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

Thies S, Friess M, Frischknecht L, Korol D, Felley-Bosco E, Stahel R, Vrugt B, Weder W, Opitz I, Soltermann A - PLoS ONE (2015)

Bottom Line: EMT is associated with an increase of stem cell (SC) traits.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 Pla/Pem treated patients, nestin was higher in biphasic MPM compared to epithelioid.

View Article: PubMed Central - PubMed

Affiliation: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.

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.

No MeSH data available.


Related in: MedlinePlus

Associations of markers with histology according to neo-adjuvant CT.Box plots of nestin (A-C) and periostin (D-F) expression correlated with histologic variant in cohort 2 in chemo-naïve biopsies (A/D) and surgical specimens treated with with Pla/Gem (B/E) or Pla/Pem (C/F); Mann-Whitney U tests.
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pone.0139312.g003: Associations of markers with histology according to neo-adjuvant CT.Box plots of nestin (A-C) and periostin (D-F) expression correlated with histologic variant in cohort 2 in chemo-naïve biopsies (A/D) and surgical specimens treated with with Pla/Gem (B/E) or Pla/Pem (C/F); Mann-Whitney U tests.

Mentions: Itemization of neo-adjuvant chemotherapy according to histology (Fig 3) yielded following results: A significant increased nestin protein expression was observed in Pla/Pem treated biphasic MPM in comparison to epithelioid (Fig 3C). Periostin protein expression was higher in chemo-naïve sarcomatoid MPM compared to epithelioid (Fig 3D). No significant different expression among histologic variants was observed after Pla/Gem or Pla/Pem chemotherapy.


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

Thies S, Friess M, Frischknecht L, Korol D, Felley-Bosco E, Stahel R, Vrugt B, Weder W, Opitz I, Soltermann A - PLoS ONE (2015)

Associations of markers with histology according to neo-adjuvant CT.Box plots of nestin (A-C) and periostin (D-F) expression correlated with histologic variant in cohort 2 in chemo-naïve biopsies (A/D) and surgical specimens treated with with Pla/Gem (B/E) or Pla/Pem (C/F); Mann-Whitney U tests.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4589394&req=5

pone.0139312.g003: Associations of markers with histology according to neo-adjuvant CT.Box plots of nestin (A-C) and periostin (D-F) expression correlated with histologic variant in cohort 2 in chemo-naïve biopsies (A/D) and surgical specimens treated with with Pla/Gem (B/E) or Pla/Pem (C/F); Mann-Whitney U tests.
Mentions: Itemization of neo-adjuvant chemotherapy according to histology (Fig 3) yielded following results: A significant increased nestin protein expression was observed in Pla/Pem treated biphasic MPM in comparison to epithelioid (Fig 3C). Periostin protein expression was higher in chemo-naïve sarcomatoid MPM compared to epithelioid (Fig 3D). No significant different expression among histologic variants was observed after Pla/Gem or Pla/Pem chemotherapy.

Bottom Line: EMT is associated with an increase of stem cell (SC) traits.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 Pla/Pem treated patients, nestin was higher in biphasic MPM compared to epithelioid.

View Article: PubMed Central - PubMed

Affiliation: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.

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.

No MeSH data available.


Related in: MedlinePlus