Immunohistochemical and molecular markers in breast phyllodes tumors

Veselina Korcheva, Judith Levine, Carol Beadling, Andrea Warrick, Gayle Countryman, Neal R. Olson, Michael Heinrich, Christopher Corless, Megan Troxell

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Phyllodes tumors of the breast are diagnostically and managerially enigmatic, as their malignant potential is difficult to predict based on the standard morphologic criteria. Thus, there is a need for additional markers of biologic potential. Although a number of ancillary tests have been reported, consensus in the literature is lacking. We studied 38 cellular fibroadenomas and phyllodes tumors of various grade (World Health Organization benign, borderline, and malignant) with a panel of immunohistochemical stains (p53, CD117, phospho-Histone3, mdm2, cdk4) and screened 26 of the tumors for mutations across 30 cancer-related genes using PCR and mass-spectrometry based methods. p53 and phospho-Histone3 (mitotic marker) showed increased staining in higher grade phyllodes tumors. CD117, mdm2, and cdk4 showed no difference in expression across different grades of phyllodes tumors. Mutational analysis revealed an S8R substitution in FBX4 (an E3 ubiquitin ligase) in 3 cases: 1 benign and 2 borderline. The S8R substitution seems to be more common in phyllodes tumors (11.5%) as compared with other cancers. FBX4 S8R cases had high cyclin D1 expression, but this finding was not specific. Our data support earlier studies showing that p53 has potential use in pathologic assessment of phyllodes tumors, and we newly characterized phospho-Histone3 for this application. Further studies are needed to characterize the molecular pathogenesis of the phyllodes tumors, as we were unable to identify activating mutations despite screening for a large panel of activating hotspot mutations. The significance of the FBX4 substitution deserves further investigation.

Original languageEnglish (US)
Pages (from-to)119-125
Number of pages7
JournalApplied Immunohistochemistry and Molecular Morphology
Volume19
Issue number2
DOIs
StatePublished - Mar 2011

Fingerprint

Phyllodes Tumor
Breast Neoplasms
Mutation
Fibroadenoma
Ubiquitin-Protein Ligases
Neoplasm Genes
Cyclin D1
Mass Spectrometry
Neoplasms
Breast
Coloring Agents
Biomarkers
Staining and Labeling
Polymerase Chain Reaction

Keywords

  • Breast
  • cyclin D1
  • FBX4
  • KIT
  • MDM2
  • phospho-H3
  • phyllodes
  • TP53

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medical Laboratory Technology
  • Histology

Cite this

Immunohistochemical and molecular markers in breast phyllodes tumors. / Korcheva, Veselina; Levine, Judith; Beadling, Carol; Warrick, Andrea; Countryman, Gayle; Olson, Neal R.; Heinrich, Michael; Corless, Christopher; Troxell, Megan.

In: Applied Immunohistochemistry and Molecular Morphology, Vol. 19, No. 2, 03.2011, p. 119-125.

Research output: Contribution to journalArticle

Korcheva, Veselina ; Levine, Judith ; Beadling, Carol ; Warrick, Andrea ; Countryman, Gayle ; Olson, Neal R. ; Heinrich, Michael ; Corless, Christopher ; Troxell, Megan. / Immunohistochemical and molecular markers in breast phyllodes tumors. In: Applied Immunohistochemistry and Molecular Morphology. 2011 ; Vol. 19, No. 2. pp. 119-125.
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