Research article

Nectin-4 is a new histological and serological tumor associated marker for breast cancer

Stéphanie Fabre-Lafay^1,2,3,6 , Florence Monville^1,2,4 , Sarah Garrido-Urbani^1,2,3 , Carole Berruyer-Pouyet^1,2,3 , Christophe Ginestier^1,2,4,7 , Nicolas Reymond^1,2,3,8 , Pascal Finetti^1,2,4 , Richard Sauvan^1,2,5 , José Adélaïde^1,2,4 , Jeannine Geneix^1,2,4 , Eric Lecocq^1,2,3 , Cornel Popovici^1,2,4 , Patrice Dubreuil^1,2,3 , Patrice Viens^1,2,5 , Anthony Gonçalves^1,2,5 , Emmanuelle Charafe-Jauffret^1,2,4 , Jocelyne Jacquemier^1,2,4 , Daniel Birnbaum^1,2,4 and Marc Lopez^1,2,3

¹Inserm, UMR599, Centre de Recherche en Cancérologie de Marseille, Marseille, F-13009, France

²Univ. Méditerranée, Marseille, F-13007, France

³Institut Paoli-Calmettes, Marseille, F-13009, France

⁴Institut Paoli-Calmettes, Laboratoire d'oncologie moléculaire, Marseille, F-13009, France

⁵Institut Paoli-Calmettes, Département d'oncologie médicale, Marseille, F-13009, France

⁶Centre d'Immunologie Pierre Fabre, St Julien en Genevois, F-74164, France

⁷Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA

⁸Ludwig Institute for Cancer Research, London W1W 7BS, UK

author email corresponding author email

BMC Cancer 2007, 7:73doi:10.1186/1471-2407-7-73

Published:	2 May 2007

Abstract

Introduction

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.

Conclusion

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.