title: Assessment and prognostic significance of mitotic index using the mitosis marker phospho-histone H3 in low and intermediate-grade infiltrating astrocytomas.
abstract: Distinguishing between grade II and grade III diffuse astrocytomas is important both for prognosis and for treatment decision-making. However, current methods for distinguishing between grades based on proliferative potential are suboptimal, making identification of clear cutoffs difficult. In this study, we compared the results from immunohistochemical staining for phospho-histone H3 (pHH3), a specific marker of cells undergoing mitosis, with standard mitotic counts (number of mitoses/10 high-power fields) and MIB-1 labeling index values for assessing proliferative activity. We tested the relationship between pHH3 staining and tumor grade and prognosis in a retrospective series of grade II and III infiltrating astrocytomas from a single institution. The pHH3 index (per 1000 cells), MIB-1 index (per 1000 cells), and number of mitoses per 10 high-power fields were determined for each of 103 cases of grade II and III diffuse astrocytomas from patients with clinical follow-up. pHH3 staining was found to be a simple and reliable method for identifying mitotic figures, allowing a true mitotic index to be determined. The pHH3 mitotic index was significantly associated both with the standard mitotic count and with the MIB-1 index. Univariate analyses revealed that all 3 measurements of proliferation were significantly associated with survival. However, the pHH3 mitotic index accounted for a larger proportion of variability in survival than standard mitotic count or MIB-1/Ki-67 labeling index. After adjusting for age, extent of resection, and performance score, the pHH3 mitotic index remained an independent predictor of survival. Thus, pHH3 staining provides a simple and reliable method for quantifying proliferative potential and for the stratification of patients with diffuse astrocytomas into typical grade II and III groups. These results also suggest that pHH3 staining may be a useful method in other neoplasms in which accurate determination of proliferation potential is relevant to tumor grading or clinical treatment decision-making.
authors.affiliation: Department of Neuro-Oncology, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. hcolman@mdanderson.org
authors.forename: Howard
authors.initials: H
authors.lastname: Colman
authors.forename: Caterina
authors.initials: C
authors.lastname: Giannini
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.forename: Javier
authors.initials: J
authors.lastname: Gonzalez
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hess
authors.forename: Janet
authors.initials: J
authors.lastname: Bruner
authors.forename: Gregory
authors.initials: G
authors.lastname: Fuller
authors.forename: Lauren
authors.initials: L
authors.lastname: Langford
authors.forename: Christopher
authors.initials: C
authors.lastname: Pelloski
authors.forename: Joann
authors.initials: J
authors.lastname: Aaron
authors.forename: Peter
authors.initials: P
authors.lastname: Burger
authors.forename: Ken
authors.initials: K
authors.lastname: Aldape
mesh_terms: D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D006657:Histones; D019394:Ki-67 Antigen