Prognostic significance of p16 INK4a alteration for Ewing sarcoma: a meta-analysis.
BACKGROUND
Despite findings from individual studies regarding prognostic factors for Ewing sarcoma, no conclusive results have been produced, partly because of small sample sizes. The objective of the current study was to evaluate whether the presence of p16(INK4a) alteration is associated with a poorer prognosis in patients with Ewing sarcomas.


METHODS
A review was conducted of publications that assessed associations between p16(INK4a) status and 2-year survival among patients with Ewing sarcoma. The association between metastatic disease at initial diagnosis and 2-year survival was evaluated by synthesizing data in the form of risk ratios.


RESULTS
Of 11 studies that were identified in the initial search strategy, 6 studies, representing 188 patients, met the inclusion criteria and, consequently, were pooled for quantitative analyses. The estimated pooled risk ratio of p16(INK4a) aberration was 2.17 (95% confidence interval [95% CI], 1.55-3.03; P < .001), whereas the estimated pooled risk ratio of metastasis at diagnosis among the 164 eligible patients was 2.60 (95% CI, 1.71-3.97; P < .001). There was no statistically significant difference in the pooled estimated risk ratios of p16(INK4a) aberration for a poor prognosis between patients with and without metastasis at diagnosis (1.86 and 2.21, respectively; P > .59).


CONCLUSIONS
The presence of p16(INK4a) alteration was a statistically significant predictor of prognosis for patients with Ewing sarcoma. Along with other prognostic factors, such as metastasis, the p16(INK4a) alteration may be a potential candidate for improving the risk-stratifying strategy for patients with these tumors.
Department of Orthopedic Surgery, Nara Medical University, Nara, Japan. kahonoki@naramed-u.ac.jp
Kanya
K
Honoki
Elizabeth
E
Stojanovski
Mark
M
McEvoy
Hiromasa
H
Fujii
Toshifumi
T
Tsujiuchi
Akira
A
Kido
Yoshinori
Y
Takakura
John
J
Attia
D014408:Biomarkers, Tumor / Q000378:metabolism*; D001859:Bone Neoplasms / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D006801:Humans; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011379:Prognosis; D012107:Research Design; D012512:Sarcoma, Ewing / Q000378:metabolism*; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16