title: Gene expression ratio test distinguishes normal lung from lung tumors in solid tissue and FNA biopsies.
abstract: Lung cancer is the leading cause of cancer-related deaths worldwide. Prognosis and survival are dependent on cell type, early detection, and surgical treatment. Hence, optimal screening strategies and new therapies are urgently required. Although surveillance with low-dose computed tomography can reduce lung cancer mortality by 20%, the number of false-positive detections is significant. Tissue diagnosis aids in the identification of benign nodules, reducing the number of false positive detections. To determine whether molecular testing of fine-needle aspirations (FNAs) can reduce false-positive detections, we developed a gene expression-based test that distinguishes normal from cancerous lung tissues. The test first was applied to published microarray data, showing overall sensitivity and specificity values of 95% (95% CI, 90%-98%) and 100% (95% CI, 40%-100%), respectively. Subsequently, it was validated on 30 solid and ex vivo FNA lung cancer tumor samples and matched normal lung specimens using real-time PCR. The validation test was 93% (95% CI, 78%-99%) sensitive and 100% (95% CI, 88%-100%) specific for the detection of tumor versus normal lung on solid samples, whereas FNA specimens yielded a sensitivity of 91% (95% CI, 72%-99%) and a specificity of 94% (95% CI, 70%-100%). This study supports the hypothesis that the gene-ratio approach reliably distinguishes normal lung from cancerous tissues in FNA samples and can be optimized to diagnose benign nodules.
authors.affiliation: Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program, Division of Thoracic Surgery, Brigham and Women's Hospital, Boston, Massachusetts; Department of Surgery, Harvard Medical School, Boston, Massachusetts.
authors.forename: Assunta
authors.initials: A
authors.lastname: De Rienzo
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, Massachusetts; Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Beow Y
authors.initials: BY
authors.lastname: Yeap
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Edmund S
authors.initials: ES
authors.lastname: Cibas
authors.affiliation: Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program, Division of Thoracic Surgery, Brigham and Women's Hospital, Boston, Massachusetts; Department of Surgery, Harvard Medical School, Boston, Massachusetts.
authors.forename: William G
authors.initials: WG
authors.lastname: Richards
authors.affiliation: Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program, Division of Thoracic Surgery, Brigham and Women's Hospital, Boston, Massachusetts; Department of IT Research Computing, Harvard Medical School, Boston, Massachusetts.
authors.forename: Lingsheng
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts; Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Ritu R
authors.initials: RR
authors.lastname: Gill
authors.affiliation: Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program, Division of Thoracic Surgery, Brigham and Women's Hospital, Boston, Massachusetts; Department of Surgery, Harvard Medical School, Boston, Massachusetts.
authors.forename: David J
authors.initials: DJ
authors.lastname: Sugarbaker
authors.affiliation: Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program, Division of Thoracic Surgery, Brigham and Women's Hospital, Boston, Massachusetts; Department of Surgery, Harvard Medical School, Boston, Massachusetts. Electronic address: rbueno@partners.org.
authors.forename: Raphael
authors.initials: R
authors.lastname: Bueno
mesh_terms: D044963:Biopsy, Fine-Needle; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods*; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity