RESUMO
BACKGROUND: Low-dose computed tomography (LDCT) screening detects early-stage lung cancer and reduces mortality. We proposed a sequential approach targeted to a high-risk group as a potentially efficient screening strategy. METHODS: LungSEARCH was a national multicentre randomised trial. Current/ex-smokers with mild/moderate chronic obstructive pulmonary disease (COPD) were allocated (1:1) to have 5â years surveillance or not. Screened participants provided annual sputum samples for cytology and cytometry, and if abnormal were offered annual LDCT and autofluorescence bronchoscopy (AFB). Those with normal sputum provided annual samples. The primary end-point was the percentage of lung cancers diagnosed at stage I/II (nonsmall cell) or limited disease (small cell). RESULTS: 1568 participants were randomised during 2007-2011 from 10 UK centres. 85.2% of those screened provided an adequate baseline sputum sample. There were 42 lung cancers among 785 screened individuals and 36 lung cancers among 783 controls. 54.8% (23 out of 42) of screened individuals versus 45.2% (14 out of 31) of controls with known staging were diagnosed with early-stage disease (one-sided p=0.24). Relative risk was 1.21 (95% CI 0.75-1.95) or 0.82 (95% CI 0.52-1.31) for early-stage or advanced cancers, respectively. Overall sensitivity for sputum (in those randomised to surveillance) was low (40.5%) with a cumulative false-positive rate (FPR) of 32.8%. 55% of cancers had normal sputum results throughout. Among sputum-positive individuals who had AFB, sensitivity was 45.5% and cumulative FPR was 39.5%; the corresponding measures for those who had LDCT were 100% and 16.1%, respectively. CONCLUSIONS: Our sequential strategy, using sputum cytology/cytometry to select high-risk individuals for AFB and LDCT, did not lead to a clear stage shift and did not improve the efficiency of lung cancer screening.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Pequenas/patologia , Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/patologia , Escarro/citologia , Adenocarcinoma de Pulmão/complicações , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/patologia , Broncoscopia , Carcinoma de Células Grandes/complicações , Carcinoma de Células Grandes/diagnóstico por imagem , Carcinoma de Células Grandes/patologia , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma de Células Pequenas/complicações , Carcinoma de Células Pequenas/diagnóstico por imagem , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Técnicas Citológicas , Feminino , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Imagem Óptica , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Medição de Risco , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X , Reino UnidoRESUMO
RATIONALE: Patients with isolated mediastinal lymphadenopathy (IML) are a common presentation to physicians, and mediastinoscopy is traditionally considered the "gold standard" investigation when a pathological diagnosis is required. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is established as an alternative to mediastinoscopy in patients with lung cancer. OBJECTIVE: To determine the efficacy and health care costs of EBUS-TBNA as an alternative initial investigation to mediastinoscopy in patients with isolated IML. METHODS: Prospective multicenter single-arm clinical trial of 77 consecutive patients with IML from 5 centers between April 2009 and March 2011. All patients underwent EBUS-TBNA. If EBUS-TBNA did not provide a diagnosis, then participants underwent mediastinoscopy. MEASUREMENTS AND MAIN RESULTS: EBUS-TBNA prevented 87% of mediastinoscopies (95% confidence interval [CI], 77-94%; P < 0.001) but failed to provide a diagnosis in 10 patients (13%), all of whom underwent mediastinoscopy. The sensitivity and negative predictive value of EBUS-TBNA in patients with IML were 92% (95% CI, 83-95%) and 40% (95% CI, 12-74%), respectively. One patient developed a lower respiratory tract infection after EBUS-TBNA, requiring inpatient admission. The cost of the EBUS-TBNA procedure per patient was £1,382 ($2,190). The mean cost of the EBUS-TBNA strategy was £1,892 ($2,998) per patient, whereas a strategy of mediastinoscopy alone was significantly more costly at £3,228 ($5,115) per patient (P < 0.001). The EBUS-TBNA strategy is less costly than mediastinoscopy if the cost per EBUS-TBNA procedure is less than £2,718 ($4,307) per patient. CONCLUSIONS: EBUS-TBNA is a safe, highly sensitive, and cost-saving initial investigation in patients with IML. Clinical trial registered with ClinicalTrials.gov (NCT00932854).
