title: Nectin-4 is a new histological and serological tumor associated marker for breast cancer.
abstract: BACKGROUND
  Breast cancer is a complex and heterogeneous disease at the molecular level. Evolution is difficult to predict according to classical histoclinical prognostic factors. Different studies highlight the importance of large-scale molecular expression analyses to improve taxonomy of breast cancer and prognostic classification. Identification of new molecular markers that refine this taxonomy and improve patient management is a priority in the field of breast cancer research.Nectins are cell adhesion molecules involved in the regulation of epithelial physiology. We present here Nectin-4/PVRL4 as a new histological and serological tumor associated marker for breast carcinoma.
  
  
  METHODS
  Expression of Nectin-4 protein was measured on a panel of 78 primary cells and cell lines from different origins and 57 breast tumors by FACS analysis and immunohistochemistry (IHC), respectively. mRNA expression was measured by quantitative PCR. Serum Nectin-4 was detected by ELISA and compared with CEA and CA15.3 markers, on panels of 45 sera from healthy donors, 53 sera from patients with non-metastatic breast carcinoma (MBC) at diagnosis, and 182 sera from patients with MBC. Distribution of histological/serological molecular markers and histoclinical parameters were compared using the standard Chi-2 test.
  
  
  RESULTS
  Nectin-4 was not detected in normal breast epithelium. By contrast, Nectin-4 was expressed in 61% of ductal breast carcinoma vs 6% in lobular type. Expression of Nectin-4 strongly correlated with the basal-like markers EGFR, P53, and P-cadherin, and negatively correlated with the luminal-like markers ER, PR and GATA3. All but one ER/PR-negative tumors expressed Nectin-4. The detection of Nectin-4 in serum improves the follow-up of patients with MBC: the association CEA/CA15.3/Nectin-4 allowed to monitor 74% of these patients compared to 67% with the association CEA/CA15.3. Serum Nectin-4 is a marker of disease progression, and levels correlate with the number of metastases (P = 0.038). Serum Nectin-4 is also a marker of therapeutic efficiency and correlates, in 90% of cases, with clinical evolution.
  
  
  CONCLUSIONS
  Nectin-4 is a new tumor-associated antigen for breast carcinoma. Nectin-4 is a new bio-marker whose use could help refine breast cancer taxonomy and improve patients' follow-up. Nectin-4 emerges as a potential target for breast cancer immunotherapy.
authors.affiliation: Inserm, UMR599, Centre de Recherche en Cancérologie de Marseille, Marseille, France. stephanie.fabre.lafay@pierre-fabre.com <stephanie.fabre.lafay@pierre-fabre.com>
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Fabre-Lafay
authors.forename: Florence
authors.initials: F
authors.lastname: Monville
authors.forename: Sarah
authors.initials: S
authors.lastname: Garrido-Urbani
authors.forename: Carole
authors.initials: C
authors.lastname: Berruyer-Pouyet
authors.forename: Christophe
authors.initials: C
authors.lastname: Ginestier
authors.forename: Nicolas
authors.initials: N
authors.lastname: Reymond
authors.forename: Pascal
authors.initials: P
authors.lastname: Finetti
authors.forename: Richard
authors.initials: R
authors.lastname: Sauvan
authors.forename: José
authors.initials: J
authors.lastname: Adélaïde
authors.forename: Jeannine
authors.initials: J
authors.lastname: Geneix
authors.forename: Eric
authors.initials: E
authors.lastname: Lecocq
authors.forename: Cornel
authors.initials: C
authors.lastname: Popovici
authors.forename: Patrice
authors.initials: P
authors.lastname: Dubreuil
authors.forename: Patrice
authors.initials: P
authors.lastname: Viens
authors.forename: Anthony
authors.initials: A
authors.lastname: Gonçalves
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Charafe-Jauffret
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Jacquemier
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
authors.forename: Marc
authors.initials: M
authors.lastname: Lopez
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000097:blood*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D000075983:Nectins
chemical_list: D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C442228:NECTIN4 protein, human; D000075983:Nectins