Immunohistochemical assessment of cyclin D1 and p53 is associated with survival in childhood malignant peripheral nerve sheath tumor.


Journal

Cancer biomarkers : section A of Disease markers
ISSN: 1875-8592
Titre abrégé: Cancer Biomark
Pays: Netherlands
ID NLM: 101256509

Informations de publication

Date de publication:
2019
Historique:
pubmed: 19 3 2019
medline: 6 8 2019
entrez: 19 3 2019
Statut: ppublish

Résumé

Malignant peripheral nerve sheath tumor (MPNST) is rare, aggressive soft tissue sarcoma which may affect children. We aimed to assess prognostic significance of immunohistochemical (IHC) markers, osteopontin, fibronectin, survivin, cyclin D1 and p53, in pediatric MPNST. A total of 26 pediatric MPNST patients were enrolled in the current study with a median follow-up of 51 months. IHC staining using commercially available monoclonal antibodies were employed to detect analyzed antigens on tissue microarrays. Eventually, all markers were subclassified to high (H) and low (L) expression categories in all analyzed tumors. High IHC expressions of survivin, cyclin D1, osteopontin, fibronectin, and p53 were detected in 18 (69.2%), 13 (50%), 16 (61.5%), 16 (61.5%), and 13 (50%) tumors, respectively. A significant correlation was demonstrated between cyclin D1 and osteopontin (p= 0.004). Both markers were associated with neurofibromatosis type 1 (NF1) status (p= 0.041 and p= 0.037, respectively). H-fibronectin was more prevalent in deeply located tumors (p= 0.046). None of the markers was associated with IRS stage, age at diagnosis, and tumor size. Univariate analysis identified IRS stage, regional lymph node metastases, NF1, and cyclin D1 as variables associated with overall survival (OS), whereas tumor depth, osteopontin, and cyclin D1 - for relapse-free survival (RFS). Subsequent multivariate analysis identified cyclin D1 and p53 as independent variables predicting RFS, whereas cyclin D1 and regional lymph nodes status were independent predictors for OS.

Sections du résumé

BACKGROUND BACKGROUND
Malignant peripheral nerve sheath tumor (MPNST) is rare, aggressive soft tissue sarcoma which may affect children.
OBJECTIVE OBJECTIVE
We aimed to assess prognostic significance of immunohistochemical (IHC) markers, osteopontin, fibronectin, survivin, cyclin D1 and p53, in pediatric MPNST.
METHODS METHODS
A total of 26 pediatric MPNST patients were enrolled in the current study with a median follow-up of 51 months. IHC staining using commercially available monoclonal antibodies were employed to detect analyzed antigens on tissue microarrays. Eventually, all markers were subclassified to high (H) and low (L) expression categories in all analyzed tumors.
RESULTS RESULTS
High IHC expressions of survivin, cyclin D1, osteopontin, fibronectin, and p53 were detected in 18 (69.2%), 13 (50%), 16 (61.5%), 16 (61.5%), and 13 (50%) tumors, respectively. A significant correlation was demonstrated between cyclin D1 and osteopontin (p= 0.004). Both markers were associated with neurofibromatosis type 1 (NF1) status (p= 0.041 and p= 0.037, respectively). H-fibronectin was more prevalent in deeply located tumors (p= 0.046). None of the markers was associated with IRS stage, age at diagnosis, and tumor size. Univariate analysis identified IRS stage, regional lymph node metastases, NF1, and cyclin D1 as variables associated with overall survival (OS), whereas tumor depth, osteopontin, and cyclin D1 - for relapse-free survival (RFS). Subsequent multivariate analysis identified cyclin D1 and p53 as independent variables predicting RFS, whereas cyclin D1 and regional lymph nodes status were independent predictors for OS.

Identifiants

pubmed: 30883338
pii: CBM181572
doi: 10.3233/CBM-181572
doi:

Substances chimiques

Biomarkers, Tumor 0
Tumor Suppressor Protein p53 0
Cyclin D1 136601-57-5

Types de publication

Journal Article

Langues

eng

Pagination

351-361

Auteurs

Malgorzata A Krawczyk (MA)

Department of Pediatrics, Hematology and Oncology, Medical University of Gdansk, Gdansk, Poland.
Department of Pediatrics, Hematology and Oncology, Medical University of Gdansk, Gdansk, Poland.

Gabrielle Karpinsky (G)

Children's Hospital of Michigan, Detroit, MI, USA.
Department of Pediatrics, Hematology and Oncology, Medical University of Gdansk, Gdansk, Poland.

Ewa Izycka-Swieszewska (E)

Department of Pathology and Neuropathology, Medical University of Gdansk, Gdansk, Poland.

Anna Gabrych (A)

Department of Pediatrics, Hematology and Oncology, University Clinical Centre, Gdansk, Poland.

Michal Kunc (M)

Department of Pathomorphology, Medical University of Gdansk, Gdansk, Poland.

Aleksandra Fatyga (A)

Department of Pediatrics, Hematology and Oncology, University Clinical Centre, Gdansk, Poland.

Monika Garstka (M)

The English Division Pediatric Oncology Scientific Circle, Medical University of Gdansk, Gdansk, Poland.

Malgorzata Styczewska (M)

The English Division Pediatric Oncology Scientific Circle, Medical University of Gdansk, Gdansk, Poland.

Ewa M Sokolewicz (EM)

The English Division Pediatric Oncology Scientific Circle, Medical University of Gdansk, Gdansk, Poland.

Agnieszka Szlagatys-Sidorkiewicz (A)

Department of Pediatrics, Gastroenterology, Hepatology and Nutrition, Medical University of Gdansk, Gdansk, Poland.

Bernarda Kazanowska (B)

The English Division Pediatric Oncology Scientific Circle, Medical University of Gdansk, Gdansk, Poland.

Ewa Bien (E)

Department of Pediatrics, Hematology and Oncology, Medical University of Gdansk, Gdansk, Poland.

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Classifications MeSH