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1.
Anticancer Res ; 40(1): 201-211, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892568

RESUMO

BACKGROUND/AIM: This retrospective study focused on the correlation between molecular markers and prognostic outcomes of colon cancer patients depending on sidedness. MATERIALS AND METHODS: A total of 117 stage I-III colon cancer patients who underwent colectomy were enrolled. Novel methylation markers (KIF1A, PAX5 and VGF) were selected for epigenetic evaluation and p53 and ERCC1 protein expression was examined for the investigation of genetic alterations. RESULTS: High frequency of methylation was observed in 68.2% of right-sided and 39.7% of left-sided colon cancer cases (p=0.004). Abnormal p53 was identified in 52.3% of right-sided and 75.3% of left-sided cases (p=0.015). In right-sided cases, highly methylated genes demonstrated significantly favorable disease-free survival (p=0.049). Regarding left-sided cases, advanced T stage (p=0.028) and abnormal p53 (p=0.028) were revealed to be significant predictive factors of the disease-free survival outcome. CONCLUSION: Molecular alterations, as significant prognostic factors, might differ depending on the sidedness of colon cancers.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Idoso , Metilação de DNA/genética , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Análise Multivariada , Proteínas de Neoplasias/metabolismo , Curva ROC , Análise de Sobrevida
2.
Anticancer Res ; 40(1): 261-269, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892575

RESUMO

BACKGROUND: Pulmonary pleomorphic carcinoma (PPC) is a rare aggressive neoplasm, with dismal prognosis. Whether tumor immunity is associated with the progressive biological behavior of PPC remains unclear. The purpose of this study was to examine the prognostic significance of tumor immunity-related markers such as programmed death-1 ligand (PD-L1) and CD4+ or CD8+ tumor-infiltrating lymphocytes (TILs) in patients with surgically resected PPC. PATIENTS AND METHODS: Ninety-nine patients with surgically resected PPC were assessed by immunohistochemistry. The expression of PD-L1, CD4, and CD8 was examined in specimens of the resected tumors. RESULTS: PD-L1 was highly expressed in 61% (60/99) of lesions and high expression of CD4 and CD8 was identified in 42% (42/99) and 51% (51/99) of lesions, respectively. There was no relationship between the expression PD-L1 and the numbers of CD4+ or CD8+ TILs. The expression of PD-L1 was not identified as a significant prognostic marker; however, a low number of CD4+ TILs was identified as an independent marker for predicting a worse outcome after surgical resection of PPC, especially in patients with an epithelial component of adenocarcinoma or early stage of disease. By univariate analysis, a low number of CD8+ TILs was found to be a significant prognostic marker linked to poor overall survival in patients with non-adenocarcinoma components. CONCLUSION: A low number of CD4+ TILs is an independent marker for predicting a favorable prognosis after surgical resection in patients with PPC, especially in patients with adenocarcinoma components or early stage of disease.


Assuntos
Adenoma Pleomorfo/imunologia , Imunidade , Neoplasias Pulmonares/imunologia , Adenoma Pleomorfo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Antígenos CD4/metabolismo , Antígenos CD8/metabolismo , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico
3.
Anticancer Res ; 40(1): 341-347, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892585

RESUMO

BACKGROUND/AIM: The prognostic significance of biomarkers related to gastric cancer prognosis has not been fully elucidated. The aim of study was to use immunohistochemical biomarkers to reveal prognosis. PATIENTS AND METHODS: A total of 682 patients who had undergone curative surgery were evaluated regarding the correlation of prognosis and immunohistochemical biomarkers. RESULTS: The COX2-positive groups showed a poor 5-year overall and disease-free survival. Further analysis revealed that COX2 positivity was a significant risk factor for poorer disease-free survival in the group with clinical stage I disease (p=0.016). We also noted a marked trend between COX2 positivity and poorer overall survival. The COX2-positive group showed general postoperative pathological up-staging compared with the COX2-negative group. CONCLUSION: This study showed the potential of COX2 as a biomarker for gastric cancer prognosis. Preoperative evaluation of COX2 might be a useful tool for generating optimal treatment strategies in patients with clinical stage I gastric cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Ciclo-Oxigenase 2/metabolismo , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/patologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sobrevida
4.
J Urol ; 203(1): 62-72, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31112107

