Department of Obstetrics and Gynecology, University Hospital, LMU Munich, 80337, Munich, Germany.
Institute of Pathology, Faculty of Medicine, LMU Munich, 80337, Munich, Germany.
J Cancer Res Clin Oncol. 2020 Jul;146(7):1847-1855. doi: 10.1007/s00432-020-03178-x. Epub 2020 Mar 10.
Ligand-dependent corepressor (LCoR) and receptor-interacting protein 140 (RIP140/NRIP1) play an important role in the regulation of multiple oncogenic signaling pathways and the development of cancer. LCoR and RIP140 form a nuclear complex in breast cancer cells and are of prognostic value in further prostate and cervical cancer. The purpose of this study was to analyze the regulation of these proteins in the development of cervical intraepithelial neoplasia (CIN I-III).
Immunohistochemical analysis was obtained to quantify RIP140 and LCoR expression in formalin-fixed paraffin embedded tissue sections of cervical intraepithelial neoplasia samples. Tissue (n = 94) was collected from patients treated in the Department of Gynecology and Obstetrics, Ludwig-Maximilians-University of Munich, Germany, between 2002 and 2014. Correlations of expression levels with clinical outcome were carried out to assess for prognostic relevance in patients with CIN2 progression. Kruskal-Wallis test and Mann-Whitney U test were used for data analysis.
Nuclear LCoR overexpression correlates significantly with CIN II progression. Nuclear RIP140 expression significantly increases and nuclear LCoR expression decreases with higher grading of cervical intraepithelial neoplasia. Cytoplasmic RIP140 expression is significantly higher in CIN III than in CIN I or CIN II.
A decrease of nuclear LCoR expression in line with an increase of dedifferentiation of CIN can be observed. Nuclear LCoR overexpression correlates with CIN II progression indicating a prognostic value of LCoR in cervical intraepithelial neoplasia. Nuclear and cytoplasmic RIP140 expression increases significantly with higher grading of cervical intraepithelial neoplasia underlining its potential role in the development of pre-cancerous lesions. These findings support the relevance of LCoR and RIP140 in the tumorigenesis indicating a possible role of LCoR and RIP140 as targets for novel therapeutic approaches in cervical intraepithelial neoplasia and cervical cancer.
配体依赖性核受体辅助抑制因子（LCoR）和受体相互作用蛋白 140（RIP140/NRIP1）在调节多种致癌信号通路和癌症发展中发挥重要作用。LCoR 和 RIP140 在乳腺癌细胞中形成核复合物，并且在进一步的前列腺癌和宫颈癌中具有预后价值。本研究的目的是分析这些蛋白在宫颈上皮内瘤变（CIN I-III）发展中的调控作用。
通过免疫组织化学分析，对来自德国慕尼黑路德维希-马克西米利安大学妇产科接受治疗的患者的宫颈上皮内瘤变样本的福尔马林固定石蜡包埋组织切片中的 RIP140 和 LCoR 表达进行定量。组织（n=94）收集于 2002 年至 2014 年之间。对表达水平与临床结果的相关性进行了分析，以评估 CIN2 进展患者的预后相关性。采用 Kruskal-Wallis 检验和 Mann-Whitney U 检验进行数据分析。
核 LCoR 过表达与 CIN II 进展显著相关。随着宫颈上皮内瘤变分级的升高，核 RIP140 表达显著增加，核 LCoR 表达减少。CIN III 中的细胞质 RIP140 表达明显高于 CIN I 或 CIN II。
在 CIN 去分化的过程中，可以观察到核 LCoR 表达的减少。核 LCoR 过表达与 CIN II 进展相关，表明 LCoR 在宫颈上皮内瘤变中的预后价值。随着宫颈上皮内瘤变分级的升高，核和细胞质 RIP140 表达显著增加，强调了其在癌前病变发展中的潜在作用。这些发现支持了 LCoR 和 RIP140 在肿瘤发生中的相关性，表明 LCoR 和 RIP140 可能作为宫颈上皮内瘤变和宫颈癌新治疗方法的靶点。
