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[PMID]:29484748
[Au] Autor:Peurala E; Tuominen M; Löyttyniemi E; Syrjänen S; Rautava J
[Ad] Endereço:Department of Oral Pathology and Oral Radiology, Institute of Dentistry, Faculty of Medicine, University of Turku, Turku, Finland.
[Ti] Título:Eosinophilia is a favorable prognostic marker for oral cavity and lip squamous cell carcinoma.
[So] Source:APMIS;126(3):201-207, 2018 Mar.
[Is] ISSN:1600-0463
[Cp] País de publicação:Denmark
[La] Idioma:eng
[Ab] Resumo:Eosinophils are frequently encountered with squamous cell carcinomas (SCC) and it has been proposed that tumor-associated tissue eosinophilia (TATE) could be of prognostic significance in oral SCC. The aim was to evaluate TATE in 83 oral cavity and 16 lip SCCs as well as the best possible use of TATE as a prognostic marker. The number of eosinophils was counted per high power fields (HPF, ×400) in three different representative areas of the tumor and its stroma. The degree of TATE was analyzed in relation to clinicopathological features of tumors and patients' survival (follow-up mean 40.7 months) using Fisher's exact test. TATE was detected in 58 (70%) oral and 8 (50%) lip SCC samples. The median number of eosinophils between oral and lip SCC was different (p = 0.028) but TATE was similar per HPF (p = 0.085). Totally, 6% of lip and 21% of oral SCC patients died during the follow-up. The patients with the higher TATE had significantly better survival than the patients with the lower TATE (p = 0.0136). The best cut-off value predicting the survival was 4 eosinophils/HPF. TATE is a prognostic marker for oral and lip SCC: more than 4 eosinophils/HPF may predict more favorable prognosis.
[Mh] Termos MeSH primário: Carcinoma de Células Escamosas/patologia
Eosinofilia/patologia
Eosinófilos/patologia
Neoplasias Labiais/patologia
Lábio/patologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Consumo de Bebidas Alcoólicas/efeitos adversos
Biomarcadores Tumorais/metabolismo
Carcinoma de Células Escamosas/mortalidade
Intervalo Livre de Doença
Eosinófilos/citologia
Feminino
Seres Humanos
Contagem de Leucócitos
Neoplasias Labiais/mortalidade
Masculino
Meia-Idade
Estudos Retrospectivos
Fumar/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180228
[St] Status:MEDLINE
[do] DOI:10.1111/apm.12809


  2 / 115838 MEDLINE  
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[PMID]:29399882
[Au] Autor:Mitra S; Chatterjee D; Das A; Gupta K; Radotra BD; Mandal AK
[Ad] Endereço:Department of Histopathology, PGIMER, Chandigarh, India.
[Ti] Título:Urothelial tumors with villous morphology: Histomorphology and role of immunohistochemistry in diagnosis.
[So] Source:APMIS;126(3):191-200, 2018 Mar.
[Is] ISSN:1600-0463
[Cp] País de publicação:Denmark
[La] Idioma:eng
[Ab] Resumo:Villous adenoma and urothelial carcinoma with villoglandular differentiation (UCVGD) are rare urothelial tumours showing villous morphology, the former being a preneoplastic entity and the latter being a malignant one. The detailed immunohistochemistry of these entities is previously not described in the literature. Moreover, a limited biopsy sample of UCVGD or a villous adenoma with or without adenocarcinoma may be difficult to distinguish on the basis of the histomorphology alone. An immunohistochemical panel comprising of GATA3, p63, ß-catenin, CK7 and CK20 was performed on five cases of UCVGD and three cases of villous adenoma with the aim of studying the expression of the proteins thereby aiding in the diagnosis of these entities in a limited surgical pathology specimen. The mean age of UCVGD was 66.8 years and all the patients were male. All the cases of UCVGD were associated with high grade papillary urothelial carcinoma with lamina propria invasion. The immunohistochemical panel showed strong nuclear GATA3 expression in the urothelial component of UCVGD. Interestingly, the high grade and the low grade villoglandular components of UCVGD also expressed GATA3 (nuclear) with a progressive loss of expression from the high grade to the low grade component. The villous adenomas showed negativity or aberrant cytoplasmic positivity for GATA3. The ß-catenin showed a gradual loss of membranous expression from villous adenoma to low grade and high grade villoglandular components of UCVGD with a patchy membranous expression in the urothelial component of the UCVGD. p63 showed strong nuclear positivity in the urothelial component and uniform negativity in the villous adenoma and villoglandular component of UCVGD irrespective of its grade, thereby distinguishing the villoglandular component from the urothelial component. The urothelial component of UCVGD showed strong membranous CK7 expression and was higher than the CK20 expression in the urothelial component. In contrast, CK20 expression was higher in villous adenoma as compared to CK7. There was no difference in the expression of CK7 and CK20 in the villoglandular components and low grade and high grade villoglandular areas. The above-mentioned immunohistochemical pattern may help to distinguish the UCVGD from the villous adenoma.
