Methylation assay for the diagnosis of lung cancer on bronchial aspirates: a cohort study
| Autor: | Helmut E. Gabbert, Rainer Kappes, Claus Dieter Gerharz, Alfred Böcking, Hans Juergen Grote, Viola Schmiemann, Alexandre Sherlley Casimiro Onofre, Marietta Kazimirek |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Adult
Male Cancer Research Pathology medicine.medical_specialty Lung Neoplasms Adenomatous polyposis coli Receptors Retinoic Acid Biopsy Adenomatous Polyposis Coli Protein Bronchi Malignancy Polymerase Chain Reaction Cohort Studies Cell Line Tumor Bronchoscopy medicine Humans Sulfites False Positive Reactions Lung cancer Lung Cyclin-Dependent Kinase Inhibitor p16 Aged DNA Primers Retrospective Studies Aged 80 and over biology business.industry Reverse Transcriptase Polymerase Chain Reaction Tumor Suppressor Proteins Respiratory disease Temperature Retrospective cohort study Methylation DNA Methylation Middle Aged medicine.disease medicine.anatomical_structure Oncology Case-Control Studies biology.protein Female business Cohort study |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 11(21) |
| ISSN: | 1078-0432 |
| Popis: | Purpose: Recent studies have detected aberrant promoter methylation of adenomatous polyposis coli promoter 1 A (APC), cyclin-dependent kinase inhibitor-2A (p16INK4a), retinoic acid receptor β2, and RAS association domain family protein 1 (RASSF1A) in bronchial aspirates and suggested their use as biomarkers for lung cancer diagnostics. The purpose of this study was to validate these candidate marker genes in a retrospective cohort study. Experimental Design: Bronchial aspirates collected from a cohort comprising 247 patients with suspected lung cancer were investigated retrospectively regarding aberrant promoter methylation using a quantitative methylation-specific real-time PCR (QMSP). Results: Eighty-nine patients were diagnosed with primary lung cancer, 102 had benign lung disease, and 56 showed miscellaneous other conditions. A panel consisting of APC, p16INK4a, and RASSF1A emerged as useful combination. This panel detected aberrant methylation in bronchial aspirates of 22 of 35 (63%) and 21 of 44 (44%) centrally and peripherally located primary lung cancers, respectively. Bronchial aspirates also showed aberrant methylation in 5 of 7 (71%) patients with a recurrent lung cancer and in 8 of 30 (27%) cases without tumor recurrence. In contrast, only 1 of 102 patients with benign lung disease displayed a (false) positive test result. Rarely, aberrant methylation was found in patients with other malignancies (3 of 16). The QMSP assay correctly confirmed lung cancer in 8 of 12 (67%) cases with an ambiguous cytology. Moreover, it disclosed 9 of 26 (35%) of peripheral tumors lacking simultaneous cytologic or histologic diagnosis of malignancy. Conclusions: Our findings suggest that the QMSP assay could be applied as a reflex test in cases of suspected lung cancer that defy a definite diagnosis by conventional methods. Thus, the assay could be a useful diagnostic adjunct especially regarding peripheral tumors. |
| Databáze: | OpenAIRE |
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