Clinicopathological significance of cell cycle regulation markers in a large series of genetically confirmed Ewing's sarcoma family of tumors.
More than 90% of all Ewing's Sarcoma Family of Tumors (ESFT) exhibit specific chromosomal rearrangements between the EWS gene on chromosome 22 and various members of the ETS gene family of transcription factors. The gene fusion type and other secondary genetic alterations, mainly involving cell cycle regulators, have been shown to be of prognostic relevance in ESFT. However, no conclusive results have been reported. We analyzed the clinicopathological significance of relevant cell cycle regulators in genetically confirmed ESFT. A total of 324 cases were analyzed for the immunohistochemical expression of p53, p21(Waf1/Cip1) , p27(Kip1) and Ki67 and the chromosomal alterations of the p53 and 9p21 locus by fluorescent in situ hybridization. We observed that expression of p53 (p = 0.025), p21(Waf1/Cip1) (p = 0.015) and p27(Kip1) (p = 0.013) was higher in disseminated than in localized disease. Furthermore, a cohort of 217 patients with localized disease was considered for studying the prognosis involvement of these factors on patient follow-up. The median follow-up was 39 months (range: 0.17-452) with an overall survival (OS) of 55%. Ki67 was expressed in 34% of cases and constituted an independent prognostic factor for progression free survival and OS independently of the type of treatment [hazard ratio of 2.0 (95% CI: 1.3-3.1; p = 0.003) and 1.9 (95% IC: 1.3-2.9; p = 0.007) for progression free survival and OS, respectively, being especially relevant in the group of patients which incorporated radiotherapy in their regimen schedules. In conclusion, this study demonstrates that Ki67 expression constitutes a valuable indicator of poor prognosis in localized ESFT.
López-Guerrero
José Antonio
JA
Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain. antonio.llombart@uv.es
Machado
Isidro
I
Scotlandi
Katia
K
Noguera
Rosa
R
Pellín
Antonio
A
Navarro
Samuel
S
Serra
Massimo
M
Calabuig-Fariñas
Silvia
S
Picci
Piero
P
Llombart-Bosch
Antonio
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002453:Cell Cycle; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22; D015331:Cohort Studies; D005260:Female; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D008875:Middle Aged; D034802:RNA-Binding Protein EWS / Q000235:genetics; D012512:Sarcoma, Ewing / Q000235:genetics / Q000473:pathology*; D055815:Young Adult
D014408:Biomarkers, Tumor; D034802:RNA-Binding Protein EWS