Skip to main content

Advertisement

SpringerLink
Log in

Expression of Tumor Antigens and Heat-Shock Protein 70 in Breast Cancer Cells After High-Intensity Focused Ultrasound Ablation

  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

ABSTRACT

Background

Previous results have shown that high-intensity focused ultrasound (HIFU) ablation can potentially activate a host antitumor immunity. The goal of this study was to investigate whether the tumor antigens expressed on breast cancer cells may be preserved after HIFU treatment, and to explore the potential mechanisms regarding the enhanced antitumor response.

Methods

The primary lesion in 23 patients with biopsy-proven breast cancer were treated with HIFU, then submitted to modified radical mastectomy. By using biotin-streptavidin-peroxidase immunohistochemical technology, a variety of cellular molecules expressed on breast cancer cells, including tumor antigens and heat-shock protein 70 (HSP-70), were stained in all breast specimens. A complete absence of staining was recorded as negative, and immunoreaction of the tumor cells was considered to be positive for antigen expression.

Results

Nuclear positivity of breast cancer cells for proliferating cell nuclear antigen, estrogen receptor, and progesterone receptor was detected in 0%, 9%, and 9% of the treated samples, respectively. The positive rate of cytoplasmic staining for matrix metalloproteinase 9, carbohydrate antigen 15–3, vascular endothelial growth factor, transforming growth factors β1 and β2, interleukin 6, and interleukin 10 was 0%, 52%, 30%, 57%, 70%, 48%, and 61% in the treated cancer cells, respectively. The positive rate of cellular membrane staining for epithelial membrane antigen, CD44v6, and HSP−70 was 100%, 0%, and 100% in the zones of treated cancer cells, respectively.

Conclusions

After HIFU ablation, some tumor antigens remained in the tumor debris. This could provide a potential antigen source to stimulate antitumor immune response.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

FIG. 1.

Similar content being viewed by others

References

  1. Kennedy JE. High-intensity focused ultrasound in the treatment of solid tumours. Nat Rev Cancer 2005; 5:321–7

    Article  PubMed  CAS  Google Scholar 

  2. Chaussy C, Thuroff S, Rebillard X, Gelet A. Technology insight: high-intensity focused ultrasound for urologic cancers. Nat Clin Prac Urol 2005; 2:191–8

    Article  Google Scholar 

  3. Wu F, Wang ZB, Zhu H, et al. Extracorporeal high intensity focused ultrasound treatment for patients with breast cancer. Breast Cancer Res Treat 2005; 92:51–60

    Article  PubMed  Google Scholar 

  4. Gianfelice D, Khiat A, Boulanger Y, Amara M, Belblidia A. Feasibility of magnetic resonance imaging–guided focused ultrasound surgery as an adjunct to tamoxifen therapy in high-risk surgical patients with breast carcinoma. J Vasc Interv Radiol 2003; 14:1275–82

    PubMed  Google Scholar 

  5. Wu F, Wang ZB, Chen WZ, et al. Extracorporeal high intensity focused ultrasound ablation in the treatment of patients with large hepatocellular carcinoma. Ann Surg Oncol 2004; 11:1061–9

    Article  PubMed  Google Scholar 

  6. Wu F, Wang ZB, Chen WZ, Bai J, Zhu H, Qiao TY. Preliminary experience using high intensity focused ultrasound for the treatment of patients with advanced stage renal malignancy. J Urol 2003; 170:2237–40

    Article  PubMed  Google Scholar 

  7. Chen W, Zhou K. High-intensity focused ultrasound ablation: a new strategy to manage primary bone tumors. Curr Opin Orthop 2005; 16:494–500

    Article  Google Scholar 

  8. Wu F, Wang ZB, Zhu H, et al. Feasibility of ultrasound-guided high intensity focused ultrasound treatment for patients with advanced pancreatic cancer initial experience. Radiology 2005; 236:1034–40

    PubMed  Google Scholar 

  9. Yang R, Reilly CR, Rescorla FJ, et al. Effects of high-intensity focused ultrasound in the treatment of experimental neuroblastoma. J Pediatr Surg 1992; 27:246–51

    Article  PubMed  CAS  Google Scholar 

  10. Rosberger DF, Coleman DJ, Silverman R, Woods S, Rondeau M, Cunningham-Rundles S. Immunomodulation in choroidal melanoma: reversal of inverted CD4/CD8 ratios following treatment with ultrasonic hyperthermia. Biotechnol Ther 1994; 5:59–68

    PubMed  CAS  Google Scholar 

  11. Wu F, Wang ZB, Lu P, et al. Activated anti-tumour immunity in cancer patients after high intensity focused ultrasound ablation. Ultrasound Med Biol 2004; 30:1217–22

    Article  PubMed  Google Scholar 

  12. Hu Z, Yang XY, Liu Y, et al. Release of endogenous danger signals from HIFU-treated tumor cells and their stimulatory effects on APCs. Biochem Biophys Res Commun 2005; 335:124–31