Assuntos
Doenças Linfáticas/diagnóstico por imagem , Doenças Linfáticas/patologia , Doenças do Mediastino/diagnóstico por imagem , Doenças do Mediastino/patologia , Mediastinoscopia , Ultrassonografia de Intervenção/métodos , Adulto , Idoso , Biópsia por Agulha , Broncoscopia/economia , Broncoscopia/métodos , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Método Simples-Cego , Ultrassonografia de Intervenção/economiaRESUMO
RATIONALE: The current management of advanced non-small cell lung cancer (NSCLC) requires differentiation between squamous and nonsquamous subtypes as well as epidermal growth factor receptor (EGFR) mutation status. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is increasingly used for the diagnosis and staging of lung cancer. However, it is unclear whether cytology specimens obtained with EBUS-TBNA are suitable for the subclassification and genotyping of NSCLC. OBJECTIVES: To determine whether cytology specimens obtained from EBUS-TBNA in routine practice are suitable for phenotyping and genotyping of NSCLC. METHODS: Cytological diagnoses from EBUS-TBNA were recorded from 774 patients with known or suspected lung cancer across five centers in the United Kingdom between 2009 and 2011. MEASUREMENTS AND MAIN RESULTS: The proportion of patients with a final diagnosis by EBUS-TBNA in whom subtype was classified was 77% (95% confidence interval [CI], 73-80). The rate of NSCLC not otherwise specified (NSCLC-NOS) was significantly reduced in patients who underwent immunohistochemistry (adjusted odds ratio, 0.50; 95% CI, 0.28-0.82; P = 0.016). EGFR mutation analysis was possible in 107 (90%) of the 119 patients in whom mutation analysis was requested. The sensitivity, negative predictive value, and diagnostic accuracy of EBUS-TBNA in patients with NSCLC were 88% (95% CI, 86-91), 72% (95% CI, 66-77), and 91% (95% CI, 89-93), respectively. CONCLUSIONS: This large, multicenter, pragmatic study demonstrates that cytology samples obtained from EBUS-TBNA in routine practice are suitable for subtyping of NSCLC and EGFR mutation analysis and that the use of immunohistochemistry reduces the rate of NSCLC-NOS.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Endossonografia/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Biópsia por Agulha Fina , Broncoscopia/métodos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Estudos de Coortes , Intervalos de Confiança , Citodiagnóstico/métodos , Feminino , Genótipo , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Excisão de Linfonodo/métodos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Razão de Chances , Prognóstico , Estudos Retrospectivos , Sensibilidade e Especificidade , Análise de Sobrevida , Reino UnidoRESUMO
OBJECTIVE: To compare the outcomes and evaluate the relative risk of thyroid cancer by using the UK thyroid fine-needle aspiration (FNA) cytological diagnostic categories, with the main objective being the clarity of patient management. STUDY DESIGN: Results of thyroid FNA reported as Thy3a, Thy3f, Thy4, and Thy5 were correlated with histological outcomes. The specificity and positive predictive value (PPV; risk of malignancy) for each reporting category was assessed. RESULTS: Of a total of 873 thyroid FNAs, 237 (27%) were reported as 'abnormal': 40 (4.6%) as Thy3a, 119 (13.6%) as Thy3f, 20 (2.2%) as Thy4, and 58 (6.6%) as Thy 5. The final outcomes were available in 136 (57%) cases which underwent surgical resection (25, 60, 55, and 74% of Thy3a, Thy3f, Thy4, and Thy5, respectively). The known outcomes of the Thy3a category were too low to be statistically significant. The specificity and PPV of the Thy3f, Thy4, and Thy5 (equivalent to the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) IV, V, and VI) categories were 50, 50, and 100% and 28, 64, and 100%, respectively. The PPV of Thy3f for diagnosis of 'neoplasms' (benign and malignant) was 63%. CONCLUSION: The current thyroid FNA classification system used in the UK, which is comparable to TBSRTC, offers a sound basis for clear communication on which the management of patients with abnormal thyroid FNA findings can be based. Categories Thy3f, Thy4, and Thy5 carry a progressively rising risk of malignancy, justifying their continuing use. Diagnostic category Thy5 'malignant' is robust and can be used as a sure indication of a definitive surgical management.
