title: Phosphohistone H3 expression correlates with manual mitotic counts and aids in identification of "hot spots" in fibroepithelial tumors of the breast.
abstract: Classification of mammary fibroepithelial tumors (FETs) relies on assessment of mitotic activity, among other histopathologic parameters. Routine hematoxylin and eosin (H&E) mitotic counts can be subjective and time consuming. Difficulty may arise in identifying "true" mitoses for a variety of reasons. Phosphorylation of histone H3 protein (PHH3) is correlated with mitotic chromatin condensation. The utility of PHH3 immunohistochemical staining to identify mitoses has been demonstrated in multiple organ systems. In this study, we examined the utility of PHH3 in assessing mitotic activity in FETs and compared PHH3- with H&E-determined mitotic counts. PHH3-stained mitoses were readily identifiable at ×10 magnification and allowed for rapid identification of mitotic "hot spots." Median mitotic counts/10 high-power fields for fibroadenoma, benign phyllodes tumor, borderline phyllodes tumor (BlnPT), and malignant phyllodes tumor (MPT) were 0, 0.5, 4.25, and 9, respectively on H&E, and 0, 0.75, 4.5, and 8, respectively for PHH3. Among all FETs, there was a strong positive correlation between H&E- and PHH3-determined mitotic counts (r=0.91, P<.001). Using PHH3, 2 cases would be reclassified, both from BlnPT to MPT. PHH3-determined counts correlated with H&E-determined counts in FETs. Using PHH3, a small number of cases were reclassified from BlnPT to MPT, for which treatment is similar. Although H&E-determined counts remain the criterion standard for assessing mitotic activity in FETs, PHH3 may be a useful adjunctive tool in some cases and is helpful in identifying mitotic hot spots.
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065. Electronic address: psg9003@med.cornell.edu.
authors.forename: Paula S
authors.initials: PS
authors.lastname: Ginter
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Shin
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065.
authors.forename: Yifang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, NY 10065.
authors.forename: Zhengming
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: D'Alfonso
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology*; D005260:Female; D006657:Histones / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D008938:Mitosis; D008940:Mitotic Index; D060787:Neoplasm Grading; D018225:Neoplasms, Fibroepithelial / Q000737:chemistry* / Q000473:pathology*; D010766:Phosphorylation; D003557:Phyllodes Tumor / Q000737:chemistry* / Q000473:pathology*; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D006657:Histones
keywords: Breast; Fibroadenoma; Fibroepithelial; Mitoses; PHH3; Phosphohistone H3; Phyllodes