Molecular prognosticators of complex karyotype soft tissue sarcoma outcome: a tissue microarray-based study

Ann Oncol. 2010 May;21(5):1112-20. doi: 10.1093/annonc/mdp459. Epub 2009 Oct 29.

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).

Materials and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Cell Nucleus / metabolism
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Karyotyping
  • Male
  • Matrix Metalloproteinase 2 / metabolism*
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Prognosis
  • Prospective Studies
  • Sarcoma / diagnosis
  • Sarcoma / metabolism*
  • Survival Rate
  • Tissue Array Analysis
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Biomarkers, Tumor
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • MMP2 protein, human
  • Matrix Metalloproteinase 2