Assuntos
Biópsia por Agulha Fina , Transformação Celular Neoplásica/patologia , Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Gerenciamento Clínico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Prognóstico , Risco , Terminologia como Assunto , Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/classificação , Nódulo da Glândula Tireoide/diagnóstico por imagem , Ultrassonografia , Reino UnidoRESUMO
INTRODUCTION: Mediastinal lymphadenopathy in patients with an extrathoracic malignancy is a common clinical scenario. Invasive sampling of intrathoracic lymph nodes may be performed by mediastinoscopy or endoscopic ultrasound-guided fine needle aspiration. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an alternative to mediastinoscopy and endoscopic ultrasound in patients with lung cancer and sarcoidosis. The utility of EBUS-TBNA in patients with extrathoracic malignancy was evaluated. METHODS: Consecutive patients who were suspected to have intrathoracic lymph node metastases from an extrathoracic malignancy underwent EBUS-TBNA. When EBUS-TBNA did not provide a specific diagnosis, patients underwent mediastinoscopy or clinical follow-up of at least 6 months duration. RESULTS: One hundred sixty-one patients meeting the inclusion criteria underwent EBUS-TBNA in five UK centers over a 3-year period. EBUS-TBNA diagnosed mediastinal or hilar metastases in 71 (44%) patients, new lung cancer in 20 (12%) patients, and sarcoidosis in 14 (9%) patients. The sensitivity, negative predictive value for malignancy, and overall accuracy for EBUS-TBNA were 87%, 73% and 88%, respectively. One hundred ten (68%) patients in the study had a final diagnosis of malignant intrathoracic lymphadenopathy. CONCLUSION: Because of the high prevalence of alternative diagnoses, pathological evaluation is important in patients with extrathoracic malignancy and suspected mediastinal or hilar lymph node metastases. EBUS-TBNA is a safe and sensitive technique and may be considered a first-line investigation in these patients.
Assuntos
Biópsia por Agulha Fina , Broncoscopia , Endossonografia , Doenças Linfáticas/diagnóstico , Neoplasias/complicações , Doenças Torácicas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Doenças Linfáticas/etiologia , Metástase Linfática , Masculino , Mediastinoscopia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/patologia , Prognóstico , Sensibilidade e Especificidade , Taxa de Sobrevida , Doenças Torácicas/etiologia , Adulto JovemRESUMO
The overall interobserver reproducibility of thyroid fine-needle aspiration (FNA) has not been comprehensively assessed. A blinded 6-rater interobserver reproducibility study was conducted of 200 thyroid FNA cases using the UK System, which is similar to The Bethesda System for Reporting Thyroid Cytology: Thy1, nondiagnostic; Thy2, nonneoplastic; Thy3a, atypia, probably benign; Thy3f, follicular lesion; Thy4, suspicious of malignancy; and Thy5, malignant. There was good interobserver agreement for the Thy1 (κ = 0.69) and Thy5 (κ = 0.61), moderate agreement for Thy2 (κ = 0.55) and Thy3f (κ = 0.51), and poor agreement for Thy3a (κ = 0.11) and Thy4 (κ = 0.17) categories. Combining categories implying surgical management (Thy3f, Thy4, and Thy5) achieved good agreement (κ = 0.72), as did combining categories implying medical management (Thy1, Thy2, and Thy3a; κ = 0.72). The UK thyroid FNA terminology is a reproducible and clinically relevant system for thyroid FNA reporting. This study demonstrates that international efforts to harmonize and refine thyroid cytology classification systems can improve consistency in the clinical management of thyroid nodules.
