SHOX2 DNA Methylation is a Biomarker for the diagnosis of lung cancer based on bronchial aspirates

Marker discovery was carried out by differential methylation hybridization (DMH) and real-time PCR. The real-time PCR based HeavyMethyl technology was used for quantitative analysis of DNA methylation of SHOX2 using bronchial aspirates from two clinical centres in a case-control study. Fresh-frozen and Saccomanno-fixed samples were used to show the tumor marker performance in different sample types of clinical relevance.Valid measurements were obtained from a total of 523 patient samples (242 controls, 281 cases). DNA methylation of SHOX2 allowed to distinguish between malignant and benign lung disease, i.e. abscesses, infections, obstructive lung diseases, sarcoidosis, scleroderma, stenoses, at high specificity (68% sensitivity [95% CI 62-73%], 95% specificity [95% CI 91-97%]).Hypermethylation of SHOX2 in bronchial aspirates appears to be a clinically useful tumor marker for identifying subjects with lung carcinoma, especially if histological and cytological findings after bronchoscopy are ambiguous.Lung cancer is the second most common cancer in both men and women representing about 15% of all cancer diagnoses [1]. In the absence of screening, lung cancer patients either exhibit symptoms or are accidentally diagnosed by clinical imaging performed for other indications. Patients suspected of having malignant lung disease usually undergo clinical investigation (workup) including CT-scanning of the thorax and bronchoscopy, which is mainly undertaken in those individuals with central tumours. The latter is the method of choice for confirming the diagnosis of a suspected lung neoplasm by pathological assessment of tissue or a cytological specimen obtained during the procedure.The prevalence of lung cancer in this group of patients investigated for suspected lung cancer is approximately 30-40% (personal communication Prof. Field). Establishing a final diagnosis after the first bronchoscopy fails in about half of these patients [2], triggering additional invasive diagnos