Department of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai, China.
J Cancer Res Clin Oncol. 2012 May;138(5):819-25. doi: 10.1007/s00432-012-1149-7. Epub 2012 Jan 25.
Osteosarcoma is a primary malignancy of bone. Although new therapies continue to emerge, osteosarcoma-related morbidity and mortality remain high. Various studies have evaluated the prognostic value of VEGF levels in osteosarcoma patients, but they have yielded conflicting results.
The 5-year survival of each study was aggregated following a methodological assessment, and a systematic review of eligible studies with meta-analysis and univariate analysis was performed to quantitatively review the correlation of VEGF overexpression with 5-year survival in patients with osteosarcoma.
A total of 387 patients in eleven papers were finally considered to be eligible for inclusion in our analysis. Aggregation of the 6 positive results in Kaplan-Meier curve showed a risk ratio of 2.84 (95% CI: 1.39-5.83, P = 0.004) associated with VEGF-positive conditions in comparison with VEGF-negative conditions, suggesting that there was significant association between VEGF positive and the 5-year mortality. But univariate analysis of eleven studies showed that there was a small inverse but not significant relationship between VEGF expression level and the 5-year survival of osteosarcoma patients, but stage III, neo-chemotherapy, the primary tumor location, osteoblastic histological subtype and the source of patients showed a significant impact on the 5-year survival of patients.
The prognostic significance of VEGF expression in all its isoforms is still unknown based on the limited data available, but we find VEGF165 may play an important role. Future studies should examine the relationship between VEGF isoform expression and patients' survival and the relationship between VEGF isoform expression and EMMPRIN expression, which could be helpful for predicting the prognosis of patients with osteosarcoma. Once the conclusion of whether the VEGF and its isoforms playing a role in osteosarcoma were reached, it would help guide clinical decision-making regarding therapy and outcomes. In addition, we recommend a >25% positive staining of the cells as a VEGF-positive cut-off value in immunohistochemistry, since we find a relatively strict detecting method is likely to yield significant result in the 5-year survival of patients.
骨肉瘤是一种原发性骨恶性肿瘤。尽管新的治疗方法不断涌现，但骨肉瘤的发病率和死亡率仍然很高。多项研究评估了血管内皮生长因子（VEGF）水平在骨肉瘤患者中的预后价值，但结果存在争议。
对每一项研究的 5 年生存率进行方法学评估，对符合条件的研究进行系统回顾和荟萃分析及单变量分析，定量评价 VEGF 过表达与骨肉瘤患者 5 年生存率的相关性。
共有 11 篇文献中的 387 例患者最终被认为符合纳入标准。对 Kaplan-Meier 曲线中 6 个阳性结果进行汇总，结果显示 VEGF 阳性组的风险比为 2.84（95%CI：1.39-5.83，P=0.004），表明 VEGF 阳性与 5 年死亡率之间存在显著关联。但对 11 项研究的单变量分析显示，VEGF 表达水平与骨肉瘤患者 5 年生存率之间存在较小的负相关，但无统计学意义，而 III 期、新辅助化疗、原发肿瘤位置、成骨组织学亚型和患者来源对患者 5 年生存率有显著影响。
根据现有有限的数据，VEGF 所有同工型的表达与预后的关系仍不明确，但我们发现 VEGF165 可能起重要作用。未来的研究应进一步检测 VEGF 同工型表达与患者生存之间的关系，以及 VEGF 同工型表达与 EMMPRIN 表达之间的关系，这可能有助于预测骨肉瘤患者的预后。一旦确定 VEGF 及其同工型是否在骨肉瘤中发挥作用，将有助于指导治疗和预后的临床决策。此外，我们建议免疫组织化学检测中以细胞阳性染色>25%作为 VEGF 阳性的截断值，因为我们发现较严格的检测方法可能会对患者的 5 年生存率产生显著影响。
