Cicchillitti Lucia, Corrado Giacomo, Carosi Mariantonia, Dabrowska Malgorzata Ewa, Loria Rossella, Falcioni Rita, Cutillo Giuseppe, Piaggio Giulia, Vizza Enrico
Department of Research, Advanced Diagnostics and Technological Innovation, Area of Translational Research, Regina Elena National Cancer Institute, Rome, Italy.
Department of Experimental Clinical Oncology, Gynecologic Oncology Unit, Regina Elena National Cancer Institute, Rome, Italy.
Oncotarget. 2017 Jan 31;8(5):7935-7945. doi: 10.18632/oncotarget.13854.
Although most cases of low grade (G1) endometrial cancer (EC) do not behave aggressively, in rare instances, can progress in a highly aggressive manner. In this study we analyzed formalin-fixed, paraffin-embedded (FFPE) EC tissues to find novel clinical and biological features to help diagnosis and treatment of G1 ECs s in order to better stratify patient risk of recurrence. A retrospective cohort of FFPE specimens from patients with EC (n=87) and benign tissue specimens (NE) from patients who underwent a hysterectomy to treat other benign disease (n = 13) were collected. Total RNA and proteins were extracted and analyzed, respectively, by quantitative PCR and western blotting. NF-YAs is expressed and lamin A is down-modulated in all high grade (G2 and G3) ECs. In G1 ECs, NF-YAs expression is heterogeneous being expressed only in a subset of these tumours. Interestingly, the G1 ECs that express NF-YAs display low levels of lamin A similar to those present in G2 and G3 ECs. Of note, this pattern of NF-YAs and lamin A expression correlates with tumor aggressiveness assessed by comparative analysis with estrogen receptor (ER) status and epithelial-mesenchymal transition (EMT) markers thus suggesting its potential role as biomarker of tumour aggressiveness in G1 EC. In all grade ECs, lamin A is strongly downmodulated, being its expression inversely correlated with tumor aggressiveness and its loss of expression. We identified NF-YAs and lamin A expression levels as novel potential biomarkers useful to identify G1 ECs patients with risk of recurrence.
虽然大多数低级别（G1）子宫内膜癌（EC）病例并不具有侵袭性，但在极少数情况下，可能会以高度侵袭性的方式进展。在本研究中，我们分析了福尔马林固定、石蜡包埋（FFPE）的EC组织，以寻找新的临床和生物学特征，以帮助诊断和治疗G1 EC，从而更好地分层患者的复发风险。收集了EC患者的FFPE标本的回顾性队列（n = 87）和接受子宫切除术治疗其他良性疾病的患者的良性组织标本（NE）（n = 13）。分别通过定量PCR和蛋白质印迹法提取并分析总RNA和蛋白质。NF-YAs在所有高级别（G2和G3）EC中表达，而核纤层蛋白A被下调。在G1 EC中，NF-YAs表达是异质性的，仅在这些肿瘤的一个子集中表达。有趣的是，表达NF-YAs的G1 EC显示出与G2和G3 EC中相似的低水平核纤层蛋白A。值得注意的是，NF-YAs和核纤层蛋白A的这种表达模式与通过与雌激素受体（ER）状态和上皮-间质转化（EMT）标志物的比较分析评估的肿瘤侵袭性相关，因此表明其在G1 EC中作为肿瘤侵袭性生物标志物的潜在作用。在所有级别的EC中，核纤层蛋白A都被强烈下调，其表达与肿瘤侵袭性呈负相关且表达缺失。我们将NF-YAs和核纤层蛋白A的表达水平确定为可用于识别有复发风险的G1 EC患者的新的潜在生物标志物。
