@ARTICLE{10.3389/fmed.2019.00200, AUTHOR={Zeindler, Jasmin and Soysal, Savas Deniz and Piscuoglio, Salvatore and Ng, Charlotte K. Y. and Mechera, Robert and Isaak, Andrej and Weber, Walter Paul and Muenst, Simone and Kurzeder, Christian}, TITLE={Nectin-4 Expression Is an Independent Prognostic Biomarker and Associated With Better Survival in Triple-Negative Breast Cancer}, JOURNAL={Frontiers in Medicine}, VOLUME={6}, YEAR={2019}, URL={https://www.frontiersin.org/articles/10.3389/fmed.2019.00200}, DOI={10.3389/fmed.2019.00200}, ISSN={2296-858X}, ABSTRACT={Background: Triple-negative breast cancer (TNBC) represents about 10-20% of all invasive breast cancers and is associated with a poor prognosis. The nectin cell adhesion protein 4 (Nectin-4) is a junction protein involved in the formation and maintenance of cell junctions. Nectin-4 has previously shown to be expressed in about 60% of TNBC as well as in TNBC metastases, but to be absent in normal breast tissue, which makes it a potential specific target for TNBC therapy. Previous studies have shown an association of Nectin-4 protein expression with worse prognosis in TNBC in a small patient cohort. The aim of our study was to explore the role of Nectin-4 in TNBC and confirm its impact on survival in a larger TNBC patient cohort.Material and Methods: We performed immunohistochemical staining for Nectin-4 on a tissue microarray encompassing 148 TNBC cases with detailed clinical annotation and outcomes data.Results: A high expression of Nectin-4 was present in 86 (58%) of the 148 TNBC cases. In multivariate survival analysis, high expression of Nectin-4 was associated with a significantly better overall survival when compared with low expression of Nectin-4 (p < 0.001). Nectin-4-high expression was also significantly associated with a lower tumor stage (p = 0.025) and pN0 lymph node stage (p = 0.034).Conclusion: Our results confirm that expression of Nectin-4 serves as a potential prognostic marker in TNBC and is associated with a significantly better overall survival. In addition, Nectin-4 represents a potential target in TNBC, and its role in molecular defined breast cancer subtype should be investigated in larger patient cohorts.} }