RESUMO

PURPOSE: Studies indicate that molecular subtypes in muscle invasive bladder cancer predict the clinical outcome. We evaluated whether subtyping by a simplified method and established classifications could predict the clinical outcome. MATERIALS AND METHODS: We subtyped institutional cohort 1 of 52 patients, including 39 with muscle invasive bladder cancer, an Oncomine™ data set of 151 with muscle invasive bladder cancer and TCGA (The Cancer Genome Atlas) data set of 402 with muscle invasive bladder cancer. Subtyping was done using simplified panels (MCG-1 and MCG-Ext) which included only transcripts common in published studies and were analyzed for predicting metastasis, and cancer specific, overall and recurrence-free survival. TCGA data set was further analyzed using the Lund taxonomy, the Bladder Cancer Molecular Taxonomy Group Consensus and TCGA 2017 mRNA subtype classifications. RESULTS: Muscle invasive bladder cancer specimens from cohort 1 and the Oncomine data set showed intratumor heterogeneity for transcript and protein expression. MCG-1 subtypes did not predict the outcome on univariate or Kaplan-Meier analysis. On multivariate analysis N stage (p ≤0.007), T stage (p ≤0.04), M stage (p=0.007) and/or patient age (p=0.01) predicted metastasis, cancer specific and overall survival, and/or the cisplatin based adjuvant chemotherapy response. In TCGA data set publications showed that subtypes risk stratified patients for overall survival. Consistently the MCG-1 and MCG-Ext subtypes were associated with overall but not recurrence-free survival on univariate and Kaplan-Meier analyses. TCGA data set included 21 low grade specimens of the total of 402 and subtypes associated with tumor grade (p=0.005). However, less than 1% of muscle invasive bladder cancer cases are low grade. In only high grade specimens the MCG-1 and MCG-Ext subtypes could not predict overall survival. On univariate analysis subtypes according to the Bladder Cancer Molecular Taxonomy Group Consensus, TCGA 2017 and the Lund taxonomy were associated with tumor grade (p <0.0001) and overall survival (p=0.01 to <0.0001). Regardless of classification, subtypes had about 50% to 60% sensitivity and specificity to predict overall and recurrence-free survival. On multivariate analyses N stage and lymphovascular invasion consistently predicted recurrence-free and overall survival (p=0.039 and 0.003, respectively). CONCLUSIONS: Molecular subtypes reflect bladder tumor heterogeneity and are associated with tumor grade. In multiple cohorts and subtyping classifications the clinical parameters outperformed subtypes for predicting the outcome.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Gradação de Tumores , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco , Transcriptoma
5.
J Urol ; 203(1): 73-82, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31389764

RESUMO

PURPOSE: Prostate specific antigen testing results in unnecessary biopsy and over diagnosis with consequent overtreatment. Tissue biopsy is an invasive procedure associated with significant morbidity. More accurate noninvasive or minimally invasive diagnostic approaches should be developed to avoid unnecessary prostate biopsy and over diagnosis. We investigated the potential of using circulating tumor cell analysis in cancer diagnosis, particularly to predict clinically significant prostate cancer in prebiopsy cases. MATERIALS AND METHODS: We enrolled 155 treatment naïve patients with prostate cancer and 98 before biopsy for circulating tumor cell enumeration. RNA was extracted from circulating tumor cells of 184 patients for gene expression analysis. The Kruskal-Wallis and Spearman rank tests, multivariate logistic regression and the random forest method were applied to assess the association of circulating tumor cells with aggressive prostate cancer. RESULTS: Of patients with localized prostate cancer 54% were scored as having positive circulating tumor cells, which was associated with a higher Gleason score (p=0.0003), risk group (p <0.0001) and clinically significant prostate cancer (p <0.0001). In the prebiopsy group a positive circulating tumor cell score combined with prostate specific antigen predicted clinically significant prostate cancer (AUC 0.869). A 12-gene panel prognostic for clinically significant prostate cancer was also identified. When combining the prostate specific antigen level, the circulating tumor cell score and the 12-gene panel, the AUC of clinically significant prostate cancer prediction was 0.927. Adding those data to cases with available multiparametric magnetic resonance imaging data significantly increased prediction accuracy (AUC 0.936 vs 0.629). CONCLUSIONS: Circulating tumor cell analysis has the potential to significantly improve patient stratification by prostate specific antigen and/or multiparametric magnetic resonance imaging for biopsy and treatment.


