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

Details

Serval ID
serval:BIB_E27960F87405
Type
Article: article from journal or magazin.
Collection
Publications
Title
Expression of the Stem Cell Factor Nestin in Malignant Pleural Mesothelioma Is Associated with Poor Prognosis.
Journal
PLoS One
Author(s)
Thies S., Friess M., Frischknecht L., Korol D., Felley-Bosco E., Stahel R., Vrugt B., Weder W., Opitz I., Soltermann A.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
10
Number
9
Pages
e0139312
Language
english
Abstract
BACKGROUND: 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.
PATIENTS AND METHODS: 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).
RESULTS: 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 <0.05).
CONCLUSIONS: The SC marker nestin and the EMT marker periostin allow for further prognostic stratification among histologic variants of MPM. Their expression level is influenced by neo-adjuvant chemotherapy.
Pubmed
Web of science
Open Access
Yes
Create date
12/01/2016 19:02
Last modification date
20/08/2019 16:06
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