[Mh] Termos MeSH primário: Adenoma Viloso/diagnóstico
Fator de Transcrição GATA3/metabolismo
Queratina-7/metabolismo
Proteínas de Membrana/metabolismo
Neoplasias Urológicas/diagnóstico
beta Catenina/metabolismo
[Mh] Termos MeSH secundário: Adenoma Viloso/patologia
Idoso
Biomarcadores Tumorais/metabolismo
Feminino
Hematúria/patologia
Seres Humanos
Imuno-Histoquímica
Queratina-20/metabolismo
Masculino
Meia-Idade
Neoplasias Urológicas/patologia
Urotélio/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (CKAP4 protein, human); 0 (GATA3 Transcription Factor); 0 (GATA3 protein, human); 0 (KRT20 protein, human); 0 (KRT7 protein, human); 0 (Keratin-20); 0 (Keratin-7); 0 (Membrane Proteins); 0 (beta Catenin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180206
[St] Status:MEDLINE
[do] DOI:10.1111/apm.12799


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[PMID]:29381830
[Au] Autor:Sioud M
[Ad] Endereço:Department of Cancer Immunology, Oslo University Hospital, The Norwegian Radium Hospital, Montebello, Oslo, Norway.
[Ti] Título:T-cell cross-reactivity may explain the large variation in how cancer patients respond to checkpoint inhibitors.
[So] Source:Scand J Immunol;87(3), 2018 Mar.
[Is] ISSN:1365-3083
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The therapeutic use of the immune system to specifically attack tumours has been a long-standing vision among tumour immunologists. Recently, the use of checkpoint inhibitors to turn-off immunosuppressive signals has proven to be effective in enhancing T-cell reactivity against patient-specific neoantigens, resulting from somatic mutations. Several of the identified T-cell epitopes share similarity with common bacterial and viral antigens, suggesting the involvement of pre-existing microbial cross-reactive T cells in rapid and durable tumour regression seen in some patients. This notion of T-cell cross-reactivity is further supported by the findings that intestinal bacteria can influence checkpoint-blockade therapy. Moreover, early data indicate the presence of such T cells in long-term survival breast cancer patients. This review highlights the main challenges for cancer immunotherapy and discusses the potential contribution of T-cell cross-reactivity in cancer immunotherapy and whether it can be used as a biomarker to predict the responsiveness to checkpoint inhibitors.
[Mh] Termos MeSH primário: Reações Cruzadas/imunologia
Imunoterapia/métodos
Neoplasias/imunologia
Neoplasias/terapia
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Antígenos de Bactérias/imunologia
Antígenos de Neoplasias/imunologia
Antígenos Virais/imunologia
Biomarcadores Tumorais/imunologia
Antígeno CTLA-4/antagonistas & inibidores
Células Dendríticas/imunologia
Epitopos de Linfócito T/imunologia
Seres Humanos
Ativação Linfocitária/imunologia
Receptor de Morte Celular Programada 1/antagonistas & inibidores
Receptores Imunológicos/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antigens, Bacterial); 0 (Antigens, Neoplasm); 0 (Antigens, Viral); 0 (Biomarkers, Tumor); 0 (CTLA-4 Antigen); 0 (Epitopes, T-Lymphocyte); 0 (PDCD1 protein, human); 0 (Programmed Cell Death 1 Receptor); 0 (Receptors, Immunologic); 0 (TIGIT protein, human)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180131
[St] Status:MEDLINE
[do] DOI:10.1111/sji.12643


  4 / 115838 MEDLINE  
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[PMID]:29366405
[Au] Autor:Walaszczyk A; Pietrowska M; Wojakowska A; Abramowicz A; Chmura A; Maslyk B; Rodziewicz P; Polanska J; Behrendt K; Nowicka E; Tarnawski R; Widlak P
[Ti] Título:Therapy-Related Changes in the Serum Proteome Patterns of Early Stage Breast Cancer Patients with Different Outcomes.
