title: Activated c-SRC in ductal carcinoma in situ correlates with high tumour grade, high proliferation and HER2 positivity.
abstract: Overexpression and/or activity of c-Src non-receptor tyrosine kinase is associated with progression of several human epithelial cancers including breast cancer. c-Src activity in 'pure' ductal carcinoma in situ (DCIS) was measured to assess whether this predicts recurrence and/or correlates with HER2 expression and other clinical parameters. Activated c-Src levels were evaluated in DCIS biopsies from 129 women, with median follow-up at 60 months. High levels of activated c-Src correlated with HER2 positivity, high tumour grade, comedo necrosis and elevated epithelial proliferation. In univariate analysis, high activated c-Src level associated with lower recurrence-free survival at 5 years (P=0.011). Thus, high c-Src activity may identify a subset of DCIS with high risk of recurrence or progression to invasive cancer where therapeutics targeting c-Src may benefit this patient subset.
authors.affiliation: Department of Academic Surgery, Research and Education Building 2nd Floor, South Manchester University Hospital, Wythenshawe, Manchester, UK.
authors.forename: G R
authors.initials: GR
authors.lastname: Wilson
authors.forename: A
authors.initials: A
authors.lastname: Cramer
authors.forename: A
authors.initials: A
authors.lastname: Welman
authors.forename: F
authors.initials: F
authors.lastname: Knox
authors.forename: R
authors.initials: R
authors.lastname: Swindell
authors.forename: H
authors.initials: H
authors.lastname: Kawakatsu
authors.forename: R B
authors.initials: RB
authors.lastname: Clarke
authors.forename: C
authors.initials: C
authors.lastname: Dive
authors.forename: N J
authors.initials: NJ
authors.lastname: Bundred
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D049109:Cell Proliferation; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D016392:Proto-Oncogene Proteins pp60(c-src); D018719:Erb-b2 Receptor Tyrosine Kinases