Increased c-myc oncogene expression in Ewing's sarcoma: correlation with Ki67 proliferation index

Tumori. 1999 May-Jun;85(3):167-73. doi: 10.1177/030089169908500304.

Abstract

Aims and background: Ewing's sarcoma is a highly malignant musculoskeletal tumor composed of small round cells. Although important results have been achieved with surgery associated with chemotherapy, recurrent disease is still a major problem. In order to define new prognostic factors useful for therapeutic decision-making, we conducted a study on 38 Ewing's sarcoma samples in which c-myc oncogene expression and Ki67 proliferation index were correlated with clinical outcome.

Methods and study design: Nineteen patients developed metastases during follow-up and 10 of these patients died. C-myc and Ki67 protein expression was evaluated by immunohistochemistry performed on 5 microm formalin-fixed and paraffin-embedded sections, while the c-myc mRNA transcript was localized using in situ hybridization.

Results: A statistically positive correlation was found between c-myc protein and Ki67 (P = 0.001) and c-myc mRNA and Ki67 expression (P = 0.047). The 38 patients were divided into two groups using as the cutoff 50% of Ki67-positive cells. The disease-free survival and overall survival estimates were 68% and 90%, respectively, in the group of patients with a percentage of Ki67-positive cells <50%, and 25% and 50%, respectively, in the group with a percentage of Ki67-positive cells > or = 50%. The difference between the survival curves was statistically significant (P <0.05 and P <0.01). Furthermore, relapsed patients had a high and uniform expression of c-myc protein and mRNA compared to disease-free patients.

Conclusion: These results suggest a possible role of the c-myc oncogene and Ki67 antigen in the malignant progression of Ewing's sarcoma.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Decision Making
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, myc* / genetics
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Ki-67 Antigen / biosynthesis*
  • Male
  • Middle Aged
  • Prognosis
  • RNA, Messenger / metabolism
  • Sarcoma, Ewing / genetics
  • Sarcoma, Ewing / immunology
  • Sarcoma, Ewing / metabolism*
  • Sarcoma, Ewing / therapy
  • Survival Analysis
  • Up-Regulation

Substances

  • Ki-67 Antigen
  • RNA, Messenger