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Background: Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. A recent study demonstrated the efficacy of anti-PD-L1 (anti-programmed death ligand-1) immunotherapy in patients with TNBC. However, the identification of TNBC patients who may benefit from immunotherapy is a critical issue. Several assays have been used to evaluate PD-L1 expression, and a few studies comparing PD-L1 expression using various primary antibodies in TNBC tissues have been reported. However, the expression profiles of the PD-L1 using the 73–10 assay have not yet been analyzed in TNBC tissues. Methods: We analyzed the PD-L1 immunohistochemical profiles of 62 women with TNBC using the 73–10, SP142 (companion diagnostic for atezolizumab), and E1L3N assays. PD-L1 expression on immune cells (ICs) and tumor cells (TCs) was also evaluated, and PD-L1 positivity was defined as a PD-L1-expressing ICs or TCs ≥ 1%. Results: The expression rates of PD-L1 were 79.0%, 67.7%, and 46.8% on ICs, and 17.7%, 6.5%, and 12.9% on TCs using the 73–10, SP142, and E1L3N assays, respectively. The concordance rates between the 73–10 and SP142 assays were 85.5% (on ICs) and 88.7% (on TCs), respectively, and substantial agreement on ICs (coefficient 0.634) and moderate agreement (coefficient 0.485) on TCs were noted. Sample age and tumor diameter did not influence the ratio of PD-L1 expression among the assays. Conclusions: The positive rate on ICs and TCs of the 73–10 assay was higher than that of the SP 142 and E1L3N assays. Although substantial agreement on ICs and moderate agreement on TCs between the 73–10 and SP142 assays was noted in the present cohort, further studies are needed to clarify the PD-L1 expression status using various primary antibodies in a larger patient population. This would lead to the establishment of an effective evaluation method to assess the predictive value of anti-PD-L1 immunotherapy. [ABSTRACT FROM AUTHOR]

Introduction: CD155 is an immune checkpoint protein. Its overexpression is an indicator of poor prognosis in some types of cancer. However, the significance of CD155 expression in patients with triple-negative breast cancer, and the relationship between CD155 and programmed death-ligand 1 (PD-L1) expression, have not yet been analyzed in detail. Methods: Using immunohistochemical staining and tissue microarrays, we analyzed the expression profiles of CD155 and PD-L1 in 61 patients with triple-negative breast cancer. Relapse-free survival and overall survival rates were compared according to CD155 expression. The correlation between CD155 expression and clinicopathological factors, including PD-L1 expression (using SP142 and 73–10 assays), was also examined. Results: CD155 expression was noted in 25 patients (41.0%) in this cohort. CD155 expression did not correlate with pathological stage, histological grade, Ki-67 labeling index, or stromal tumor-infiltrating lymphocytes. Only PD-L1 expression in tumor cells by SP142 assay significantly correlated with CD155 expression (p = 0.035); however, PD-L1 expression in tumor cells by 73–10 assay did not show a correlation (p = 0.115). Using the 73–10 assay, 59% of patients showed CD155 and/or PD-L1 expression in tumor cells. Moreover, using the SP142 assay, 63.3% of patients showed CD155 and/or PD-L1 expression in immune cells. CD155 expression did not correlate with either relapse-free survival or overall survival (p = 0.485 and 0.843, respectively). Conclusions: CD155 may be a novel target for antitumor immunotherapy. The results of this study indicate that CD155 may expand the pool of candidates with triple-negative breast cancer who could benefit from antitumor immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Stromal reaction is an important prognostic factor in several cancers, and the presence of myxoid change was assessed as a poor prognostic factor in colorectal cancer. However, the prognostic significance of myxoid change in triple-negative breast cancer (TNBC) remains unknown. This study aimed to determine the prognostic significance of myxoid change and fibrotic focus (FF), which is a fibrotic area within the tumor and considered a poor prognostic indicator in patients with TNBC. Methods: We enrolled 62 patients with TNBC and reviewed the surgically resected specimens to evaluate myxoid change and FF in the tumor using previously outlined criteria. We evaluated tumor-infiltrating lymphocytes (TILs) using hematoxylin and eosin slides. Overall survival (OS) and relapse-free survival (RFS) were compared based on the presence of myxoid change and/or FF, and the risk factors for RFS were analyzed. Results: Myxoid change and FF were observed in 25.8% and 33.9% of specimens, respectively. Based on stromal lymphocyte infiltration, 19 patients (30.6%) had high TILs, while the remaining 43 patients (69.4%) had low/intermediate TILs. Presence of myxoid change was significantly correlated with poor OS and RFS (p = 0.040 and 0.031, respectively). FF was also significantly correlated with poor OS and RFS (p = 0.012 and 0.028, respectively). The combination of myxoid change and FF was an independent and poor prognostic factor according to the multivariate analysis (HR 11.61; 95% CI 1.027–131.2; p = 0.048). Presence of myxoid change and FF were significantly associated with low/intermediate TILs in the stroma (p = 0.013). Conclusions: Histopathological assessment of myxoid change and FF in TNBC may be a useful, practical, and easily assessable method for predicting prognosis in patients with TNBC, which should be confirmed in larger prospective studies. Diagnostic criteria for the establishment of myxoid change and FF in TNBC must be established, and their underlying molecular events must be clarified. [ABSTRACT FROM AUTHOR]

Adipophilin is a lipid droplet-associated protein whose expression can act as a prognostic marker for specific cancers. Using immunohistochemical staining and tissue microarrays, we assayed the expression of adipophilin in 61 patients with triple-negative breast cancer (TNBC) who underwent surgery from January 2006–December 2018. Relapse-free survival (RFS) and its risk factors were analyzed based on adipophilin expression. Fourteen (23.0%) patients expressed adipophilin. As compared to the adipophilin-negative TNBC patients, adipophilin-positive patients exhibited poor RFS (p = 0.032). Among the TNBC patients with a high Ki-67 labeling index, patients negative for adipophilin exhibited better RFS than patients positive for adipophilin (p = 0.032). Moreover, among patients who did not undergo adjuvant chemotherapy, patients negative for adipophilin expression exhibited better RFS than adipophilin-positive patients (p = 0.080). Multivariate analysis showed that adipophilin expression correlated with a high rate of relapse (hazard ratio, 4.89; 95% confidence interval, 1.04–23.0; p = 0.044). Taken together, these results indicate that adipophilin is a novel marker for the poor prognosis of patients with TNBC. [ABSTRACT FROM AUTHOR]