[So] Source:Protein Pept Lett;24(1):37-45, 2017.
[Is] ISSN:1875-5305
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Adjuvant chemo- and/or radiotherapy is applied in a majority of patients treated for early stage breast cancer, although only a small percentage of these individuals are at high risk of metastasis or recurrence. Hence, knowledge of the biomarkers associated with the risk of disease progression might facilitate the planning of an optimal therapy and protect many patients from the toxicity of unnecessary treatment. In this study, we characterized the serum proteome of patients diagnosed with early-stage breast cancer, exhibiting either no evidence of disease five years after the end of therapy or suffering from metastasis, relapse or a second cancer during the corresponding follow-up. Samples collected before treatment and one year after the end of therapy, when no clinical symptoms of a treatment failure was evidenced, were analyzed using two classical proteomics approaches: LC-MS/MS and 2D-PAGE. A total of 42 proteins with relative quantities that were significantly different between pre- and post-treatment samples were identified in either group of patients; however, the observed changes were more frequent in the treatment-failure group. Among the posttreatment samples, 30 proteins were upregulated, and 10 proteins were downregulated, while 11 proteins were upregulated, and eight proteins were downregulated in the control group. Moreover, several proteins exhibited different patterns of changes in both groups of patients. For example, haptoglobin expression increased in the treatment-failure group but decreased in the control group (this pattern of changes was confirmed using an immunoassay). Notably, proteins affected in posttreatment samples in either group of patients could be associated with different molecular and cellular functions, including angiogenesis, blood coagulation and wound healing in the treatment-failure group and cell adhesion and cell death in the control group.
[Mh] Termos MeSH primário: Proteínas Sanguíneas/análise
Neoplasias da Mama/sangue
Neoplasias da Mama/terapia
[Mh] Termos MeSH secundário: Idoso
Biomarcadores Tumorais/análise
Biomarcadores Tumorais/sangue
Eletroforese em Gel Bidimensional
Feminino
Haptoglobinas/análise
Seres Humanos
Meia-Idade
Proteoma/análise
Proteômica
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Blood Proteins); 0 (Haptoglobins); 0 (Proteome)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180126
[St] Status:MEDLINE
[do] DOI:10.2174/0929866523666161128154412


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[PMID]:28456787
[Au] Autor:Hichert V; Scholl C; Steffens M; Paul T; Schumann C; Rüdiger S; Boeck S; Heinemann V; Kächele V; Seufferlein T; Stingl J
[Ad] Endereço:Research Division, Federal Institute for Drugs and Medical Devices, Bonn, Germany.
[Ti] Título:Predictive blood plasma biomarkers for EGFR inhibitor-induced skin rash.
[So] Source:Oncotarget;8(21):35193-35204, 2017 May 23.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Epidermal growth factor receptor overexpression in human cancer can be effectively targeted by drugs acting as specific inhibitors of the receptor, like erlotinib, gefitinib, cetuximab and panitumumab. A common adverse effect is a typical papulopustular acneiform rash, whose occurrence and severity are positively correlated with overall survival in several cancer types. We studied molecules involved in epidermal growth factor receptor signaling which are quantifiable in plasma, with the aim of identifying biomarkers for the severity of rash. With a predictive value for the rash these biomarkers may also have a prognostic value for survival and disease outcome.The concentrations of amphiregulin, hepatocyte growth factor (HGF) and calcidiol were determined by specific enzyme-linked immunosorbent assays in plasma samples from 211 patients.We observed a significant inverse correlation between the plasma concentration of HGF and overall survival in patients with an inhibitor-induced rash (p-value = 0.0075; mean overall survival low HGF: 299 days, high HGF: 240 days) but not in patients without rash. The concentration of HGF was also significantly inversely correlated with severity of rash (p-value = 0.00124).High levels of HGF lead to increased signaling via its receptor MET, which can activate numerous pathways which are normally also activated by epidermal growth factor receptor. Increased HGF/MET signaling might compensate the inhibitory effect of epidermal growth factor receptor inhibitors in skin as well as tumor cells, leading to less severe skin rash and decreased efficacy of the anti-tumor therapy, rendering the plasma concentration of HGF a candidate for predictive biomarkers.
