title: Proliferative and metabolic markers in incompletely excised pediatric pilocytic astrocytomas--an assessment of 3 new variables in predicting clinical outcome.
abstract: Although pilocytic astrocytoma (PA) is the most common brain tumor diagnosed in children, few prognostic variables have been delineated that stratify the risk of clinical progression in patients with this tumor. In this study, the MIB-1 labeling index was compared with 2 other immunohistochemical markers of cell proliferation, phospho-histone H3 (PHH3) and mini-chromosomal maintenance protein 2 (MCM2) in 80 incompletely resected PAs to see which was best able to identify patients at risk for tumor progression. 0(6)-Methylguanine-DNA methyltransferase (MGMT) protein expression, which has been predictive of progression-free survival (PFS) in high-grade gliomas in children, was also evaluated in these cases. The mean follow-up period was 7.81 ± 3.9 years, and 42.8% of tumors have shown progression at the time of censoring. A MIB-1 labeling index ≥2.0 was associated with shortened PFS as a grouped variable by log-ranked analysis (P = .03) and by Cox regression analysis as a continuous variable (P = .007). None of the other potential biomarkers was significantly predictive of PFS. Although the amount of MCM2 staining correlated with the MIB-1 labeling index (P < .001), MCM2 reactivity was not independently associated with outcome. We conclude that MIB-1 labeling remains the best predictor of PFS in pediatric PAs.
authors.affiliation: Department of Pathology, The University of Texas Southwestern Medical School, 5323 Harry Hines Blvd., Dallas, TX 75390-9073, USA. linda.margraf@childrens.com
authors.forename: Linda R
authors.initials: LR
authors.lastname: Margraf
authors.forename: Lynn
authors.initials: L
authors.lastname: Gargan
authors.forename: Yasmeen
authors.initials: Y
authors.lastname: Butt
authors.forename: Nirupa
authors.initials: N
authors.lastname: Raghunathan
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Bowers
mesh_terms: D000293:Adolescent; D001254:Astrocytoma / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D015254:DNA Modification Methylases / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D008297:Male; D064111:Minichromosome Maintenance Complex Component 2; D009687:Nuclear Proteins / Q000378:metabolism*; D011379:Prognosis; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C513496:MIB1 ligase, human; D044767:Ubiquitin-Protein Ligases; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2; D045643:DNA Repair Enzymes