    Article  PubMed  CAS  Google Scholar 

  13. Illing RO, Kennedy JE, Wu F, et al. The safety and feasibility of extracorporeal high intensity focused ultrasound (HIFU) for the treatment of liver and kidney tumours in a Western population. Br J Cancer 2005; 93:890–5

    Article  PubMed  CAS  Google Scholar 

  14. Wu F, Wang ZB, Chen WZ, et al. Extracorporeal focused ultrasound surgery for treatment of human solid carcinomas: early Chinese clinical experience. Ultrasound Med Biol 2004; 30:245–60

    Article  PubMed  Google Scholar 

  15. Wu F, Wang ZB, Cao YD, et al. A randomised clinical trial of high-intensity focused ultrasound ablation for the treatment of patients with localised breast cancer. Br J Cancer 2003; 89:2227–33

    Article  PubMed  CAS  Google Scholar 

  16. Wu F, Wang ZB, Cao YD, et al. Heat fixation of cancer cells ablated with high intensity focused ultrasound in patients with breast cancer. Am J Surg 2006; 192:179–184

    Article  PubMed  Google Scholar 

  17. Van Leenders GJLH, Beerlage HP, Ruijter ET, de la Rosette JJMCH, van de Kaa CA. Histopathological changes associated with high intensity focused ultrasound (HIFU) treatment for localised adenocarcinoma of the prostate. J Clin Pathol 2000; 53:391–4

    Article  PubMed  Google Scholar 

  18. Hansler J, Neureiter D, Strobel D, et al. Cellular and vascular reactions in the liver to radio-frequency thermo-ablation with wet needle applicators. Study on juvenile domestic pigs. Eur Surg Res 2002; 34:357–63

    Article  PubMed  CAS  Google Scholar 

  19. Wissniowski TT, Hunsler J, Neureiter D, et al. Activation of tumor-specific T lymphocytes by radio-frequency ablation of the VX2 hepatoma in rabbits. Cancer Res 2003; 63:6496–500

    PubMed  CAS  Google Scholar 

  20. den Brok MH, Sutmuller RP, van der Voort R, et al. In situ tumor ablation creates an antigen source for the generation of anti-tumor immunity. Cancer Res 2004; 64:4024–9

    Article  Google Scholar 

  21. Pockley AG. Heat shock proteins as regulators of the immune response. Lancet 2003; 362:469–76

    Article  PubMed  CAS  Google Scholar 

  22. Todryk SM, Michael J. Goughy MJ, Pockley AG. Facets of heat shock protein 70 show immunotherapeutic potential. Immunology 2003; 110:1–9

    Article  PubMed  CAS  Google Scholar 

  23. Li Z, Antoine Menoret A, Srivastava P. Roles of heat-shock proteins in antigen presentation and cross-presentation. Curr Opin Immunol 2002; 14:45–51

    Article  PubMed  CAS  Google Scholar 

  24. Lewis JJ. Therapeutic cancer vaccines: using unique antigens. PNAS 2004; 101(Suppl 2):14653–6

    Article  PubMed  CAS  Google Scholar 

  25. Schueller G, Kettenbach J, Sedivy R, et al. Expression of heat shock proteins in human hepatocellular carcinoma after radiofrequency ablation in an animal model. Oncol Rep 2004; 12:495–9

    PubMed  CAS  Google Scholar 

  26. Lepock JR, Frey HE, Ritchie KP. Protein denaturation in intact hepatocytes and isolated cellular organelles during heat shock. J Cell Biol 1993; 122:1267–76

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

We thank Dr. Tom Leslie at the Churchill Hospital of Oxford, Oxford, England, UK, for his help with the language.

Author information

Authors and Affiliations

  1. Clinical Center for Tumor Therapy of 2nd Affiliated Hospital and Institute of Ultrasonic Engineering in Medicine, Chongqing University of Medical Sciences, 1 Medical College Road, Chongqing, 400016, China

    Feng Wu MD, PhD, Zhi-Biao Wang MD, PhD, You-De Cao PhD, Qiang Zhou MD, Ying Zhang MD, Zhong-Lin Xu MD & Xue-Qiang Zhu MD

  2. HIFU Unit, The Churchill Hospital, Headington, Oxford, OX3 7LJ, UK

    Feng Wu MD, PhD

Authors
  1. Feng Wu MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhi-Biao Wang MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. You-De Cao PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qiang Zhou MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ying Zhang MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhong-Lin Xu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xue-Qiang Zhu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Feng Wu MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wu, F., Wang, ZB., Cao, YD. et al. Expression of Tumor Antigens and Heat-Shock Protein 70 in Breast Cancer Cells After High-Intensity Focused Ultrasound Ablation. Ann Surg Oncol 14, 1237–1242 (2007). https://doi.org/10.1245/s10434-006-9275-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-006-9275-6

Keywords

Search

Navigation