title: Increased c-myc oncogene expression in Ewing's sarcoma: correlation with Ki67 proliferation index.
abstract: OBJECTIVE
  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
  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.
  
  
  CONCLUSIONS
  These results suggest a possible role of the c-myc oncogene and Ki67 antigen in the malignant progression of Ewing's sarcoma.
authors.affiliation: Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna, Italy.
authors.forename: M R
authors.initials: MR
authors.lastname: Sollazzo
authors.forename: M S
authors.initials: MS
authors.lastname: Benassi
authors.forename: G
authors.initials: G
authors.lastname: Magagnoli
authors.forename: G
authors.initials: G
authors.lastname: Gamberi
authors.forename: L
authors.initials: L
authors.lastname: Molendini
authors.forename: P
authors.initials: P
authors.lastname: Ragazzini
authors.forename: M
authors.initials: M
authors.lastname: Merli
authors.forename: C
authors.initials: C
authors.lastname: Ferrari
authors.forename: A
authors.initials: A
authors.lastname: Balladelli
authors.forename: P
authors.initials: P
authors.lastname: Picci
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003657:Decision Making; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D012512:Sarcoma, Ewing / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D016019:Survival Analysis; D015854:Up-Regulation
chemical_list: D019394:Ki-67 Antigen; D012333:RNA, Messenger