Increased c-myc oncogene expression in Ewing's sarcoma: correlation with Ki67 proliferation index.
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.
Sollazzo
M R
MR
Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna, Italy.
Benassi
M S
MS
Magagnoli
G
G
Gamberi
G
G
Molendini
L
L
Ragazzini
P
P
Merli
M
M
Ferrari
C
C
Balladelli
A
A
Picci
P
P
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
D019394:Ki-67 Antigen; D012333:RNA, Messenger