Assuntos
Biópsia por Agulha Fina , Citodiagnóstico/métodos , Doenças da Glândula Tireoide/patologia , Glândula Tireoide/patologia , Citodiagnóstico/estatística & dados numéricos , Humanos , Variações Dependentes do Observador , Patologia/métodos , Patologia/estatística & dados numéricos , Reprodutibilidade dos Testes , Método Simples-Cego , Sociedades Médicas , Neoplasias da Glândula Tireoide/patologia , Reino UnidoRESUMO
BACKGROUND AND OBJECTIVE: Standard bronchoscopic techniques (transbronchial lung biopsy and endobronchial biopsy) provide a diagnosis in 70% of patients with pulmonary sarcoidosis. Previous data suggest that endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has a high sensitivity in patients with sarcoidosis. The feasibility and utility of combining EBUS-TBNA with standard bronchoscopic techniques is unknown. The aim of this study was to evaluate the feasibility, safety and efficacy of combined EBUS-TBNA and standard bronchoscopic techniques in patients with suspected sarcoidosis and enlarged mediastinal or hilar lymphadenopathy. METHODS: Forty consecutive patients with suspected pulmonary sarcoidosis and enlarged mediastinal or hilar lymph nodes (radiographical stage I and stage II) underwent EBUS-TBNA followed by transbronchial biopsies and endobronchial biopsies under conscious sedation. RESULTS: Thirty-nine out of 40 patients successfully underwent combined EBUS-TBNA and standard bronchoscopy. Twenty-seven patients were diagnosed with sarcoidosis, eight had tuberculosis, two had reactive lymphadenopathy, two had lymphoma and one had metastatic adenocarcinoma. In patients with sarcoidosis, the sensitivity of EBUS-TBNA for detection of non-caseating granulomas was 85%, compared with a sensitivity of 35% for standard bronchoscopic techniques (P < 0.001). The diagnostic yield of combined EBUS-TBNA and bronchoscopy was 93% (P < 0.0001). CONCLUSIONS: Combination of EBUS-TBNA with standard bronchoscopic techniques is safe and feasible, and optimizes the diagnostic yield in patients with pulmonary sarcoidosis and enlarged intrathoracic lymphadenopathy.
Assuntos
Biópsia por Agulha/métodos , Broncoscopia/métodos , Sarcoidose Pulmonar/diagnóstico , Adenocarcinoma/diagnóstico , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Adulto , Idoso , Brônquios/diagnóstico por imagem , Brônquios/patologia , Feminino , Humanos , Doenças Linfáticas/diagnóstico , Doenças Linfáticas/diagnóstico por imagem , Doenças Linfáticas/patologia , Linfoma/diagnóstico , Linfoma/diagnóstico por imagem , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Sarcoidose Pulmonar/diagnóstico por imagem , Sarcoidose Pulmonar/patologia , Sensibilidade e Especificidade , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/diagnóstico por imagem , Tuberculose Pulmonar/patologia , Ultrassonografia , Adulto JovemRESUMO
Fine needle aspiration (FNA) cytology, together with imaging, has become a primary diagnostic modality for investigation of pancreatic mass lesions, both cystic and solid. Advances in imaging techniques have enhanced our ability to recognize and delineate pancreatic masses and to detect them earlier as smaller mass lesions. However, definitive management often cannot be based on clinical and radiological features alone. Despite the advances in the imaging techniques, management options for patients are limited and a malignant diagnosis of solid lesions still carries a high mortality rate. The importance of a cytopathologist in preoperative diagnosis, as a member of the multidisciplinary team, is exemplified in the management of patients with neoplastic cysts. This is based on the pre-operative distinction of non-mucinous and mucinous cysts in general, and benign and malignant cysts in particular. A cytological diagnosis can be obtained with minimally invasive techniques that utilize CT US or EUS. Endoscopic Ultrasound guided FNA (EUS FNA) is evolving as the diagnostic method of choice due to its ability to more accurately stage the patient during a single procedure using EUS.
