title: Hsp70--a biomarker for tumor detection and monitoring of outcome of radiation therapy in patients with squamous cell carcinoma of the head and neck.
abstract: BACKGROUND
  Tumor but not normal cells frequently overexpress heat shock protein 70 (Hsp70) and present it on their cell surface (mHsp70) from where it can be actively released. Therefore, membrane (mHsp70) and soluble Hsp70 (sHsp70) were investigated as potential tumor biomarkers and for monitoring the outcome of radiation therapy.
  
  
  METHODS
  Biopsies and blood were collected from patients with squamous cell carcinoma of the head and neck (SCCHN) at different time points (before, during therapy and in the follow-up period). Hsp70 membrane expression was determined on single cell suspensions of tumor biopsies and reference tissues by flow cytometry, sHsp70 protein and antibody levels were determined in the serum of patients and healthy donors by ELISA and NK cell markers that are related to the presence of sHsp70 were analyzed in the patient's peripheral blood lymphocytes (PBL).
  
  
  RESULTS
  Tumor biopsies exhibited significantly increased mHsp70 expression levels compared to the reference tissue. Soluble Hsp70 levels were significantly higher in SCCHN patients compared to healthy human volunteers and high mHsp70 expression levels on tumor cells were associated with high sHsp70 levels in the serum of patients. Following surgery and radiotherapy sHsp70 levels in patients dropped in patients without tumor relapse in the follow-up period. In contrast to sHsp70 protein, anti-Hsp70 antibody levels remained nearly unaltered in the serum of SCCHN patients before and after therapy. Furthermore, sHsp70 protein but not anti-Hsp70 antibody levels were found to be associated with the tumor volume in SCCHN patients before start of therapy. The expression densities of the activatory NK cell markers CD56, CD94, NKG2D, NKp30, Nkp44, and NKp46 differed in patients following therapeutic intervention. A significant increase in the density of NKG2D was observed in SCCHN patients in the follow-up period after surgery and radiotherapy.
  
  
  CONCLUSIONS
  We suggest sHsp70 as a potential biomarker for detecting tumors and for monitoring the clinical outcome of radiotherapy in SCCHN patients.
authors.forename: Mathias
authors.initials: M
authors.lastname: Gehrmann
authors.forename: Hanno M
authors.initials: HM
authors.lastname: Specht
authors.forename: Christine
authors.initials: C
authors.lastname: Bayer
authors.forename: Markus
authors.initials: M
authors.lastname: Brandstetter
authors.forename: Barbara
authors.initials: B
authors.lastname: Chizzali
authors.forename: Marciana
authors.initials: M
authors.lastname: Duma
authors.forename: Stephanie
authors.initials: S
authors.lastname: Breuninger
authors.forename: Kathrin
authors.initials: K
authors.lastname: Hube
authors.forename: Sophie
authors.initials: S
authors.lastname: Lehnerer
authors.forename: Valerie
authors.initials: V
authors.lastname: van Phi
authors.forename: Eva
authors.initials: E
authors.lastname: Sage
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Schmid
authors.forename: Michael
authors.initials: M
authors.lastname: Sedelmayr
authors.forename: Daniela
authors.initials: D
authors.lastname: Schilling
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sievert
authors.forename: Stefan
authors.initials: S
authors.lastname: Stangl
authors.affiliation: Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. gabriele.multhoff@lrz.tum.de.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Multhoff
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000473:pathology / Q000532:radiotherapy*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D018840:HSP70 Heat-Shock Proteins / Q000097:blood*; D006258:Head and Neck Neoplasms / Q000097:blood / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011879:Radiotherapy Dosage; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D018840:HSP70 Heat-Shock Proteins