Anti-Heat Shock Protein-27 Antibody Levels in Women with Breast Cancer: Association with Disease Complications and Two-Year Disease-Free Survival

  • Homaei-Shandiz, Fatemeh (Cancer Research Center, Mashhad University of Medical Sciences) ;
  • Mehrad-Majd, Hassan (Clinical Research Unit, Mashhad University of Medical Sciences) ;
  • Tasbandi, Mojtaba (Cancer Research Center, Mashhad University of Medical Sciences) ;
  • Aledavood, Amir (Omid Hospital, Mashhad University of Medical Sciences) ;
  • Afshari, Jalil Tavakol (Department of Immunology, Bu-Ali Research Institute, Mashhad University of Medical Sciences) ;
  • Ghavami, Vahid (Biostatistics, Statistics and ICT Management, Mashhad University of Medical Sciences) ;
  • Ghayour-Mobarhan, Majid (Metabolic Syndrome Research Center, Faculty of Medicine, Mashhad University of Medical Sciences)
  • Published : 2016.10.01


Background and Aim: Breast cancer is a major healthcare problem in women. There are many reports about up-regulation of Hsp27 in cancer tissues but less is known about the potential relationship between Hsp27 antibody levels and breast cancer complications. We here investigated concentrations of serum Hsp27 antigen and antibodies in subjects with and without breast cancer and assessed potential associations with two-year disease-free survival, histological grade and number of lymph nodes. Materials and Methods: Specifically, serum Hsp27 antigen and antibody levels from 97 patients with breast cancer, and 65 healthy controls were determined by enzyme-linkedimmunosorbent assays (ELISAs). Results: Serum Hsp27 and antibody levels were significantly (p<0.001) higher in patients with breast cancer compared to the control group, but no relationship were found with two-year disease free survival, histological grade or number of lymph nodes (p> 0.6, 0.2 and 0.9 respectively). Conclusions: Elevated levels of Hsp27 antibody occur with women with breast cancer but do not appear to be associated with the presence of disease clinical complications.


Breast neoplasms;anti-Hsp27 antibody;disease-free survival


  1. Batchelder AJ, Gordon-Weeks AN, Walker RA (2009). Altered expression of anti-apoptotic proteins in non-involved tissue from cancer-containing breasts. Breast Cancer Res Treat , 114, 63-9.
  2. Batulan Z, Pulakazhi Venu VK, Li Y, et al (2016). Extracellular release and signaling by heat shock protein 27: role in modifying vascular inflammation. Front Immunol, 7, 285.
  3. Burt D, Bruno G, Chaturvedi N, et al (2009). Anti-heat shock protein 27 antibody levels and diabetes complications in the EURODIAB study. Diabetes Care, 32, 1269-71.
  4. Burut DF, Borai A, Livingstone C, et al (2010). Serum heat shock protein 27 antigen and antibody levels appear to be related to the macrovascular complications associated with insulin resistance: a pilot study. Cell Stress Chaperones 15, 379-86.
  5. Calderwood SK, Khaleque MA, Sawyer DB, et al (2006). Heat shock proteins in cancer: chaperones of tumorigenesis. Trends Biochem Sci, 31, 164-72.
  6. Child D, Williams C, Jones R, et al (1995). Heat shock protein studies in type 1 and type 2 diabetes and human islet cell culture. Diabet Med, 12, 595-99.
  7. Ciocca DR, Oesterreich S, Chamness GC, et al (1993). Biological and clinical implications of heat shock protein 27,000 (Hsp27): a review. J Natl Cancer Inst, 85, 1558-70.
  8. Ciocca DR, Calderwood SK (2005). Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones, 10, 86-103.
  9. Conroy SE, Sasieni PD, Amin V, et al (1998). Antibodies to heat-shock protein 27 are associated with improved survival in patients with breast cancer. Br J Cancer , 77, 1875-79.
  10. Didelot C, Lanneau D, Brunet M, et al (2007). Anti-cancer therapeutic approaches based on intracellular and extracellular heat shock proteins. Curr Med Chem, 14, 2839-47.
  11. Ferns G, Shams S, Shafi S (2006). Heat shock protein 27: its potential role in vascular disease. Int J Exp Pathol, 87, 253-74.
  12. Kang SH, Kang KW, Kim KH, et al (2008). Upregulated Hsp27 in human breast cancer cells reduces Herceptin susceptibility by increasing Her2 protein stability. BMC Cancer, 8, 286.
  13. Liao D, Jin Z, Baas A, et al (2000). Purification and identification of secreted oxidative stress-induced factors from vascular smooth muscle cells. J Biol Chem, 275, 189-96.
  14. Love S, King RJ (1994). A 27 kDa heat shock protein that has anomalous prognostic powers in early and advanced breast cancer. Br J Cancer, 69, 743-48.
  15. Mandal K, Jahangiri M, Xu Q (2004). Autoimmunity to heat shock proteins in atherosclerosis. Autoimmun Rev, 3, 31-7.
  16. Mehlen P, Preville X, Chareyron P, et al (1995). Constitutive expression of human hsp27, Drosophila hsp27, or human alpha B-crystallin confers resistance to TNF and oxidative stress-induced cytotoxicity in stably transfected murine L929 fibroblasts. J Immunol, 154, 363-74.
  17. Mehlen P, Schulze-Osthoff K, Arrigo A (1996). Small stress proteins as novel regulators of apoptosis. J Biol Chem, 271, 16510-514.
  18. Oesterreich S, Weng CN, Qiu M, et al (1993). The small heat shock protein hsp27 is correlated with growth and drug resistance in human breast cancer cell lines. Cancer Res, 53, 4443-48.
  19. Thanner F, Sutterlin MW, et al (2005). Heat shock protein 27 is associated with decreased survival in node-negative breast cancer patients. Anticancer Res, 25, 1649-53.
  20. Thor A, Benz C, Moore D, et al (1991). Stress response protein (srp-27) determination in primary human breast carcinomas: clinical, histologic, and prognostic correlations. J Natl Cancer Inst, 83, 170-78.
  21. Trieb K, Gerth R, Holzer G, et al (2000). Antibodies to heat shock protein 90 in osteosarcoma patients correlate with response to neoadjuvant chemotherapy. Br J Cancer, 82, 85-7.
  22. Tweedle E, Khattak I, Ang C, et al (2010). Low molecular weight heat shock protein HSP27 is a prognostic indicator in rectal cancer but not colon cancer. Gut, 59, 1501-10.
  23. Vega VL., Rodriguez-Silva M., Frey T., et al., (2008). Hsp70 translocates into the plasma membrane after stress and is released into the extracellular environment in a membrane-associated form that activates macrophages. J Immunol, 180, 4299-4307.
  24. Vidyasagar A, Wilson NA, Djamali A (2012). Heat shock protein 27 (HSP27): biomarker of disease and therapeutic target. Fibrogenesis Tissue Repair, 5, 7.