PMID- 29544697 OWN - NLM STAT- MEDLINE DCOM- 20181106 LR - 20211204 IS - 1873-2496 (Electronic) IS - 1078-1439 (Linking) VI - 36 IP - 6 DP - 2018 Jun TI - The expression of p-mTOR and COUP-TFII correlates with increased lymphangiogenesis and lymph node metastasis in prostate adenocarcinoma. PG - 311.e27-311.e35 LID - S1078-1439(18)30047-4 [pii] LID - 10.1016/j.urolonc.2018.02.007 [doi] AB - BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: Our findings suggest that increased p-mTOR and COUP-TFII expression are implicated in human prostate adenocarcinoma-induced lymphangiogenesis and LN metastasis. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Lilis, Ioannis AU - Lilis I AD - Department of Anatomy, Faculty of Medicine, University of Patras, Rio, Achaia, Greece. Electronic address: ioannislilis@upatras.gr. FAU - Giopanou, Ioanna AU - Giopanou I AD - Department of Anatomy, Faculty of Medicine, University of Patras, Rio, Achaia, Greece. Electronic address: giopanou@upatras.gr. FAU - Papadaki, Helen AU - Papadaki H AD - Department of Anatomy, Faculty of Medicine, University of Patras, Rio, Achaia, Greece. FAU - Gyftopoulos, Kostis AU - Gyftopoulos K AD - Department of Anatomy, Faculty of Medicine, University of Patras, Rio, Achaia, Greece. LA - eng PT - Journal Article DEP - 20180312 PL - United States TA - Urol Oncol JT - Urologic oncology JID - 9805460 RN - 0 (Biomarkers, Tumor) RN - 0 (COUP Transcription Factor II) RN - 0 (VEGFA protein, human) RN - 0 (VEGFC protein, human) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (Vascular Endothelial Growth Factor C) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Adenocarcinoma/metabolism/*secondary/surgery MH - Aged MH - Biomarkers, Tumor/*metabolism MH - COUP Transcription Factor II/*metabolism MH - Follow-Up Studies MH - Humans MH - *Lymphangiogenesis MH - Lymphatic Metastasis MH - Male MH - Middle Aged MH - Neoplasm Invasiveness MH - Phosphorylation MH - Prognosis MH - Prostatectomy MH - Prostatic Neoplasms/metabolism/*pathology/surgery MH - Signal Transduction MH - TOR Serine-Threonine Kinases/*metabolism MH - Vascular Endothelial Growth Factor A/metabolism MH - Vascular Endothelial Growth Factor C/metabolism OTO - NOTNLM OT - Adenocarcinoma OT - Metastasis OT - NR2F2 OT - Prostate OT - mTOR EDAT- 2018/03/17 06:00 MHDA- 2018/11/07 06:00 CRDT- 2018/03/17 06:00 PHST- 2017/06/22 00:00 [received] PHST- 2017/11/23 00:00 [revised] PHST- 2018/02/14 00:00 [accepted] PHST- 2018/03/17 06:00 [pubmed] PHST- 2018/11/07 06:00 [medline] PHST- 2018/03/17 06:00 [entrez] AID - S1078-1439(18)30047-4 [pii] AID - 10.1016/j.urolonc.2018.02.007 [doi] PST - ppublish SO - Urol Oncol. 2018 Jun;36(6):311.e27-311.e35. doi: 10.1016/j.urolonc.2018.02.007. Epub 2018 Mar 12.