Author of

• 12441

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  P3.06 - Poster Session 3 - Prognostic and Predictive Biomarkers (ID 178)

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

  • 12460

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    P3.06-020 - Prognostic Markers for Mesothelioma Patients Treated with Induction Chemotherapy Followed by Extrapleural pneumonectomy (ID 1879)

    09:30 - 09:30  |  Author(s): B. Seifert
    • Abstract

    Background
    Multimodal treatment provides the best outcome for some but not all malignant pleural mesothelioma (MPM) patients. Therefore the identification of prognostic markers helping to select patients remains a subject of key importance. Frequent loss of NF2 tumor suppressor gene, a regulator of Hippo pathway and mammalian target of rapamycin (mTOR) has been well documented in MPM. We recently observed loss of expression of phosphatase and tensin homologue (PTEN), a tumor suppressor gene of the phosphatidylinositol 3-kinase (PI3K)/mTOR pathway, in 62% of MPM patients. In this regard, increased activity of these pathways stemming from loss of abovementioned tumor suppressor genes may serve as potential prognosticator as well as therapeutic target. Here we aim to assess prognostic significance of PI3K/mTOR and Hippo pathways for MPM patients treated with a multimodal approach.

    Methods
    Large cohort of MPM patients uniformly treated with induction chemotherapy followed by extrapleural pneumonectomy was employed in this study. Tissue micro arrays were constructed composing of paired samples from patients (n = 153) collected pre- and post-induction chemotherapy. All tissues were evaluated for apoptotic index (cleaved caspase-3) and proliferation index (Ki-67). Expression levels of biomarkers of PI3K/mTOR (PTEN, p(phosphorylated)-mTOR and p-S6) and Hippo signaling pathway (nuclear-YAP and nuclear-Survivin) were evaluated by immunohistochemistry and correlated with overall survival (OAS) and progression free survival (PFS).

    Results
    Survival analysis showed that high p-S6 expression and high Ki-67 index in samples of treatment naïve patients was associated with shorter PFS (p = 0.02 and p = 0.04, respectively). High Ki-67 index after chemotherapy remained associated with shorter PFS (p = 0.03) and OAS (p = 0.02). Paired comparison of marker expression in samples prior and post induction chemotherapy revealed that decreased cytoplasmic PTEN as well as increased p-mTOR expression was associated with a worse OAS (p = 0.04 and 0.03, respectively). No correlation was observed between expression level of nuclear-YAP with PFS or OAS.

    Conclusion
    Ki-67 proliferation index has prognostic value for MPM patients treated with multimodality approach in when analyzed both pre- and post- induction chemotherapy specimens. Our results further reveal the prognostic significance of expression changes of PI3K/mTOR pathway components during induction chemotherapy. If confirmed, these data suggest PI3K/mTOR pathway to be a target for selected MPM patients.