Findings indicate that assessment of SHOX2 DNA methylation level in lymph node tissue improves the negative predictive value (NPV) of endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA), as well as endoscopic lung cancer staging in general.
“Applying SHOX2 DNA measurement to pathologic evaluation will not only improve the diagnosis of lymph nodes affected by malignant diseases, but with its high specificity also supports benign results,” say Paul Zarogoulidis (University Duisburg-Essen, Germany) and colleagues in the Annals of Oncology.
Because of the low NPV of EBUS-TBNA, patients often require follow-up diagnostic tests. Hypermethylated SHOX2 has been found to be a clinically useful tumor marker in potential lung cancer cases where previous bronchoscopy results have been unclear.
This study included data from 116 patients referred for EBUS-TBNA in 165 suspicious lymph nodes. Samples obtained from EBUS-TBNA were examined for SHOX2 DNA methylation levels, and both initial results from EBUS-TBNA and methylated SHOX2 testing were compared in a final review.
There was a greater than 80-fold increased SHOX2 methylation level found in the positive lymph nodes. Of the 79 specimens later confirmed to show cancer, 74 (93.7%) were correctly identified by SHOX2. Nearly all of the negative cases were also correctly identified by SHOX2.
In 80 of the lymph nodes, EBUS-TBNA was not diagnostic and further biopsies or other clinical follow-ups were required. In a later analysis, SHOX2 correctly classified 78 of these ambiguous cases, with a sensitivity of 94% and a specificity of 98%.
By using SHOX2, the NPV improved from 80% to 92%, compared with standard pathologic evaluation. Overall, sensitivity was 94% with SHOX2 and 82% with pathologic evaluation; specificity was 99% and 100%, respectively.
The researchers conclude: “The presented results show for the first time that the assessment of SHOX2 methylation level in lymph node tissue obtained by EBUS-TBNA can improve the accuracy of lung cancer staging compared with conventional pathology alone, and results are received within 24 h.
“Utilizing the SHOX2 methylation level, sensitivity and NPV is increased, and unnecessary invasive procedures might be avoided.”
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