[Mh] Termos MeSH primário: Exantema/induzido quimicamente
Fator de Crescimento de Hepatócito/sangue
Neoplasias/sangue
Neoplasias/tratamento farmacológico
Inibidores de Proteínas Quinases/administração & dosagem
Proteínas Proto-Oncogênicas c-met/sangue
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Anfirregulina/sangue
Biomarcadores Tumorais/sangue
Calcifediol/sangue
Cetuximab/administração & dosagem
Cetuximab/efeitos adversos
Cloridrato de Erlotinib/administração & dosagem
Cloridrato de Erlotinib/efeitos adversos
Exantema/sangue
Feminino
Seres Humanos
Masculino
Meia-Idade
Neoplasias/genética
Neoplasias/metabolismo
Estudos Prospectivos
Inibidores de Proteínas Quinases/efeitos adversos
Quinazolinas/administração & dosagem
Quinazolinas/efeitos adversos
Receptor do Fator de Crescimento Epidérmico/antagonistas & inibidores
Receptor do Fator de Crescimento Epidérmico/genética
Transdução de Sinais/efeitos dos fármacos
Análise de Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AREG protein, human); 0 (Amphiregulin); 0 (Biomarkers, Tumor); 0 (HGF protein, human); 0 (Protein Kinase Inhibitors); 0 (Quinazolines); 67256-21-7 (Hepatocyte Growth Factor); DA87705X9K (Erlotinib Hydrochloride); EC 2.7.10.1 (EGFR protein, human); EC 2.7.10.1 (MET protein, human); EC 2.7.10.1 (Proto-Oncogene Proteins c-met); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); P6YZ13C99Q (Calcifediol); PQX0D8J21J (Cetuximab); S65743JHBS (gefitinib)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.17060


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[PMID]:29267504
[Au] Autor:Mendes GA; Haag T; Trott G; Rech CGSL; Ferreira NP; Oliveira MC; Kohek MB; Pereira-Lima JFS
[Ad] Endereço:Programa de Pós-Graduação em Patologia, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brasil.
[Ti] Título:Expression of E-cadherin, Slug and NCAM and its relationship to tumor invasiveness in patients with acromegaly.
[So] Source:Braz J Med Biol Res;51(2):e6808, 2017 Dec 11.
[Is] ISSN:1414-431X
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:Pituitary adenomas account for 10-15% of primary intracranial tumors. Growth hormone (GH)-secreting adenomas account for 13% of all pituitary adenomas and cause acromegaly. These tumors can be aggressive, invade surrounding structures and are highly recurrent. The objective of this study was to evaluate E-cadherin, Slug and neural cell adhesion molecule (NCAM) expression in GH-secreting pituitary adenomas and its relationship to tumor invasiveness. A cross-sectional study of patients who underwent hypophysectomy due to GH-secreting pituitary adenoma from April 2007 to December 2014 was carried out. The medical records were reviewed to collect clinical data. Immediately after surgery, tumor samples were frozen in liquid nitrogen and stored in a biofreezer at -80°C for assessment of E-cadherin 1 (CDH1), SLUG (SNAI2), and NCAM (NCAM1) by real-time PCR. The samples were fixed in formalin and embedded in paraffin for immunohistochemical analysis of E-cadherin and NCAM. Thirty-five patients with acromegaly were included in the study. Of these, 65.7% had invasive tumors. Immunohistochemically, E-cadherin was expressed in 96.7% of patients, and NCAM in 80% of patients. There was no statistically significant relationship between tumor grade or invasiveness and immunohistochemical expression of these markers. Regarding gene expression, 50% of cases expressed CDH1, none expressed SNAI2, and 53.3% expressed NCAM1. There was no statistically significant relationship between tumor grade or invasiveness and gene expression of CDH1, SNAI2, and NCAM1. The absence of Slug overexpression and of E-cadherin and NCAM suppression suggests that expression of these markers is not associated with tumor invasiveness in GH-secreting pituitary adenomas.
