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V. Ciminale



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    MINI 24 - Epidemiology, Early Detection, Biology (ID 140)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
    • Presentations: 1
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      MINI24.13 - Molecular and Pathological Features of Different Malignant Pleural Mesothelioma (MPM) Histologic Subtypes (ID 2121)

      17:55 - 18:00  |  Author(s): V. Ciminale

      • Abstract
      • Presentation
      • Slides

      Background:
      Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis and limited treatment options. Sarcomatoid/biphasic mesotheliomas are characterized by more aggressive behaviour, characterized by a higher resistance to systemic treatments, more frequent distant spread and a poorer prognosis compared with the epithelioid subtype. To date prognostic and tailored therapeutic biomarkers are lacking

      Methods:
      The present study analyzed the expression levels of MDM2 and HIF1alpha and the presence of inflammation, necrosis and proliferation in different histologic subtypes from chemonaive MPM patients. Diagnostic biopsies of MPM patients from four Italian cancer centers were centrally collected and analyzed. MDM2, and HIF1alpha expression levels were investigated through immunohistochemistry and RT-qPCR. A pathological assessment of necrosis, inflammation and proliferation index (through Ki67 immunostaining) was also performed. Molecular markers, pathological features and clinical characteristics were related to overall (OS) and progression free survival (PFS).

      Results:
      Sixty MPM patients were included in the study (32 epithelioid and 28 non-epithelioid). Higher levels of MDM2 (p<0.001), HIFalpha (p=0.013), necrosis (p=0.013) and proliferation index (p<0.001) were significantly associated with sarcomatoid/biphasic subtypes, while higher levels of inflammation were significantly associated with epithelioid subtype (p=0.044). MDM2 expression levels were correlated with HIF1alpha (p=0.0001), necrosis (p=0.008) and Ki67 (p=0.009). Univariate analysis showed a significant correlation of non-epithelioid histology (p=0.04), high levels of necrosis (p=0.037) and proliferation index (p=0.0002) with shorter PFS. This finding, however, was not confirmed by the multivariate analysis.

      Conclusion:
      Sarcomatoid/biphasic and epithelioid mesotheliomas show different MDM2 and HIF1alpha expression levels and are characterized by different levels of necrosis, proliferation and inflammation. Further studies are warranted in order to confirm a prognostic and predictive role of such markers and features.

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