CDCP1 is a novel marker of the most aggressive human triple-negative breast cancers
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Federica Turdo1,*, Francesca Bianchi1,7,*, Patrizia Gasparini2, Marco Sandri1, Marianna Sasso1, Loris De Cecco3, Luca Forte1, Patrizia Casalini1, Piera Aiello1, Lucia Sfondrini7, Roberto Agresti4, Maria Luisa Carcangiu5, Ilaria Plantamura6, Gabriella Sozzi2, Elda Tagliabue1,#, Manuela Campiglio1,#
1Molecular Targeting Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
2Tumor Genomics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
3Functional Genomic Core Facility, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
4Division of Surgical Oncology, Breast Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
5Division of Breast Anatomy Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
6Start-Up Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
7Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy
*These authors contributed equally to this work
#These authors contributed equally and share senior authorship
Keywords: triple-negative breast cancer, CDCP1, CDCP1 copy number, prognosis, metastasis
Received: September 10, 2015 Accepted: August 27, 2016 Published: September 10, 2016
CDCP1, a transmembrane noncatalytic receptor, the expression of which has been associated with a poor prognosis in certain epithelial cancers, was found to be expressed in highly aggressive triple-negative breast cancer (TNBC) cell models, in which it promoted aggressive activities—ie, migration, invasion, anchorage-independent tumor growth, and the formation of vascular-like structures in vitro. By immunohistochemical (IHC) analysis of 100 human TNBC specimens, CDCP1 was overexpressed in 57% of samples, 38% of which exhibited a gain in CDCP1 copy number by fluorescence in situ hybridization (FISH). CDCP1 positivity was significantly associated between FISH and IHC. CDCP1 expression and gains in CDCP1 copy number synergized with nodal (N) status in determining disease-free and distant disease-free survival. The hazard ratios (HRs) of the synergies between CDCP1 positivity by IHC and FISH and lymph node positivity in predicting relapse did not differ significantly, indicating that CDCP1 overexpression in human primary TNBCs, regardless of being driven by gains in CDCP1, is for a critical factor in the progression of N-positive TNBCs. Thus, CDCP1 is a novel marker of the most aggressive N-positive TNBCs and a potential therapeutic target.
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