YB-1 in breast cancer. Our laboratory data

.We read with interest the article by Mylona et al. on YB-1 expression in invasive breast cancer. The amount of YB-1 is often increased in different kind of tumors such as prostate, lungs, ovary, colon and breast cancer.1 and 2 YB-1 is involved in many cellular processes such as proliferation and response to stress; specifically it can be considered as an oncoprotein that stimulates cell proliferation, increases multi drug resistance and promotes metastasis. In addition it also has a protective function against apoptosis: YB-1 can modulate the activity of p53, activating the genes responsible for cell cycle arrest and pro-apoptotic genes. Another key role is that of gene activation of metalloproteinase MMP-2, which determine a greater capacity for invasion, aggression, and ability to metastasize.3 In breast cancer, YB-1 has a specific role in the epithelial–mesenchymal transition.4 Mylona and coll. analyzed YB-1 in 225 invasive breast cancer and found that its citoplasmatic expression correlated with ER negativity, p53 expression and with stem cells markers (CD44/CD24). About nuclear YB1 positivity they found it exerts unfavorable impact on the disease-free survival of the unselected patients (p = 0.05) and in patients having been treated with adjuvant chemotherapy and radiotherapy (p = 0.036 and p = 0.05, respectively). They conclude that cytoplasmic YB1 is associated with an aggressive and “stem cell-like” tumor phenotype, while YB1 nuclear localization is able to discriminate patients at high risk for recurrence. We recently conducted a similar study in 97 patients [mean age 58 years (min 25–max 86)] with stage I–II invasive ductal breast cancer. Overexpression of the protein YB-1 was correlated with clinical and pathological parameters. All patients had surgery at the Department of Breast Surgery at the Policlinico “A. Gemelli” in Rome from April to November 2012 and YB1 expression was assessed using a rabbit polyclonal antibody NBP1-89945 (1:200) [Novus Biological; Cambridge, UK]. Unlike Mylona et al., we detected only a cytoplasmatic expression of YB -1. We did not detect neither nuclear nor stromal expression. As suggested by Woolley et al.,5 the variability of some studies in the literature that evaluated the expression of YB-1, could be related to the method of immunohistochemistry. They have demonstrated that the antibodies used have different binding affinities for different epitopes of YB-1 [two against N-terminal epitopes (respectively of 12 and 29 aminoacids) and one against a C-Terminal epitope (14 aminoacids)]. This is closely related to the nature of the complexes of YB-1 and this variability influences the determination of the expression of YB-1. Mylona et al. used a rabbit polyclonal antibody recognizing an N-terminal epitope of YB-1 protein (clone 2749; dil 1:30, Cell Signaling), we used an antibody (NBP1-89945; Novus Biologicals; dil. 1:200) developed against Recombinant YB-1 Protein (epitope of 98 aminoacids). For all patients YB-1 was correlated with the histological grade, the nodal status, the menopausal status, the Ki67, the hormonal receptors, the HER2 expression and finally with the St. Gallen “immunohistochemical” subtypes. We analyzed the data obtained by Fisher's exact test. Cytoplasmatic YB1 was detected more often in tumors of higher histological grade (p = 0.0001), positive nodal status (p = 0.0028), HER2 expression (p = 0.09) and with HER2 and Triple negative vs luminal A and luminal B immunophenotypes (p = 0.04). Correlation with menopausal status, Ki67 and hormonal receptors was not statistically significant. As regards the Ki67, we have considered four different cut-offs (10%; 14%; 20%; 30%) but none was found statistically significant. (Table 1) With a follow-up of 19 months, 5 out of 97 patients had local recurrence. Four of these five cases that recurred showed over-expression of YB-1. The results of our study, as well as Mylona et coll., show that over-expression of YB-1 may contribute to the acquisition of a more aggressive phenotype of breast cancer. Despite observed differences related to the type of antibody used, YB-1 can be considered a promising prognostic marker in breast cancer (Fig. 1).