title: Mcl-1, vascular endothelial growth factor-R2, and 14-3-3sigma expression might predict primary response against radiotherapy and chemotherapy in patients with locally advanced squamous cell carcinomas of the head and neck.
abstract: OBJECTIVE
  This study was done to explore whether the expression of a selected set of proteins could predict primary response to radiotherapy or concomitant radiotherapy and chemotherapy in patients with advanced head and neck cancer.
  
  
  METHODS
  Forty-three pretreatment tumor biopsies were taken during diagnostic panendoscopy and examined for Mcl-1, vascular endothelial growth factor (VEGF)-R2, CD9, and 14-3-3sigma expression by immunohistochemistry. Forty-three patients underwent primary radiotherapy, of which, 29 patients received concomitant chemotherapy (low dose daily cisplatin, mitomycin C bolus). The primary end-point was locoregional tumor control 6 months after completion of radiotherapy. Mcl-1, VEGF-R2, CD9, and 14-3-3sigma expression were correlated with patients' primary response to radiotherapy and chemotherapy and with established clinicopathologic variables.
  
  
  RESULTS
  Thirty complete and 13 partial responses were observed in our patient group. High expression levels of Mcl-1 (P=0.021), VEGF-R2 (P=0.032), and 14-3-3sigma (P=0.013), but not of CD9, in tumor biopsies was correlated with complete response. Overexpression of at least two of the three aforementioned proteins in pretreatment biopsies predicted-with a likelihood of 80%-whether a patient would achieve complete response to radiotherapy and chemotherapy. However, if only one of these proteins is overexpressed, there is a likelihood of 84.6% that this patient would not completely respond to therapy.
  
  
  CONCLUSIONS
  Determining the expression levels of Mcl-1, VEGF-R2, and 14-3-3sigma may be helpful in predicting the early clinical response in head and neck tumor patients receiving primary radiotherapy and chemotherapy and may further allow a pretherapeutic selection of patients.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Division of Oncology and Medical Statistics, Center of Excellence for Clinical and Experimental Oncology, University of Vienna Medical School, Vienna, Austria.
authors.forename: Boban M
authors.initials: BM
authors.lastname: Erovic
authors.forename: Martina
authors.initials: M
authors.lastname: Pelzmann
authors.forename: Matthäus Ch
authors.initials: MCh
authors.lastname: Grasl
authors.forename: Johannes
authors.initials: J
authors.lastname: Pammer
authors.forename: Gabriela
authors.initials: G
authors.lastname: Kornek
authors.forename: Werner
authors.initials: W
authors.lastname: Brannath
authors.forename: Edgar
authors.initials: E
authors.lastname: Selzer
authors.forename: Dietmar
authors.initials: D
authors.lastname: Thurnher
mesh_terms: D048948:14-3-3 Proteins; D015703:Antigens, CD / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D005092:Exonucleases / Q000032:analysis / Q000378:metabolism*; D005095:Exoribonucleases; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism*; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000378:metabolism*; D060245:Tetraspanin 29; D016896:Treatment Outcome; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D015703:Antigens, CD; D014408:Biomarkers, Tumor; C554869:CD9 protein, human; D008562:Membrane Glycoproteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D060245:Tetraspanin 29; D040301:Vascular Endothelial Growth Factor Receptor-2; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human