RGD Reference Report - Molecular analysis of metaplastic breast carcinoma: high EGFR copy number via aneusomy. - Rat Genome Database

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Molecular analysis of metaplastic breast carcinoma: high EGFR copy number via aneusomy.

Authors: Gilbert, JA  Goetz, MP  Reynolds, CA  Ingle, JN  Giordano, KF  Suman, VJ  Blair, HE  Jenkins, RB  Lingle, WL  Reinholz, MM  Adjei, AA  Ames, MM 
Citation: Gilbert JA, etal., Mol Cancer Ther. 2008 Apr;7(4):944-51.
RGD ID: 2293732
Pubmed: PMID:18413808   (View Abstract at PubMed)
PMCID: PMC2745608   (View Article at PubMed Central)
DOI: DOI:10.1158/1535-7163.MCT-07-0570   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
breast carcinoma  IAGP 2293732DNA:amplification:cds and 3' utr (human)RGD 
breast carcinoma  ISOEGFR (Homo sapiens)2293732; 2293732DNA:amplification:cds and 3' utr (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Egfr  (epidermal growth factor receptor)

Genes (Mus musculus)
Egfr  (epidermal growth factor receptor)

Genes (Homo sapiens)
EGFR  (epidermal growth factor receptor)


Additional Information