Abstract P5-07-11: CDCP1 as a new marker of aggressiveness in triple-negative breast cancers
Authors: E Tagliabue, F Turdo, F Bianchi, M Sandri, L Forte, P Casalini, P Gasparini, R Agresti, T Triulzi, G Sozzi, M Campiglio
Journal: Cancer Research (2016)

Abstract Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with high recurrences and mortality rate, for which no therapies besides chemotherapy are available to date. Lacking specific markers for an effective targeted therapy, TNBCs continue to represent the most important challenge for clinical oncologists. Here, we investigated the expression of CDCP1, a transmembrane non-catalytic receptor reportedly associated with poor prognosis in some solid tumors (e.g., lung and pancreatic cancer), and its association with tumor aggressiveness in a cohort of 115 human TNBC primary specimens obtained from women surgically treated in our Institute from the beginning of 2002 to the end of 2006 and selected based on immunohistochemical (IHC) criteria (&amp;lt;1% cell positivity for estrogen receptor, progesterone receptor and HER2 expression classified as 0 or 1+). CDCP1 was overexpressed in 56.5% of human primary TNBCs. FISH analysis of 75 TNBCs for which material was available delineated four different genetic categories: 1) disomic, with only two copies of CDCP1 and centromere (CDCP1&amp;lt;3, CEP3&amp;lt;3) (50/75, 67%); 2) amplified CDCP1 (CDCP1 ≥3, CEP3&amp;lt;3) (4/75, 5%); 3) polysomic CDCP1 (CDCP1≥3, CEP3≥3) (15/75, 20%); and 4) CDCP1 deleted of its centromere (CDCP1&amp;lt;3 CEP3≥3) (6/75, 8%). FISH positivity (polysomy or amplification) was significantly associated with IHC positivity (p=0.003). Permutation accuracy variable importance estimated by Random Survival Forests identified both CDCP1 protein expression and FISH positivity for CDCP1 as prognostic factors for DFS (HR=2.67, 95%CI 1.25-5.71, and HR= 2.95, 95%CI 1.33-6.53, respectively) and DDFS (HR=2.40, 95%CI 1.01-5.73, and HR= 3.40, 95%CI 1.44-8.04, respectively), together with age, lymph node involvement, tumor size, DCIS and Ki67 expression. Multivariate Cox survival analysis revealed a synergistic interaction between CDCP1 FISH/IHC status and N-status in DFS and DDFS. Indeed, while the 5-year relapse probability in N-negative patients did not differ according to CDCP1 IHC expression in tumor cells (18% and 13% in CDCP1 IHC negative and positive, respectively), the probability of developing distant metastases at 5 years of follow-up was 82% in N-positive/CDCP1 IHC-positive patients versus only 29% in N-positive/CDCP1 IHC-negative patients. Similarly, the probability of developing distant metastases at 5 years in the N-positive subgroup was 88% for CDCP1 FISH-positive versus 35% for CDCP1 FISH-negative patients, but only 16% and 14% in N-negative/CDCP1 FISH negative and positive, respectively. Together, our results strongly suggest that CDCP1 is a marker of aggressiveness able to identify cases with poorer prognosis among N-positive TNBCs and, noticeably, overexpression of CDCP1 in human primary TNBCs can reflect a CDCP1 genetic gain. Supported by AIRC. Citation Format: Tagliabue E, Turdo F, Bianchi F, Sandri M, Forte L, Casalini P, Gasparini P, Agresti R, Triulzi T, Sozzi G, Campiglio M. CDCP1 as a new marker of aggressiveness in triple-negative breast cancers. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-07-11.