do carcinoma colorretal. OBJETIVO: Analisar a expressão imuno-histoquímica do EGFR no carcinoma colorretal e nos tecidos da transição tumor-mucosa e da mucosa adjacente à neoplasia. MÉTODOS: Em 40 pacientes com carcinoma colorretal operados com intenção curativa, estudou-se a imunoexpressão do EGFR com anticorpo monoclonal anti-EGFR. Foram utilizados testes paramétricos e não paramétricos. RESULTADOS: A imunoexpressão do EGFR nas amostras de tumor apresentou diferença significante em relação ao nível de imunoexpressão em espécimes de tecido da transição tumor/mucosa (p=0,01) e no nível de imunoexpressão em tecidos da mucosa adjacente (p=0,04). CONCLUSÃO: O EGFR apresentou maior imunoexpressão na mucosa do carcinoma colorretal em comparação à expressão no epitélio de transição e na mucosa adjacente não neoplásica.
INTRODUCTION: The study of tissue immunostaining epidermal growth factor receptor (EGFR) may contribute to the understanding of its role in the prognosis of colorectal carcinoma. OBJECTIVE: To analyze the immunohistochemical expression of EGFR in colorectal carcinoma tissues and in tumor-mucosa and adjacent mucosal tissues to neoplasia METHOD: The expression of EGFR with an anti-EGFR monoclonal antibody was immunohistochemically assessed in colorectal tissue samples from 40 patients with colorectal sporadic adenocarcinoma operated on with curative intent. Parametric and non-parametric tests were used. RESULTS: The immunohistochemical expression of EGFR in tumor samples showed a significant difference in the level of immunostaining in tissue specimens of transitional tumor/mucosa (p=0.01) and the level of immunoreactivity in tissues of the adjacent mucosa (p=0.04). CONCLUSION: The EGFR showed greatest expression in the mucosa of colorectal carcinoma than in the transitional epithelium and in adjacent non-neoplastic mucosa.
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Humanos , Masculino , Feminino , Imuno-Histoquímica , Fator de Crescimento Epidérmico , Biomarcadores , Neoplasias ColorretaisRESUMO
Introduction: The study of tissue immunostaining of the epidermal growth factor receptor (EGFR) may contribute with the understanding of its role in the prognosis of colorectal carcinoma. Objective: To analyze the immunohistochemical expression of EGFR in colorectal carcinoma tissues and transitional tumor-mucosa and mucosa adjacent to neoplasia, and its relation with cancer. Method: The study was conducted with 40 patients with colorectal carcinoma who had surgery with curative intent in order to analyze the immunoexpression of EGFR with anti-EGFR. We used parametric and nonparametric tests. Results: The immunohistochemical expression of EGFR in tumor samples showed a significant difference as to the level of immunostaining in tissue specimens of transitional tumor-mucosa (p=0.01) and the level of immunoreactivity in tissues of the adjacent mucosa (p=0, 04). The immunoexpression of EGFR showed no significant relation with the size of the tumor, angiolymphatic invasion, neural invasion, cellular differentiation, level of carcinoma infiltration in the intestinal wall, lymph node metastases and liver metastases. Conclusions: The EGFR showed a more intense expression in the mucosa of colorectal carcinoma than in the transitional epithelium and adjacent non-neoplastic mucosa. The immunoexpression of EGFR did not correlate with pathological parameters of colorectal carcinoma and liver metastases. (AU)
Introdução: O estudo da imunoexpressão tecidual do receptor do fator de crescimento epitelial (EGFR) pode contribuir para o entendimento de seu papel no prognóstico do carcinoma colorretal. Objetivo: Analisar a expressão imuno-histoquímica do EGFR no carcinoma colorretal e nos tecidos da transição tumor-mucosa e da mucosa adjacente à neoplasia, e avaliar a relação com os aspectos anatomopatológicos da neoplasia. Método: Em 40 doentes com carcinoma colorretal operados com intenção curativa, estudou-se a imunoexpressão do EGFR com anticorpo anti-EGFR. Foram utilizados testes paramétricos e não paramétricos. Resultados: A imunoexpressão do EGFR nas amostras de tumores apresentou diferença significante, em relação ao nível de imunoexpressão em espécimes de tecido da transição tumor-mucosa (p=0,01), e ao nível de imunoexpressão em tecidos da mucosa adjacente (p=0,04). A imunoexpressão do EGFR não apresentou relação significante com o tamanho da neoplasia, invasão angiolinfática, invasão neural, grau de diferenciação celular, nível de infiltração do carcinoma na parede intestinal, acometimento linfonodal e metástase hepática. Conclusões: O EGFR apresentou maior imunoexpressão na mucosa do carcinoma colorretal do que no epitélio de transição e na mucosa adjacente não neoplásica. A imunoexpressão do EGFR não se relacionou com os parâmetros anatomopatológicos do carcinoma colorretal e com a presença de metástase hepática. (AU)
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/diagnóstico , Receptores ErbB , Imuno-Histoquímica , Neoplasias Colorretais/patologia , Mucosa Intestinal/patologia , Metástase NeoplásicaRESUMO
Se realizó un estudio de tipo descriptivo, retrospectivo con el objetivo de evaluar el estado de amplificación de los oncogenes ErbB-1 y ErbB-2 mediante la técnica de FISH en un grupo de casos de cáncer de mama del Instituto Nacional de Cancerología. Se incluyeron 50 casos y las muestras empleadas fueron bloques de tejido incluidos en parafina, pertenecientes a biopsias de diagnóstico o mastectomías de las pacientes después de haber recibido o no quimioterapia coadyuvante. Se encontró un 18% de casos positivos para la amplificación de ErbB-2 y ningún caso amplificado para ErbB-1. Se observó una asociación altamente significativa entre la amplificación de ErbB-2 con el compromiso ganglionar (p=0.006), y una tendencia de los casos amplificados a la negatividad en los receptores de estrógeno y progesterona (p=0.06). En los casos no amplificados para ErbB-1 y ErbB-2 se evaluó la presencia de heterogeneidad genética intratumoral, detectando además de la amplificación diferentes poblaciones celulares disómicas y monosómicas
It was a retrospective and descriptive study, the aim of this was to evaluate the status of the ERbB1 and ErbB2 oncogenes by FISH in a group of cases in breast cancer of the Institute National of Cancer of Colombia. There were fifty cases with samples of the paraffin blocks of biopsies and specimens of mastectomies with diagnosis of breast cancer of patients with or without chemotherapy adjuvant. In this study was found 18% positive cases to the ErbB2 amplification and none case showed ErbB1 amplification. The association between the ErbB2 amplification and lymph node compromised was a high significative statistic level (p= 0.06) with tend to estrogenic and progesterone receptors negatives (p=0.06). In the cases without ErbB1 and erbB2 amplification were evaluated for the presence of the intratumoral heterozigocity found population cellular different disomic and monosomic