The mitosis‐specific marker phosphohistone‐H3 ( PHH 3) is an independent prognosticator in uterine smooth muscle tumours: an outcome‐based study

Aims Accurate mitosis counting, which is important in the diagnosis of uterine smooth muscle tumours ( USMT s), is often difficult and subjective. The mitosis‐specific immunohistochemical marker phosphohistone‐H3 ( PHH 3) has been shown to be diagnostically useful, but its expression, in relation to outcome, has not been thoroughly investigated. The aim of this study is to evaluate PHH 3 as a diagnostic and prognostic marker in USMT s. Methods and results PHH 3 expression was evaluated in 55 leiomyosarcomas ( LMS s), 26 smooth muscle tumours of uncertain malignant potential ( STUMP s), 18 leiomyomas with bizarre nuclei ( LBN ), and 12 leiomyomas ( LM s). Scores were expressed as counts per 10 high‐power fields ( HPF s). Median follow‐up durations of patients with LMS , STUMP , LBN and LM were, respectively, 39, 78, 65.5 and 49.5 months. Twenty‐eight patients with LMS s (50.9%) died, and two (7.7%) patients with STUMP s experienced recurrence. The median PHH 3 scores for LMS s were significantly higher than those for other categories of tumour. A score of ≥29/10 HPF s was also independently associated with a poor outcome. To test whether the PHH 3 score could distinguish between benign USMT s with atypical histology and those that were clinically malignant, two biological groups were further delineated. Patients in group 1 (18 LBN s and 24 STUMP s) all had an uneventful outcome, whereas patients in group 2 (two recurrent STUMP s and 32 LMS s) all had a recurrence or tumour‐related death. Median PHH 3 scores for the two groups were, respectively, 2/10 HPF s and 27/10 HPF s. A PHH 3 score of ≥7/10 HPF s was highly associated with malignancy. Conclusion PHH 3 is useful in evaluation of the biological behaviour of USMT s, and may serve as a prognostic indicator for LMS s.