Is the EBUS TBNA cytology adequate for EGFR analysis (original) (raw)
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The Annals of Thoracic Surgery, 2013
The purpose of the study was to assess the efficacy of obtaining adequate cytologic specimens by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for molecular testing of lung adenocarcinomas. This was an institutional review board-approved study of all patients who had undergone EBUS-TBNA from April 2010 through March 2012 for the diagnosis, staging, or both of lung cancer. Patients with a diagnosis of adenocarcinoma were reflexively tested for molecular markers by polymerase chain reaction, sequencing, and fluorescence in situ hybridization (FISH). All procedures were performed with patients under conscious sedation in the bronchoscopy suite. Of 205 patients who underwent EBUS-TBNA, 56 patients (24 male, 32 female) had a diagnosis of adenocarcinoma warranting molecular analysis. Molecular analysis was available for epidermal growth factor receptor (EGFR), Kirsten rat sarcoma (Kras) mutation, and anaplastic lymphoma kinase (ALK) gene rearrangement. The institution's clinical protocol involved initial testing for EGFR mutation with a reflex Kras test if the EGFR test result was negative. ALK FISH molecular testing was completed if both EGFR and Kras test results were negative. A total of 52 of 56 (93%) patients had sufficient cytologic material for complete or partial molecular testing, whereas 46 of 56 (82%) patients had sufficient material for all clinically indicated testing. EGFR, Kras, and ALK analysis yielded positive results in 5 (10%), 10 (25%), and 5 (12%) tested specimens, respectively. No complications were associated with EBUS-TBNA. EBUS-TBNA performed with the patient under moderate sedation can be expected to yield sufficient tissue for sequential molecular analysis in the majority of patients. In an era of targeted therapy for lung adenocarcinomas, EBUS-TBNA is effective in clinical practice for complete diagnosis, staging, and treatment planning in these patients.
Journal of thoracic disease, 2014
Conventional transbronchial needle aspiration (TBNA) has been around for over 30 years with sensitivities approaching 70-90%. Recent development of endobronchial ultrasound (EBUS) TBNA demonstrated even higher sensitivities among experts. However EBUS-TBNA is more costly and less available worldwide than conventional TBNA. A comparison study to determine the efficacy of TBNA with and without EBUS in the diagnosis and staging of lung cancer is described. A total of 287 patients with mediastinal and hilar lymphadenopathy presenting for diagnosis and/or staging of lung cancer at enrolling institutions were included. Equal numbers of punctures were performed at the target lymph node stations using conventional TBNA techniques followed by EBUS-TBNA at the same sites. Patients and puncture sites that were biopsied by both methods and were positive for lung cancer were compared to establish efficacy of each technique on the same patients. In 253 patients at least one pair of specimens were...
Adequacy of EBUS-TBNA specimen for mutation analysis of lung cancer
The Clinical Respiratory Journal, 2018
Objective: Convex probe endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) is a minimally invasive technique with high sensitivity in the mediastinal staging of non-small cell carcinoma (NSCLC). In recent years, molecular testing has been developed to study genetic mutations in NSCLC. There are studies revealing improved survival in advanced NSCLC using targeted therapy as the first-line treatment in these patients. The aim of this study was to evaluate the adequacy of EBUS-TBNA in providing adequate size specimens for EGFR, ALK, and ROS1 genetic mutation analysis in patients with adenocarcinoma or Not Otherwise Specified (NOS) lung cancer.
EBUS-TBNA for the diagnosis and staging of lung cancer
Endoscopy, 2006
Non-small cell lung cancer (NSCLC) usually metastasizes first to hilar and mediastinal lymph nodes. Subsequently, hematogenous metastasis to distant sites may occur. Because survival is inversely correlated with stage, a meticulous staging procedure is required to determine the treatment and prognosis [1, 2]. For staging of NSCLC, the TNM classification has been developed, in which T stands for local tumor extension, N for lymph node metastasis, and M for distant metastasis. The lymph node map by Mountain et al., and its revisions are often used for the description of the N factor of the TNM classification [3]. Mediastinal lymph node staging can be divided into imaging and sampling. Computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) may be used to image mediastinal lymph nodes [4]. Pathologic sampling of suspicious lesions can be performed by mediastinoscopy, thoracoscopy, transthoracic fine-needle aspiration, transbronchial fine
Cytology smears as diagnostic material for EGFR gene testing in non-small cell lung cancer
Tumori Journal, 2015
core needle biopsy or intrabronchial biopsy) are generally preferred for mutation assays because of the higher percentage of tumor cells and the greater capacity to enrich the tumor cell content by dissection. Nonetheless, EGFR mutation testing should be performed also on specimens obtained by transthoracic needle biopsy or transbronchial fine-needle aspiration. Moreover, cytology materials are becoming much more common than histology specimens, especially in more advanced stages of lung cancer. One of the issues concerning cytology specimens is the possibility of false-negative results (1). The small number of tumor cells in cytology slides in comparison with tissue material is an important factor that influences the reliability of mutational analysis Therefore, several expert recommendations advised that molecular tests should be validated for each of the specimen types, especially for cytology specimens, and EGFR gene testing should be performed and reported only on validated specimen types (1, 2).