Assuntos
Biópsia por Agulha Fina/métodos , Pâncreas/citologia , Pâncreas/patologia , Pancreatopatias/patologia , Neoplasias Pancreáticas/patologia , Adenocarcinoma/patologia , Cistadenoma/patologia , Neoplasias das Glândulas Endócrinas/patologia , Humanos , Pancreatopatias/diagnóstico por imagem , Neoplasias Pancreáticas/classificação , Neoplasias Pancreáticas/diagnóstico por imagem , Teratoma/patologia , UltrassonografiaRESUMO
A novel method for rapidly detecting metastatic breast cancer within excised sentinel lymph node(s) of the axilla is presented. Elastic scattering spectroscopy (ESS) is a point-contact technique that collects broadband optical spectra sensitive to absorption and scattering within the tissue. A statistical discrimination algorithm was generated from a training set of nearly 3000 clinical spectra and used to test clinical spectra collected from an independent set of nodes. Freshly excised nodes were bivalved and mounted under a fiber-optic plate. Stepper motors raster-scanned a fiber-optic probe over the plate to interrogate the node's cut surface, creating a 20x20 grid of spectra. These spectra were analyzed to create a map of cancer risk across the node surface. Rules were developed to convert these maps to a prediction for the presence of cancer in the node. Using these analyses, a leave-one-out cross-validation to optimize discrimination parameters on 128 scanned nodes gave a sensitivity of 69% for detection of clinically relevant metastases (71% for macrometastases) and a specificity of 96%, comparable to literature results for touch imprint cytology, a standard technique for intraoperative diagnosis. ESS has the advantage of not requiring a pathologist to review the tissue sample.
Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/secundário , Carcinoma/diagnóstico , Carcinoma/secundário , Diagnóstico por Computador/métodos , Biópsia de Linfonodo Sentinela/métodos , Análise Espectral/métodos , Algoritmos , Técnicas de Imagem por Elasticidade/métodos , Feminino , Humanos , Luz , Metástase Linfática , Reprodutibilidade dos Testes , Espalhamento de Radiação , Sensibilidade e EspecificidadeRESUMO
Polycomb group proteins (PCGs) are involved in repression of genes that are required for stem cell differentiation. Recently, it was shown that promoters of PCG target genes (PCGTs) are 12-fold more likely to be methylated in cancer than non-PCGTs. Age is the most important demographic risk factor for cancer, and we hypothesized that its carcinogenic potential may be referred by irreversibly stabilizing stem cell features. To test this, we analyzed the methylation status of over 27,000 CpGs mapping to promoters of approximately 14,000 genes in whole blood samples from 261 postmenopausal women. We demonstrate that stem cell PCGTs are far more likely to become methylated with age than non-targets (odds ratio = 5.3 [3.8-7.4], P < 10(-10)), independently of sex, tissue type, disease state, and methylation platform. We identified a specific subset of 69 PCGT CpGs that undergo hypermethylation with age and validated this methylation signature in seven independent data sets encompassing over 900 samples, including normal and cancer solid tissues and a population of bone marrow mesenchymal stem/stromal cells (P < 10(-5)). We find that the age-PCGT methylation signature is present in preneoplastic conditions and may drive gene expression changes associated with carcinogenesis. These findings shed substantial novel insights into the epigenetic effects of aging and support the view that age may predispose to malignant transformation by irreversibly stabilizing stem cell features.
Assuntos
Envelhecimento/genética , Metilação de DNA , Inativação Gênica/fisiologia , Genes , Neoplasias/genética , Células-Tronco/metabolismo , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Metilação de DNA/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Regulação Neoplásica da Expressão Gênica , Genes/fisiologia , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/metabolismo , Regiões Promotoras Genéticas , Estudos de Validação como Assunto , Adulto JovemRESUMO
Cervical cancer is the second most common type of cancer in women worldwide. Preinvasive disease can be detected by cervical cytology. All currently available cytology technologies rely on the visual analysis of exfoliated cells from the uterine cervix. Improvement of conventional cytological screening has been proposed by the introduction of molecular-based markers applied to liquid-based cytology (LBC), the suspension of cells collected from the cervix. DNA methylation changes occur very early in carcinogenesis and identification of appropriate DNA methylation markers in such samples should be able to distinguish high-grade squamous intraepithelial lesions (HSIL) from nonspecific cytology changes and the normal cervix. To address this potential, we have undertaken a proof-of-principle study of methylation status of LBC samples from HSIL cytology cases compared against matched normal controls. Using quantitative methylation-specific PCR on 28 genes, we found SOX1, HOXA11 and CADM1 to significantly discriminate between the groups analyzed (p<0.01). Area under the receiver operating characteristic (ROC) curve (AUC) demonstrated that methylation of SOX1, HOXA11 and CADM1 could discriminate between HSIL cases and controls with high sensitivity and specificity (AUC 0.910, 0.844 and 0.760, respectively). The results were further validated in an independent set. This proof-of-principle study is the first to validate the results in an independent case/control set and presents HOXA11, a gene that is important for cervical development, as a potentially useful DNA marker in LBC samples. Further assessment of these preliminary estimates will need to be performed in a larger cohort to confirm clinical utility.
