Panagiotis Kratimenos1,2, Ioannis Koutroulis3, Vasiliki Syriopoulou4, Christina Michailidi1, Maria Delivoria-Papadopoulos5, Jerzy Klijanienko6, Stamatios Theocharis1,6. 1. a Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Children's National Medical Center , The George Washington University, School of Medicine and Health Sciences , Washington, DC , USA. 2. b First Department of Pathology , National and Kapodistrian University of Athens, School of Medicine , Athens , Greece. 3. c Department of Pediatrics, Division of Emergency Medicine, Children's National Medical Center , The George Washington University, School of Medicine and Health Sciences , Washington, DC , USA. 4. f National and Kapodistrian University of Athens , School of Medicine, Children's Hospital of Athens, Department of Pediatrics , Athens , Greece. 5. e University of Pennsylvania School of Medicine , Department of Physiology , Philadelphia , PA , USA. 6. d Department of Pathology , Institut Curie , Paris , France.
Abstract
BACKGROUND: Neuroblastoma (NB) often presents with metastatic disease and poor survival. The need for new prognostic markers remains invaluable. The FAK-Src-Paxillin protein system is associated with aggressive phenotype in adult malignancies but is largely unexplored in pediatric NB. OBJECTIVE: To assess FAK-Src-Paxillin protein expression in human NB cell lines and clinical cytology material and to delineate its association with survival. DESIGN/ METHODS: Western blot and immunohistochemistry were applied for FAK-Src-Paxillin expression in NB cell lines and 23 human cytology specimens, respectively. Protein expression in human clinical samples was correlated with clinicopathological parameters, MYCN amplification and survival. RESULTS: FAK, Src and Paxillin proteins are expressed in human NB cells lines, and can be detected in clinical cytology specimens from NB patients, (59%, 32% and 33% respectively). Simultaneous FAK-Src-Paxillin expression was noted in 30% of NB patients. Children with concomitant positivity FAK, Src, and Paxillin tumors, as well as MYCN amplification, had increased mortality compared to those without. CONCLUSIONS: FAK-Src-Paxillin system is a marker of unfavorable prognosis for human NB patients but also a promising therapeutic target.
BACKGROUND:Neuroblastoma (NB) often presents with metastatic disease and poor survival. The need for new prognostic markers remains invaluable. The FAK-Src-Paxillin protein system is associated with aggressive phenotype in adult malignancies but is largely unexplored in pediatric NB. OBJECTIVE: To assess FAK-Src-Paxillin protein expression in human NB cell lines and clinical cytology material and to delineate its association with survival. DESIGN/ METHODS: Western blot and immunohistochemistry were applied for FAK-Src-Paxillin expression in NB cell lines and 23 human cytology specimens, respectively. Protein expression in humanclinical samples was correlated with clinicopathological parameters, MYCN amplification and survival. RESULTS:FAK, Src and Paxillin proteins are expressed in human NB cells lines, and can be detected in clinical cytology specimens from NB patients, (59%, 32% and 33% respectively). Simultaneous FAK-Src-Paxillin expression was noted in 30% of NB patients. Children with concomitant positivity FAK, Src, and Paxillin tumors, as well as MYCN amplification, had increased mortality compared to those without. CONCLUSIONS:FAK-Src-Paxillin system is a marker of unfavorable prognosis for human NB patients but also a promising therapeutic target.
Authors: Panagiotis Kratimenos; Evan Z Goldstein; Ioannis Koutroulis; Susan Knoblach; Beata Jablonska; Payal Banerjee; Shadi N Malaeb; Surajit Bhattacharya; M Isabel Almira-Suarez; Vittorio Gallo; Maria Delivoria-Papadopoulos Journal: iScience Date: 2020-11-04