The use of EBUS-TBNA and ROSE in the diagnosis of lung cancer
Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie, 2017
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive method for diagnosing and staging of lung cancer. EBUS-TBNA obtained small specimens. Rapid on-site examination (ROSE) is a rapid, real-time examination method. The aim of our study is to evaluate the impact of ROSE on adequate specimen sampling, rapid results and high diagnostic rate. We present the experience of the Department of Bronchology, "Leon Daniello" Clinic of Pulmonology, Cluj-Napoca, Romania, with EBUS-TBNA as a tool for diagnostic of adenopathies of unknown etiology. We evaluated the diagnostic capacity of ROSE for malignant tumors, by considering the histopathological examination as the diagnostic "gold standard". In our retrospective and descriptive study, we analyze the data of 147 EBUS-TBNA examinations with ROSE and histopathological exam, performed for diagnostic purposes for hilar and mediastinal adenopathies of unknown origin. The age of the p...
Vojnosanitetski pregled, 2019
Background/Aim. Adenocarcinoma of the lung is the most common histological type of lung cancer. The most reliable method in detecting epidermal growth factor receptor (EGFR) mutations is real-time polymerase chain reaction (PCR). It is recommended to sample three to five biopsy samples with a minimum of 200?400 preserved tumor cells. We analyzed the suitability of biopsy samples for EGFR molecular testing in lung adenocarcinoma. Methods. This retrospective analysis included 60 patients diagnosed with lung adenocarcinoma at the Institute for Pulmonary Diseases in Sremska Kamenica, Serbia from 2010 to 2015. Biopsy samples were obtained using transbronchial, bronchoscopic, or catheter biopsy procedures. All cases included the identification of morphometric parameters, the concentration of isolated DNA, and EGFR mutations. The proportion of tumors in biopsy samples was assessed in histological sections using computer-aided morphometry. Results. Biopsy samples were most commonly obtained...
The Journal of Molecular Diagnostics, 2010
EGFR mutant-specific antibodies directed toward the exon 21 L858R EGFR mutation and exon 19 E746-750 deletions represent an effective screening test for predicting lung cancer response to EGFR-tyrosine kinase inhibitors chemotherapy. Background: Practical lung cancer testing algorithms already include EGFR and KRAS mutation assays and are likely to include EML4-ALK and BRAF assays in the near future. Objective: To evaluate 2 antibodies "…on a large series of lung adenocarcinomas with molecular data available for EGFR mutation status." Materials/Methods: 218 paraffin-embedded lung adenocarcinomas were identified at Memorial Sloan-Kettering Cancer Center (MSKCC). These were enriched to contain 33% positivity for EGFR mutation, greater than the 20% prevalence of EGFR mutations in submitted specimens at MSKCC. Paraffin tumor sections were manually immunostained with 2 rabbit monoclonal antibodies specific for (a) exon 21 L858R EGFR mutation and (b) 15bp exon 19 E746-750 deletion (Cell Signaling Technology) using alkaline EDTA antigen retrieval and overnight antibody incubation at 55°C. Cytoplasmic and/or membrane staining was semiquantitated: 0, no to faint staining intensity in <10% of tumor cells; 1+, faint staining in >10% of tumor cells; 2+, moderate staining; and 3+, strong staining. Results: Among 218 lung adenocarcinomas, 18 contained EGFR exon 21 substitution mutation L858R (detected by PCR-restriction fragment length polymorphism or mass spectrometry) and 55 cases contained exon 19 deletions. Twenty-two (10.1%) were immunopositive using the L858R mutant-specific antibody and 39 (17.9%) were immunopositive using the exon 19 EGFR deletion-specific antibody. Using a threshold of 1+ staining, the L858R-specific antibody was 95.2% sensitive and 99% specific for molecular L858R mutation. Using a threshold of 2+ staining, the L858R antibody was 76% sensitive and 100% specific. Staining with the exon 19 specific antibody was 100% sensitive and 98.8% specific for 15-bp exon 19 deletions. However, this antibody was less accurate for predicting larger and smaller exon 19 deletions, staining only half of these cases. Based on the size distribution for exon 19 deletion in lung adenocarcinomas, the exon 19-specific antibody is predicted to have an overall sensitivity of 85% and a specificity of 99% for predicting all EGFR exon 19 deletions. Conclusions: EGFR mutant-specific antibodies are likely to play a key role in molecular classification of pulmonary adenocarcinoma, possibly as a primary screening test requiring reflex DNA testing of negative results. Reviewer's Comments: Currently, these antibodies are for research use only. They require both technical and clinical validation before implementation as clinical assay reagents. However, it seems quite likely that will have clinical utility as part of a structured reflex-testing algorithm or for stand-alone testing of biopsy fragments that are too limited for DNA assays. (Reviewer-Guy E. Nichols, MD, PhD).
