Molecular Nodal Staging Using miRNA Expression in Lung Cancer Patients by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration

Nakajima, Takahiro; Itoga, Sakae; Ishige, Takayuki; Fujiwara, Taiki; Sakairi, Yuichi; Wada, Hironobu; Suzuki, Hidemi; Iwata, Takekazu; Chiyo, Masako; Yoshida, Shigetoshi; Matsushita, Hiroshi; Yasufuku, Kazuhiro; Yoshino, Ichiro

doi:10.1159/000489178

Cited by 6 publications

(4 citation statements)

References 31 publications

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“…We did not study the use of smears for PD-L1 staining, but emerging data suggest its feasibility and equivalence with core biopsy samples [54, 55]. Theoretically, it would be possible to save some smears with over 100 cells for PD-L1 assessment whilst using the remainder for NGS; further study in this area is needed.…”

Section: Discussionmentioning

confidence: 99%

Diff-Quik Cytology Smears from Endobronchial Ultrasound Transbronchial Needle Aspiration Lymph Node Specimens as a Source of DNA for Next-Generation Sequencing Instead of Cell Blocks

et al. 2019

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Background: Next-generation sequencing (NGS) in lung cancer specimens from endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is usually performed on formalin-fixed paraffin-embedded cell block material. Objectives: Since DNA can be damaged by this process, we investigated the potential of using DNA extracted from Diff-Quik cytology smears made for rapid on-site evaluation during EBUS-TBNA. Methods: In a prospective study, 67 patients undergoing diagnostic EBUS-TBNA were analysed. We compared cell blocks and smears for DNA yields and sequencing (TruSeq Amplicon Cancer Panel) outcomes. Smears were also evaluated for tumour cell fraction and overall cellularity (cell count). Results: Primary lung cancer was diagnosed in 64 patients and metastatic malignancy in 3 patients. The DNA yield from smears was significantly higher than that obtained from matched cell blocks (mean 1,740 vs. 434 ng; p = 0.001). For 33 cases with matched smears and cell blocks the mutation profiles were similar. Smears with abundant malignant cells (using a cut-off of > 25% tumour cell fraction and > 1,000 cells) accurately predicted high (> 50 ng) DNA yield and therefore success in triaging samples to sequencing. In terms of tissue workflow, using only smears as source DNA for sequencing was an improvement in the use of only cell blocks (54/67 [80.6%] vs. 41/67 [61.2%]); however, the use of cell blocks when smears were not available or did not yield sufficient DNA further improved the success rate to 62/67 (92.5%) cases. Conclusion: We recommend smears in laboratory workflows as the primary source of DNA for NGS following an EBUS procedure.

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Section: Discussionmentioning

confidence: 99%

Diff-Quik Cytology Smears from Endobronchial Ultrasound Transbronchial Needle Aspiration Lymph Node Specimens as a Source of DNA for Next-Generation Sequencing Instead of Cell Blocks

et al. 2019

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“…Human telomerase catalytic subunit gene ( hTERT ) was also suggested as a biomarker for detecting micrometastasis [38]. More recently, expression of miRNAs was also assessed for molecular staging of nodes using EBUS-TBNA samples [41]. Among the five candidates evaluated in 39 malignant and 11 benign lymph nodes, miR-200c showed the highest diagnostic yield, resulting in a 97.4% sensitivity, an 81.8% specificity, and a 90.0% NPV.…”

Section: Discussionmentioning

confidence: 99%

Methylation Assessment for the Prediction of Malignancy in Mediastinal Adenopathies Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Patients with Lung Cancer

