Tumor expression of survivin, p53, cyclin D1, osteopontin and fibronectin in predicting the response to neo-adjuvant chemotherapy in children with advanced malignant peripheral nerve sheath tumor

Journal of Cancer Research and Clinical Oncology - Tập 144 - Trang 519-529 - 2018
Gabrielle Karpinsky1, Malgorzata A. Krawczyk2, Ewa Izycka-Swieszewska3, Aleksandra Fatyga4, Agnieszka Budka4, Walentyna Balwierz5, Grazyna Sobol6, Beata Zalewska-Szewczyk7, Magdalena Rychlowska-Pruszynska8, Teresa Klepacka9, Bozenna Dembowska-Baginska10, Bernarda Kazanowska11, Anna Gabrych4, Ewa Bien2
1Children's Hospital of Michigan, Detroit, USA
2Department of Pediatrics, Hematology and Oncology, Medical University of Gdansk, Gdansk, Poland
3Department of Pathology and Neuropathology, Medical University of Gdansk, Gdansk, Poland
4Department of Pediatrics, Hematology and Oncology, University Clinical Centre, Gdansk, Poland
5Department of Pediatric Oncology and Hematology, Jagiellonian University Medical College, Krakow, Poland
6Department of Pediatrics, Medical University of Silesia, Katowice, Poland
7Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland
8Department of Surgical Oncology, Institute of Mother and Child, Warsaw, Poland
9Department of Pathology, Institute of Mother and Child, Warsaw, Poland
10Department of Oncology, Children’s Memorial Health Institute, Warsaw, Poland
11Department of Pediatric Bone Marrow Transplantation, Oncology and Hematology, Wroclaw Medical University, Wroclaw, Poland

Tóm tắt

Selected cell-cycle regulators and extracellular matrix proteins were found to play roles in malignant peripheral nerve sheath tumor (MPNST) biology. We aimed to analyze whether initial tumor tissue expressions of survivin, p53, cyclin D1, osteopontin (OPN) and fibronectin (FN) correlate with the response to neo-adjuvant CHT (naCHT) in children with advanced inoperable MPNST. The study included 26 children with MPNST (M/F 14/12, median age 130 months) treated in Polish centers of pediatric oncology between 1992 and 2013. Tissue expression of markers was studied immunohistochemically in the manually performed tissue microarrays and assessed semi-quantitatively as low and high, based on the rate of positive cells and staining intensity. Good response to naCHT was noted in 47.6%, while poor—in 52.4% of patients. The response to naCHT was influenced negatively by the presence of neurofibromatosis NF1 and high initial tumor tissue expression of OPN, survivin, p53 and cyclin D1. Patients with high tumor expression of either OPN, survivin or p53 and those with simultaneous high expression of ≥ 3 of the markers, responded significantly worse to naCHT, than patients, in whom expression of ≤ 2 markers were detected at diagnosis. Nearly, 85% of patients expressing ≥ 3 markers, responded poor to CHT; while 87.5% of children, expressing ≤ 2 markers, were good responders. The initial tumor tissue expression of OPN, survivin, p53 and cyclin D1 may serve as markers to predict response to naCHT in pediatric advanced MPNST. Future studies in more numerous group of patients are needed to confirm these preliminary results.

Tài liệu tham khảo

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