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J.A. Boys



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    P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P3.04-096 - A Feasibility Pilot Study Testing Six DNA Methylation Markers to Improve Detection of Malignant Pleural Effusions in Lung Cancer (ID 1382)

      09:30 - 09:30  |  Author(s): J.A. Boys

      • Abstract
      • Slides

      Background:
      Patients presenting with pleural effusion and suspected primary lung cancer raise suspicion for pleural metastasis. Accurate diagnosis is critical; metastatic pleural effusion indicates stage IV disease with significantly different treatment and prognosis. Currently diagnosis is obtained by cytology, however the mean sensitivity of cytology is only 60%. Lung cancer-specific DNA methylation markers may improve sensitivity. Here we determine whether six previously identified DNA methylation markers can detect malignancy in pleural effusions of lung cancer patients.

      Methods:
      Pleural effusions were collected from one small cell lung cancer (SCLC), 5 non-small cell lung cancer (NSCLC) and 3 patients with benign conditions not suspicious for cancer, presenting to USC Keck Hospital and Los Angeles County Hospital (June 2013 to March 2015). The 6 lung cancer patients underwent drainage and pleural fluid cytology. Samples were centrifuged (3000g, 10 minutes) to remove cellular material. DNA was extracted from 1 ml of pleural fluid and bisulfite converted. MethyLight was used to quantitate the methylation levels of the markers. The preliminary specificity and sensitivity were calculated.

      Results:
      Percent of methylated reference (PMR, a measure of methylation levels compared to enzymatically fully methylated DNA) is shown in Table 1. Markers LuCa-1 and LuCa-2 had 100% sensitivity and 100% specificity (Table 2). Two patients (5 and 6) had negative cytology but positive malignancy based on markers. Pathologic confirmation of malignant involvement of the pleura was obtained in both cases, one with a different cytology specimen and the other by thoracoscopic exploration. Figure 1

      Table 2 DNA Methylation Marker Sensitivity & Specificity
      Marker Sensitivity Specificity
      LuCa-1 100% 100%
      LuCa-2 100% 100%
      LuCa-3 100% 67%
      LuCa-4 100% 33%
      LuCa-5 100% 33%
      LuCa-6 100% 33%




      Conclusion:
      This pilot study indicates that DNA methylation markers can detect lung cancer in pleural effusions, potentially with sensitivity and specificity that exceed routine cytology. Further analysis of these 6 markers, used separately or in combination as a multiplexed panel to detect pleural malignancy is warranted.

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