title: Expression of pERK and pAKT in human astrocytomas: correlation with IDH1-R132H presence, vascular endothelial growth factor, microvascular characteristics and clinical outcome.
abstract: Although pERK and pAKT are reportedly activated in various neoplasms, little information is available about their significance in astrocytomas. Paraffin-embedded tissue from 82 patients with diffuse infiltrating astrocytomas (grades II to IV) was investigated for the association of pERK and pAKT activation with clinicopathological features, vascular endothelial growth factor (VEGF), isocitrate dehydrogenase 1 and microvascular parameters. Nuclear pERK labelling index (LI) increased with increasing cytoplasmic pERK LI and nuclear and cytoplasmic pAKT LI (p = 0.0019, p = 0.0260 and p = 0.0012, respectively). Accordingly, cytoplasmic pERK increased with increasing levels of nuclear (p = 0.0001) and marginally with cytoplasmic pAKT LI (p = 0.0526). Nuclear and cytoplasmic pERK LI and nuclear pAKT LI were positively correlated with tumour histological grade (p = 0.0040, p = 0.0238 for pERK and p = 0.0004 for pAKT, respectively). VEGF expression was correlated with nuclear pERK (p = 0.0099) and nuclear pAKT LI (p = 0.0002). Interestingly, pERK cytoplasmic LI increased with microvessel calibre (p = 0.0287), whereas pAKT nuclear LI was marginally related to microvessel density (p = 0.0685). The presence of IDH1-R132H was related only to histological grade and lower microvessel calibre. Multivariate survival analysis in the entire cohort selected cytoplasmic pAKT LI (p = 0.045), histological grade, microvessel calibre (p = 0.028), patients' age, gender and surgical excision as independent predictors of survival. Moreover, in glioblastomas, pERK nuclear LI emerged as a favourable prognosticator in the presence of IDH1-R132H. pERK and pAKT in astrocytomas are interrelated and associated with tumour grade and angiogenesis. Moreover, the importance of cytoplasmic pAKT immunoexpression in patients' prognosis and nuclear pERK immunoexpression in glioblastomas is confirmed.
authors.affiliation: First Department of Pathology, Laiko Hospital, National and Kapodistrian University of Athens, Medical School, 75 Mikras Asias Street, Athens, Greece. asaetta@med.uoa.gr
authors.forename: Angelica A
authors.initials: AA
authors.lastname: Saetta
authors.forename: Georgia
authors.initials: G
authors.lastname: Levidou
authors.forename: Elias A
authors.initials: EA
authors.lastname: El-Habr
authors.forename: Ioannis
authors.initials: I
authors.lastname: Panayotidis
authors.forename: Vassilis
authors.initials: V
authors.lastname: Samaras
authors.forename: Irene
authors.initials: I
authors.lastname: Thymara
authors.forename: Stratigoula
authors.initials: S
authors.lastname: Sakellariou
authors.forename: Efstathios
authors.initials: E
authors.lastname: Boviatsis
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: Penelope
authors.initials: P
authors.lastname: Korkolopoulou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001254:Astrocytoma / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D014408:Biomarkers, Tumor / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D016543:Central Nervous System Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012189:Retrospective Studies; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases