Correlation of gamma-catenin expression with good prognosis in medulloblastomas.
OBJECTIVE
Medulloblastoma is a malignant cerebellar tumor of childhood and is difficult to cure due to frequent cerebrospinal fluid dissemination. Amplification of the c-myc gene (4%) and messenger (mRNA) overexpression (50%) are known to be adverse prognostic indicators. Because mRNA overexpression cannot be explained by gene amplification alone, mechanisms other than gene amplification are postulated. Molecules on the Wnt signal pathway in primary tumors were examined.


METHODS
Immunohistochemical and cytogenetic examinations of beta- and gamma-catenin, c-myc, N-myc, and cyclin D1 in 24 primary medulloblastomas were conducted, and their clinical relevance was evaluated. Cytoplasmic/membranous staining of beta- and gamma-catenin was detected in 19 (79%) and nine (37%) cases, respectively, and nuclear expression of cyclin D1 and c-myc was detected in six (25%) and 21 (83%) cases, respectively. The expression levels of gamma-catenin in Western blot analysis and immunohistochemistry were similar. By differential polymerase chain reaction, c-myc and N-myc were amplified separately in two large cell/anaplastic medulloblastomas. No cyclin D1 amplification, or beta- or gamma-catenin mutations were found. Kaplan-Meier analysis revealed no dissemination at diagnosis (Chang Grade M0) and gamma-catenin expression was correlated with good prognosis (p = 0.0002 and 0.003, respectively). Expression of gamma-catenin was also significant in the M0 group (p = 0.022). Expression of cyclin D1 showed a trend toward adverse outcome (p = 0.057) and all patients in whom cyclin D1 expression was found died of disease.


CONCLUSIONS
Expression of gamma-catenin is of great prognostic value and its immunohistochemistry may be useful for further stratification of treatment. Cyclin D expression may have the potential to be an adverse prognostic indicator.
Misaki
Koichi
K
Department of Neurosurgery, Graduate School of Medical Science, Division of Diagnostic Molecular Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Marukawa
Kohei
K
Hayashi
Yutaka
Y
Fukusato
Toshio
T
Minamoto
Toshinari
T
Hasegawa
Mitsuhiro
M
Yamashita
Junkoh
J
Fujisawa
Hironori
H
D000293:Adolescent; D000328:Adult; D000912:Antibodies, Neoplasm / Q000276:immunology; D015153:Blotting, Western; D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000276:immunology; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D051180:Desmoplakins; D019940:Genes, bcl-1 / Q000276:immunology; D016259:Genes, myc / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008527:Medulloblastoma / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology; D051176:beta Catenin; D051185:gamma Catenin
D000912:Antibodies, Neoplasm; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D051180:Desmoplakins; C495292:JUP protein, human; D012333:RNA, Messenger; D015534:Trans-Activators; D051176:beta Catenin; D051185:gamma Catenin