Analysis of plasma HER2 copy number in cell-free DNA of breast cancer patients: a comparison with HER2 extracellular domain protein level in serum.

BACKGROUND: HER2 (human epidermal growth factor receptor 2) status has been evaluated in breast cancer (BC) tissues by immunohistochemistry or in situ hybridization. We evaluated HER2 copy number (CN) assay in plasma cell-free DNA (cfDNA) from blood samples and compared it with protein measurements of HER2 extracellular domain (ECD) in serum. METHODS: Serum HER2-ECD levels were measured by chemi-luminescence immunoassay using anti-HER2 monoclonal antibodies. Analyses were performed on 120 cases of primary BC, 30 cases of metastatic BC and 34 cases treated by neoadjuvant chemotherapy (NAC). This study was approved by Medical Research Review Advancement No. 1857 for Kumamoto University. RESULTS: There was a positive correlation between HER2-CN ratios and HER2-ECD levels, in primary (n = 54) and metastatic (n = 30) HER2-positive BC (P = 0.003 and P < 0.001, respectively). HER2-ECD levels were significantly higher in patients with a larger number of metastatic sites (P = 0.02). The usefulness of HER2 levels in discriminating primary and metastatic HER2-positive BC evaluated by ROC curve analysis was better in the HER2-ECD assay than in the HER2-CN assay. In 34 patients who received NAC, there was a small decrease in HER2-CN ratios between before and after NAC (P = 0.10), while there was an obvious decrease in HER2-ECD levels between before and after NAC (P < 0.001). CONCLUSION: Compared to HER2-ECD levels, the clinical usefulness of HER2-CN ratio was somewhat inferior. Improved measurement methods and further examination of the association with long-term prognosis and the response to anti-HER2 treatment analyzed by HER2-CN and HER2-ECD assay are required.

Influence of surgical stress on cellular immunity and the induction of plastic adherent suppressor cells of spleen in mice.

Surgical stress animal models were established by performing laparotomies on mice. It was found that this type of stress could suppress the natural killer (NK) cytotoxicity and the proliferation of spleen cells induced by conA or lipopolysaccharide (LPS). Dynamic changes showed that the stress-mediated immunosuppression was reversible, as the responses to conA and LPS would be restored with time. The sensitivity to the stress-mediated suppression was different according to variations in immunological parameters. Furthermore, the macrophages in spleen were tested by isolation by the plastic-adherent procedure. The results showed clearly that these adherent cells (Plastic Adherent Cells, PAC) possessed an immunosuppressive effect on mitogen-induced lymphocyte proliferation in post-operative mice, but not in normal mice. Treatment of mice with indomethacin blocked the PAC-mediated immunosuppression. Surgical stress appeared to increase the level of prostaglandins, which in turn induced the production of suppressor PAC.