Assuntos
Células Neoplásicas Circulantes , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Biomarcadores Tumorais/sangue , Biópsia , MicroRNA Circulante/sangue , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Gradação de Tumores , Valor Preditivo dos Testes , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Sensibilidade e Especificidade
6.
J Urol ; 203(1): 83-91, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31430244

RESUMO

PURPOSE: The PROPHET (Prostate Cancer: Prostate Health Index Trial) is a prospective study to clarify the diagnostic impact of laboratory based and prostate volume adjusted p2PSA ([-2] proenzyme prostate specific antigen) related indexes on prostate cancer and clinically significant prostate cancer with prostate specific antigen less than 10 ng/ml. MATERIALS AND METHODS: Between April 2015 and March 2017, 421 men 50 to 79 years old in the prostate specific antigen range above age specific cutoffs and below 10 ng/ml were registered in the PROPHET. We investigated the diagnostic impacts of various clinical laboratory based free prostate specific antigen related and p2PSA related indexes on any grade and high Gleason grade group prostate cancer. RESULTS: Of the 363 eligible participants 179, 141 and 80 were diagnosed with any grade, and Gleason Grade Group 2-5 and 3-5 prostate cancer, respectively. The AUC-ROCs distinguishing nonprostate cancer vs prostate cancer, nonprostate cancer plus low Gleason Grade Group and low volume vs remaining prostate cancer with a higher Gleason Grade group or a higher volume on the PHI (Prostate Health Index) were significantly superior to the AUC-ROCs of prostate specific antigen and free-to-total prostate specific antigen. At 90% sensitivity in all investigated p2PSA related indexes the false-positive rate was superior to that of prostate specific antigen and free-to-total prostate specific antigen in any group comparison in terms of the Gleason Grade Group and positive biopsy cores. In 35% to 42% of men without prostate cancer and/or those with less aggressive prostate cancer the PHI would avoid unnecessary biopsy. CONCLUSIONS: Laboratory based p2PSA related indexes were significantly superior for detecting clinically significant prostate cancer compared to free-to-total prostate specific antigen. The indexes those would avoid up to 42% of prostate biopsies in men without aggressive cancer while maintaining 90% sensitivity.


Assuntos
Biomarcadores Tumorais/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Idoso , Biópsia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Prospectivos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Precursores de Proteínas
7.
Bioelectrochemistry ; 131: 107352, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31494386

RESUMO

The designed synthesis of efficient materials can significantly enhance the performance of electrochemical immunoassay in the detection of diseases, pesticide residues and environmental pollutants. The hollow AgPt@Pt core-shell nanoparticles (AgPt@Pt HNs) have exhibited high catalytic efficiency to the hydrogen peroxide (H2O2) reduction for its high mass activity from their hollow structure. Their limitation of instability can be overcome by loading on polypyrrole nanosheet (PPy NS). Besides, PPy NS exhibits good conductivity, and there exists environmentally-friendly method for its synthetic. Thus, AgPt@Pt HNs loaded on PPy NS (AgPt@Pt HNs/PPy NS) exhibits high catalytic efficiency to the reduction of H2O2 and good stability. Furthermore, the quick electron transfer of AgPt@Pt HNs/PPy NS modified glassy carbon electrode has been evidenced by the finding that the large constant of apparent electron transfer rate has also enlarged the current signal when the amount of electron is invariant. The modified electrode has fabricated a label-free amperometric immunosensor to detect sensitively prostate-specific antigen (PSA) with H2O2 as the electroactive material. The immunosensor in hollow core-shell nanosheet structure exhibiting good detection performance of PSA shows its promising applications in the clinical diagnosis.


