Molecular analysis of metaplastic breast carcinoma

High EGFR copy number via aneusomy

Judith A. Gilbert, Matthew Philip Goetz, Carol A. Reynolds, James N. Ingle, Karin F. Giordano, Vera Jean Suman, Hilary E. Blair, Robert Brian Jenkins, Wilma L. Lingle, Monica M. Reinholz, Alex Adjei, Matthew M. Ames

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Metaplastic breast carcinoma, a rare tumor composed of adenocarcinomatous and nonglandular growth patterns, is characterized by a propensity for distant metastases and resistance to standard anticancer therapies. We sought confirmation that this tumor is a basal-like breast cancer, expressing epidermal growth factor receptor (EGFR) and stem cell factor receptor (KIT). EGFR activating mutations and high copy number (associated with response to tyrosine kinase inhibitor gefitinib) and KIT activating mutations (associated with imatinib sensitivity) were then investigated. Seventy-seven metaplastic cases were identified (1976-2006); 38 with tumor blocks available underwent pathologic confirmation before EGFR and KIT immunohistochemical analyses. A tissue microarray of malignant glandular and metaplastic elements was constructed and analyzed immunohistochemically for cytokeratin 5/6, estrogen receptor, progesterone receptor, and p63, and by fluorescence in situ hybridization for EGFR and HER-2/neu. DNA isolated from individual elements was assessed for EGFR and KIT activating mutations. All assessable cases were negative for estrogen receptor, progesterone receptor, and (except one) HER2. The majority were positive for cytokeratin 5/6 (58%), p63 (59%), and EGFR overexpression (66%); 24% were KIT positive. No EGFR or KIT activating mutations were present; 26% of the primary metaplastic breast carcinomas were fluorescence in situ hybridization-positive, displaying high EGFR copy number secondary to aneusomy (22%) and amplification (4%). We report here that metaplastic breast carcinoma is a basal-like breast cancer lacking EGFR and KIT activating mutations but exhibiting high EGFR copy number (primarily via aneusomy), suggesting that EGFR tyrosine kinase inhibitors should be evaluated in this molecular subset of breast carcinomas.

Original languageEnglish (US)
Pages (from-to)944-951
Number of pages8
JournalMolecular Cancer Therapeutics
Volume7
Issue number4
DOIs
StatePublished - Apr 1 2008

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Epidermal Growth Factor Receptor
Breast Neoplasms
Mutation
Keratin-6
Keratin-5
Progesterone Receptors
Fluorescence In Situ Hybridization
Estrogen Receptors
Protein-Tyrosine Kinases
Proto-Oncogene Proteins c-kit
Neoplasms
Neoplasm Metastasis
DNA

ASJC Scopus subject areas

  • Oncology
  • Drug Discovery
  • Pharmacology

Cite this

Molecular analysis of metaplastic breast carcinoma : High EGFR copy number via aneusomy. / Gilbert, Judith A.; Goetz, Matthew Philip; Reynolds, Carol A.; Ingle, James N.; Giordano, Karin F.; Suman, Vera Jean; Blair, Hilary E.; Jenkins, Robert Brian; Lingle, Wilma L.; Reinholz, Monica M.; Adjei, Alex; Ames, Matthew M.

In: Molecular Cancer Therapeutics, Vol. 7, No. 4, 01.04.2008, p. 944-951.

Research output: Contribution to journalArticle

Gilbert, JA, Goetz, MP, Reynolds, CA, Ingle, JN, Giordano, KF, Suman, VJ, Blair, HE, Jenkins, RB, Lingle, WL, Reinholz, MM, Adjei, A & Ames, MM 2008, 'Molecular analysis of metaplastic breast carcinoma: High EGFR copy number via aneusomy', Molecular Cancer Therapeutics, vol. 7, no. 4, pp. 944-951. https://doi.org/10.1158/1535-7163.MCT-07-0570
Gilbert, Judith A. ; Goetz, Matthew Philip ; Reynolds, Carol A. ; Ingle, James N. ; Giordano, Karin F. ; Suman, Vera Jean ; Blair, Hilary E. ; Jenkins, Robert Brian ; Lingle, Wilma L. ; Reinholz, Monica M. ; Adjei, Alex ; Ames, Matthew M. / Molecular analysis of metaplastic breast carcinoma : High EGFR copy number via aneusomy. In: Molecular Cancer Therapeutics. 2008 ; Vol. 7, No. 4. pp. 944-951.
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AU - Suman, Vera Jean

AU - Blair, Hilary E.

AU - Jenkins, Robert Brian

AU - Lingle, Wilma L.

AU - Reinholz, Monica M.

AU - Adjei, Alex

AU - Ames, Matthew M.

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