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The morbidity and mortality of lung cancer rank first in the world. Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) can significantly prolong survival of patients with advanced non-small cell lung cancer (NSCLC). 18F-FDG PET/CT can evaluate EGFR mutation status and EGFR-TKI efficacy. This article reviews the role of 18F-FDG PET/CT in predicting EFGR mutation, the efficacy and survival prognosis evaluation of EGFR-TKI therapy, as well as the development of latest EGFR-TKI PET imaging agents.
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Objective:To investigate the value of pre-therapy 18F-FDG PET/CT radiomic models in differentiating epidermal growth factor receptor (EGFR) exon 19 deletion from exon 21 L858R missense in patients with non-small cell lung cancer (NSCLC). Methods:A total of 172 patients with EGFR mutant NSCLC (54 males, 118 females, age: (56.2±12.5) years) in the Fourth Hospital of Hebei Medical University between January 2015 and November 2019 were retrospectively included. Exon 19 mutation was found in 75 patients and exon 21 mutation was identified in 97 patients. The patients were divided into training set ( n=121) and validation set ( n=51) in a 7∶3 ratio by using random number table. The LIFEx 4.00 package was used to extract texture features of PET/CT images of lesions. The least absolute shrinkage and selection operator (LASSO) algorithm was used for feature screening. Three machine learning models, namely logistic regression (LR), random forest (RF), and support vector machine (SVM) models, were constructed based on the selected optimal feature subsets. The ROC curve analysis was performed to assess the predictive performance of those models. Finally, decision curve analysis (DCA) was used to evaluate the clinical value of the models. Results:Nine radiomics features, including 6 PET features (histogram (HISTO)_Kurtosis, SHAPE_Sphericity, gray level run length matrix (GLRLM)_ low gray-level run emphasis (LGRE), GLRLM_ run length non-uniformity (RLNU), neighborhood grey level different matrix (NGLDM)_Contrast, gray level zone length matrix (GLZLM)_ short-zone low gray-level emphasis (SZLGE)), and 3 CT features (gray level co-occurrence matrix (GLCM)_Correlation, GLRLM_ run percentage (RP), NGLDM_Contrast), were screened by LASSO algorithm. Three machine learning models had similar predictive performance in the training and validation sets: AUCs for the RF model were 0.79, 0.77, and those for the SVM model were 0.76, 0.75, for the LR model were 0.77, 0.75. The DCA showed that the 3 machine learning models had good net benefits and clinical values in predicting EGFR mutation subtypes.Conclusion:18F-FDG PET/CT radiomics provide a non-invasive method for the identification of EGFR exon 19 deletion and exon 21 L858R missense mutations in patients with NSCLC, which may help the clinical decision-making and the formulation of individualized treatment plan.
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Objective:To construct and validate a nomogram model based on clinical factors and PET/CT metabolic parameters of 18F-FDG for predicting epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma. Methods:From January 2014 to January 2019, 114 patients (59 males, 55 females, age (60.0±10.8) years) with lung adenocarcinoma in the First Affiliated Hospital of Harbin Medical University were retrospectively enrolled. Clinical data (smoking status, tumor location, clinical stage and carcinoembryonic antigen (CEA) level), 18F-FDG PET/CT metabolic parameters (SUV max, metabolic tumor volume (MTV) and total lesion glycolysis (TLG)) and EGFR mutation status were analyzed. Patients were divided into training group (80 cases) and validation group (34 cases). In the training group, univariate analyses (independent-sample t test, Wilcoxon rank sum test, χ2 test or Fisher′s exact probability method) were used for categorical variables. Variables that showed significant differences between EGFR mutation group and wild type group were selected. Variance inflation factors (VIF) were calculated and the collinearity variables were deleted, and a nomogram model of optimal logistic model was constructed based on Akaike information criterion (AIC). The effect of the model was evaluated by the concordance index (C-index), sensitivity, specificity, accuracy, calibration and decision curve analysis (DCA) in the training group and the validation group. Results:Among 114 patients, 56 were with EGFR mutations and 58 were with EGFR wild type. In the training group, there were significant differences in gender (male/female: 14/26 vs 25/15; χ2=6.05, P=0.014), smoking status (with/without smoking history: 4/36 vs 22/18; χ2=18.46, P<0.001) and SUV max (5.72(3.90, 8.32) vs 8.09(4.56, 12.55); W=1 045.50, P=0.018) between EGFR mutation group and wild type group. However, there were no significant differences in other factors ( t=-0.54, χ2 values: 0.20 and 0.20, W values: 921.50 and 983.00, all P>0.05). The VIF of gender, smoking status and SUV max were all less than 10, and the nomogram model with three factors showed the minimum AIC (90.06). In the training group, C-index value of the model was 0.798 (95% CI: 0.699-0.897), with the sensitivity of 85.0%(34/40), the specificity of 70.0%(28/40) and the accuracy of 77.5%(62/80). In the validation group, C-index value was 0.854(95% CI: 0.725-0.984), with the sensitivity of 13/16, the specificity of 14/18, and the accuracy of 79.4%(27/34). The calibration curve and the goodness of fit test showed good calibration, and DCA showed that the model could benefit patients clinically within a large risk threshold range (training group: 0-0.59, validation group: 0-0.65). Conclusion:The nomogram model based on gender, smoking status and SUV max can be used to easily predict EGFR mutation status in lung adenocarcinoma.