Assuntos
Técnicas Biossensoriais , Eletrodos , Ouro/química , Nanopartículas Metálicas/química , Nanoestruturas/química , Platina/química , Polímeros/química , Pirróis/química , Biomarcadores Tumorais/análise , Catálise , Peróxido de Hidrogênio/química , Limite de Detecção , Oxirredução , Antígeno Prostático Específico/análise
8.
Bioelectrochemistry ; 131: 107372, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31759220

RESUMO

Pyrroloquinoline quinone (PQQ)-dependent glucose dehydrogenase is one of the extensively studied sugar-oxidizing enzymes used as a biocatalyst for biosensors and biofuel cells. A novel pyranose dehydrogenase (CcPDH) derived from the basidiomycete Coprinopsis cinerea is the first discovered eukaryotic PQQ-dependent enzyme. This enzyme carries a b-type cytochrome domain that is homologous to the cytochrome domain of cellobiose dehydrogenase (CDH); thus, CcPDH is a quinohemoprotein. CcPDH catalyzes the oxidation of various aldose sugars and shows significant activity toward the reverse-chair conformation of pyranoses. Interdomain electron transfer occurs in CcPDH similar to CDH, from the PQQ cofactor in the catalytic domain to the heme b in the cytochrome domain. This enzyme is able to direct electrical communication with electrodes, without artificial electron mediators, thus allowing direct electron transfer (DET)-type bioelectrocatalysis. In this review, we briefly describe recent progress in research on the biochemical discovery of CcPDH and the development of (bio)electrochemical applications (an amperometric biosensor) based on DET reactions.


Assuntos
Técnicas Eletroquímicas/instrumentação , Hemeproteínas/química , Quinonas/química , Biomarcadores Tumorais/metabolismo , Técnicas Biossensoriais , Eucariotos
9.
J Clin Pathol ; 73(1): 35-41, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31296605

RESUMO

AIMS: Precision medicine therapy is remodelling the diagnostic landscape of cancer. The success of these new therapies is often based on the presence or absence of a specific mutation in a tumour. The Idylla platform is designed to determine the mutational status of a tumour as quickly and accurately as possible, as a rapid, accurate diagnosis is of the utmost importance for the treatment of patients. This is the first complete prospective study to investigate the robustness of the Idylla platform for EGFR, KRAS and BRAF mutations in non-small cell lung cancer, metastatic colorectal cancer and metastatic melanoma, respectively. METHODS: We compared prospectively the Idylla platform with the results we obtained from parallel high-throughput next-generation sequencing, which is the current gold standard for mutational testing. Furthermore, we evaluated the benefits and disadvantages of the Idylla platform in clinical practice. Additionally, we reviewed all the published Idylla performance articles. RESULTS: There was an overall agreement of 100%, 94% and 94% between the next-generation panel and the Idylla BRAF, KRAS and EGFR mutation test. Two interesting discordant findings among 48 cases were observed and will be discussed together with the advantages and shortcoming of both techniques. CONCLUSION: Our observations demonstrate that the Idylla cartridge for the EGFR, KRAS and BRAF mutations is highly accurate, rapid and has a limited hands-on time compared with next-generation sequencing.


Assuntos
Biomarcadores Tumorais/genética , Análise Mutacional de DNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Mutação , Neoplasias/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Melanoma/genética , Melanoma/secundário , Neoplasias/patologia , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Fluxo de Trabalho
10.
J Clin Pathol ; 73(1): 17-22, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31300530

RESUMO

OBJECTIVE: Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy, most frequently affecting the head and neck. Treatment often requires surgery and can have significant functional morbidity. Research into disease pathogenesis and second line medical management of cSCC is limited. We assess genetic mutations in high-risk, primary head and neck cutaneous squamous cell carcinomas (HNcSCC) that may hinder or be beneficial for use of targeted therapy in disease management. METHODS: Genetic alterations and variant allele frequencies (VAFs) were analysed using a clinically relevant 48 gene panel in 10 primary high-risk non-metastatic treatment-naïve HNcSCC to evaluate applicability of targeted therapeutics. Variants present at all VAFs were evaluated for pathogenicity. Somatic mutation patterns of individual tumours were analysed. RESULTS: High-risk HNcSCC showed a high proportion (82%) of C to T transitions in keeping with ultraviolet-mediated damage. There was significant intratumour genetic heterogeneity in this cohort (MATH scores 20-89) with the two patients <45 years of age showing highest intratumour heterogeneity. TP53 was altered at VAF >22% in all cases, and mutations with highest VAF were observed in tumour suppressor genes in 80%. 70% of cases demonstrated at least one mutation associated with treatment resistance (KIT S821F, KIT T670I, RAS mutations at codons 12 and 13). CONCLUSION: We demonstrate high proportion tumour suppressor loss of function mutations, high intratumour genetic heterogeneity, and presence of well recognised resistance mutations in treatment naïve primary HNcSCC. These factors pose challenges for successful utilisation of targeted therapies.


