Calbindin-d(28k): a marker of recurrence for medulloblastomas.
BACKGROUND
The expression of the Ca(2+)-binding protein calbindin-D(28k) was analyzed in medulloblastomas in relation to clinical features and other biologic markers related to cell proliferation, differentiation, p53, and cerebellar developmental regulated gene expression.


METHODS
Immunohistochemistry was carried out on histologic slides from a first retrospective series of 29 nonmetastatic and 10 metastatic medulloblastoma formalin-fixed, paraffin-embedded tissues, using specific antibodies against calbindin-D(28k), calretinin, alpha-parvalbumin and beta-parvalbumin, and S100 proteins. Informed consent was obtained from the subjects and/or guardians. Other biologic markers for differentiation, cell proliferation, the expression of the p53 tumor suppressor gene protein, and cerebellar developmental regulated genes were similarly investigated. A second series of 16 medulloblastomas from young patients (younger than 15 years) was added in order to validate the results obtained in the first series.


RESULTS
Of all the markers investigated, only calbindin-D(28k) was significantly associated with prognosis. Survival and remission (i.e. recurrence free) time analysis performed on all the cases (n = 55) confirmed a high risk of death (P = 0.004) and recurrence (P = 0.003) associated with calbindin-positivity. As calbindin-positivity was predominantly observed in tumors from young patients, the authors confirmed its prognostic value in the subgroup of patients younger than 15 years (n = 37). Cox regression analysis showed a significant and independent prognostic value for calbindin expression and, to a lesser extent, the type of surgery (total or subtotal). Three risk groups were thus identified, distinguishing among the cases characterized by a total resection and calbindin-negativity (good prognosis), by a subtotal resection and calbindin-negativity (intermediary), and by calbindin-positivity (bad prognosis).


CONCLUSIONS
The current study suggests that calbindin-positive medulloblastomas represent a subclass of aggressive tumors more frequently seen in younger patients.
Department of Pediatrics, Hôpital des Enfants, Brussels, Belgium.
Karine
K
Pelc
Sylvie
S
Vincent
Marie-Magdeleine
MM
Ruchoux
Robert
R
Kiss
Roland
R
Pochet
Eric
E
Sariban
Christine
C
Decaestecker
Claus W
CW
Heizmann
D000293:Adolescent; D000328:Adult; D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor / Q000008:administration & dosage*; D064026:Calbindins; D002528:Cerebellar Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008527:Medulloblastoma / Q000737:chemistry / Q000175:diagnosis* / Q000401:mortality / Q000556:secondary; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D064030:S100 Calcium Binding Protein G / Q000032:analysis*; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor; D064026:Calbindins; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D064030:S100 Calcium Binding Protein G; D016159:Tumor Suppressor Protein p53