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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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Humans , Male , Female , Genes, erbB-1 , ErbB Receptors , Squamous Cell Carcinoma of Head and Neck/pathology , Head and Neck Neoplasms/pathology , Mutation , Protein-Tyrosine KinasesABSTRACT
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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Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Polymorphism, Genetic/genetics , Brain Neoplasms/genetics , Apoptosis/genetics , Glioma/genetics , Brain Neoplasms/pathology , Brain Neoplasms/therapy , Combined Modality Therapy , Antineoplastic Agents, Alkylating/administration & dosage , Dacarbazine/administration & dosage , Dacarbazine/analogs & derivatives , Kaplan-Meier Estimate , Real-Time Polymerase Chain Reaction , Temozolomide , Genotype , Glioma/pathology , Glioma/therapy , Life Style , Neovascularization, PathologicABSTRACT
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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Humans , Male , Female , Adult , Aged , Aged, 80 and over , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/pathology , Cholangiocarcinoma/mortality , Cholangiocarcinoma/pathology , ErbB Receptors/analysis , Prognosis , Reference Values , Staining and Labeling , Immunohistochemistry , Sex Distribution , Kaplan-Meier Estimate , Middle AgedABSTRACT
Objective To explore the effectiveness of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) patients with EGFR double mutations containing rare mutations.Methods From March 2007 to January 2017,NSCLC patients with EGFR double mutations containing rare mutations confirmed by histopathology and EGFR mutation detections at Renmin Hospital of Wuhan University,Zhongnan Hospital of Wuhan University and Hubei Cancer Hospital were enrolled.According to the mutation types,patients were divided into double activating mutations group and activating mutations with insensitive mutations group.The effectiveness of TKIs in NSCLC patients with EGFR double mutations containing rare mutations and different mutation types was analysis.Results Among the 2 637 NSCLC patients underwent EGFR mutation detections,19 patients were confirmed as EGFR double mutations containing rare mutations.Fifteen patients received EGFR-TKIs therapy,the objective response rate (ORR),disease control rate (DCR) and median progression free survival (PFS) were 46.7% (7/15),73.3% (11/15) and 8.1 months,respectively.In patients with double activating mutations,two patients had partial response (PR),one patient had a stable disease (SD).In the activating mutations with insensitive mutations group,five patients had PR,three patients had SD,four patients had no effect.Conclusion Patients with EGFR double mutations containing rare mutations have a general response to EGFR-TKIs,and this result can provide a reference for the treatment of those patients.