Assuntos
Biomarcadores Tumorais/genética , Heterogeneidade Genética , Neoplasias de Cabeça e Pescoço/genética , Mutação , Neoplasias Cutâneas/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Tomada de Decisão Clínica , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Predisposição Genética para Doença , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Seleção de Pacientes , Fenótipo , Medicina de Precisão , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Transcriptoma
11.
J Clin Pathol ; 73(1): 23-29, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31422372

RESUMO

AIMS: The histological distinction of intrahepatic cholangiocarcinoma (ICC) from metastatic adenocarcinoma remains a challenge. The primary goal was to evaluate the diagnostic value of morphology and albumin expression in the diagnosis of ICC. METHODS: We evaluated morphological patterns in 120 ICCs and 677 non-hepatic adenocarcinomas and performed in situ hybridisation (ISH) stain for albumin in the former cohort (retrospective cohort). We also identified 119 samples from primary and metastatic lesions, the validation cohort, in which albumin ISH was performed as part of the diagnostic workup. Targeted sequencing was performed on selected cases. We also mined existing expression profiling data including cases from The Cancer Genome Atlas (TCGA) (41 760 unique samples). RESULTS: In the retrospective cohort, 45% of ICCs and <1% of non-hepatic adenocarcinomas showed a cholangiolar pattern; albumin ISH was positive in 93% of ICCs with significant intratumorous heterogeneity. In the validation cohort, 29% of ICCs showed a cholangiolar pattern and 88% expressed albumin, while all metastatic non-hepatic neoplasms were negative (n=37) (sensitivity 88% and specificity 100%). Targetable genetic alterations (IDH mutations and FGFR2 fusions) were identified in 31% of ICCs (10 of 32). An analysis of the TCGA data validated the specificity of the albumin assay. CONCLUSIONS: The cholangiolar pattern and albumin RNA ISH distinguishes ICC from metastatic adenocarcinoma with high specificity. Given the high prevalence of targetable mutations in ICC, albumin RNA ISH is an essential component in the workup of tumours of uncertain origin. A specific diagnosis of ICC could trigger molecular testing and uncover targetable genetic alterations.


Assuntos
Albuminas/genética , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Biomarcadores Tumorais/genética , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Hibridização In Situ , Adenocarcinoma/genética , Adenocarcinoma/secundário , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/secundário , Biópsia por Agulha , Diagnóstico Diferencial , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Transcriptoma , Adulto Jovem
12.
BJOG ; 127(1): 99-105, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31502397

RESUMO

OBJECTIVE: To evaluate if the intraoperative human papillomavirus (IOP-HPV) test has the same prognostic value as the HPV test performed at 6 months after treatment of high-grade squamous intraepithelial lesion (HSIL) to predict treatment failure. DESIGN: Prospective cohort study. SETTING: Barcelona, Spain. POPULATION: A cohort of 216 women diagnosed with HSIL and treated with loop electrosurgical excision procedure (LEEP). METHODS: After LEEP, an HPV test was performed using the Hybrid Capture 2 system. If this was positive, genotyping was performed with the CLART HPV2 technique. The IOP-HPV test was compared with HPV test at 6 months and with surgical margins. MAIN OUTCOME MEASURE: Treatment failure. RESULTS: Recurrence rate of HSIL was 6%. There was a strong association between a positive IOP-HPV test, a positive 6-month HPV test, positive HPV 16 genotype, positive surgical margins and HSIL recurrence. Sensitivity, specificity, and positive and negative predictive values of the IOP-HPV test were 85.7, 80.8,24.0 and 98.8% and of the HPV test at 6 months were 76.9, 75.8, 17.2 and 98.0%. CONCLUSION: Intraoperative HPV test accurately predicts treatment failure in women with cervical intraepithelial neoplasia grade 2/3. This new approach may allow early identification of patients with recurrent disease, which will not delay the treatment. Genotyping could be useful in detecting high-risk patients. TWEETABLE ABSTRACT: IOP-HPV test accurately predicts treatment failure in women with CIN 2/3.


