Molecular identification of bronchopulmonary neuroendocrine tumours and neuroendocrine genotype in lung neoplasia using the NETest liquid biopsy. (11th February 2020)

• Record Type: Journal Article
• Authors: Filosso, Pier Luigi; Öberg, Kjell; Malczewska, Anna; Lewczuk, Anna; Roffinella, Matteo; Aslanian, Harry; Bodei, Lisa
• Is Part Of: European journal of cardio-thoracic surgery. Volume 57:Number 6(2020)
• Page Start: 1195
• Page End: 1202
• Publication Date: 2020-02-11
• Subjects: Bronchopulmonary carcinoid -- Neuroendocrine -- Carcinoid -- NETest -- Lung surgery -- Lung cancer -- Chromogranin A; Heart -- Surgery -- Periodicals; Chest -- Surgery -- Periodicals; 617.54
• DOI: 10.1093/ejcts/ezaa018
• Languages: English
• ISSNs: 1010-7940

Abstract

Abstract: OBJECTIVES: Diagnosing lung neuroendocrine neoplasia (NEN) requires a biopsy or an operation. We evaluated a 'liquid biopsy' (NETest) as an in vitro diagnostic tool for identifying NEN and compared it to chromogranin A (CgA). METHODS: We identified 4 study cohorts: patients with bronchopulmonary carcinoids ( n = 99, including 62 typical and 37 atypical carcinoids), lung cancers [ n = 101, including 41 adenocarcinomas, 37 squamous carcinomas (SQC), 16 small-cell lung cancers and 7 large-cell neuroendocrine carcinomas]; benign disease (50 idiopathic pulmonary fibrosis) and healthy controls ( n = 102). Transcript levels measured quantitatively (activity scores: 0–100) were compared to CgA (enzyme-linked immunosorbent assay; normal < 109 ng/ml) levels. RESULTS: The results of the NETest were positive (>20) in 94% of patients with bronchopulmonary carcinoid compared to 8% of the controls (Fisher's exact test; P < 0.001) and were significantly more accurate as a diagnostic test (McNemar's test; P < 0.001, χ 2 = 72) than was CgA (positive: 19% bronchopulmonary carcinoid, 15% controls). Small-cell lung cancers (87%), large-cell neuroendocrine carcinomas (86%), adenocarcinoma (42%) and SQC (35%) were also NETest-positive. Increasing the NETest cut-off score to >40 was useful for detecting all NENs and differentiating these tumours from either controls/benign lung diseases (specificity 97%) or adenocarcinoma/SQC (specificity 94%). CgA was positive in 15–44% irrespective of pathology and had no diagnostic value. CONCLUSIONS: A gene-based liquid biopsy is an effective and accurate method for diagnosing lung tumours with neuroendocrine gene expression. CgA has no value. An NETest score >40 provides an accurate (94–97%) rule-in for the diagnosis of NEN and a rule-out for benign and other neoplastic diseases. Because neuroendocrine gene expression is associated with a poor prognosis, NETest levels may have utility both in the diagnosis of and the treatment stratification for lung neoplasia.