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Objective To investigate the relationship between epidermal growth factor receptor (EGFR) gene mutation and computed tomography (CT) features and clinical features in non-small cell lung cancer (NSCLCs) patients. Methods The clinical data of 187 patients with NSCLCs admitted in our hospital from September 2014 to July 2016 were retrospectively analyzed. All the patients accepted the EGFR mutated gene detection, and they were divided into effective mutation group (n=67) and non-effective mutation group (n=120). The clinical data and lung CT imaging data were complete in the two groups. The univariate and multivariate Logistic regression analysis were used to analyze the differences of imaging and clinical features between the two groups. Results Comparing with the non-mutation group, there were higher proportion of women and lower smoking index in the EGFR effective mutation group. Lesions in the lung tissue showed a clear edge, leaf and burr, and containing ground-glass opacity (GGO) component, usually accompanied by airway bronchogram and pleural indentation, and associated with cancer lymphatic inflammation and lung metastasis in mutation group (all P < 0.05). There were no significant differences in the proportion of necrosis, cavitation, calcification, halo sign and vacuole sign between the two groups (P > 0.05). Logistic regression analysis showed that female, GGO containing composition, burr, air bronchogram, carcinomatous lymphangitis and lesion density showed obvious airway involvement were the predictive risk factors in patients with EGFR effective mutation. Conclusion The EGFR mutation occurs more oftern in female. The reliable predictive signs of CT include GGO composition, burr, airway bronchogram and carcinoid lymphangitis. In critical patients who are not easy to obtain clinical pathology, it has a guiding significance to radiographic assessment for EGFR effective mutation.
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Objective@#To investigate the efficacy of tyrosine kinase inhibitor (TKI) treatment on non-small cell lung cancer (NSCLC) patients with postoperative recurrence who harbored uncommon EGFR mutations, and discuss the relationship between TKI treatment and prognosis.@*Methods@#A total of 39 relapsed NSCLC patients after surgery with EGFR uncommon mutations who were detected at Cancer Hospital, Chinese Academy of Medical Sciences between January 1999 and December 2013 were retrospectively analyzed in this study. Twenty patients were treated with EGFR-TKI after recurrence and 19 cases were not. The clinical characteristics of patients with EGFR uncommon mutations were evaluated, and the prognosis of TKI-treatment group and non-TKI treatment group was compared.@*Results@#In 39 relapsed NSCLC patients with EGFR uncommon mutations, insertion mutations and point mutations were included. The highest frequency of EGFR uncommon mutation happened in exon 20 (20/39, 51.3%). A total of 13 uncommon point mutations were detected in exon 18, 20 and 21. The most frequent rare point mutations located in exon 21, and there were 7 different point mutation sites in exon 21. G719S/C/A mutation in exon 18 was the most common type of point mutation (14/25, 56.0%). Survival after postoperative recurrence in TKI treatment group was obviously better than that in non-TKI treatment group, the median time after recurrence were 44 months and 23 months, respectively (P=0.044). However, the postoperative overall survival showed no differences between two groups (48 months vs 43 months, P=0.129).@*Conclusion@#NSCLC patients with postoperative recurrence who harbored rare EGFR mutations should be treated with TKI agent.
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Somatic mutations that lead to hyperactivation of epidermal growth factor receptor (EGFR) signaling are detected in approximately 50% of lung adenocarcinoma in people from the Far East population and tyrosine kinase inhibitors are now the standard first line treatment for advanced disease. They have led to a doubling of progression-free survival and an increase in overall survival by more than 2 years. However, emergence of resistant clones has become the primary cause for treatment failure, and has created a new challenge in the daily management of patients with EGFR mutations. Identification of mechanisms leading to inhibitor resistance has led to new therapeutic modalities, some of which have now been adapted for patients with unsuccessful tyrosine kinase inhibitor treatment. In this review, we describe mechanisms of tyrosine kinase inhibitor resistance and the available strategies to overcoming resistance.
