Droeser Raoul A, Mechera Robert, Däster Silvio, Weixler Benjamin, Kraljević Marko, Delko Tarik, Güth Uwe, Stadlmann Sylvia, Terracciano Luigi, Singer Gad
Department of Surgery, University Hospital Basel, Spitalstrasse 21, 4031, Basel, Switzerland.
Institute for Surgical Research and Hospital Management ICFS, Hebelstrasse 20, 4031, Basel, Switzerland.
BMC Cancer. 2016 Aug 17;16:639. doi: 10.1186/s12885-016-2673-7.
Cancer of the ovary is mostly discovered at a late stage and cannot be removed by surgery alone. Therefore surgery is usually followed by adjuvant chemotherapy. However, few reliable biomarkers exist to predict response to chemotherapy of ovarian cancer. Previously, we could demonstrate that IL-17 density is indicative for chemosensitivity. This study focuses on the predictive value of myeloperoxidase (MPO) concerning response to chemotherapy of ovarian cancer.
Biopsies of mostly high-grade primary serous ovarian carcinomas and their matched recurrences were stained with MPO after fixation in formalin and embedding in paraffin. For this staining the technique of tissue-microarray was used. Recurrence within 6 months of the completion of platinum-based chemotherapy was defined as chemoresistance as previously publised. Data for MPO could be analyzed in 92 biopsies.
MPO and IL-17 positive immune cells correlated significantly in biopsies of primary and recurrent carcinomas (r s = 0.41; p = 0.004 and r s = 0.40; p = 0.007, respectively). MPO expression alone did not predict response to chemotherapy, but in multivariate cox regression analysis including age, residual disease, number of chemotherapy cycles, FIGO classification and combined categorized MPO and IL-17 cell densities of primary cancer biopsies, the combination of both immune markers was an independent prognostic factor for recurrence-free survival (p = 0.013, HR = .23, 95CI = 0.07-0.73). There was no chemoresistant patient in the subgroup of MPO + IL-17+, neither in primary nor in recurrent cancer biopsies.
High MPO positive cell density enhances the indicative value of IL-17 for response to chemotherapy in ovarian carcinoma. Although, these results have to be validated in a larger cohort.
卵巢癌大多在晚期才被发现,无法仅通过手术切除。因此,手术后通常需要进行辅助化疗。然而,很少有可靠的生物标志物可用于预测卵巢癌对化疗的反应。此前,我们能够证明白细胞介素-17(IL-17)密度可指示化疗敏感性。本研究聚焦于髓过氧化物酶(MPO)对卵巢癌化疗反应的预测价值。
大多数高级别原发性浆液性卵巢癌活检组织及其配对的复发病灶在福尔马林固定、石蜡包埋后用MPO染色。对于此次染色,采用了组织微阵列技术。如先前发表的那样,以铂类化疗完成后6个月内复发定义为化疗耐药。92份活检组织的MPO数据可进行分析。
原发性和复发性癌活检组织中,MPO和IL-17阳性免疫细胞显著相关(分别为rs = 0.41;p = 0.004和rs = 0.40;p = 0.007)。单独的MPO表达不能预测化疗反应,但在多因素Cox回归分析中,纳入年龄、残留病灶、化疗周期数、国际妇产科联盟(FIGO)分期以及原发性癌活检组织中MPO和IL-17细胞密度的联合分类,这两种免疫标志物的联合是无复发生存的独立预后因素(p = 0.013,风险比[HR]=0.23,95%置信区间[CI]=0.07 - 0.73)。在MPO + IL-17+亚组中,无论是原发性还是复发性癌活检组织,均无化疗耐药患者。
高MPO阳性细胞密度增强了IL-17对卵巢癌化疗反应的指示价值。尽管如此,这些结果仍需在更大的队列中进行验证。