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Oncotarget. 2016 Oct 25;7(43):69649-69665. doi: 10.18632/oncotarget.11935.

CDCP1 is a novel marker of the most aggressive human triple-negative breast cancers.

Author information

1
Molecular Targeting Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
2
Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy.
3
Tumor Genomics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
4
Functional Genomic Core Facility, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
5
Division of Surgical Oncology, Breast Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
6
Division of Breast Anatomy Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
7
Start-Up Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Abstract

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.

KEYWORDS:

CDCP1; CDCP1 copy number; metastasis; prognosis; triple-negative breast cancer

PMID:
27626701
PMCID:
PMC5342505
DOI:
10.18632/oncotarget.11935
[Indexed for MEDLINE]
Free PMC Article

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