Assessment and prognostic significance of mitotic index using the mitosis marker phospho-histone H3 in low and intermediate-grade infiltrating astrocytomas

Distineuishine 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 dentification of clear cutoffs difficult In this study, we compared the results from immunohistochemical staining to]phospho-histone H3 (pHH3). a specific marker of cells undergoine 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), MIBI index (per 1000 cells), and number of mitoses per 10 high-power fields were determined for each of 103 cases of grade 11 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 analvses 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 11 and I I I 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.