Skip to main content
Log in

Plasma nucleosome levels in node-negative breast cancer patients

  • Published:
Breast Cancer Aims and scope Submit manuscript

Abstract

Background

A nucleosome is a primary repeating unit of organized DNA 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.

Materials and Methods

We investigated PNLs in 96 patients with stage 0–III breast cancer (nodenegative, n=57; node-positive, n=39), and in 111 women without any evidence of disease as healthy controls. PNLs were detected using the Cell Death Detection ELISAplus kit (Boehringer Mannheim, Japan).

Results

The PNLs in normal controls were 0.010±0.012 units (mean±SD), while PNLs were significantly higher in both node-negative breast cancer (0.153±0.242) and node-positive breast cancer patients (0.116±0.172) (p<0.01). When PNLs were classified as high (>0.10) and low (≤0.l0), no correlation was found between high PNLs and clinicopathological factors such as tumor size, menopausal status, estrogen receptor status, histological type and lymphatic or venous spread in node-negative breast cancer. The relapse-free survival of patients with high PNLs tended to be better than those with low PNLs in both node-negative and node-positive breast cancer.

Conclusion

Increased PNLs were found in breast cancer patients, and PNLs seem promising as a new prognostic factor for both node-negative and node-positive breast cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

PNLs:

Plasma nucleosome levels

RFS:

Relapse-free survival

ELISA:

Enzyme-linked immunosorbent assay

NK:

Natural killer

Al:

Apoptotic index

References

  1. Fournie GJ: Circulating DNA and lupus nephritis.Kidney Int 33:487–497, 1988.

    Article  PubMed  CAS  Google Scholar 

  2. Leon SA, Shapiro B, Sklaroff DM,et al: Free DNA in the serum of cancer patients and the effect of therapy.Cancer Res 37:646–650, 1977.

    PubMed  CAS  Google Scholar 

  3. Shapiro B, Chakrabarty M, Cohn EM,et al: Determination of circulating DNA levels in patients with benign or malignant gastrointestinal disease.Cancer 51:2116–2120, 1983.

    Article  PubMed  CAS  Google Scholar 

  4. Stroun M, Anker P, Lyautey J,et al: Isolation and characterization of DNA from the plasma of cancer patients.Eur J Cancer Oncol 23:707–712, 1987.

    Article  CAS  Google Scholar 

  5. Giacona MB, Ruben GC, Iczkowski KA,et al: Cellfree DNA in human blood plasma; Length measurements in patients with pancreatic cancer and healthy controls.Pancreas 17:89–97, 1998.

    Article  PubMed  CAS  Google Scholar 

  6. Vasioukhin V, Anker P, Maurice P,et al: Point mutations of the N-ras gene in the blood plasma DNA of patients with myelodysplastic syndrome or acute myelogeneous leukaemia.Br J Haematol 86:774–779, 1994.

    Article  PubMed  CAS  Google Scholar 

  7. Chen YQ, Stroun M, Magnenat JL,et al: Micro satellite alterations in plasma DNA of small cell lung cancer patients.Nat Med 9:1033–1034, 1996.

    Article  Google Scholar 

  8. Nawroz H, Koch W, Anker P,et al: Microsatellite alterations in serum DNA of head and neck cancer patients.Nat Med 9:1035–1037, 1996.

    Article  Google Scholar 

  9. Japanese Breast Cancer Society: General Rules for Clinical and Pathological Recording of Breast Cancer, 12th ed, Kanehara, Tokyo, ppl-56, 1996.

    Google Scholar 

  10. Le Lann AD, Fournie GJ, Boissier L,et al: In vitro inhibition of natural-killer-mediated lysis by chromatin fragments.Cancer Immunol Immunother 39:185–192, 1994.

    Google Scholar 

  11. Kajiwara M, Toyoshima S, Yao T,et al: Apoptosis and cell proliferation in medullary carcinoma of the breast; A comparative study between medullary and non-medullary carcinoma using the TUNEL method and immunohistochemistry.J Surg Oncol 70:209–216, 1999.

    Article  PubMed  CAS  Google Scholar 

  12. Kerr JFR, Winterford CM: Apoptosis; Its significance in cancer and cancer therapy.Cancer 73:2013–2026, 1994.

    Article  PubMed  CAS  Google Scholar 

  13. Thompson C: Apoptosis in the pathogenesis and treatment of disease.Science 267:1456–1462, 1995.

    Article  PubMed  CAS  Google Scholar 

  14. Shao AM, Jiang M, Wu J,et al: Identification of spontaneous programmed cell death during development of human breast cancer.Oncology Rep 3:1133–1136, 1996.

    Google Scholar 

  15. Lipponen P, Aaltomaa S, Kosma VM,et al: Apoptosis in breast cancer as related to histopathological characteristics and prognosis.Eur J Cancer 30:2068–2073, 1994.

    Article  Google Scholar 

  16. Zhang GJ, Kimijima I, Abe R,et al: Apopototic index correlates to bcl-2 and p-53 protein expression, histological grade and prognosis in invasive breast cancers.Anticancer Res 18:1989–1998, 1998.

    PubMed  CAS  Google Scholar 

  17. Vakkala M, Lahteenmaki K, Raunio H,et al: Apoptosis during breast carcinoma progression.Clin Cancer Res 5:319–324, 1999.

    PubMed  CAS  Google Scholar 

  18. Gavrieli Y, Sherman Y, Ben-Sasson SA: Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.J Cell Biol 119:493–501, 1992.

    Article  PubMed  CAS  Google Scholar 

  19. Leon SA, Shapiro B, Servei P,et al: A comparison of DNA and DNA-binding protein levels in malignant disease.Eur J Cancer 17:533–538, 1981.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

About this article

Cite this article

Kuroi, K., Tanaka, C. & Toi, M. Plasma nucleosome levels in node-negative breast cancer patients. Breast Cancer 6, 361–364 (1999). https://doi.org/10.1007/BF02966454

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02966454

Key words

Navigation