+1 Recommend
1 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Diagnostic value of PD-1 mRNA expression combined with breast ultrasound in breast cancer patients

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.



          This study explored the value of measuring programmed death 1 (PD-1) in peripheral blood, combined with breast ultrasound using the Breast Imaging Reporting and Data System (BI-RADS) classification, for differentiation between benign and malignant breast tumors.

          Materials and methods

          We enrolled 113 patients with breast cancer and 66 patients with benign breast tumors who were admitted to Hangzhou First People’s Hospital from September 2014 to August 2017. The mRNA level of PD-1 was detected by quantitative real-time polymerase chain reaction.


          The mRNA levels of PD-1 were significantly higher in the peripheral blood of patients with breast cancer than those in patients with benign breast tumors. The diagnostic sensitivity of PD-1 mRNA expression was 0.805, the specificity was 0.788, and the area under the curve (AUC) was 0.848 ( P < 0.001); the sensitivity of breast ultrasound-based BI-RADS classification was 0.752, the specificity was 0.909, and the AUC was 0.906 ( P < 0.001); and the combined sensitivity, specificity, and AUC of the two assays were 0.920, 0.879, and 0.938, respectively ( P < 0.001). Progesterone receptor-positive breast cancer patients exhibited high levels of PD-1 expression ( P < 0.001).


          This study suggests that the measurement of PD-1 combined with breast ultrasound-based BI-RADS classification represents a significant improvement for breast cancer diagnosis compared with diagnoses based on either method alone.

          Related collections

          Most cited references 40

          • Record: found
          • Abstract: found
          • Article: not found

          In situ tumor PD-L1 mRNA expression is associated with increased TILs and better outcome in breast carcinomas.

          Blockade of the PD-1/PD-L1 axis emerged as a promising new therapeutic option for cancer that has resulted in lasting responses in metastatic renal, lung carcinomas, and melanomas. Tumor PD-L1 protein expression may predict response to drugs targeting this pathway. Measurement of PD-L1 protein is limited by the lack of standardized immunohistochemical methods and variable performance of antibodies. Our goal was to correlate PD-L1 mRNA expression with clinical variables in primary breast carcinomas. The fluorescent RNAscope paired-primer assay was used to quantify in situ PD-L1 mRNA levels in 636 stage I-III breast carcinomas on two sets of tissue microarrays [YTMA128 (n = 238) and YTMA201 (n = 398)]. Tumor-infiltrating lymphocytes (TIL) were assessed by hematoxylin/eosin stain and quantitative fluorescence. On YTMA128 and YTMA201, 55.7% and 59.5% of cases showed PD-L1 mRNA expression, respectively. Higher PD-L1 mRNA expression was significantly associated with increased TILs (P = 0.04) but not with other clinical variables. Elevated TILs (scores 2 and 3+) occurred in 16.5% on YTMA128 and 14.8% on YTMA201 and was associated with estrogen receptor-negative status (P = 0.01 on YTMA128 and 0.0001 on YTMA201). PD-L1 mRNA expression was associated with longer recurrence-free survival (log-rank P = 0.01), which remained significant in multivariate analysis including age, tumor size, histologic grade, nodal metastasis, hormone receptor, HER2 status, and the extent of TILs (HR, 0.268; CI, 0.099-0.721; P = 0.009). PD-L1 mRNA expression is identified in nearly 60% of breast tumors and it is associated with increased TILs and improved recurrence-free survival. These observations support the evaluation of PD-1/PD-L1-targeted therapies in breast cancer. ©2014 American Association for Cancer Research.
            • Record: found
            • Abstract: found
            • Article: not found

            Identification of circulating microRNA signatures for breast cancer detection.