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Humans , Adenocarcinoma , Clone Cells , Disease-Free Survival , Drug Resistance , Epidermal Growth Factor , Asia, Eastern , Genes, erbB-1 , Lung , Protein-Tyrosine Kinases , ErbB Receptors , Treatment FailureABSTRACT
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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Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Quinazolines/therapeutic use , Adenocarcinoma/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/secondary , Brazil , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/secondary , Erlotinib Hydrochloride , Follow-Up Studies , Hospitals, General , Hospitals, Proprietary , Lung Neoplasms/mortality , Lung Neoplasms/secondary , Mutation/genetics , Retrospective Studies , ErbB Receptors/genetics , Sex Distribution , Survival Rate , Treatment OutcomeABSTRACT
BACKGROUND: Glioblastomas may develop de novo (primary glioblastomas, P-GBLs) or through progression from lower-grade astrocytomas (secondary glioblastomas, S-GBLs). The aim of this study was to compare the immunohistochemical classification of glioblastomas with clinically determined P-GBLs and S-GBLs to identify the best combination of antibodies for immunohistochemical classification. METHODS: We evaluated the immunohistochemical expression of epidermal growth factor receptor (EGFR), p53, and isocitrate dehydrogenase 1 (IDH-1) in 150 glioblastoma cases. RESULTS: According to clinical history, the glioblastomas analyzed in this study consisted of 146 P-GBLs and 4 S-GBLs. Immunohistochemical expression of EGFR, p53, and IDH-1 was observed in 62.6%, 49.3%, and 11.1%, respectively. Immunohistochemical profiles of EGFR(+)/p53(-), IDH-1(-)/EGFR(+)/p53(-), and EGFR(-)/p53(+) were noted in 41.3%, 40.2%, and 28.7%, respectively. Expression of IDH-1 and EGFR(-)/p53(+) was positively correlated with young age. The typical immunohistochemical features of S-GBLs comprised IDH-1(+)/EGFR(-)/p53(+), and were noted in 3.6% of clinically P-GBLs. The combination of IDH-1(-) or EGFR(+) was the best set of immunohistochemical stains for identifying P-GBLs, whereas the combination of IDH-1(+) and EGFR(-) was best for identifying S-GBLs. CONCLUSIONS: We recommend a combination of IDH-1 and EGFR for immunohistochemical classification of glioblastomas. We expect our results to be useful for determining treatment strategies for glioblastoma patients.
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Humans , Antibodies , Astrocytoma , Classification , Coloring Agents , Genes, erbB-1 , Genes, p53 , Glioblastoma , Immunohistochemistry , Isocitrate Dehydrogenase , ErbB ReceptorsABSTRACT
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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Humans , Male , Female , Immunohistochemistry , Epidermal Growth Factor , Biomarkers , Colorectal NeoplasmsABSTRACT
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)
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Colorectal Neoplasms/diagnosis , ErbB Receptors , Immunohistochemistry , Colorectal Neoplasms/pathology , Intestinal Mucosa/pathology , Neoplasm MetastasisABSTRACT
Objective To detect epidermal growth factor receptor (EGFR) 19, 21 exon gene mutation and gene copy number in lung adenocarcinoma tissue, and to analyze the relationship of EGFR 19, 21 mutation with copies number. MethodsEGFR mutations and gene copy number in the tissue samples embedded by paraffin and fixed by for marlin from 58 cases of lung adenocarcinoma were detected by RT-PCR and FISH. The statistical data were analyzed by chi-square test.ResultsOf 58 cases, the overall single mutation rate of EGFR exon 19, 21 was 43.1% (25/58), and 2 cases contained both types of the mutation.The overall FISH positive rate of EGFR was 51.7 % (30/58), including 8 positive amplification and 22 highly ploidy amplification. The testing results showed that there had no statistically differences in FISH positive rates of EGFR mutation among different differentiation lung adenocarcinoma tissues(P >0.05), and the FISH positive rates of EGFR mutation in poorly differentiated cancer were lower than those in moderatedly differentiated and well-differentiated cancer (P <0.05). EGFR mutation was closely related to EGFR gene copies (P <0.01). ConclusionThere are high EGFR mutation frequencies and FISH positive rates in lung adenocarcinoma tissue; Combined detection of EGFR mutation and gene copy number may provide a better approach in selecting patients who may benefit from anti-EGFR target therapy.
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The main therapies of NSCLC are surgery, chemotherapy, radiotherapy and targeted therapy. With development of targeted therapy, it was found that tyrosine kinase inhibitor(TKI) for patients with mutations in the EGFR gene was effective. Screening of such drugs before treatment is a premise of individualized treatment, and tissue samples are the current gold standard for genetic testing. However, it is hard to acquire the tumor tissues of patients with advanced NSCLC, so EGFR mutations detection of free DNA in peripheral blood had become an option. This article reviews the detections of TKIs-sensitive mutation,exon 19/21 mutation, and TKIs-acquired resistant mutation, T790M mutation at exon20, in serum or plasma of NSCLC patients.
