Original ArticlesAssessment and Prognostic Significance of Mitotic Index Using the Mitosis Marker Phospho-histone H3 in Low and Intermediate-grade Infiltrating AstrocytomasColman, Howard MD, PhD*; Giannini, Caterina MD†; Huang, Li MD‡; Gonzalez, Javier MD*; Hess, Kenneth PhD§; Bruner, Janet MD‡; Fuller, Gregory MD‡; Langford, Lauren MD‡; Pelloski, Christopher MD∥; Aaron, Joann MA¶; Burger, Peter MD#; Aldape, Ken MD‡Author Information Departments of *Neuro-Oncology ‡Pathology §Biostatistics ∥Radiation Oncology, and ¶Community Oncology, UT MD Anderson Cancer Center, Houston TX †Department of Pathology, Mayo Clinic, Rochester, MN #Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD Reprints: Howard Colman, MD, PhD, Department of Neuro-Oncology, Box 431, UT MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston TX 77030 (e-mail: email@example.com). The American Journal of Surgical Pathology: May 2006 - Volume 30 - Issue 5 - p 657-664 doi: 10.1097/01.pas.0000202048.28203.25 Buy SDC Metrics 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. © 2006 Lippincott Williams & Wilkins, Inc.