PURPOSE: DNA methylation at specific promoter regions is associated with cancer development. We collected bronchoalveolar lavage (BAL) and pleural fluid to study the rates of DNA methylation in lung cancer, non-pulmonary cancers, and controls without cancer.
METHODS: We offered enrollment to all patients scheduled for bronchoscopy or thoracentesis in our clinic. Cells from BAL and pleural fluid were evaluated using methylation specific PCR. Genes linked to cancer formation and progression were assessed for methylation: p16, MGMT, DAPK1, H-Cad and GATA5. Statistical analysis was performed using SPSS 17.
RESULTS: A total of 50 patients were enrolled, and 31 had methylation results completed for this analysis. Mean age and BMI were 54.8±18.0 and 25.8±6.44 respectively, and 51.6% were female. Twelve patients had a current or previous diagnosis of cancer, and two of these were lung cancers. Although the results did not reach statistical significance, 3/12 (25%) patients with a current or previous cancer diagnosis had ≥ 3 genes methylated, versus 3/19 patients without cancer (p=0.45). The p16 and GATA5 genes were methylated in 6/12 (50%) and 5/12 (41.7%) patients with cancer respectively, versus 5/19 (26.3%) and 3/19 (15.8%) patients without cancer (p16: p=0.26; GATA5: p=0.21). The two patients with lung cancer had 2.5±2.1 genes methylated, versus 1.3±1.5 in the patients without lung cancer (p=0.35). All 3 patients with malignant effusions had H-Cad methylated.
CONCLUSION: Initial results show an increased rate of gene methylation in cancer patients that does not reach statistical significance. This may be due to small sample size and type II error, or to the complicated molecular pathways involved in cancer development and spread.
CLINICAL IMPLICATIONS: Assessment of DNA-methylation offers a potential strategy for cancer screening, diagnosis, and staging. Larger studies are needed to better define a role for this test.
DISCLOSURE: Jesse Greer, No Financial Disclosure Information; No Product/Research Disclosure Information