title: Uterine smooth muscle tumors: utility of classification by proliferation, ploidy, and prognostic markers versus traditional histopathology.
abstract: BACKGROUND
  Accurate categorization of uterine smooth muscle neoplasms by light microscopic examination is difficult. Multiple classification schemes have been proposed based on mitotic rate, nuclear atypia, and the presence or absence of necrosis. None of these classification systems has been entirely successful. Multiple ancillary techniques have been tested for their ability to predict behavior of uterine smooth muscle tumors.
  
  
  OBJECTIVE
  We assayed 45 smooth muscle neoplasms for a variety of proliferation markers, oncogene protein products, and DNA ploidy level to determine if these markers supplied prognostically useful information over and above that obtained by routine light microscopic assessment.
  
  
  METHODS
  Forty-five uterine smooth muscle neoplasms were assessed for DNA ploidy; silver-staining nucleolar organizer regions (AgNORs); percent nuclear proliferating cell nuclear antigen (PCNA); expression of p53, Her-2/neu, and MDM-2 protein; mitotic rate; and nuclear grade. These markers were correlated with histologic diagnosis and the occurrence of a clinically adverse event (death, metastasis, or recurrence).
  
  
  RESULTS
  Diagnostic category (P <.001), nuclear grade (P <.002), mitotic activity (P <.001), mean AgNORs (P <.001), percent nuclear PCNA (P =.02), and expression of p53 (P =.02) all correlated with clinical outcome. No statistically significant correlation between clinical outcome and the categories MDM-2 expression, Her-2/neu expression, or DNA ploidy was seen. Nuclear grade, p53 expression, mitotic rate, AgNORs, and percent nuclear PCNA correlated with diagnosis.
  
  
  CONCLUSIONS
  Diagnostic category, mitotic rate, AgNOR counts, PCNA, and p53 expression dichotomized uterine smooth muscle neoplasms into prognostically favorable and unfavorable groups. Although highly significant, the category AgNORs was no more successful than mitotic rate in dividing uterine smooth muscle neoplasms into prognostically favorable and unfavorable groups. Expression of p53 and percent nuclear PCNA dichotomized uterine smooth muscle neoplasms into prognostic groups, but neither technique reached the level of significance achieved by mitotic rate. Our data indicate that mitotic rate and the classification system of Kempson and Bari are at least as effective as the tested markers in separating uterine smooth muscle neoplasms into prognostic categories.
authors.affiliation: Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Layfield
authors.forename: K
authors.initials: K
authors.lastname: Liu
authors.forename: R
authors.initials: R
authors.lastname: Dodge
authors.forename: S H
authors.initials: SH
authors.lastname: Barsky
mesh_terms: D000782:Aneuploidy; D014408:Biomarkers, Tumor; D002469:Cell Separation; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007889:Leiomyoma / Q000145:classification* / Q000378:metabolism / Q000473:pathology; D007890:Leiomyosarcoma / Q000145:classification* / Q000378:metabolism / Q000473:pathology; D008940:Mitotic Index; D019042:Muscle Neoplasms / Q000145:classification* / Q000378:metabolism / Q000473:pathology; D009130:Muscle, Smooth / Q000473:pathology*; D009367:Neoplasm Staging; D009697:Nucleolus Organizer Region; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014594:Uterine Neoplasms / Q000145:classification* / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D018809:Proliferating Cell Nuclear Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53