Clinical Significance of Plasma Nucleosome Levels in Cancer Patients

The nucleosome is the primary repeating unit of DNA organization in chromatin, and cell death may lead to increased levels of circulating nucleosomes in plasma (PNLs) in various circumstances such as inflammation, pulmonary embolism, autoimmune disease, and cancer. Cell death can also be induced by chemotherapeutic agents. We investigated PNLs in 99 patients with primary breast cancer, 26 with recurrent disease, 11 with benign breast disease, and 27 with other histological types of cancer. In 18 patients with recurrent breast cancer who received docetaxel (D, 60 mg/m2) every 3 weeks as second line therapy after an anthracycline-based regimen, PNLs were investigated before and during the administration of D. One hundred and seventy-four healthy controls (111 females, 63 males) without any evidence of disease were also investigated. PNLs were detected using the cell death detection ELISAplus kit. PNLs were significantly higher in patients with primary breast cancer (mean +/- SD: 0.135 +/- 0.213) and in recurrent breast cancer (0.182 +/- 0.196) as compared with healthy female controls (0.010 +/- 0.012) (p < 0.01). In patients with primary breast cancer, no correlation was found between PNLs and clinicopathological characteristics. On the other hand, PNLs were decreased after mastectomy (p < 0.05). Patients with other histological types of cancer (0.244+/-0.383) also showed significantly higher PNLs as compared to healthy controls (p < 0.01), and PNLs were elevated independently of the histological type of cancer. In patients with recurrent breast cancer, PNLs showed a transient increase 24 h after the administration of D, and these increases correlated with the degree of subsequent leukopenia. In a follow-up study, pretreatment baseline PNLs decreased markedly when a response was obtained, whereas there was no decrease in either stable disease or progressive disease. Thus, increased PNLs were found in cancer patients, and PNLs seem to be a sensitive marker of cell death that could be predictive of both leukopenia and response to chemotherapy.