Assuntos
Carcinoma de Células Escamosas/diagnóstico , Colo do Útero/patologia , Metilação de DNA , Proteínas de Homeodomínio/genética , Infecções por Papillomavirus/diagnóstico , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/virologia , Estudos de Casos e Controles , Técnicas Citológicas , Feminino , Humanos , Programas de Rastreamento , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/genética , Reação em Cadeia da Polimerase , Prognóstico , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal , Displasia do Colo do Útero/genética , Displasia do Colo do Útero/virologiaRESUMO
The aim of this review is to highlight the continuing role of fine needle aspiration cytology (FNAC) in the diagnosis of breast lesions, against a background of its diminishing use in some centres, particularly those involved in breast screening, because of its controversial inadequate rate and suboptimal accuracy. This review explores the current practice and confirms the continuing role of FNAC in the diagnosis and management of breast lesions. The three main areas where FNAC still plays a major role are the following: (a) diagnosis of benign disease in symptomatic palpable lumps as part of triple assessment; (b) staging of breast carcinoma, in particular preoperative axillary lymph node FNAC and intraoperative sentinel node imprints; and (c) diagnosis of metastatic disease at distant sites following treatment for carcinoma. Excision biopsy of the lesion to establish whether it is benign or malignant is not an acceptable mode of diagnosis any more. When triple assessment is concordant, final treatment may be ensued without open biopsy. Triple assessment is a cost effective, easy to perform and time saving approach, however, it can only be used at those institutions where excellent imaging facilities as well as services of a cytopathologist are available. The majority of European countries use similar reporting system for breast FNAC (C1-C5), in keeping with European guidelines for quality assurance in breast cancer screening and diagnosis. A clear reporting system ensures that an unequivocal cytological diagnosis of malignancy is reliable, and in cases where mammography/ultrasonography and clinical examination are in agreement with FNAC, frozen section examination is unnecessary. Suggested thresholds for cytology performance (where therapy is partially based on FNAC) according to the UK NHSBSP are the following: absolute sensitivity (C5 only) >70%, complete sensitivity (C3, C4, C5) >90%, specificity >65%, positive predictive value >99%, false negative <4%, false positive <0.5%, inadequate rate <15%, inadequate rate from cancers <5% and suspicious rate <15%. The issue of optimal sampling to obtain adequate cell material in sufficient quantity is of paramount importance when assessing the accuracy of FNAC. The inadequate rates in FNAC from different sources are lowest when FNAC is performed by a cytopathologist and highest when done by a non-cytopathologist. The multidisciplinary approach is necessary to amplify FNAC quality and to reduce its diagnostic limits. Only when this model of activity is not available, the role of FNAC is less effective and the addition of core biopsy (CB) to FNAC should be considered. CB as an alternative diagnostic modality should be used advisedly, in situations where it is more likely to yield diagnostic information, e.g., in the diagnosis of impalpable masses, microcalcifications or a clinically apparent malignancy where preoperative chemotherapy is planned. CB should not be used as a substitute for poor performance at FNAC. The methods are not mutually exclusive. Where there is access to skilled cytopathologists, FNAC and CB can complement each other and provide a highly accurate, rapid and cost-effective means of patient triage. FNAC has an advantage of being an immediate and excellent method for on-site examination and one-stop diagnosis at breast outpatient clinics. Since the majority of patients attending a breast clinic have benign disease, they benefit from rapid diagnosis and discharge from the clinic. Sentinel node biopsy, now used routinely during the operation for breast carcinoma with the aim of achieving "one-step" surgery can be reduced by one third of patients who ultimately require axillary node dissection if preoperative image guided FNAC of the axilla is used. Positive intraoperative imprint cytology is a reliable tool for proceeding to axillary node dissection, the method having a very high specificity in all published series. FNAC remains the method of choice of diagnosing metastatic disease at extramammary sites. Hormone receptor status, but not HER 2, can be reliably assessed from cytological material. Cells carry a promise of molecular diagnosis and targeted treatment in the future. The future of breast FNAC is bright.