Oncology Reports, 2013
The epidermal growth factor receptor (EGFR) mutation status in the tyrosine kinase domain is known to be a predictor of the response to gefitinib or erlotinib in lung cancer; thus, a non-surgical procedure of tumor specimen collection is critical for mutation analysis. The aim of the present study was to analyze the EGFR, KRAS and BRAF status in limited cytological material. To the best of our knowledge, this is the first time that the quantitative scale of tumor cells and the percentage of tumor cells in cytological material were evaluated at the early stages of pathomorphological material qualification for EGFR, KRAS and BRAF mutation analysis. Our results revealed that even 100-1,000 tumor cells from fine needle aspiration (FNA) samples provided reliable results of mutation analysis when sensitive real-time polymerase chain reaction (PCR) methods were used. EGFR mutations were detected in 10% (7/71) and KRAS mutations were detected in 35% (19/54) of the lung adenocarcinoma cases. In addition, we reported the most common inhibiting mutation (p.T790M) found in coexistence with p.L858R in an FNA sample from a patient, for whom shortterm improvement after erlotinib treatment was observed before further progression of the disease. Subsequently, mutual exclusion of EGFR and KRAS mutations was observed. Cytological samples with a small number of tumor cells obtained via FNA, endobronchial ultrasound (EBUS)-transbronchial needle aspiration (TBNA) or brushing are suggested to be used for diagnostic purposes after careful selection by cytopathologists and analysis using a validated, sensitive real-time PCR method.
Endobronchial ultrasound-guided transbronchial needle aspiration for identifying EGFR mutations
European Respiratory Journal, 2010
Intrathoracic lymph node enlargement is a common finding in patients with extrathoracic malignancies. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a technique that is commonly used for lung cancer diagnosis and staging but that has not been widely investigated for the diagnosis of enlarged mediastinal and lobar lymph nodes in patients with extrathoracic malignancies. We conducted a retrospective study of 117 patients with extrathoracic malignancies who underwent EBUS-TBNA for diagnosis of intrathoracic lymph node enlargement from October 2005 to December 2009 and compared the EBUS-TBNA findings with the final diagnoses. EBUS-TBNA diagnosed mediastinal metastases in 51 of the 117 (43.6 %) cases and gave an alternate diagnosis or ruled out the presence of malignancy in 35 (56.4 %). Fourteen of these 35 patients underwent further surgical investigation, while the remaining 21 had clinical and radiological follow-up for 18 months. No false negatives were found in the surgery group. In the follow-up group, 13 patients had stable or regressive lymphadenopathy, and eight developed clinicoradiological progression and were assumed to have been false negatives by EBUS-TBNA. The sensitivity and negative predictive value of EBUS-TBNA were 86.4 and 75 %, respectively. Immunohistochemical staining (IHC) was performed in 80.4 % of the samples obtained by EBUS-TBNA. In samples obtained from ten patients with metastatic breast cancer, estrogen receptor expression was successfully assessed in eight patients and progesterone receptor and human epidermal growth factor receptor 2 in four. EBUS-TBNA is an accurate procedure for the diagnosis of thoracic lymph node metastases in patients with extrathoracic malignancies and should be an initial diagnostic tool in these patients. Furthermore, EBUS-TBNA can obtain high-quality specimens from metastatic lymph nodes for use in molecular analyses.