Oncoproteins and proliferation markers in synovial sarcomas: a clinicopathologic study of 19 cases

J Cancer Res Clin Oncol. 2002 Nov;128(11):610-6. doi: 10.1007/s00432-002-0389-3. Epub 2002 Oct 29.

Abstract

Purpose: The objective of this study was to evaluate synovial sarcomas for the expression of oncogenic proteins (Her2/neu, EGFR, Bcl-2, p53) and proliferation markers (Ki-67, Topoisomerase 2alpha), as possible markers of prognostic significance.

Methods: From 17 patients with synovial sarcomas 19 tumors (15 primary, 2 recurrent, and 2 metastatic) were selected on the basis of characteristic histology, the expression of at least one epithelial marker, and/or the presence of t(X;18). Adequate follow-up was available in all cases.

Results: The tumors were tested immunohistochemically and were found to express multiple oncogenic proteins. Four of 19 synovial sarcomas (21%) demonstrated nuclear over-expression of p53 protein; 18 of 19 tumors (94%) stained positive for Bcl-2; and 13 of 19 tumors (68%) were immunoreactive with EGFR. Of particular interest was the frequent expression of Her2/neu, an oncogenic protein more commonly observed in epithelial neoplasms. Ten of 19 tumors (52%, 7 monophasic and 3 biphasic) showed positive cytoplasmic and membranous staining with Her2/neu (HercepTest, DAKO). The staining intensity ranged from 1+ to 2+. Cellular expression of Her2/neu was independent of EGFR positivity and showed no association with proliferative activity of the tumors. FISH analysis of eight positive cases showed no evidence of Her2/neu gene amplification. Among the non-metastatic tumors, we found a significant correlation between Ki-67 and Topoisomerase 2alpha. Spearman's correlation co-efficient was 0.86 with P=0.001 ( n=17).

Conclusions: In this relatively small series of cases, we found no definite correlation between the over-expression of Her2/neu and clinical outcome. The over-expression of p53 was significantly associated with clinical outcome (Fisher's exact test, P=0.02).

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm
  • Biomarkers, Tumor / metabolism*
  • DNA Topoisomerases, Type II / metabolism
  • DNA-Binding Proteins
  • ErbB Receptors / metabolism
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoenzyme Techniques
  • In Situ Hybridization, Fluorescence
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Sarcoma, Synovial / genetics
  • Sarcoma, Synovial / metabolism*
  • Sarcoma, Synovial / pathology
  • Soft Tissue Neoplasms / genetics
  • Soft Tissue Neoplasms / metabolism*
  • Soft Tissue Neoplasms / pathology
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Ki-67 Antigen
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • ErbB Receptors
  • Receptor, ErbB-2
  • DNA Topoisomerases, Type II