title: Malignant phyllodes tumours show stromal overexpression of c-myc and c-kit.
abstract: Phyllodes 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.
authors.affiliation: Molecular and Population Genetics Laboratory, Cancer Research UK, London, UK. elinor.sawyer@cancer.org.uk
authors.forename: Elinor J
authors.initials: EJ
authors.lastname: Sawyer
authors.forename: Richard
authors.initials: R
authors.lastname: Poulsom
authors.forename: F Toby
authors.initials: FT
authors.lastname: Hunt
authors.forename: Rosemary
authors.initials: R
authors.lastname: Jeffery
authors.forename: George
authors.initials: G
authors.lastname: Elia
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
authors.forename: Paul
authors.initials: P
authors.lastname: Ellis
authors.forename: Ian P M
authors.initials: IP
authors.lastname: Tomlinson
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Hanby
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D004848:Epithelium / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000235:genetics; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D009363:Neoplasm Proteins / Q000032:analysis; D003557:Phyllodes Tumor / Q000235:genetics* / Q000473:pathology; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis; D017422:Sequence Analysis, DNA / Q000379:methods; D017154:Stromal Cells / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc; D012334:RNA, Neoplasm; D019009:Proto-Oncogene Proteins c-kit