Prognostic significance of bcl-2, c-myc, survivin and tumor grade in synovial sarcoma

Turk Patoloji Derg. 2014;30(1):55-65. doi: 10.5146/tjpath.2013.01221.

Abstract

Objective: We aimed to determine the prognostic value of bcl-2, c-myc and survivin in synovial sarcoma cases and to evaluate the relationship between the conventional morphological findings with prognosis.

Material and method: In this study, we evaluated 81 synovial sarcoma cases referred to our tertiary tumor center during a period of 20 years. We applied bcl-2, c-myc and survivin immunohistochemically and investigated the relationship with prognosis for those 65 cases with follow-up. The relationship between the conventional morphological findings (mitosis, necrosis, grade) with prognosis was also investigated.

Results: Five-year disease free survival rate was 44% and ten-year progression free survival rate was 38%, reflecting the aggressive behavior of synovial sarcoma. Tumor grade (according to FNCLCC) was the most significant prognostic input in this study. We obtained a significant difference between grade II (40 cases) and grade III (24 cases) group regarding progression-free survival and overall survival (p < 0.001 and p < 0.001 respectively). Grade II was divided into two groups according to mitotic index and necrosis (grade IIa and IIb) and there was a significant difference between them regarding prognosis (p=0.013 for progression free survival, p=0.003 for overall survival). There was a significant relationship between bcl-2 negative plus focally weak positive cases (9 cases) and focally strong cases (21 cases) and diffuse strong cases (35 cases) (p=0.042 and p=0.016 respectively). There was a significant relation between c-myc negative cases (25 cases) and nuclear positive cases (17 cases) regarding overall survival (p=0.043) and between c-myc negative cases and cytoplasmic positive cases (23 cases) regarding progression free survival (p=0.05). The relation between survivin and prognosis was not significant.

Conclusion: Tumor grade was the most significant prognostic parameter in this study. The grade IIa group (with less than 10 mitoses in 10 HPF, without necrosis) had a better prognosis than both the grade IIb and III groups. The grade IIb group was closer to grade III regarding the prognosis. Bcl-2 and c-myc (nuclear and/or cytoplasmic) immunohistochemical positivity had prognostic value but this finding has to be confirmed by large series.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Cell Proliferation
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Inhibitor of Apoptosis Proteins / analysis*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Mitotic Index
  • Necrosis
  • Neoplasm Grading
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Proto-Oncogene Proteins c-bcl-2 / analysis*
  • Proto-Oncogene Proteins c-myc / analysis*
  • Sarcoma, Synovial / chemistry*
  • Sarcoma, Synovial / mortality
  • Sarcoma, Synovial / pathology
  • Sarcoma, Synovial / therapy
  • Soft Tissue Neoplasms / chemistry*
  • Soft Tissue Neoplasms / mortality
  • Soft Tissue Neoplasms / pathology
  • Soft Tissue Neoplasms / therapy
  • Survivin
  • Tertiary Care Centers
  • Time Factors
  • Young Adult

Substances

  • BIRC5 protein, human
  • Biomarkers, Tumor
  • Inhibitor of Apoptosis Proteins
  • MYC protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-myc
  • Survivin