Prognostic significance of Ki-67 (MIB-1) proliferation index in childhood primitive neuroectodermal tumors of the central nervous system.
BACKGROUND
Primitive neuroectodermal tumors (PNET) of the central nervous system, including medulloblastomas, are the most common malignant brain tumors of childhood. Whereas some patients experience prolonged disease control after surgery and adjuvant therapy, others with tumors that appear comparable will relapse and eventually die from progressive disease.


METHODS
Because proliferative activity may provide a potential correlate of biologic aggressiveness, PNETs of 78 well-characterized patients were evaluated by Ki-67 (MIB-1) immunohistochemistry. Proliferation indices (PI) were determined by counting Ki-67 (MIB-1) positive tumor cells either in the highest staining region (hot spot PI), or in at least 15 randomly chosen fields (random PI).


RESULTS
Twenty-five of 78 PNETs showed amore than twofold higher value of hot spot PI (median 9.3%; range 0.6-56%), compared to random PI (median 5.6%; range 0.2-41.3%), Univariate Cox regression analysis revealed that PNETs with a high hot spot PI had a significantly greater risk of progression and death than PNETs with a low hot spot PI (hazard ratio 1.58, P = 0.04). The hazard ratio remained significant after adjusting for M-stage in multivariate analysis. In contrast to hot spot PI, random PI proved not to be a significant prognostic predictor.


CONCLUSIONS
Hot spot PI is a significant and independent prognostic factor in PNETs. Its assessment is uncomplicated, reliable, and may supplement routine histologic examination as a means for improving the accuracy of predicting the biologic behavior of childhood PNETs.
Grotzer
M A
MA
Division of Neurology and Oncology, The Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
Geoerger
B
B
Janss
A J
AJ
Zhao
H
H
Rorke
L B
LB
Phillips
P C
PC
D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology*; D002455:Cell Division; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D019394:Ki-67 Antigen / Q000032:analysis*; D018242:Neuroectodermal Tumors, Primitive / Q000401:mortality / Q000473:pathology*; D011379:Prognosis
D019394:Ki-67 Antigen