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J. Shih
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-106 - Expression of AEG-1 Associated with Increase of TS Contributes to Chemoresistance of Pemetrexed in Lung Adenocarcinoma (ID 668)
09:30 - 09:30 | Author(s): J. Shih
- Abstract
Background:
Previous studies have suggested that astrocyte-elevated gene-1 (AEG‑1) contributes to a broad spectrum of resistance to various chemotherapeutics. Expression of thymidylate synthase (TS) has implication for effectiveness of pemetrexed in treatment of lung cancer. In this study, we investigated the AEG-1 activity to determine whether its expression is correlated with TS increasing resulted in chemoresistance of pemetrexed in patients with advanced lung adenocarcinoma.
Methods:
Patients with advanced lung adenocarcinoma treated with pemetrexed plus cisplatin as first-line chemotherapy were enrolled. Re-biopsy was performed until disease progression. Immunohistochemical stain of AEG-1 and TS were studied in all patients' tissue before chemotherapy and after disease progression. The primary antibodies used were anti-AEG-1 (1:1,000; chicken polyclonal), anti-actin (1:1,000; rabbit polyclonal; Santa Cruz), and anti-TS (1:1,000; mouse monoclonal; Abcam). The expression of TS and AEG-1 were calculated by H-score. The medical records were reviewed and analyzed, including data on age, gender, smoking status, epidermal growth factor receptor (EGFR) mutation status, treatment responses, and survival.
Results:
A total of six patients (3 male and 3 female) received first-line chemotherapy as pemetrexed/cisplatin for 6 cycles and continuation maintenance therapy with pemetrexed. The mean age was 57.2 years old. Overall best treatment response were partial response. The median of progression-free survival was 5.8 months. Re-biopsy was performed in all of them after disease progression. The expression of AEG-1 level increased from baseline to disease progression (mean, AEG-1, 133.3 to 175.0, p = 0.001), associated with elevation of TS level (mean, TS, 57.9 to 116,1, p = 0.01).
Conclusion:
Expression of AEG-1 associated with increase of TS contributes to chemoresistance of pemetrexed in lung adenocarcinoma. TS expression might be regulated by AEG-1 associated with development of chemoresistance to pemetrexed.