[Mh] Termos MeSH primário: Acromegalia/patologia
Adenoma/patologia
Caderinas/análise
Moléculas de Adesão de Célula Nervosa/análise
Neoplasias Hipofisárias/patologia
Fatores de Transcrição da Família Snail/análise
[Mh] Termos MeSH secundário: Acromegalia/genética
Acromegalia/metabolismo
Adenoma/química
Adenoma/genética
Adolescente
Adulto
Idoso
Biomarcadores Tumorais/análise
Antígeno CD56/análise
Estudos Transversais
Feminino
Expressão Gênica
Seres Humanos
Imuno-Histoquímica
Masculino
Meia-Idade
Gradação de Tumores
Invasividade Neoplásica
Neoplasias Hipofisárias/química
Neoplasias Hipofisárias/genética
Reação em Cadeia da Polimerase em Tempo Real
Estatísticas não Paramétricas
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (CD56 Antigen); 0 (Cadherins); 0 (NCAM1 protein, human); 0 (Neural Cell Adhesion Molecules); 0 (SNAI1 protein, human); 0 (Snail Family Transcription Factors)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE


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[PMID]:29489701
[Au] Autor:Yang Y; Yan S; Tian H; Bao Y
[Ad] Endereço:Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China.
[Ti] Título:Macrophage inhibitory cytokine-1 versus carbohydrate antigen 19-9 as a biomarker for diagnosis of pancreatic cancer: A PRISMA-compliant meta-analysis of diagnostic accuracy studies.
[So] Source:Medicine (Baltimore);97(9):e9994, 2018 Mar.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Because of the high malignant degree of pancreatic cancer (PC), the early diagnosis of PC is of great concern. Macrophage inhibitory cytokine-1 (MIC-1) was reported to be a potential diagnostic biomarker, but its diagnostic value is indeterminate. Therefore, we performed this meta-analysis to compare it to carbohydrate antigen 19-9 (CA19-9), the most frequently used serum biomarker in PC. MATERIAL AND METHODS: After a systematic review of the relevant studies, the pooled diagnostic indices, including sensitivity, specificity, positive/negative likelihood ratio (PLR/NLR), diagnostic odds ratio (DOR), summary receiver operating characteristic curve (sROC), and area under the SROC curve (AUC) were used to evaluate the diagnostic value of MIC-1 and CA19-9 for PC. These indices were pooled with random-effects models. We explored the heterogeneity by meta-regression. RESULTS: Fourteen studies comprising a total of 2826 subjects were included in our meta-analysis. The summary estimates for MIC-1 and CA19-9 are listed as follows: sensitivity, 80% [95% confidence interval (CI) 78-82] versus 71% (95% CI 68-73); specificity, 85% (95% CI 83-87) versus 88% (95% CI 86-90); DOR, 24.57 (95% CI 14.00-43.10) versus 17.65 (95% CI 11.65-26.76); area under sROC (AUC), 0.8945 versus 0.8322; PLR, 5.18 (95% CI 3.24-8.26) versus 5.34 (95% CI 3.78-7.54); and NLR, 0.23 (95% CI 0.19-0.29) versus 0.32 (95% CI 0.28-0.37). CONCLUSION: These data demonstrate that serum MIC-1 has a comparable diagnostic accuracy to CA19-9 for PC.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/sangue
Antígeno CA-19-9/sangue
Fator 15 de Diferenciação de Crescimento/sangue
Neoplasias Pancreáticas/diagnóstico
[Mh] Termos MeSH secundário: Adulto
Idoso
Feminino
Seres Humanos
Masculino
Meia-Idade
Razão de Chances
Curva ROC
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (CA-19-9 Antigen); 0 (GDF15 protein, human); 0 (Growth Differentiation Factor 15)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180301
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009994


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[PMID]:29206995
[Au] Autor:Wyatt AW; Annala M; Aggarwal R; Beja K; Feng F; Youngren J; Foye A; Lloyd P; Nykter M; Beer TM; Alumkal JJ; Thomas GV; Reiter RE; Rettig MB; Evans CP; Gao AC; Chi KN; Small EJ; Gleave ME
[Ad] Endereço:Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland; Department of Medicine and Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive
[Ti] Título:Concordance of Circulating Tumor DNA and Matched Metastatic Tissue Biopsy in Prostate Cancer.
