Malignant phyllodes tumours show stromal overexpression of c‐myc and c‐kit Journal Articles

abstract

• AbstractPhyllodes tumours are fibroepithelial neoplasms of the breast, the stroma of which can undergo malignant progression to sarcoma. The frequency of malignant lesions varies in different series from 5% to 30%. The aim of this study was to elucidate potential molecular mechanisms in the progression to malignancy in phyllodes tumours. c‐myc and c‐kit were studied at the protein, RNA(c‐myc only) and DNA level. We chose to study c‐myc as we have previously shown that Wnt signalling is important in benign, but not malignant, phyllodes tumours. If c‐myc is constitutively activated in malignant tumours, this may provide an explanation for why the Wnt pathway is no longer important in these tumours. c‐kit is a membrane‐bound tyrosine kinase receptor and overexpression is characteristic of gastrointestinal stromal tumours. A previous report suggested that this may also be the case in malignant phyllodes tumours, and we wished to confirm this. We assessed expression of c‐myc and c‐kit in 30 phyllodes tumours (10 malignant) using in situ hybridization (c‐myc) and immunohistochemistry (c‐myc and c‐kit). 9/10 malignant tumours showed c‐myc expression in the stroma, compared to 7/20 benign tumours (p = 0.006, Fisher's exact test). Stromal c‐kit expression was found in 5/10 malignant tumours, compared to 1/20 benign tumours (p = 0.008, Fisher's exact test). One tumour had high‐level amplification of c‐myc, but we found no evidence of mutations of c‐kit. We hypothesize that the overexpression of c‐myc may drive stromal proliferation in malignant phyllodes tumours, and that c‐kit overexpression contributes to the growth of these lesions. c‐kit may also be a new therapeutic target in these tumours. Copyright © 2003 John Wiley & Sons, Ltd.

authors

• Sawyer, Elinor J
• Poulsom, Richard
• Hunt, F Toby
• Jeffery, Rosemary
• Elia, George
• Ellis, Ian O
• Ellis, Peter
• Tomlinson, Ian PM
• Hanby, Andrew M

status

• published 

publication date

• May 2003

has subject area

• 1103 Clinical Sciences (FoR)
• Breast Neoplasms (MeSH)
• DNA, Neoplasm (MeSH)
• Epithelium (MeSH)
• Female (MeSH)
• Gene Expression (MeSH)
• Genes, myc (MeSH)
• Humans (MeSH)
• Immunohistochemistry (MeSH)
• In Situ Hybridization (MeSH)
• Neoplasm Proteins (MeSH)
• Pathology (Science Metrix)
• Phyllodes Tumor (MeSH)
• Proto-Oncogene Proteins c-kit (MeSH)
• Proto-Oncogene Proteins c-myc (MeSH)
• RNA, Neoplasm (MeSH)
• Sequence Analysis, DNA (MeSH)
• Stromal Cells (MeSH)

published in

• Journal of Pathology  Journal

keywords

• Breast Neoplasms
• DNA, Neoplasm
• Epithelium
• Female
• Gene Expression
• Genes, myc
• Humans
• Immunohistochemistry
• In Situ Hybridization
• Neoplasm Proteins
• Phyllodes Tumor
• Proto-Oncogene Proteins c-kit
• Proto-Oncogene Proteins c-myc
• RNA, Neoplasm
• Sequence Analysis, DNA
• Stromal Cells

Digital Object Identifier (DOI)

• 10.1002/path.1318

PubMed ID

• 12692842

start page

• 59

end page

• 64

volume

• 200

issue

• 1