title: The mitosis-specific marker phosphohistone-H3 (PHH3) is an independent prognosticator in uterine smooth muscle tumours: an outcome-based study.
abstract: OBJECTIVE
  Accurate mitosis counting, which is important in the diagnosis of uterine smooth muscle tumours (USMTs), is often difficult and subjective. The mitosis-specific immunohistochemical marker phosphohistone-H3 (PHH3) 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 PHH3 as a diagnostic and prognostic marker in USMTs.
  
  
  RESULTS
  PHH3 expression was evaluated in 55 leiomyosarcomas (LMSs), 26 smooth muscle tumours of uncertain malignant potential (STUMPs), 18 leiomyomas with bizarre nuclei (LBN), and 12 leiomyomas (LMs). Scores were expressed as counts per 10 high-power fields (HPFs). 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 LMSs (50.9%) died, and two (7.7%) patients with STUMPs experienced recurrence. The median PHH3 scores for LMSs were significantly higher than those for other categories of tumour. A score of ≥29/10 HPFs was also independently associated with a poor outcome. To test whether the PHH3 score could distinguish between benign USMTs with atypical histology and those that were clinically malignant, two biological groups were further delineated. Patients in group 1 (18 LBNs and 24 STUMPs) all had an uneventful outcome, whereas patients in group 2 (two recurrent STUMPs and 32 LMSs) all had a recurrence or tumour-related death. Median PHH3 scores for the two groups were, respectively, 2/10 HPFs and 27/10 HPFs. A PHH3 score of ≥7/10 HPFs was highly associated with malignancy.
  
  
  CONCLUSIONS
  PHH3 is useful in evaluation of the biological behaviour of USMTs, and may serve as a prognostic indicator for LMSs.
authors.affiliation: Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.
authors.forename: Kin-Long
authors.initials: KL
authors.lastname: Chow
authors.affiliation: Obstetrics and Gynaecology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.
authors.forename: Ka-Yu
authors.initials: KY
authors.lastname: Tse
authors.affiliation: Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Ching-Lung
authors.initials: CL
authors.lastname: Cheung
authors.affiliation: Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.
authors.forename: Ka-Wing
authors.initials: KW
authors.lastname: Wong
authors.affiliation: Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.
authors.forename: Annie N Y
authors.initials: AN
authors.lastname: Cheung
authors.affiliation: Pathology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, Hong Kong.
authors.forename: Richard W C
authors.initials: RW
authors.lastname: Wong
authors.affiliation: Pathology, Kwong Wah Hospital, Hong Kong, Hong Kong.
authors.forename: Alice N H
authors.initials: AN
authors.lastname: Chan
authors.affiliation: Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.
authors.forename: Nancy W F
authors.initials: NW
authors.lastname: Yuen
authors.affiliation: Obstetrics and Gynaecology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.
authors.forename: Hextan Y S
authors.initials: HY
authors.lastname: Ngan
authors.affiliation: Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.
authors.forename: Philip P C
authors.initials: PP
authors.lastname: Ip
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D006657:Histones / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D008938:Mitosis; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D012680:Sensitivity and Specificity; D018235:Smooth Muscle Tumor / Q000401:mortality / Q000473:pathology*; D014594:Uterine Neoplasms / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D006657:Histones
keywords: leiomyoma with bizarre nuclei; leiomyosarcoma; phosphohistone-H3; smooth muscle tumour of uncertain malignant potential; uterus