Assuntos
Neoplasia Intraepitelial Cervical/cirurgia , Detecção Precoce de Câncer/métodos , Eletrocirurgia , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/cirurgia , Adulto , Alphapapillomavirus , Biomarcadores Tumorais/metabolismo , Neoplasia Intraepitelial Cervical/virologia , Colposcopia/estatística & dados numéricos , Feminino , Genótipo , Testes de DNA para Papilomavírus Humano/métodos , Humanos , Biópsia Guiada por Imagem , Cuidados Intraoperatórios/métodos , Recidiva Local de Neoplasia/virologia , Estudos Prospectivos , Sensibilidade e Especificidade , Falha de Tratamento , Neoplasias do Colo do Útero/virologia
13.
J Clin Pathol ; 73(1): 51-56, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31662438

RESUMO

Fibroepithelial tumours are biphasic neoplasms of the breast comprising the common benign fibroadenomas and the less common phyllodes tumours (PTs), which have recurrent potential. PTs are classified into benign, borderline or malignant, based on five histopathological criteria, with malignant PTs having the highest metastatic capability. Accurate diagnosis can be challenging due to the subjective assessment of histopathological parameters. Fibroadenomas bear morphological similarities to benign PTs, while borderline and malignant PTs can sometimes be difficult to distinguish from other spindle cell tumours of the breast. From clonality studies to whole-genome sequencing, much research has been conducted to elucidate the molecular pathogenesis of fibroepithelial tumours, which, in turn, have allowed leveraging the findings for diagnostic applications, including grading of PTs. The most noteworthy discovery was of recurrent MED12 mutations in both fibroadenomas and PTs. Subsequent studies also uncovered relatively frequent genetic mutations in TERT promoter and RARA A customised panel of 16 most frequently mutated genes in fibroepithelial tissues has been compiled previously and has contributed to resolving a few diagnostic dilemmas. This review will introduce the 16 genes and focus on the top three that are most frequently mutated in fibroepithelial tumours: MED12, TERT, and RARA.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Complexo Mediador/genética , Mutação , Neoplasias Fibroepiteliais/genética , Receptor alfa de Ácido Retinoico/genética , Telomerase/genética , Neoplasias da Mama/patologia , Feminino , Predisposição Genética para Doença , Humanos , Taxa de Mutação , Neoplasias Fibroepiteliais/patologia , Fenótipo , Fatores de Risco , Transcriptoma
14.
Br J Radiol ; 93(1105): 20190719, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31670571

RESUMO

OBJECTIVE: To compare therapeutic outcomes between hepatic resection (HR) and radiofrequency ablation (RFA) for small hepatic masses diagnosed as hepatocellular carcinoma (HCC) on pre-treatment imaging study. METHODS: Our institutional review board approved this retrospective study, and informed consent was waived. Patients with a single (≤3 cm) mass diagnosed as HCC on pre-treatment imaging study between January 2008 and December 2009 who underwent HR (n = 145) or RFA (n = 178) were included. Recurrence-free survival (RFS) and overall survival (OS) were assessed. In the HR group, the false-positive rate for imaging diagnosis was calculated. For the RFA group, the local tumor progression rate was calculated. RESULTS: RFS rates at 5 years were 59.3% for the HR group and 32.2% for the RFA group. OS rates at 5 years were 85.4% for the HR group and 76.8% for the RFA group. In the RFA group, cumulative local tumor progression rates were 8.3 and 20.2% at 1 and 3 years. Treatment modality was not an independent prognostic factor for either RFS or OS on multivariate analysis. The false-positive rate for HCC diagnosis based on imaging criteria was 4.8% in the HR group. CONCLUSION: The imaging criteria for diagnosis of HCC have a high positive predictive value. Multivariate analysis showed that RFS and OS rates were not significantly different between HR and RFA for small hepatic masses diagnosed as HCC on pre-treatment imaging. ADVANCES IN KNOWLEDGE: Treatment modality (hepatic resection vs RFA) was not an independent prognostic factor for both RFS and OS for small masses (≤3 cm) diagnosed as hepatocellular carcinoma on pre-treatment imaging.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Ablação por Radiofrequência , Biomarcadores Tumorais/sangue , Meios de Contraste , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
15.
Gut ; 69(1): 52-61, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30971436