            There is a quest for novel noninvasive diagnostic markers for the detection of breast cancer. The goal of this study is to identify circulating microRNA (miRNA) signatures using a cohort of Asian Chinese patients with breast cancer, and to compare miRNA profiles between tumor and serum samples. miRNA from paired breast cancer tumors, normal tissue, and serum samples derived from 32 patients were comprehensively profiled using microarrays or locked nucleic acid real-time PCR panels. Serum samples from healthy individuals (n = 22) were also used as normal controls. Significant serum miRNAs, identified by logistic regression, were validated in an independent set of serum samples from patients (n = 132) and healthy controls (n = 101). The 20 most significant miRNAs differentially expressed in breast cancer tumors included miRNA (miR)-21, miR-10b, and miR-145, previously shown to be dysregulated in breast cancer. Only 7 miRNAs were overexpressed in both tumors and serum, suggesting that miRNAs may be released into the serum selectively. Interestingly, 16 of the 20 most significant miRNAs differentially expressed in serum samples were novel. MiR-1, miR-92a, miR-133a, and miR-133b were identified as the most important diagnostic markers, and were successfully validated; receiver operating characteristic curves derived from combinations of these miRNAs exhibited areas under the curves of 0.90 to 0.91. The clinical use of miRNA signatures as a noninvasive diagnostic strategy is promising, but should be further validated for different subtypes of breast cancers. ©2013 AACR.
              • Record: found
              • Abstract: found
              • Article: not found

              The presence of programmed death 1 (PD-1)-positive tumor-infiltrating lymphocytes is associated with poor prognosis in human breast cancer.

              Programmed death 1 (PD-1) is a co-inhibitory receptor in the CD28/CTL-4 family, and functions as a negative regulator of the immune system. Tumor-infiltrating lymphocytes (TIL) in many epithelial cancers express PD-1, suggesting that antitumor immunity may be modulated by the PD-1/PD-L1 signaling pathway, and promising results from two recent clinical trials with monoclonal antibodies targeting PD-1 or PD-L1 confirm the clinical relevance of this pathway in human cancer. To explore the role of PD-1(+) TIL in human breast cancer, we performed immunohistochemistry studies on a tissue microarray encompassing 660 breast cancer cases with detailed clinical annotation and outcomes data. PD-1(+) TIL were present in 104 (15.8 %) of the 660 breast cancer cases. Their presence was associated with tumor size, grade, and lymph node status, and was differentially associated with the intrinsic subtypes of breast cancer. In univariate survival analyses, the presence of PD-1(+) TIL was associated with a significantly worse overall survival (HR = 2.736, p < 0.001). In subset analyses, the presence of PD-1(+) TIL was associated with significantly worse overall survival in the luminal B HER2(-) subtype (HR = 2.678, p < 0.001), the luminal B HER2(+) subtype (HR = 3.689, p < 0.001), and the basal-like subtype (HR = 3.140, p < 0.001). This is the first study to demonstrate that the presence of PD-1(+) TIL is associated with poor prognosis in human breast cancer, with important implications for the potential application of antibody therapies targeting the PD-1/PD-L1 signaling pathway in this disease.

                Author and article information

                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                28 August 2018
                : 14
                : 1527-1535
                [1 ]Department of Ultrasonography, Hangzhou First People’s Hospital, Hangzhou 310006, People’s Republic of China, baolingyun976@ 123456sina.com
                [2 ]Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People’s Republic of China
                [3 ]Department of Breast and Chest Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou 570102, People’s Republic of China
                [4 ]Department of Ultrasound, The First Affiliated Hospital of Hainan Medical University, Haikou 570102, People’s Republic of China
                Author notes
                Correspondence: Lingyun Bao, Department of Ultrasonography, Hangzhou First People’s Hospital, No 261 Huansha Road, Hangzhou 310006, People’s Republic of China, Tel +86 571 5600 7130, Email baolingyun976@ 123456sina.com

                These authors contributed equally to this work

                © 2018 Fang et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Original Research


                breast cancer, pd-1, diagnosis, breast ultrasound


                Comment on this article