title: Molecular prognosticators of complex karyotype soft tissue sarcoma outcome: a tissue microarray-based study.
abstract: BACKGROUND
  Molecular markers are currently being utilized as sensitive prognosticators of cancer patient outcome. We sought to identify prognostic biomarkers for complex karyotype soft tissue sarcoma (STS).
  
  
  METHODS
  A large (n = 205) clinically annotated tissue microarray (TMA) was constructed and immunostained for several tumor-related markers. Staining was scored via an automated Ariol image analysis system; data were statistically analyzed to evaluate the correlation of clinicopathological and molecular variables with overall survival (OS) and local recurrence.
  
  
  RESULTS
  Multivariable analysis identified older age [hazard ratio (HR) 1.62, P < 0.0001], nonextremity location (HR 2.95, P = 0.001), high tumor grade (HR 2.5, P = 0.02), and increased matrix metalloproteinase (MMP) 2 expression (HR 1.74, P = 0.04) as predictors for poor OS. Similarly, older age (HR 1.51, P = 0.008), nonextremity location (HR 4.09, P = 0.001), and increased MMP2 expression (HR 6.28, P = 0.006) were all found to correlate with shorter local recurrence-free interval. High nuclear p53 expression was associated with shorter STS local recurrence-free interval, with a trend toward significance.
  
  
  CONCLUSIONS
  Data presented indicate that a clinically annotated TMA can be utilized to identify STS-related prognostic markers. Specifically, MMP2 and nuclear p53 should be further evaluated for their potential inclusion in complex karyotype STS staging systems.
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: G
authors.initials: G
authors.lastname: Lahat
authors.forename: D
authors.initials: D
authors.lastname: Tuvin
authors.forename: C
authors.initials: C
authors.lastname: Wei
authors.forename: W L
authors.initials: WL
authors.lastname: Wang
authors.forename: R E
authors.initials: RE
authors.lastname: Pollock
authors.forename: D A
authors.initials: DA
authors.lastname: Anaya
authors.forename: B N
authors.initials: BN
authors.lastname: Bekele
authors.forename: L
authors.initials: L
authors.lastname: Corely
authors.forename: A J
authors.initials: AJ
authors.lastname: Lazar
authors.forename: P W
authors.initials: PW
authors.lastname: Pisters
authors.forename: D
authors.initials: D
authors.lastname: Lev
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007621:Karyotyping; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D011446:Prospective Studies; D012509:Sarcoma / Q000175:diagnosis / Q000378:metabolism*; D015996:Survival Rate; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2