[So] Source:J Natl Cancer Inst;109(12), 2017 Dec 01.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Real-time knowledge of the somatic genome can influence management of patients with metastatic castration-resistant prostate cancer (mCRPC). While routine metastatic tissue biopsy is challenging in mCRPC, plasma circulating tumor DNA (ctDNA) has emerged as a minimally invasive tool to sample the tumor genome. However, no systematic comparisons of matched "liquid" and "solid" biopsies have been performed that would enable ctDNA profiling to replace the need for direct tissue sampling. Methods: We performed targeted sequencing across 72 clinically relevant genes in 45 plasma cell-free DNA (cfDNA) samples collected at time of metastatic tissue biopsy. We compared ctDNA alterations with exome sequencing data generated from matched tissue and quantified the concordance of mutations and copy number alterations using the Fisher exact test and Pearson correlations. Results: Seventy-five point six percent of cfDNA samples had a ctDNA proportion greater than 2% of total cfDNA. In these patients, all somatic mutations identified in matched metastatic tissue biopsies were concurrently present in ctDNA. Furthermore, the hierarchy of variant allele fractions for shared mutations was remarkably similar between ctDNA and tissue. Copy number profiles between matched liquid and solid biopsy were highly correlated, and individual copy number calls in clinically actionable genes were 88.9% concordant. Detected alterations included AR amplifications in 22 (64.7%) samples, SPOP mutations in three (8.8%) samples, and inactivating alterations in tumor suppressors TP53 , PTEN , RB1 , APC , CDKN1B , BRCA2 , and PIK3R1 . In several patients, ctDNA sequencing revealed robust changes not present in paired solid biopsy, including clinically relevant alterations in the AR, WNT, and PI3K pathways. Conclusions: Our study shows that, in the majority of patients, a ctDNA assay is sufficient to identify all driver DNA alterations present in matched metastatic tissue and supports development of DNA biomarkers to guide mCRPC patient management based on ctDNA alone.
[Mh] Termos MeSH primário: DNA Tumoral Circulante/sangue
Neoplasias de Próstata Resistentes à Castração/genética
Neoplasias de Próstata Resistentes à Castração/patologia
[Mh] Termos MeSH secundário: Proteína da Polipose Adenomatosa do Colo/genética
Proteína BRCA2/genética
Biomarcadores Tumorais/sangue
Biomarcadores Tumorais/genética
Inibidor de Quinase Dependente de Ciclina p27/genética
Variações do Número de Cópias de DNA
Seres Humanos
Biópsia Líquida
Masculino
Mutação
Metástase Neoplásica
Proteínas Nucleares/genética
PTEN Fosfo-Hidrolase/genética
Fosfatidilinositol 3-Quinases/genética
Receptores Androgênicos/genética
Proteínas Repressoras/genética
Proteínas de Ligação a Retinoblastoma/genética
Proteína Supressora de Tumor p53/genética
Ubiquitina-Proteína Ligases/genética
Via de Sinalização Wnt/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (APC protein, human); 0 (Adenomatous Polyposis Coli Protein); 0 (BRCA2 Protein); 0 (BRCA2 protein, human); 0 (Biomarkers, Tumor); 0 (CDKN1B protein, human); 0 (Circulating Tumor DNA); 0 (Nuclear Proteins); 0 (RB1 protein, human); 0 (Receptors, Androgen); 0 (Repressor Proteins); 0 (Retinoblastoma Binding Proteins); 0 (SPOP protein, human); 0 (TP53 protein, human); 0 (Tumor Suppressor Protein p53); 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 2.7.1.- (PIK3R1 protein, human); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 3.1.3.67 (PTEN Phosphohydrolase); EC 3.1.3.67 (PTEN protein, human)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171206
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx118


