Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.
Department of Gynecology and Obstetrics, University of Heidelberg, 69120, Heidelberg, Germany.
J Cancer Res Clin Oncol. 2019 Oct;145(10):2519-2527. doi: 10.1007/s00432-019-03017-8. Epub 2019 Sep 4.
Prostaglandin-mediated inflammatory reactions play a major role in different cancers. Recently, it has been observed that prostaglandin E2-receptor 3 (EP3) might be an independent prognostic factor for overall survival in cervical and endometrial cancer. The role of EP3 expression in ovarian cancer is currently unknown.
EP3 expression was analyzed by immunohistochemistry in 156 patient samples using the IR-scoring system. Expression levels were correlated with clinical and pathological parameters and with overall survival (OS) to assess for prognostic relevance. Data analysis was performed using Spearman's correlations, Kruskal-Wallis test and Kaplan-Meier estimates.
EP3 expression was significantly higher in clear-cell carcinoma (p < 0.001) compared to the other histological subtypes. No further correlations with clinical parameters could be found. EP3 expression correlated significantly with FSH-receptor expression (p < 0.001), galectin-1 expression in the tumor (p = 0.012) and with cytoplasmatic TA-MUC1 expression (p = 0.001). None of these parameters showed significant correlation with OS. In the TA-MUC1 negative subgroup, EP3 negative patients showed significantly longer OS (median OS: 102 months vs. 34 months in EP3 positive patients, p = 0.035), while EP3 did not appear to have prognostic relevance in the TA-MUC1-positive subgroup.
The potential prognostic relevance of EP3 expression for OS in TA-MUC1 negative patients might reflect an interplay between the COX and the MUC1 pathway, as it has been shown that MUC1 could induce COX2 expression. Our findings support the importance of the prostanoid signaling in TA-MUC1 negative ovarian cancer; however, future studies are necessary to characterize specific pathways and possible interactions.
前列腺素介导的炎症反应在不同癌症中起主要作用。最近,有人观察到前列腺素 E2 受体 3(EP3)可能是宫颈癌和子宫内膜癌总生存的独立预后因素。EP3 表达在卵巢癌中的作用目前尚不清楚。
采用免疫组织化学法,使用 IR 评分系统,对 156 例患者样本中的 EP3 表达进行分析。分析表达水平与临床和病理参数的相关性以及与总生存(OS)的相关性,以评估其预后相关性。采用 Spearman 相关性分析、Kruskal-Wallis 检验和 Kaplan-Meier 估计进行数据分析。
EP3 表达在透明细胞癌中明显高于其他组织学亚型(p<0.001)。未发现与临床参数的进一步相关性。EP3 表达与 FSH 受体表达(p<0.001)、肿瘤中半乳糖凝集素-1 表达(p=0.012)和细胞质 TA-MUC1 表达(p=0.001)显著相关。这些参数均与 OS 无显著相关性。在 TA-MUC1 阴性亚组中,EP3 阴性患者的 OS 明显延长(中位 OS:EP3 阳性患者 102 个月 vs. 34 个月,p=0.035),而在 TA-MUC1 阳性亚组中,EP3 似乎无预后相关性。
EP3 表达对 TA-MUC1 阴性患者 OS 的潜在预后意义可能反映了 COX 和 MUC1 途径之间的相互作用,因为已经表明 MUC1 可以诱导 COX2 表达。我们的研究结果支持了 TA-MUC1 阴性卵巢癌中前列腺素信号的重要性;然而,未来的研究有必要对特定途径和可能的相互作用进行研究。