Mustea Alexander, Könsgen Dominique, Braicu Elena Ioana, Pirvulescu Cristina, Sun Pengming, Sofroni Dumitru, Lichtenegger Werner, Sehouli Jalid
Charité, Department of Obstetrics and Gynecology, Medical University Berlin, D - 13353 Berlin, Germany.
Anticancer Res. 2006 Mar-Apr;26(2C):1715-8.
Cytokines are involved in the pathogenesis of different gynecological malignancies. Additionally, they stimulate the spread of cancer cells. Interleukin 10 (IL-10) was described as a pro-inflammatory factor and seems to be implicated in the immune deficiency of patients with cancer. The aim of this study was to determine whether the level of IL-10 in the serum and ascites was associated with the prognosis of advanced ovarian cancer (OC).
In a prospective study from 2001 to 2003, the concentration of IL-10 in the serum and ascites of 117 consecutive patients with advanced OC and 30 women with benign disease who underwent surgery as a control group (CG), was analyzed by the enzyme-linked immunosorbent assay. For statistical analyses, the Chi-square test by Pearson, Fisher's exact test and the Mann-Whitney test were employed.
The concentrations of IL-10 were a median of 9.87 pg/ml (range 7.8 to 500 pg/ml) in the serum and a median of 43.70 pg/ml (range 7.8 to 389.4 pg/ml) in the ascites of the OC patients. The IL-10 level in the sera of the CG was a median of 7.80 pg/ml (range 7.8 to 62.8 pg/ml) and 18.34 pg/ml (range 7.8 to 88.72 pg/ml) in the peritoneal fluid. A significant association was observed between the IL-10 serum levels (p = 0.003) and levels in the peritoneal fluid (p = 0.03) in both OC and the CG. IL-10 was significantly more expressed in the ascites of patients with OC than in their sera (p = 0.003). The concentration of IL-10 correlated significantly with proven conventional prognostic factors such as recurrence status (p = 0.005), volume of (ascites, p < 0.001, serum, p = 0.03), histological grading (p = 0.053) and histological type (ascites p = 0.005/ serum p = 0.09). There was no significant correlation between the levels of lL-10 in the ascites and/or serum and FIGO stage, residual tumor mass or age. The cut-off value of 8.0 pg/ml for IL-10 serum levels had a positive predictive value of 84% (95% CI: 76-91) and a negative predictive value of 29% (95% CI: 16-41), with a specificity and sensibility of 47% (95% CI: 29-65) and 70% (95% CI: 62-78), respectively.
Due to the fact that the levels of IL-10 were significantly higher in the ascites and serum of OC patients than in those of the CG, IL-10 may play an important immunosuppressive role in the pathogenesis of OC. The association between high IL-10 levels in ascites and serum and the histological type of the tumor, as well as between the levels in the peritoneal cavity and grading, suggest that IL-10 could be a prognostic factor in OC.
细胞因子参与不同妇科恶性肿瘤的发病机制。此外,它们还会刺激癌细胞的扩散。白细胞介素10(IL-10)被描述为一种促炎因子,似乎与癌症患者的免疫缺陷有关。本研究的目的是确定血清和腹水中IL-10水平是否与晚期卵巢癌(OC)的预后相关。
在2001年至2003年的一项前瞻性研究中,采用酶联免疫吸附测定法分析了117例连续的晚期OC患者血清和腹水中IL-10的浓度,并将30例接受手术的良性疾病女性作为对照组(CG)。统计分析采用Pearson卡方检验、Fisher精确检验和Mann-Whitney检验。
OC患者血清中IL-10浓度中位数为9.87 pg/ml(范围7.8至500 pg/ml),腹水中位数为43.70 pg/ml(范围7.8至389.4 pg/ml)。CG组血清中IL-10水平中位数为7.80 pg/ml(范围7.8至62.8 pg/ml),腹腔液中为18.34 pg/ml(范围7.8至88.72 pg/ml)。OC组和CG组的IL-10血清水平(p = 0.003)和腹腔液水平(p = 0.03)之间均观察到显著相关性。OC患者腹水中IL-10的表达明显高于血清(p = 0.003)。IL-10浓度与已证实的传统预后因素显著相关,如复发状态(p = 0.005)、腹水体积(p < 0.001,血清p = 0.03)、组织学分级(p = 0.053)和组织学类型(腹水p = 0.005/血清p = 0.09)。腹水中和/或血清中IL-10水平与国际妇产科联盟(FIGO)分期、残留肿瘤肿块或年龄之间无显著相关性。IL-10血清水平的截断值为8.0 pg/ml,阳性预测值为84%(95%置信区间:76 - 91),阴性预测值为29%(95%置信区间:16 - 41),特异性和敏感性分别为47%(95%置信区间:29 - 65)和70%(95%置信区间:62 - 78)。
由于OC患者腹水中和血清中IL-10水平明显高于CG组,IL-10可能在OC发病机制中起重要的免疫抑制作用。腹水中和血清中高IL-10水平与肿瘤组织学类型之间的关联,以及腹腔内水平与分级之间的关联,表明IL-10可能是OC的一个预后因素。