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

Article type: Research Article

Authors: Krawczyk, Malgorzata A.^{a; 1} | Karpinsky, Gabrielle^{b; 1} | Izycka-Swieszewska, Ewa^c | Gabrych, Anna^d | Kunc, Michal^e | Fatyga, Aleksandra^d | Garstka, Monika^f | Styczewska, Malgorzata^f | Sokolewicz, Ewa M.^f | Szlagatys-Sidorkiewicz, Agnieszka^g | Kazanowska, Bernarda^f | Bien, Ewa^{a; *}

Affiliations: [a] Department of Pediatrics, Hematology and Oncology, Medical University of Gdansk, Gdansk, Poland | [b] Children’s Hospital of Michigan, Detroit, MI, USA | [c] Department of Pathology and Neuropathology, Medical University of Gdansk, Gdansk, Poland | [d] Department of Pediatrics, Hematology and Oncology, University Clinical Centre, Gdansk, Poland | [e] Department of Pathomorphology, Medical University of Gdansk, Gdansk, Poland | [f] The English Division Pediatric Oncology Scientific Circle, Medical University of Gdansk, Gdansk, Poland | [g] Department of Pediatrics, Gastroenterology, Hepatology and Nutrition, Medical University of Gdansk, Gdansk, Poland | [h] Department of Pediatric Bone Marrow Transplantation, Oncology and Hematology, Wroclaw Medical University, Wroclaw, Poland

Correspondence: [*] Corresponding author: Ewa Bien, Department of Pediatrics, Hematology and Oncology, Medical University of Gdansk, 7 Debinki Street, 80-211 Gdansk, Poland. Tel.: +48 58 3492880 or +48 661950108; Fax: +48 58 3492950; E-mail: [email protected].

Note: [1] Malgorzata A. Krawczyk and Gabrielle Karpinsky contributed equally to the study.

Abstract: BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is rare, aggressive soft tissue sarcoma which may affect children. OBJECTIVE: We aimed to assess prognostic significance of immunohistochemical (IHC) markers, osteopontin, fibronectin, survivin, cyclin D1 and p53, in pediatric MPNST. 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: 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.

DOI: 10.3233/CBM-181572

Journal: Cancer Biomarkers, vol. 24, no. 3, pp. 351-361, 2019