Membranous Nectin-4 expression is a risk factor for distant relapse of T1-T2, N0 luminal-A early breast cancer

作者：Lattanzio R; Ghasemi R; Brancati F; Sorda R L; Tinari N; Perracchio L; Iacobelli S^*; Mottolese M; Natali P G; Piantelli M

来源：Oncogenesis, 2014, 3: e118.

DOI：10.1038/oncsis.2014.32

Nectins are Ca2+-independent immunoglobulin-like cell adhesion molecules that compose a family of four members that regulate several cellular activities such as movement, proliferation, survival, differentiation, polarization, and the entry of viruses. Nectin-4 has recently emerged as a metastatis-associated protein in several cancers. Here, we have evaluated the association between the expression of Nectin-4 and the clinical outcome of patients with node-negative, T1/T2 breast cancers. The study group consisted of 197 patients presenting with primary unilateral breast carcinoma (T1/T2), with no evidence of nodal involvement and distant metastases. Nectin-4 protein expression was assessed by immunohistochemistry on tissue microarrays, and the results correlated with the clinical data using Kaplan-Meier curves and multivariate Cox regression analysis. Thirty-four out of 197 tumors (17.3%) exhibited Nectin-4 expression on cell membrane (m-Nectin-4) and 122 out of the 163m-Nectin-4 negative tumors (74.8%) showed high cytoplasmic expression of Nectin-4 (c-Nectin-4(High)). At Kaplan-Meier analysis, m-Nectin-4 positivity was significantly associated with a lower disease-free survival (DFS) and distant relapse-free survival (DRFS) rate in patients with a luminal-A phenotype (P = 0.030 and P = 0.002, respectively). Multivariate analysis showed that in luminal-A tumors m-Nectin-4 positivity is an independent prognostic factor for DFS (P = 0.018) and DRFS (P = 0.004), but not for local relapse-free survival (LRFS). On the other hand, c-Nectin-4(High) was significantly associated with higher rates of DFS and LRFS, but not DRFS, in the whole population (P = 0.008 and P = 0.004, respectively) and in patients with luminal-A tumors (P = 0.022 and P = 0.018, respectively). In patients with luminal-A tumors, multivariate analysis showed that the prognostic value of c-Nectin-4(Low/Negative) is limited to DFS (P = 0.012) and LRFS (P = 0.022). We suggest that Nectin-4 represents a prognostic factor and a therapeutic target in luminal-A early stage breast cancer.

• 出版日期2014-9