Author of

• 11543

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  P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11588

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    P2.06-045 - c-Met Expression in Malignant Mesotheliomas (ID 3216)

    09:30 - 09:30  |  Author(s): R. Sharma
    • Abstract

    Background
    Met is a receptor tyrosine kinase that is encoded by c-Met a proto-oncogne. Abnormal c-met expression has been described in several solid tumors most notably in non small cell lung carcinoma and gastric carcinoma where tumor growth and survival is driven by met signaling. Furthermore, met is also a resistance pathway for EGFR tyrosine kinase inhibitors. Met-targeted therapies are currently being tested in clinical trials and met IHC is being used as one of the methods to evaluate met expression. Malignant mesothelioma is an aggressive tumor with limited treatment options and short survival. Met-based therapies could be considered in mesotheliomas with deregulated c-Met expression.

    Methods
    The study cohort included 39 malignant mesothelioma (Age 15-91 years; Sex: 11 female and 28 male; Histologic type: 1 sarcomatoid, 7 biphasic and 21 epithelioid, primary location: 8 peritoneal and 31 pleural). Immunohistochemistry was performed using an anti-total c-Met rabbit monoclonal antibody (clone SP-44, Ventana Medical Systems, Tucson, AZ, USA) using 4 micron sections of large biopsies or resection specimens and an automated platform (Ventana Benchmark Ultra, Ventana Medical Systems, Tucson, AZ, USA). The staining was evaluated for intensity (none, week, moderate, strong) and extent (percent of tumor staining) and a score was assigned to each tumor on a scale from 0 to 3+ (0: no staining, 1+: any staining in less than 50% of tumor, 2+: moderate to strong staining in >50% of tumor, 3+: strong staining in >50% of tumor). Tumors with and IHC score of 3+ and 2+ were considered positive.

    Results
    Twenty (20) tumors were scored negative and 19 tumors positive. Strong (3+) staining was seen in 3 epithelioid mesotheliomas (all pleural), 2+ staining was seen in 1 biphasic and 15 epithelioid mesotheliomas, while the remaining 6 biphasic, 1 sarcomatoid and 13 epithelioid mesotheliomas were negative (1+: 19; 0: 1).

    Conclusion
    c-Met positivity (3+ or 2+) is seen in the majority of epithelioid mesothelomas (18 of 21) and in the minority of biphasic mesotheliomas (1 of 7), while the single sarcomatoid mesothelioma was negative. Since the majority of malignant mesotheliomas are of the epithelioid subtype we expect the majority of malignant mesotheliomas be considered met positive as determined by immunohistochemistry and potentially amenable to met-targeted therapy. Correlation with met amplification and activating c-met mutations needs to be investigated to better understand the mechanisms of c-met over expression in malignant mesotheliomas.