Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.
Department of Pathology, LMU Munich, Thalkirchnerstrasse 36, 80337, Munich, Germany.
J Cancer Res Clin Oncol. 2019 Feb;145(2):313-319. doi: 10.1007/s00432-018-2785-3. Epub 2018 Nov 7.
Prostaglandin-mediated inflammatory reactions play a major role in different cancers. Prostaglandin E2-receptor 3 (EP3) expression correlates with FIGO stages in cervical cancer and has been shown to be an independent prognostic factor for overall survival. EP3 expression levels in cervical intraepithelial neoplasia (CIN) as the precursor lesion of cervical cancer are currently unknown.
EP3 expression was analyzed by immunohistochemistry in 124 patient samples (CIN 1-3 and healthy controls) using the IR-scoring system. Expression levels were correlated with clinical outcome to assess for prognostic relevance in patients with CIN 2. Data analysis was performed using Kruskal-Wallis and Mann-Whitney U test.
EP3 expression levels significantly correlated with different grades of cervical dysplasia. Median EP3-IRS in healthy cervical tissue was 12 (n = 13) compared to 9 in CIN 1 (n = 38; p = 0.031 vs. healthy control), 6 in CIN 2 (n = 45; p < 0.001 vs. CIN 1) and 4 in CIN 3 (n = 28, p = 0.008 vs. CIN 2). The percentage of EP3 expressing cells in CIN 2 lesions was significantly lower in progressive than in regressive cases (mean percentage of EP3 positive cells in progress: 3.8%, n = 18; in regress: 9.3%, n = 20; p = 0.040).
EP3 expression significantly decreases with higher grades of cervical intraepithelial neoplasia-which is in line with published IR scores in cervical cancer patients-and seems to be a prognostic marker for regression or progression of CIN 2 lesions. Our findings support the importance of the prostanoid pathway in cervical cancer and could help to identify targets for future therapies.
前列腺素介导的炎症反应在不同癌症中起主要作用。前列腺素 E2 受体 3（EP3）的表达与宫颈癌的 FIGO 分期相关，并且已被证明是总生存的独立预后因素。宫颈癌前病变宫颈上皮内瘤变（CIN）中 EP3 的表达水平目前尚不清楚。
使用 IR 评分系统，通过免疫组织化学分析 124 例患者样本（CIN1-3 和健康对照）中的 EP3 表达。将表达水平与临床结果相关联，以评估 CIN2 患者的预后相关性。使用 Kruskal-Wallis 和 Mann-Whitney U 检验进行数据分析。
EP3 表达水平与宫颈发育不良的不同程度显著相关。健康宫颈组织中 EP3-IRS 的中位数为 12（n=13），而 CIN1 为 9（n=38；p=0.031 与健康对照组相比），CIN2 为 6（n=45；p<0.001 与 CIN1 相比），CIN3 为 4（n=28，p=0.008 与 CIN2 相比）。CIN2 病变中 EP3 表达细胞的百分比在进展性病例中明显低于退行性病例（进展病例中 EP3 阳性细胞的平均百分比为 3.8%，n=18；退行病例为 9.3%，n=20；p=0.040）。
EP3 表达随着宫颈上皮内瘤变程度的增加而显著降低-这与宫颈癌患者的发表的 IR 评分一致-并且似乎是 CIN2 病变消退或进展的预后标志物。我们的研究结果支持前列腺素途径在宫颈癌中的重要性，并有助于确定未来治疗的靶点。