Assuntos
Biópsia por Agulha Fina , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Citodiagnóstico , Feminino , Humanos , Sensibilidade e Especificidade , Biópsia de Linfonodo SentinelaRESUMO
OBJECTIVE: Cervical intraepithelial neoplasias (CIN) show markedly variable clinical behavior. Clinically, it is important to distinguish CIN lesions with different behaviors and identify those likely to persist and progress. The purpose of this study is to explore whether CIN lesions with different clinical behaviors can be stratified by analysis of loss of heterozygosity (LOH) at multiple loci. METHODS: One hundred sixty-four cases of CIN (54 CIN1, 59 CIN2 and 51 CIN3) were screened for LOH at 12 microsatellite markers including 10 from 3p14, 3p21-22, 6p21 and 11q23. LOH was correlated with clinical follow-up data and high-risk HPV infection. RESULTS: In a pilot study of 71 cases of CIN, screening of 12 microsatellite markers identified four (D3S1300, D3S1260, D11S35, and D11S528) at which LOH was significantly associated with disease persistence/progression. These four markers were further investigated in a larger cohort, which brought the total number of cases examined to 164. Combined analysis of LOH at the above four loci permitted the identification of 22-47% of CIN lesions depending on the histological grade, which showed disease persistence/progression. LOH at these loci was significantly associated with HPV16 infection. Bioinformatic analysis identified several candidate genes including the fragile histidine triad gene and progesterone receptor gene that may be the target of deletions. CONCLUSIONS: LOH at D3S1300, D3S1260, D11S35 and D11S528 was significantly associated with cins that showed persistence/progression, and combined LOH analyses at these loci could be used to identify such cases.
Assuntos
Perda de Heterozigosidade , Displasia do Colo do Útero/genética , Neoplasias do Colo do Útero/genética , Adulto , Idoso , Alelos , Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 3/genética , Cromossomos Humanos Par 6/genética , Feminino , Deleção de Genes , Humanos , Pessoa de Meia-Idade , Papillomaviridae , Infecções por Papillomavirus/induzido quimicamente , Reação em Cadeia da Polimerase , Prognóstico , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/virologiaRESUMO
OBJECTIVE: To establish a polymerase chain reaction (PCR)-based clonality assay for archival cervical smears and examine its value in the detection of cervical intraepithelial neoplasia (CIN) and prediction of its clinical behavior. STUDY DESIGN: Dyskaryotic cells were microdissected from archival cervical smears of 33 cases and subjected to PCR-based clonality analysis of the androgen receptor gene. High-risk HPV subtypes were screened by PCR. RESULTS: Monoclonal patterns were found in 9/9 CIN 3 and 15/21 CIN 2, while polyclonal patterns were observed in the remaining 6 CIN 2 and 3/3 CIN 1. All patients with monoclonal CIN lesions, including 15 CIN 2, showed recurrence of the disease despite treatment. The original CIN 2 and recurrent CIN lesion in each of the 6 examined cases showed the same monoclonal pattern, suggesting a clonal link. In contrast, the patients with polyclonal CIN 1 or 2 became negative and remained disease free. High-risk HPV subtypes were found in all monoclonal CIN lesions, including 9 CIN 3 and 15 CIN 2, and in 4/6 polyclonal CIN 2 but not in CIN 1 lesions. CONCLUSION: Clonality analysis of cervical smears is potentially valuable in the identification of true neoplastic cells and prediction of clinical behavior of CIN 2 lesions.