RESUMO

OBJECTIVE: Despite improvements in imaging, serum CA19-9 and pathological evaluation, differentiating between benign and malignant bile duct strictures remains a diagnostic conundrum. Recent developments in next-generation sequencing (NGS) have opened new opportunities for early detection and management of cancers but, to date, have not been rigorously applied to biliary specimens. DESIGN: We prospectively evaluated a 28-gene NGS panel (BiliSeq) using endoscopic retrograde cholangiopancreatography-obtained biliary specimens from patients with bile duct strictures. The diagnostic performance of serum CA19-9, pathological evaluation and BiliSeq was assessed on 252 patients (57 trainings and 195 validations) with 346 biliary specimens. RESULTS: The sensitivity and specificity of BiliSeq for malignant strictures was 73% and 100%, respectively. In comparison, an elevated serum CA19-9 and pathological evaluation had sensitivities of 76% and 48%, and specificities of 69% and 99%, respectively. The combination of BiliSeq and pathological evaluation increased the sensitivity to 83% and maintained a specificity of 99%. BiliSeq improved the sensitivity of pathological evaluation for malignancy from 35% to 77% for biliary brushings and from 52% to 83% for biliary biopsies. Among patients with primary sclerosing cholangitis (PSC), BiliSeq had an 83% sensitivity as compared with pathological evaluation with an 8% sensitivity. Therapeutically relevant genomic alterations were identified in 20 (8%) patients. Two patients with ERBB2-amplified cholangiocarcinoma received a trastuzumab-based regimen and had measurable clinicoradiographic response. CONCLUSIONS: The combination of BiliSeq and pathological evaluation of biliary specimens increased the detection of malignant strictures, particularly in patients with PSC. Additionally, BiliSeq identified alterations that may stratify patients for specific anticancer therapies.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Doenças Biliares/diagnóstico , Doenças Biliares/genética , Doenças Biliares/patologia , Biomarcadores Tumorais/sangue , Antígeno CA-19-9/sangue , Constrição Patológica/diagnóstico , Constrição Patológica/genética , Diagnóstico Diferencial , Feminino , Humanos , Cirrose Hepática Biliar/diagnóstico , Cirrose Hepática Biliar/genética , Cirrose Hepática Biliar/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Manejo de Espécimes/métodos , Adulto Jovem
16.
Gut ; 69(1): 103-111, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31023832

RESUMO

OBJECTIVE: We assessed the effect of surgical resection of colorectal cancer (CRC) on perioperative plasma vitamin D (25OHD) and C-reactive protein (CRP) level. We investigated the relationship between circulating vitamin D level and CRC survival. DESIGN: We sequentially sampled 92 patients undergoing CRC resection, and measured plasma 25OHD and CRP. For survival analyses, we assayed 25OHD and CRP in two temporally distinct CRC patient cohorts (n=2006, n=2100) and investigated the association between survival outcome, circulating vitamin D and systemic inflammatory response. RESULTS: Serial sampling revealed a postoperative fall (mean 17.3 nmol/L; p=3.6e-9) in plasma 25OHD (nadir days 1-2). CRP peaked 3-5 days postoperatively (143.1 mg/L; p=1.4e-12), yet the postoperative fall in 25OHD was independent of CRP. In cohort analyses, 25OHD was lower in the 12 months following operation (mean=48.8 nmol/L) than preoperatively (54.8 nmol/L; p=1.2e-5) recovering after 24 months (52.2 nmol/L; p=0.002). Survival analysis in American Joint Committee on Cancer stages I-III demonstrated associations between 25OHD tertile and CRC mortality (HR=0.69; 95% CI 0.46 to 0.91) and all-cause mortality (HR=0.68; 95% CI 0.50 to 0.85), and was independent of CRP. We observed interaction effects between plasma 25OHD and rs11568820 genotype (functional VDR polymorphism) with a strong protective effect of higher 25OHD only in patients with GG genotype (HR=0.51; 95% CI 0.21 to 0.81). We developed an online tool for predicted survival (https://apps.igmm.ed.ac.uk/mortalityCalculator/) that incorporates 25OHD with clinically useful predictive performance (area under the curve 0.77). CONCLUSIONS: CRC surgery induces a fall in circulating 25OHD. Plasma 25OHD level is a prognostic biomarker with low 25OHD associated with poorer survival, particularly in those with rs11568820 GG genotype. A randomised trial of vitamin D supplementation after CRC surgery has compelling rationale.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/cirurgia , Vitamina D/análogos & derivados , Idoso , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Feminino , Seguimentos , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prognóstico , Receptores de Calcitriol/genética , Análise de Sobrevida , Síndrome de Resposta Inflamatória Sistêmica/sangue , Vitamina D/sangue
19.
Arkh Patol ; 81(6): 56-62, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31851193