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[PMID]:28922790
[Au] Autor:Marisa L; Svrcek M; Collura A; Becht E; Cervera P; Wanherdrick K; Buhard O; Goloudina A; Jonchère V; Selves J; Milano G; Guenot D; Cohen R; Colas C; Laurent-Puig P; Olschwang S; Lefèvre JH; Parc Y; Boige V; Lepage C; André T; Fléjou JF; Dérangère V; Ghiringhelli F; de Reynies A; Duval A
[Ad] Endereço:Programme "Cartes d'Identité des Tumeurs," Ligue Nationale Contre le Cancer, Paris, France; INSERM, UMRS 938 - Centre de Recherche Saint-Antoine, Equipe "Instabilité des Microsatellites et Cancers," Equipe labellisée par la Ligue Nationale contre le Cancer, Paris, France; Sorbonne Université, UPMC U
[Ti] Título:The Balance Between Cytotoxic T-cell Lymphocytes and Immune Checkpoint Expression in the Prognosis of Colon Tumors.
[So] Source:J Natl Cancer Inst;110(1), 2018 Jan 01.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Immune checkpoint (ICK) expression might represent a surrogate measure of tumor-infiltrating T cell (CTL) exhaustion and therefore be a more accurate prognostic biomarker for colorectal cancer (CRC) patients than CTL enumeration as measured by the Immunoscore. Methods: The expression of ICKs, Th1, CTLs, cytotoxicity-related genes, and metagenes, including Immunoscore-like metagenes, were evaluated in three independent cohorts of CRC samples (260 microsatellite instable [MSI], 971 non-MSI). Their associations with patient survival were analyzed by Cox models, taking into account the microsatellite instability (MSI) status and affiliation with various Consensus Molecular Subgroups (CMS). PD-L1 and CD8 expression were examined on a subset of tumors with immunohistochemistry. All statistical tests were two-sided. Results: The expression of Immunoscore-like metagenes was statistically significantly associated with improved outcome in non-MSI tumors displaying low levels of both CTLs and immune checkpoints (ICKs; CMS2 and CMS3; hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.43 to 0.92, P = .02; and HR = 0.55, 95% CI = 0.34 to 0.90, P = .02, respectively), but clearly had no prognostic relevance in CRCs displaying higher levels of CTLs and ICKs (CMS1 and CMS4; HR = 0.46, 95% CI = 0.10 to 2.10, P = .32; and HR = 1.13, 95% CI = 0.79 to 1.63, P = .50, respectively), including MSI tumors. ICK metagene expression was statistically significantly associated with worse prognosis independent of tumor staging in MSI tumors (HR = 3.46, 95% CI = 1.41 to 8.49, P = .007). ICK expression had a negative impact on the proliferation of infiltrating CD8 T cells in MSI neoplasms (median = 0.56 in ICK low vs median = 0.34 in ICK high, P = .004). Conclusions: ICK expression cancels the prognostic relevance of CTLs in highly immunogenic colon tumors and predicts a poor outcome in MSI CRC patients.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/genética
Biomarcadores Tumorais/imunologia
Neoplasias Colorretais/genética
Neoplasias Colorretais/imunologia
Linfócitos do Interstício Tumoral
Linfócitos T Citotóxicos
[Mh] Termos MeSH secundário: Antígenos CD/genética
Antígeno B7-H1/análise
Antígeno B7-H1/genética
Antígenos CD8/análise
Antígeno CTLA-4/genética
Colo/química
Neoplasias Colorretais/química
Neoplasias Colorretais/patologia
Feminino
Expressão Gênica
Receptor Celular 2 do Vírus da Hepatite A/genética
Seres Humanos
Proteína Coestimuladora de Linfócitos T Induzíveis/genética
Masculino
Instabilidade de Microssatélites
Meia-Idade
Estadiamento de Neoplasias
Prognóstico
Proteína 2 Ligante de Morte Celular Programada 1/genética
Receptor de Morte Celular Programada 1/genética
Estudos Retrospectivos
Taxa de Sobrevida
Células Th1
