Author of

• 18972

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  P2.02 - Biology/Pathology (ID 616)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Biology/Pathology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 23266

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    P2.02-068 - BRG1 and p53 Expression in Resected Stage I – III Non-Small Cell Lung Cancer (ID 10199)

    09:30 - 09:30  |  Author(s): M. Koebel
    • Abstract

    Background:
    Evidence suggests a striking significance of BRG1 in non-small cell lung cancer (NSCLC) development and prognosis including its ability to modulate NSCLC response to commonly used chemotherapy. The human SW1/SNF (switching defective/ sucrose non-fermenting) family of chromatin remodeling complexes are composed of multi-subunit proteins among which are the BRG1 and INI-1. Both BRG1 (SMARCA4) and INI-1 (SMARCB1, BAF47, SNF7) are implicated in different cancers. We aimed at identifying the frequency of the SW1/SNF protein components loss and the significance in NSCLC. Given that inactivating BRG1 mutations could coexist with TP53 alterations in NSCLC cell lines, we also included the tumor suppressor protein p53 in our analysis.
    
    Method:
    We analyzed the expression of the SW1/SNF subunits (BRG1 and INI-1) and p53 proteins from resected stage I – III NSCLC using the immunohistochemistry. Mouse monoclonal anti-p53 (DO-7, Dako Omnis) and anti-INI-1 (MRQ-27, Cell Marque) antibodies were used for p53 and INI-1 protein detection respectively. BRG1 was detected using the rabbit monoclonal anti-BRG1 antibody (EPNCIR111A, Abcam). Clinical data were obtained from the Glans-Look lung cancer database and patients diagnosed of NSCLC from 2003 to 2006 were included in the study.
    
    Result:
    A total of 150 cases were identified, {Adenocarcinoma n =82 (54.7%), Squamous cell carcinoma n = 50 (33.3%), Large cell carcinoma n = 7 (4.7%) and others n = 11 (7.3%: Adenosquamous, Bronchioalveolar and Giant cell carcinomas)}.The BRG1 protein was absent in 6% (9/150) of cases with the overall highest number (3.3%) seen in adenocarcinoma. Whereas, normal INI-1 protein was expressed in all samples. Within NSCLC subtypes, the rate of BRG1 loss was highest in the large cell carcinomas at 28.1% (2/7) and lowest in squamous cell subtype at 2% (1/50) while only 6.1% (5/82) of adenocarcinoma showed BRG1 loss. The frequency of aberrant p53 protein expression (including overexpression, cytoplasmic and complete expression loss) was at 63% (95/150) and 6 (2 large cell and 4 adenocarcinoma) of the 95 abnormal p53 cases (6.3%) had BRG1 loss.
    
    Conclusion:
    BRG1 loss seems to be a low occurrence in NSCLC. Although a high rate of BRG1 inactivating mutations were previously reported in NSCLC cell lines, the present result suggests that these mutations may still result in the expression of possibly an abnormal BRG1. BRG1 loss appears to coexist with p53 abnormality in NSCLC. Additional multivariate and outcome analysis will be presented.