RESUMO

OBJECTIVE: To evaluate the influence of clinical and morphological factors and HER2 copy numbers on pathologic complete response (pCR) rates in patients with HER2-positive stage II-III breast cancer (BC). MATERIAL AND METHODS: Treatment results were studied in 73 patients with HER2-positive Stage II-III BC, who received treatment at the N.N. Blokhin National Medical Research Center of Oncology in 2015 to 2018. Treatment included neoadjuvant chemotherapy (NACT) with HER2-blockade and radical surgery followed by the evaluation of a pathologic response in the primary tumor and regional lymph nodes. The patients` age varied from 29 to 71; its median was 51.5; 45.2% of patients had primary operable stages (T1-3N0-1) and 54.8% had locally advanced tumors. All the patients had grade 2-3 anaplasia; luminal HER2-positive BC was diagnosed in 41.4% of patients; hormone-negative tumors were seen in 58.9%; 91.5% of patients had Ki-67 ≥20% in 75.3% of patients, preoperative systemic therapy included anthracycline-containing regimens (4AC + 4 x paclitaxel 175 mg/m2/12 × weekly administrations of paclitaxel 80 mg/m2; trastuzumab therapy was simultaneously performed with the administration of taxanes in the standard regimen) and anthracycline-free regimen TCH ± Pertuzumab regimen in 24.7% of cases. After NACT patients underwent surgery (radical mastectomy in 78.1%, breast-sparing treatment in 21.9%) with the assessment of morphological findings. Biopsy specimens obtained before the treatment was restudied; HER2 amplification was detected using a Dako HER2 IQFISH pharmDx kit according to its instruction and the 2018 ASCO/CAP guidelines. In 87.1% of cases, the HER2-positive status corresponded to the first category of the 2018 ASCO/CAP criteria for HER2-positive BC; clustered HER2 amplification was found in 30.1% of cases. The authors analyzed the frequency of bpCR and tpCR attainment by various clinical and morphological factors, as well as the impact of a HER2 amplification level on pCR rates. RESULTS: A breast pCR (bpCR) was achieved in 57.4% patients; bpCR and lymph node CR (lnCR) were noted in 48.9% patients. The rates of bpCR significantly depended on female age, chemotherapy regimen, addition of Pertuzumab, and HER2 copy number. That of bpCR in women less than 35 years of age, in those aged 36-50 years, and in those aged older than 50 years was 22.2, 57.7 and 71.9%, respectively (p=0.026). The maximum bpCR rate observed with the TCH±P regimen was 80.0%, that with anthracycline-containing regimes was 52.8% (p=0.045), and the addition of Pertuzumab increased complete response rates up to 88.9% (that with Trastuzumab was 54.2% (p=0.049). The relationship of bpCR rates to the detection of cluster amplification turned out to be highly significant (81% in its detection and 48.9% in its absence (p=0.013). In addition, clustered HER2 amplification was the only significant predictive factor for complete regression in the primary tumor and lymph nodes: in its presence, the tpCR rate reached 68.8% versus 38.7%. CONCLUSION: Clustered amplification of the HER2 gene is the most significant factor of sensitivity to anti-HER2 therapy for Stage II-III BC, and is associated with the maximum rate of both bpCR and total pCR. Further study of this factor may assist in optimizing the treatment algorithm for HER2 + BC.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores Tumorais , Neoplasias da Mama/terapia , Feminino , Amplificação de Genes , Humanos , Mastectomia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Receptor ErbB-2 , Trastuzumab
20.
Arkh Patol ; 81(6): 82-85, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31851198

RESUMO

A summary of the updated recommendations of the 2018 American Society of Clinical Oncology (ASCO) / College of American Pathologists (CAP), devoted to testing type 2 human epidermal growth factor receptor (HER2) in breast cancer.


Assuntos
Neoplasias da Mama , Biomarcadores Tumorais , Humanos , Hibridização in Situ Fluorescente , Receptor ErbB-2
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