The mTOR Signaling Pathway Is Associated With the Prognosis of Malignant Pleural Mesothelioma After Multimodality Therapy

Anticancer Res. 2019 Nov;39(11):6241-6247. doi: 10.21873/anticanres.13833.

Abstract

Background/aim: We performed multimodality therapy comprising preoperative chemotherapy, extrapleural pneumonectomy (EPP), and radiation therapy for patients with malignant pleural mesothelioma (MPM). Although multimodality therapy resulted in good prognosis, further improvement is required. Therefore, herein, we analysed the prognostic factors using surgical specimens and searched for suitable molecular targets to improve the prognosis after multidisciplinary treatment.

Patients and methods: Forty-six patients with MPM underwent multimodality therapy. Paraffin-embedded surgical samples were used for immunohistochemistry to evaluate the expression of phosphorylated (p-) AKT, extracellular signal-regulated kinase (ERK), mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and S6 ribosomal protein (S6RP).

Results: On univariate and multivariate analyses, significant differences were observed according to the histological type, pathological stage, and p-mTOR expression rate.

Conclusion: The prognosis of MPM is affected by p-mTOR expression, suggesting that molecular-targeted treatment might be used during multimodal therapy for MPM.

Keywords: extrapleural pneumonectomy; mTOR signal pathway; malignant pleural mesothelioma.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / metabolism
  • Cisplatin / administration & dosage
  • Combined Modality Therapy / methods
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / therapy
  • Male
  • Mesothelioma / enzymology*
  • Mesothelioma / mortality
  • Mesothelioma / therapy
  • Mesothelioma, Malignant
  • Middle Aged
  • Mitogen-Activated Protein Kinase 1 / analysis*
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Molecular Targeted Therapy
  • Pemetrexed / administration & dosage
  • Pleural Neoplasms / enzymology*
  • Pleural Neoplasms / mortality
  • Pleural Neoplasms / therapy
  • Pneumonectomy
  • Prognosis
  • Protein Serine-Threonine Kinases / analysis
  • Protein Serine-Threonine Kinases / metabolism
  • TOR Serine-Threonine Kinases / analysis*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Biomarkers, Tumor
  • Pemetrexed
  • MTOR protein, human
  • Protein Serine-Threonine Kinases
  • TOR Serine-Threonine Kinases
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Cisplatin