Lilis Ioannis, Giopanou Ioanna, Papadaki Helen, Gyftopoulos Kostis
Department of Anatomy, Faculty of Medicine, University of Patras, Rio, Achaia, Greece.
Department of Anatomy, Faculty of Medicine, University of Patras, Rio, Achaia, Greece.
Urol Oncol. 2018 Jun;36(6):311.e27-311.e35. doi: 10.1016/j.urolonc.2018.02.007. Epub 2018 Mar 12.
Mammalian target of rapamycin (mTOR) is a central regulator of major cellular processes such as growth and proliferation. Deregulated mTOR signaling is implicated in a wide spectrum of human malignancies including prostate cancer. The aim of this study is to address the role of phosphorylated mTOR (p-mTOR) in prostate adenocarcinoma-induced lymphangiogenesis and lymph node metastasis as well as to investigate its relationship with chicken ovalbumin upstream promoter transcriptional factor 2 (COUP-TFII) and the vascular endothelial growth factors A/C (VEGF A/C).
We analyzed 92 paraffin embedded specimens from patients with prostate cancer who underwent radical prostatectomy with pelvic lymph node (LN) dissection. Twenty-four of these men were pathologically assessed to have regional LN metastasis (pN1 group) and 68 with negative lymph nodes (pN0 group). Lymph vessel density was measured using anti-D2-40 and anti-LYVE-1 antibodies. The expression of p-mTOR, COUP-TFII, and VEGF A/C was also evaluated by immunohistochemistry.
Specimens from pN1 group exhibited higher cytoplasmic p-mTOR expression compared to pN0 specimens. Mean vessel densities assessed by COUP-TFII and D2-40 were increased in pN1 tumors and positively associated with higher p-mTOR expression. Interestingly, increased expression of p-mTOR was positively associated with COUP-TFII expression in cancer cells and elevated immunoreactivity for both VEGF A and C, which in turn exhibited higher expression in pN1 group.
Our findings suggest that increased p-mTOR and COUP-TFII expression are implicated in human prostate adenocarcinoma-induced lymphangiogenesis and LN metastasis.
雷帕霉素哺乳动物靶点（mTOR）是细胞生长和增殖等主要细胞过程的核心调节因子。mTOR信号失调与包括前列腺癌在内的多种人类恶性肿瘤有关。本研究旨在探讨磷酸化mTOR（p-mTOR）在前列腺腺癌诱导的淋巴管生成和淋巴结转移中的作用，并研究其与鸡卵清蛋白上游启动子转录因子2（COUP-TFII）以及血管内皮生长因子A/C（VEGF A/C）的关系。
我们分析了92例接受前列腺癌根治术及盆腔淋巴结清扫术患者的石蜡包埋标本。其中24例男性经病理评估有区域淋巴结转移（pN1组），68例淋巴结阴性（pN0组）。使用抗D2-40和抗LYVE-1抗体测量淋巴管密度。还通过免疫组织化学评估p-mTOR、COUP-TFII和VEGF A/C的表达。
与pN0标本相比，pN1组标本的细胞质p-mTOR表达更高。pN1肿瘤中通过COUP-TFII和D2-40评估的平均血管密度增加，且与较高的p-mTOR表达呈正相关。有趣的是，p-mTOR表达增加与癌细胞中COUP-TFII表达呈正相关，并且VEGF A和C的免疫反应性升高，而VEGF A和C在pN1组中表达更高。
我们的研究结果表明，p-mTOR和COUP-TFII表达增加与人类前列腺腺癌诱导的淋巴管生成和淋巴结转移有关。
