Freier Kolja, Pungs Susanne, Sticht Carsten, Flechtenmacher Christa, Lichter Peter, Joos Stefan, Hofele Christof
Klinik für Mund-Kiefer-Gesichtschirurgie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 400, Heidelberg, Germany.
Int J Cancer. 2007 Feb 15;120(4):942-6. doi: 10.1002/ijc.22380.
Oral squamous cell carcinoma (OSCC) is a solid neoplasm exhibiting aggressive tumor phenotypes with unpredictable biological behavior. Recent studies suggested that high expression of the antiapoptotic protein survivin might be associated with adverse outcome in oral cancer patients. To investigate, whether increased copy numbers of the survivin-encoding gene BIRC5 results in elevated survivin levels and whether BIRC5 and survivin could serve as progression markers in the clinical course of OSCC, tumor tissue microarray analysis was performed applying fluorescence in situ hybridization and immunohistochemistry to 296 OSCC specimens. Gene copy number gain of BIRC5 was detected in 33.9% (150/227) of cases, which correlated significantly with high UICC stage and the presence of lymph node metastases (p = 0.003 and p = 0.001, respectively), but not with unfavorable patients' outcome (p > 0.05) in multivariate analysis. High survivin expression was found in 67.3% (169/251) of cases to predict increased 5- and 10-year overall survival of patients in a multivariate model including UICC stage and age as covariables (p = 0.035 and p = 0.026, respectively). Within a subgroup of patients, who received radiation therapy (n = 121), high survivin expression was found to be the only predictor of favorable 3-, 5- and 10-year overall survival in a multivariate cox regression analysis including UICC stage and age as covariables (p = 0.001, p = 0.004 and p = 0.006, respectively). In conclusion, high survivin expression might be useful to identify OSCC patients, who would benefit from radiotherapy.
口腔鳞状细胞癌(OSCC)是一种实体瘤,具有侵袭性肿瘤表型,其生物学行为难以预测。最近的研究表明,抗凋亡蛋白survivin的高表达可能与口腔癌患者的不良预后相关。为了研究编码survivin的基因BIRC5的拷贝数增加是否会导致survivin水平升高,以及BIRC5和survivin是否可作为OSCC临床病程中的进展标志物,我们应用荧光原位杂交和免疫组化技术对296例OSCC标本进行了肿瘤组织微阵列分析。在33.9%(150/227)的病例中检测到BIRC5基因拷贝数增加,这与高UICC分期和淋巴结转移显著相关(分别为p = 0.003和p = 0.001),但在多变量分析中与患者的不良预后无关(p > 0.05)。在67.3%(169/251)的病例中发现高survivin表达,在包括UICC分期和年龄作为协变量的多变量模型中,这预测了患者5年和10年总生存率的增加(分别为p = 0.035和p = 0.026)。在接受放射治疗的患者亚组(n = 121)中,在包括UICC分期和年龄作为协变量的多变量cox回归分析中,高survivin表达被发现是3年、5年和10年总生存率良好的唯一预测因素(分别为p = 0.001、p = 0.004和p = 0.006)。总之,高survivin表达可能有助于识别将从放疗中获益的OSCC患者。