Prognostic significance of p16^INK4a alteration for Ewing sarcoma

Abstract

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 p16INK4a alteration is associated with a poorer prognosis in patients with Ewing sarcomas. METHODS. A review was conducted of publications that assessed associations between p16INK4a 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 p16INK4a 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 p16INK4a 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 p16INK4a alteration was a statistically significant predictor of prognosis for patients with Ewing sarcoma. Along with other prognostic factors, such as metastasis, the p16INK4a alteration may be a potential candidate for improving the risk‐stratifying strategy for patients with these tumors. © 2007 American Cancer Society.

Array comparative genomic hybridization reveals frequent alterations of G1/S checkpoint genes in undifferentiated pleomorphic sarcoma of bone

“…No association between inactivation of CDKN2A and survival was seen in our UPSb patients. This differs from what was seen in other sarcomas, including osteosarcoma (Benassi et al, 2001;Maitra et al, 2001;Oh et al, 2006) and Ewing sarcoma (Wei et al, 2000;Lopez-Guerrero et al, 2001;Huang et al, 2005;Honoki et al, 2007), in which alterations or loss of expression of CDKN2A have been shown to associate with poor prognosis. The trends of survival seen in our analyses need to be confirmed with a larger series of patients to take also other factors potentially influencing outcome, such as treatment or size of tumor, into account.…”

Molecular pathogenesis and targeted therapeutics in Ewing sarcoma/primitive neuroectodermal tumours

“…Inducible expression of EWS-FLI-1 led to up-regulation of c-Myc and marked down-regulation of p57 KIP2 [88]. p16 INK4a status predicted 2-year survival amongst patients with Ewing sarcoma/PNET ( P < .001) [89]. Also cyclin-dependent kinase 2 (CDK2) was over-expressed in patients with poor outcomes in a microarray-based study [90].…”

Personalized therapy of sarcomas: Integration of biomarkers for improved diagnosis, prognosis, and therapy selection

“…Examples include survivin [ 18 , 19 ], ezrin [ 20 ], MDM2 [ 21 , 22 ], Bcl-2 [ 23 ], p16 INK4a [ 24 ], Glut-1 [ 25 ], EGFR [ 26 ], STAT3 [ 27 ], Fas [ 28 ], MYC [ 29 ], CD99 [ 30 ], and insulin-like growth factor 1 (IGF-1) receptor [ 31 , 32 ]. In some cases, targeted therapies against them remain in the preclinical phase, while others are now being evaluated in early-phase human clinical trials.…”