Leiro-Fernández

Chiara

Rodríguez-Girondo

et al. 2019

Cancers

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The evaluation of mediastinal lymph nodes is critical for the correct staging of patients with lung cancer (LC). Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive technique for mediastinal staging, though unfortunately lymph node micrometastasis is often missed by cytological analysis. The aim of this study was to evaluate the predictive capacity of methylation biomarkers and provide a classification rule for predicting malignancy in false negative EBUS-TBNA samples. The study included 112 patients with a new or suspected diagnosis of LC that were referred to EBUS-TBNA. Methylation of p16/INK4a, MGMT, SHOX2, E-cadherin, DLEC1, and RASSF1A was quantified by nested methylation-specific qPCR in 218 EBUS-TBNA lymph node samples. Cross-validated linear regression models were evaluated to predict malignancy. According to EBUS-TBNA and final diagnosis, 90 samples were true positives for malignancy, 110 were true negatives, and 18 were false negatives. MGMT, SHOX2, and E-cadherin were the methylation markers that better predicted malignancy. The model including sex, age, short axis diameter and standard uptake value of adenopathy, and SHOX2 showed 82.7% cross-validated sensitivity and 82.4% specificity for the detection of malignant lymphadenopathies among negative cytology samples. Our results suggest that the predictive model approach proposed can complement EBUS-TBNA for mediastinal staging.

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“…The low NPV, in particular in case of NSCLC restaging, is one of the main limitations of EBUS-TBNA, and studies are being carried out to overcome the high number of false negative cases with new more specific detection targets. Inage and colleagues ( 86 ) investigated the role of microRNAs assessment as tumor markers in patients undergoing NSCLC restaging after chemo-radiotherapy with encouraging results, as they were able to reach a NPV of 100%. However, further trials are needed to definitely improve the effectiveness of EBUS-TBNA in this field.…”

Section: Next-generation Sequencing (Ngs) and Future Perspectivesmentioning

confidence: 99%

The role of EBUS-TBNA in lung cancer restaging and mutation analysis

Muriana¹,

Rossetti²

2020

Mediastinum

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In recent years, several molecules targeting specific genetic aberrations were released for the treatment of patients affected by locally advanced and metastatic non-small cell lung cancer (NSCLC), leading to an improvement in survival. Moreover, inhibitors of PD-1 and PD-L1 immune checkpoints showed to improve survival, and they are now indicated as first-line treatment in selected patients. Hence, the collection of adequate samples for diagnosis, staging, genotyping and immunohistochemical analysis is a fundamental step in NSCLC treatment planning. When feasible, EBUS-TBNA is suggested as the first-choice diagnostic tool by most of the guidelines. Several studies demonstrated that mutation analysis is viable with high levels of accuracy on both cytological and histological samples obtained by EBUS-TBNA. No technical factor (type of needle, number of passes, use of rapid-on-site-examination, material processing, detection method) has been identified as uniquely influencing the diagnostic yield of molecular analysis. EBUS-TBNA demonstrated to be useful for the restaging of patients affected by locally advanced NSCLC who underwent induction chemotherapy or chemo-radiotherapy, as well as in those who show acquired resistance to targeted therapy and immunotherapy. Nevertheless, most authors agree that a high number of false negative results should be expected due to the likely presence of necrosis and fibrosis induced by neoadjuvant treatments. Therefore, in case of EBUS-TBNA negative sample, pathologic confirmation by surgical biopsy is recommended for the planning of definitive treatment. As suggested by a few preliminary experiences, a wide application of next-generation sequencing (NGS) on EBUS-TBNA specimens will lead to the development of better tailored treatments with simultaneous identification of a large number of gene alterations on a single sample at the time of diagnosis.

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Molecular Nodal Staging Using miRNA Expression in Lung Cancer Patients by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration

Cited by 6 publications

References 31 publications

Diff-Quik Cytology Smears from Endobronchial Ultrasound Transbronchial Needle Aspiration Lymph Node Specimens as a Source of DNA for Next-Generation Sequencing Instead of Cell Blocks

Diff-Quik Cytology Smears from Endobronchial Ultrasound Transbronchial Needle Aspiration Lymph Node Specimens as a Source of DNA for Next-Generation Sequencing Instead of Cell Blocks

Methylation Assessment for the Prediction of Malignancy in Mediastinal Adenopathies Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Patients with Lung Cancer

The role of EBUS-TBNA in lung cancer restaging and mutation analysis

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