title: Prognostic significance of multiple kallikreins in high-grade astrocytoma.
abstract: BACKGROUND
  Kallikreins have clinical value as prognostic markers in a subset of malignancies examined to date, including kallikrein 3 (prostate specific antigen) in prostate cancer. We previously demonstrated that kallikrein 6 is expressed at higher levels in grade IV compared to grade III astrocytoma and is associated with reduced survival of GBM patients.
  
  
  METHODS
  In this study we determined KLK1, KLK6, KLK7, KLK8, KLK9 and KLK10 protein expression in two independent tissue microarrays containing 60 grade IV and 8 grade III astrocytoma samples. Scores for staining intensity, percent of tumor stained and immunoreactivity scores (IR, product of intensity and percent) were determined and analyzed for correlation with patient survival.
  
  
  RESULTS
  Grade IV glioma was associated with higher levels of kallikrein-immunostaining compared to grade III specimens. Univariable Cox proportional hazards regression analysis demonstrated that elevated KLK6- or KLK7-IR was associated with poor patient prognosis. In addition, an increased percent of tumor immunoreactive for KLK6 or KLK9 was associated with decreased survival in grade IV patients. Kaplan-Meier survival analysis indicated that patients with KLK6-IR < 10, KLK6 percent tumor core stained < 3, or KLK7-IR < 9 had a significantly improved survival. Multivariable analysis indicated that the significance of these parameters was maintained even after adjusting for gender and performance score.
  
  
  CONCLUSIONS
  These data suggest that elevations in glioblastoma KLK6, KLK7 and KLK9 protein have utility as prognostic markers of patient survival.
authors.affiliation: Department of Physical Medicine and Rehabilitation, Mayo Medical and Graduate School, Mayo Clinic Rochester, 200 First Street SW, Rochester, MN, 55905, USA. drucker.kristen@mayo.edu.
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Drucker
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Medical and Graduate School, Mayo Clinic Rochester, 200 First Street SW, Rochester, MN, 55905, USA. giannini.caterina@mayo.edu.
authors.forename: Caterina
authors.initials: C
authors.lastname: Gianinni
authors.affiliation: Biomedical Statistics and Informatics, Mayo Medical and Graduate School, Mayo Clinic Rochester, 200 First Street SW, Rochester, MN, 55905, USA. decker.paul@mayo.edu.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Decker
authors.affiliation: Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave, Toronto, ON, M5T 3 L9, Canada. ediamandis@mtsinai.on.ca.
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Diamandis
authors.affiliation: Department of Physical Medicine and Rehabilitation, Mayo Medical and Graduate School, Mayo Clinic Rochester, 200 First Street SW, Rochester, MN, 55905, USA. scarisbrick.isobel@mayo.edu.|Department of Physiology and Biomedical Engineering, Mayo Medical and Graduate School, Mayo Clinic Rochester, 200 First Street SW, Rochester, MN, 55905, USA. scarisbrick.isobel@mayo.edu.
authors.forename: Isobel A
authors.initials: IA
authors.lastname: Scarisbrick
mesh_terms: D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007610:Kallikreins / Q000378:metabolism*; D011379:Prognosis; D016019:Survival Analysis; D046888:Tissue Array Analysis / Q000379:methods; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C103551:KLK6 protein, human; C082472:KLK7 protein, human; C410801:KLK9 protein, human; D007610:Kallikreins