PML expression in soft tissue sarcoma: prognostic and predictive value in alkylating agents/antracycline-based first line therapy

J Cell Physiol. 2012 Apr;227(4):1657-62. doi: 10.1002/jcp.22889.

Abstract

Soft tissue sarcomas are aggressive tumors representing <1% of all adult neoplasms. Aim of our study was to evaluate promyelocytic leukemia gene expression value as prognostic factor and as a factor predicting response to alkylating agents/antracycline-based first line therapy. One hundred eleven patients affected by locally advanced and metastatic soft tissue sarcoma were selected. PML expression was evaluated by immunohistochemical analysis in pathological samples and in the corresponding normal tissue from each case. PML immunohistochemical results were correlated with prognosis and with radiological response to alkylating agents/antracycline-based first line therapy. PML expression was significantly reduced in synovial sarcomas (P < 0.0001), in myofibroblastic sarcomas (P < 0.0001), angiosarcomas (P < 0.0001), in leiomyosarcomas (P = 0.003), in mixoid liposarcomas (P < 0.0001), and in dedifferentiated liposarcomas (P < 0.0001). No significant difference was found for pleomorphic sarcoma [31.8 (95% CI: 16.7-41.0); P = 0.21]. and pleomorphic liposarcomas (P = 0.51). Loss of PML expression was found to be statistically correlated with TTP (P < 0.0001), median duration of response (P = 0.007), and OS (P = 0.02). No correlation was observed between PML expression and treatment efficacy. PML IHC expression is down-regulated in synovial sarcomas, myofibroblastic sarcomas, angiosarcomas, liposarcoma, and leiomyosarcomas and its expression correlated with prognosis.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anthracyclines / therapeutic use*
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Down-Regulation
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Nuclear Proteins / metabolism*
  • Predictive Value of Tests
  • Prognosis
  • Promyelocytic Leukemia Protein
  • Retrospective Studies
  • Sarcoma / drug therapy*
  • Sarcoma / metabolism*
  • Sarcoma / secondary
  • Soft Tissue Neoplasms / drug therapy*
  • Soft Tissue Neoplasms / metabolism*
  • Transcription Factors / metabolism*
  • Tumor Suppressor Proteins / metabolism*
  • Young Adult

Substances

  • Anthracyclines
  • Antineoplastic Agents, Alkylating
  • Nuclear Proteins
  • Promyelocytic Leukemia Protein
  • Transcription Factors
  • Tumor Suppressor Proteins
  • PML protein, human