Mitosis-specific marker phospho-histone h3 in the assessment of mitotic index in uterine smooth muscle tumors: A pilot study

The assessment of an accurate mitotic index (MI) is one of the major parameters in the proper classification of uterine smooth muscle tumors. This assessment can be hampered by the presence of increased number of apoptotic bodies or piknotic nuclei, which frequently mimic mitoses. Phospho-histone H3 (PHH3) is a recently described immunomarker specific for cells undergoing mitoses. In this study, we evaluated the MI of 2 subsets of uterine smooth muscle tumors-6 leiomyosarcomas (LMS) and 6 smooth muscle tumors of undetermined malignant potential (STUMP)-using PHH3-labeled sections and hematoxylin and eosin (H&E)-stained slides. In the STUMP group, the MI on H&E ranged from 0 to 9 mitoses/10 high-power fields (HPFs) (mean, 3.2), and in the LMS group, it ranged from 0 to 37 mitoses/10 HPFs (mean, 19). PHH3 showed 0 to 16 mitoses/10 HPFs (mean, 3.8) in the STUMP group and 0 to 61 mitoses/10 HPFs (mean, 26) in the LMS group. In 7 cases, the MI difference (MID) between H&E-stained and PHH3-stained slides varied from 0 to 3 mitoses (mean, 1.6). In only one LMS, the PHH3 MI was lower than on H&E-stained slides (MID 7). The MI on H&E-stained and PHH3-stained slides were comparable in 7 cases, 5 of which were STUMPs. In 4 other cases, 3 of which were LMS, the PHH3 MI was significantly higher than the one obtained on H&E. The higher MI obtained with PHH3-labeled sections in some cases is most likely due to the recognition of true mitoses by the antibody, which were initially misinterpreted as apoptotic bodies and/or piknotic nuclei on H&E and not included in the formal count, and the fact that the phosphorilation of histone H3 starts just before the prophase and at this stage mitoses cannot be identified by H&E.