Assessment of SHOX2 methylation in EBUS-TBNA specimen improves accuracy in lung cancer staging
Menée sur des échantillons ganglionnaires prélevés par aspiration transbronchique à l'aiguille fine guidée par échographie endobronchique sur 105 patients atteints d'un cancer du poumon, cette étude montre que la mesure du niveau de méthylation de l'ADN de SHOX2 améliore la précision de la stadification de la maladie
Background : Endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) is a well-established method to assess mediastinal lymph nodes for lung cancer. However, a proportion of patients require further investigation, due to the low negative predictive value (NPV). The objective of this study was to determine whether the assessment of short stature homeobox 2 (SHOX2) DNA methylation level in lymph node tissue obtained by EBUS-TBNA improves the accuracy of mediastinal staging.
Patients and methods : EBUS-TBNA was carried out for suspicious lymph nodes of 154 patients. Negative or ambiguous histological results were confirmed by surgical means and clinical follow-up over 6 months. EBUS-TBNA was assessed on 80 positive and 85 negative classified lymph nodes and compared with the result of the SHOX2 DNA methylation real-time PCR analysis. Relative methylation measured by delta–delta cycle threshold (
ΔΔCt) was used to classify the samples. Clinical performance of the EBUS-TBNA procedure with and without the additional SHOX2 assessment was calculated against the final classification according to the gold standard.
Results
:
Based on data from 105 patients, an average 80-fold increase in the SHOX2 methylation level was measured for positive compared with negative lymph nodes. SHOX2 results with a ΔΔCt value of <6.5 indicate positive lymph nodes. Applying this molecular analysis to EBUS-TBNA cases, not diagnosed by pathologic assessment, the sensitivity of staging was improved by 17%
–99%. The NPV increased from 80% to 99%.
Conclusions : The combination of EBUS-TBNA and SHOX2 methylation level strongly improves the assessment of the nodal status by identifying additional malignant lesions and confirming benign nodes and therefore avoiding invasive follow-up procedures.
Annals of Oncology , résumé, 2013