Duncan Timothy J, Rolland Phil, Deen Suha, Scott Ian V, Liu David T Y, Spendlove Ian, Durrant Lindy G
Academic and Clinical Department of Oncology, University of Nottingham, Nottingham, UK.
Clin Cancer Res. 2007 Jul 15;13(14):4139-45. doi: 10.1158/1078-0432.CCR-06-2833.
There is evidence that IFN gamma plays an important role in ovarian cancer development. IFN gamma produces numerous antitumor effects and it may be evasion of these effects which allows tumor progression. We postulate that genetic instability in tumor cells may lead to modulation of expression of the IFN gamma receptor, thus leading to altered tumor biology and patient prognosis. This hypothesis would support the theory of immunoediting in ovarian cancer.
Using tissue microarray technology of 339 primary ovarian cancers, the expression of IFN gamma receptor was assessed immunohistochemically. Coupled to a comprehensive database of clinicopathologic variables, its effect on these factors was studied.
Tumors expressing high levels of IFN gamma receptor had significantly improved survival (P=0.017) compared with tumors expressing low levels of the receptor; this was also seen with complete receptor loss (P=0.014). Factors shown to predict prognosis independently of each other were the following: age, International Federation of Gynecologists and Obstetricians stage, and the absence of macroscopic disease after surgery. The level of IFN gamma receptor expression and complete receptor loss were independently predictive of prognosis on multivariate analysis. There was no correlation between receptor status and any of the standard clinicopathologic variables.
Loss of IFN gamma receptor independently predicts poor prognosis in ovarian cancer. Loss of receptor expression may be responsible for the limited success in the therapeutic use of IFN gamma in ovarian cancer trials and highlights a subgroup of high expressing IFN gamma receptor tumors which are more likely to be susceptible to such treatments.
有证据表明，干扰素γ在卵巢癌发展中起重要作用。干扰素γ具有多种抗肿瘤作用，肿瘤进展可能是由于逃避了这些作用。我们推测肿瘤细胞中的基因不稳定性可能导致干扰素γ受体表达的调节，从而导致肿瘤生物学特性改变和患者预后变化。这一假设将支持卵巢癌免疫编辑理论。
利用339例原发性卵巢癌的组织芯片技术，通过免疫组化评估干扰素γ受体的表达。结合临床病理变量综合数据库，研究其对这些因素的影响。
与低水平表达干扰素γ受体的肿瘤相比，高水平表达该受体的肿瘤患者生存率显著提高（P = 0.017）；完全缺失受体的情况也是如此（P = 0.014）。相互独立预测预后的因素如下：年龄、国际妇产科联盟分期以及术后无肉眼可见疾病。在多变量分析中，干扰素γ受体表达水平和完全缺失受体可独立预测预后。受体状态与任何标准临床病理变量之间均无相关性。
干扰素γ受体缺失独立预测卵巢癌预后不良。受体表达缺失可能是卵巢癌试验中干扰素γ治疗效果有限的原因，并凸显了一组高表达干扰素γ受体的肿瘤亚组，这类肿瘤更可能对这种治疗敏感。