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Objective To observe the influence of specific short hairpin siRNA targeting EGFR gene on apoptosis of human ovarian cancer Skov-3 cells in vitro. Methods A plasmid of a short hairpin siRNA targeting EGFR was constructed, and it was transfeeted into Skov-3 cell line by lipofectamine 2000. Human ovarian carcinoma cells of the line Skov-3 were cultured and divided into 3 groups: control group; non-specific group, transfected with non-specific plasmid vector; and specific group, transfected with specific small hairpin RNA expression vector. The expression of EGFR mRNA and protein were examined by RT-PCR and immunocytochemistry, Flow cytometry (FCM) was adopted to analyze quantitatively apoptotic cells in each group. Results After transfection of pshRNA-EGFR, mRNA and protein levels of EGFR gene in Skov-3 cells were obviously reduced. Flow cytometry analysis revealed that apoptosis could be induced in Skov-3 cells line transfected with pshRNA-EGFR in a time-dependent manner, no obvious apoptosis were detected in control group and non-specific group. Conclusion The plasmid expressive vector target at EGFR in our study is capable of suppressing EGFR expression of human ovarian cancer Skov-3 cells and inducing apoptosis, which provide a new way for the gene therapy of human ovarian cancer.
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ObjectiveTo investigate mutations in exons 19, 20 and 21 of epidermal growth factor receptor (EGFR) gene in elderly patients with non-small cell lung cancer (NSCLC). MethodsEGFR gene mutations in exons 19, 20 and 21 were detected by nested PCR amplification and DNA sequencing in 46 elderly patients with non-small cell lung cancer. The relationship between mutations and clinical characteristics of these patients was analyzed. ResultsEGFR gene mutations were found in 56.5% (26/46) patients and 41.3% (19/46)were non-silent mutations. Mutation of exon 19 was detected in 6 cases (13.0%), mutation of exon 20 in 13 cases(28.2%) and that of exon 21 in 14 cases (30.4%). Seven patients among them had double mutations and the rest only had a single mutation. The incidence of EGFR gene mutations was higher in non-smokers than in smokers(P< 0.01). Higher EGFR mutation rate in exon 19, 20 and 21 were found in patients with clinical benefit who were treated with tyrosine kinase inhibitor(TKl)(P<0.05). There was no difference in EGFR mutation rate between 60~69 age group and 70~85 age group. ConclusionsThe data suggest that the characteristics of EGFR gene mutations in elderly patients with NSCLC is the same as in the general NSCLC patients. The forecast informations of TKI treatment can be obtained by gene detection in elderly NSCLC patients.
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Objective To study Caveolin-1,EGFR expression in bladder transitional call carcinoma and their prognostic value. Methods Immunohistochemical method was used to detect Caveolin-1,EGFR in 89 cases.of bladder transitional call carcinoma.Results In 89 cases,the percentage of abnormal Caveolin-1 and EGFR expression were 37.1% and 50.6 % respectively.Significant change was observed in different grade case,P
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ObjectiveTo find a new approach of transfecting the objective gene safely and effectively according to the cavitation effect of ultrasound mediated microbubble destruction which could increase the permeability of macromolecule (such as DNA) across the eucell membrane.MethodsEGFP gene was transfected to Cos 7 cell as mark one in vitro by ultrasound mediated microbubble destruction and liposome as control. The transfection effect was surveyed by laser microscope and flow cytometry qualitively and quantitively. Trypan blue staining was adopted to measure the cell vitality.ResultsUltrasound mediated microbubble destruction at 0.8 MHz , 1.0 W/cm 2, 10% duty cycle, 60 s can get the most stable effective expression of EGFP gene in Cos 7 cell and no cytotoxicity. ConclusionsAlbumin microbubble made by us is a new and effective carrier of objective gene in gene therapy. At some specific ultrasound condition, microbubble destruction can enhance the objective gene transfection and expression and have a good targetivation. Ultrasound mediated destruction of albumin coated microbubble is a promising method in gene therapy.