Allotype imbalance or microsatellite mutation in low-grade soft tissue sarcomas of the extremities in adults

J Pathol. 2002 Sep;198(1):21-9. doi: 10.1002/path.1177.


The ability to repair DNA double-strand breaks is essential to maintain chromosomal stability. Virtually all soft tissue sarcomas contain chromosomal instabilities, including clonal aberrations and cytogenetic aberrations. However, the relevance of DNA-dependent protein kinase (DNA-PK) in the pathogenesis of soft tissue sarcoma has not been clarified. The main aim of this work is to compare the prognostic impact of genotypic imbalance in low-grade soft tissue sarcomas of the extremities, and to correlate this with the translational level of DNA-PK. This study investigated 28 adult low-grade malignant spindle cell tumours of the extremities, predominantly fibrosarcomas, for loss of heterozygosity (LOH) and microsatellite mutation on flanking regions of each DNA-PK subunit, with identical immunophenotypes. Twelve different polymorphic markers flanking the specific loci of three subunits comprise the genetic map of DNA-PK, at 22q13, 2q35, and 8q11. Translational activity was also analysed by western blot and conventional immunohistochemistry. The overall sarcoma 5-year survival rate was 61.7%. LOH was identified in the specific coding region of DNA-PK in 39.29% for the DNA-PK catalytic subunit (cs), 17.86% for Ku70, and only 7.14% for Ku80. A positive LOH for DNA-PKcs was shown to be a significant factor for poor survival (log rank test p = 0.0160). Immunoreactivity and immunoblot results correlated with the loss of DNA-PKcs allotype in soft tissue sarcoma (Fisher's exact test p = 0.0037). Ku70 and DNA-PKcs were almost identical in terms of immunoreactivity. In conclusion, whereas microsatellite mutation seems an uncommon event during the evolution of low-grade fibrosarcoma of the extremities in adults, the loss of DNA-PKcs defines a biologically more aggressive subset.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Blotting, Western
  • DNA, Neoplasm / genetics*
  • DNA-Activated Protein Kinase
  • DNA-Binding Proteins*
  • Female
  • Fibrosarcoma / genetics
  • Follow-Up Studies
  • Humans
  • Loss of Heterozygosity*
  • Male
  • Microsatellite Repeats / genetics
  • Middle Aged
  • Mutation
  • Nuclear Proteins
  • Prognosis
  • Protein Biosynthesis
  • Protein Serine-Threonine Kinases / genetics*
  • Sarcoma / genetics*
  • Soft Tissue Neoplasms / genetics*
  • Survival Rate


  • DNA, Neoplasm
  • DNA-Binding Proteins
  • Nuclear Proteins
  • DNA-Activated Protein Kinase
  • PRKDC protein, human
  • Protein Serine-Threonine Kinases