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Antigens, CD); 0 (B7-H1 Antigen); 0 (Biomarkers, Tumor); 0 (CD223 antigen); 0 (CD274 protein, human); 0 (CD8 Antigens); 0 (CTLA-4 Antigen); 0 (HAVCR2 protein, human); 0 (Hepatitis A Virus Cellular Receptor 2); 0 (ICOS protein, human); 0 (Inducible T-Cell Co-Stimulator Protein); 0 (PDCD1 protein, human); 0 (PDCD1LG2 protein, human); 0 (Programmed Cell Death 1 Ligand 2 Protein); 0 (Programmed Cell Death 1 Receptor)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx136


  10 / 115838 MEDLINE  
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[PMID]:28859291
[Au] Autor:Heindl A; Sestak I; Naidoo K; Cuzick J; Dowsett M; Yuan Y
[Ad] Endereço:Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK; Centre for Molecular Pathology, Royal Marsden Hospital, London, UK; Division of Molecular Pathology, The Institute of Cancer Research, London, UK; Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Qu
[Ti] Título:Relevance of Spatial Heterogeneity of Immune Infiltration for Predicting Risk of Recurrence After Endocrine Therapy of ER+ Breast Cancer.
[So] Source:J Natl Cancer Inst;110(2), 2018 Feb 01.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Despite increasing evidence supporting the clinical utility of immune infiltration in the estrogen receptor-negative (ER-) subtype, the prognostic value of immune infiltration for ER+ disease is not well defined. Methods: Quantitative immune scores of cell abundance and spatial heterogeneity were computed using a fully automated hematoxylin and eosin-stained image analysis algorithm and spatial statistics for 1178 postmenopausal patients with ER+ breast cancer treated with five years' tamoxifen or anastrozole. The prognostic significance of immune scores was compared with Oncotype DX 21-gene recurrence score (RS), PAM50 risk of recurrence (ROR) score, IHC4, and clinical treatment score, available for 963 patients. Statistical tests were two-sided. Results: Scores of immune cell abundance were not associated with recurrence-free survival. In contrast, high immune spatial scores indicating increased cell spatial clustering were associated with poor 10-year, early (0-5 years), and late (5-10 years) recurrence-free survival (Immune Hotspot: LR-χ2 = 14.06, P < .001, for 0-10 years; LR-χ2 = 6.24, P = .01, for 0-5 years; LR-χ2 = 7.89, P = .005, for 5-10 years). The prognostic value of spatial scores for late recurrence was similar to that of IHC4 and RS in both populations, but was not as strong as other tests in comparison for recurrence across 10 years. Conclusions: These results provide a missing link between tumor immunity and disease outcome in ER+ disease by examining tumor spatial architecture. The association between spatial scores and late recurrence suggests a lasting memory of protumor immunity that may impact disease progression and evolution of endocrine treatment resistance, which may be exploited for therapeutic advances.
[Mh] Termos MeSH primário: Neoplasias da Mama/imunologia
Neoplasias da Mama/patologia
Linfócitos do Interstício Tumoral/imunologia
Recidiva Local de Neoplasia/imunologia
Receptores Estrogênicos/análise
[Mh] Termos MeSH secundário: Idoso
Antineoplásicos/uso terapêutico
Biomarcadores Tumorais/imunologia
Neoplasias da Mama/química
Neoplasias da Mama/tratamento farmacológico
Intervalo Livre de Doença
Feminino
Seres Humanos
Contagem de Linfócitos
Meia-Idade
Nitrilos/uso terapêutico
Fatores de Risco
Tamoxifeno/uso terapêutico
Triazóis/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Biomarkers, Tumor); 0 (Nitriles); 0 (Receptors, Estrogen); 0 (Triazoles); 094ZI81Y45 (Tamoxifen); 2Z07MYW1AZ (anastrozole)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170902
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx137



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