title: Analysis of PI3K/AKT/mTOR signalling pathway in high risk neuroblastic tumours.
abstract: Neuroblastoma (NB) represents one of the most common paediatric tumours. Despite advance in NB research and treatment, the outcome of the patients from the high-risk group remains poor. PI3K/AKT/mTOR signalling pathway which is involved in oncogenesis and cancer progression of many tumours, in parallel constitutes the target for the biologically based oncological therapy. In this study we analyzed the status of PI3K/AKT/mTOR signalling route in the primary tumour tissue samples from a group of 39 high-risk NB. The pathway activation state was assessed immunohistochemically using antibodies with specificity towards PI3Kp85, PI3Kp110, phospho-AKT, phospho-mTOR, phospho-p70S6K and phospho-4EBP1. Moreover, expression of PTEN, bcl2 and cyclin D1 was examined. We found that most of tumours were positive for PI3Kp85 and PI3Kp110, as well as for p-AKT, p-mTOR and its downstream effectors p-p70S6K and p-4EBPI. PTEN was expressed in all cases, bcl2 and cyclin D1 staining was found in more than 90% of examined NB. Statistical analysis revealed that p-AKT expression was correlated with p-mTOR and strong cyclin D1 labelling. Furthermore, high expression of p-4EBP1 was significantly associated with p-p70S6K expression, high cyclin D1 and lower differentiation of the tumour. PI3K/AKT/mTOR signalling pathway activation is a common event in high-risk NB and it seems that this group of patients may benefit from targeted therapy with kinase inhibitors.
authors.affiliation: Department of Pathomorphology, Medical University of Gdańsk. eczis@wp.pl
authors.forename: Ewa
authors.initials: E
authors.lastname: Iżycka-Świeszewska
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Drożyńska
authors.forename: Robert
authors.initials: R
authors.lastname: Rzepko
authors.forename: Grażyna
authors.initials: G
authors.lastname: Kobierska-Gulida
authors.forename: Wiesława
authors.initials: W
authors.lastname: Grajkowska
authors.forename: Danuta
authors.initials: D
authors.lastname: Perek
authors.forename: Anna
authors.initials: A
authors.lastname: Balcerska
mesh_terms: D000008:Abdominal Neoplasms; D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D014408:Biomarkers, Tumor / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C546842:MTOR protein, human; D058539:Phosphatidylinositol 3-Kinase; D051058:Oncogene Protein v-akt; D058570:TOR Serine-Threonine Kinases