Assuntos
Arquivos , Receptores Androgênicos/genética , Displasia do Colo do Útero/genética , Displasia do Colo do Útero/patologia , Esfregaço Vaginal/métodos , Biomarcadores Tumorais/genética , Células Clonais/patologia , Análise Citogenética , DNA/análise , DNA/genética , Mecanismo Genético de Compensação de Dose , Feminino , Humanos , Masculino , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Papillomaviridae/genética , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Prognóstico , Fatores de Tempo , Esfregaço Vaginal/tendênciasRESUMO
Formalin-fixed and paraffin-embedded tissues are increasingly used for analysis of gene expression. However, a large proportion of archival fixed histologic specimens including spare paraffin sections and stained slides, as well as archival cytologic materials, have not been investigated for their suitability for RNA-based analysis. The current study addressed this issue by reverse transcription and polymerase chain reaction (RT-PCR) of the glucose-6-phosphate dehydrogenase (G6PD) transcript in a series of archival histologic and cytologic specimens. The histologic specimens included freshly prepared paraffin sections, spare paraffin sections, hematoxylin and eosin-stained slides, immunostained slides, and decalcified bone marrow trephines. The cytologic specimens comprised cervical smears and various stained and unstained needle aspirates and cell sediments. The G6PD was amplified for five different fragment sizes ranging from 67 bp to 453 bp. It was found that the majority of archival materials were amenable to RT-PCR of small fragments with the overall success rates of 95% and 79% for 67 bp and 151 bp of the G6PD mRNA, respectively. Neither staining nor prolonged storage up to 15 years had major negative effects on RT-PCR, although fine-needle aspirates showed a higher rate of RT-PCR of 242-bp fragment than other types of cytologic specimens and so did Papanicolaou-stained samples than May Grounwald and Giemsa-stained samples. RT-PCR of minute cell populations microdissected from immunostained sections of tonsils and t(11;18)-positive mucosa-associated lymphoid tissue lymphomas showed that as few as 100 cells were adequate for RT-PCR of G6PD and translocation-associated fusion transcript as long as the target fragment was limited to less than 150 bp. Our results demonstrate that archival fixed histologic and cytologic specimens are valuable resources for RT-PCR-based molecular investigations.
Assuntos
RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Dissecação , Estudos de Viabilidade , Feminino , Glucosefosfato Desidrogenase/genética , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Manejo de Espécimes/métodos , Fatores de TempoRESUMO
Archival cervical smears: a versatile resource for molecular investigations Archival cervical smears represent a huge resource of pathological specimens. This, together with long clinical follow-up data, makes archival smears the most valuable resource for cervical cancer research. Despite this huge potential, only a few molecular investigations have been carried out based on archival smears. It has been shown that archival smears can be used for amplification of genomic sequences by polymerase chain reaction (PCR). However, it is unknown whether PCR can be applied to minute dyskaryotic cells microdissected from archival cervical smears and whether these archival materials are suitable for reverse transcription PCR (RT-PCR). To address these issues, we prepared DNA and RNA samples from dyskaryotic cells microdissected from archival cervical smears with a storage time of 11 years and systematically tested the extent that these materials can be used for PCR-based molecular investigations at both DNA and RNA levels. Our results showed that a crude DNA preparation simply by proteinase K digestion was suitable for PCR amplification of genomic sequences. By targeting the amplified genomic sequence to 250 bp or less, most if not all archival smears could be used for PCR and are therefore suitable for screening gene mutations and loss of heterozygosity, human papillomavirus typing, etc. Purified DNA samples from microdissected dyskaryotic cells were adequate for restriction enzyme digestion and could be used for a PCR-based clonality analysis of the androgen receptor gene. Finally, RNA samples extracted from dyskaryotic cells microdissected from archival smears were adequate for RT-PCR as long as a gene-specific primer was used for the RT reaction and the target sequence was restricted to 150 bp or less. In summary, our results demonstrated that archival cervical smears are suitable for a range of molecular investigations at both DNA and RNA levels. The potential gain of knowledge on cervical cancer by the molecular study of archival smears is immense.