title: TrkA expression is associated with an elevated level of apoptosis in classic medulloblastomas.
abstract: Medulloblastomas represent the most common central nervous system malignancies in children. Despite intensive modality treatment with craniospinal irradiation and multiple drug chemotherapy, their prognosis remains dismal. In the present study, we examined the potential roles of cellular differentiation, proliferation and apoptosis in 21 pediatric patients with newly diagnosed classic medulloblastomas treated by conventional radiation therapy and adjuvant chemotherapy. The expression of glial fibrillary acidic protein, S-100, synaptophysin, TrkA and TrkC, and the proliferation index of MIB-1 were evaluated by immunohistochemistry and the apoptotic index was determined using terminal deoxytransferase-mediated deoxyuridine-5'-triphosphate nick-end labeling assay. The prognostic value of these biological markers was also assessed. Immunoreactive glial fibrillary acidic protein, S-100, synaptophysin, TrkA and TrkC were observed in seven (33%), four (19%), 12 (57%), 14 (67%) and 11 (52%) of the 21 cases, respectively. TrkA expression was positively correlated with the MIB-1 staining index (P = 0.0228) and the apoptotic index (P = 0.0058). None of the immunohistochemical markers was found to be of value in predicting the prognosis. Although the present small sample size does not provide sufficient power to discount biological variables as prognostic markers, it was the well-established clinical prognostic factors, i.e. tumor stage and extent of surgery, that stood out as the most important predictors of survival. The close association between apoptosis and TrkA expression is consistent with in vitro data demonstrating the capacity of the NGF/TrkA signaling pathway to increase medulloblastoma apoptotic cell death, suggesting that this pathway may yield alternative therapeutic targets for novel therapies.
authors.affiliation: Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohta
authors.forename: Takao
authors.initials: T
authors.lastname: Watanabe
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Katayama
authors.forename: Jun
authors.initials: J
authors.lastname: Kurihara
authors.forename: Atsuo
authors.initials: A
authors.lastname: Yoshino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishimoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kishimoto
mesh_terms: D000293:Adolescent; D017209:Apoptosis / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002528:Cerebellar Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007223:Infant; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008527:Medulloblastoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D020917:Receptor, trkA / Q000096:biosynthesis*; D020812:Receptor, trkC / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism; D016019:Survival Analysis; D015996:Survival Rate; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D009418:S100 Proteins; D016708:Synaptophysin; D020917:Receptor, trkA; D020812:Receptor, trkC