Expression of the Stem Cell Factor Nestin in Malignant Pleural Mesothelioma Is Associated with Poor Prognosis

• Published in: PloS one 2015-09, Vol.10 (9), p.e0139312
• Main Authors: Thies, Svenja, Friess, Martina, Frischknecht, Lukas, Korol, Dimitri, Felley-Bosco, Emanuela, Stahel, Rolf, Vrugt, Bart, Weder, Walter, Opitz, Isabelle, Soltermann, Alex
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antigens; Antineoplastic Agents - therapeutic use; Automation; Biological markers; Biomarkers, Tumor - metabolism; Bone marrow; Calretinin; Cancer; Cell Adhesion Molecules - metabolism; Cell Line, Tumor; Chemotherapy; Chemotherapy, Adjuvant; Cohort Studies; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Diagnostic systems; Disease-Free Survival; Epithelial-Mesenchymal Transition; Female; Gemcitabine; Histology; Humans; Immunoreactivity; Induction Chemotherapy; Lung Neoplasms - diagnosis; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Lung Neoplasms - surgery; Male; Medical prognosis; Melanoma; Mesenchyme; Mesothelioma; Mesothelioma - diagnosis; Mesothelioma - drug therapy; Mesothelioma - metabolism; Mesothelioma - surgery; Mesothelioma, Malignant; Middle Aged; Nestin; Nestin - metabolism; Neural crest; Oncology; Pathology; Patients; Pemetrexed - therapeutic use; Physiological aspects; Platinum; Platinum - therapeutic use; Pleural Neoplasms - diagnosis; Pleural Neoplasms - drug therapy; Pleural Neoplasms - metabolism; Pleural Neoplasms - surgery; Pneumonectomy - methods; Prognosis; Sarcoma - diagnosis; Sarcoma - metabolism; Stem cell factor; Stem Cell Factor - metabolism; Stem cells; Surgery; Survival; Thoracic surgery; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0139312

The epithelioid and sarcomatoid histologic variants of malignant pleural mesothelioma (MPM) can be considered as E- and M-parts of the epithelial-mesenchymal transition (EMT) axis; the biphasic being an intermediate. EMT is associated with an increase of stem cell (SC) traits. We correlated the neural crest SC marker nestin and the EMT marker periostin with histology, type of neo-adjuvant chemotherapy (CT) and overall survival (OS) of MPM patients. Tumor tissues of a historic cohort 1 (320 patients) and an intended induction chemotherapy followed by extrapleural pneumonectomy (EPP) cohort 2 (145 patients) were immunohistochemically H-scored (intensity of immunoreactivity multiplied by frequency of stained cells). Paired chemo-naïve biopsies and -treated surgical specimens were available for 105/145 patients. CT included platinum/gemcitabine (Pla/Gem) or platinum/pemetrexed (Pla/Pem). Expression of any cytosolic nestin progressively increased from epithelioid to biphasic to sarcomatoid MPM in cohort 1, whereas the diagnostic markers calretinin and podoplanin decreased. In cohort 2, Pla/Pem CT increased the expression level of nestin in comparison to Pla/Gem, whereas the opposite was found for periostin. In Pla/Pem treated patients, nestin was higher in biphasic MPM compared to epithelioid. In addition to non-epithelioid histology, any expression of nestin in chemo-naïve biopsies (median overall survival: 22 vs. 17 months) and chemo-treated surgical specimens (18 vs. 12 months) as well as high periostin in biopsies (23 vs. 15 months) were associated with poor prognosis. In the multivariate survival analysis, any nestin expression in chemo-naïve biopsies proved to be an independent prognosticator against histology. In both pre- and post-CT situations, the combination of nestin or periostin expression with non-epithelioid histology was particularly/ dismal (all p-values