PMID- 24239474 OWN - NLM STAT- MEDLINE DCOM- 20140926 LR - 20211203 IS - 1873-2496 (Electronic) IS - 1078-1439 (Linking) VI - 32 IP - 1 DP - 2014 Jan TI - Expression of molecular markers associated with the mammalian target of rapamycin pathway in nonmetastatic renal cell carcinoma: Effect on prognostic outcomes following radical nephrectomy. PG - 49.e15-21 LID - S1078-1439(13)00305-0 [pii] LID - 10.1016/j.urolonc.2013.07.014 [doi] AB - OBJECTIVES: To evaluate the expression of multiple molecular markers involved in mammalian target of rapamycin (mTOR) signaling pathway in renal cell carcinoma (RCC) to determine the prognostic significance of these markers following radical nephrectomy. MATERIAL AND METHODS: The expression levels of 5 markers, including PTEN, phosphorylated (p)-Akt, p-mTOR, p-p70 ribosomal S6 kinase, and p-4E-binding protein 1 (4E-BP1), were measured in radical nephrectomy specimens from 137 patients with nonmetastatic RCC by immunohistochemical staining. RESULTS: During the follow-up period of this series (median, 63.5 mo), disease recurrence occurred in 59 of the 137 patients (43.0%), with a 5-year recurrence-free survival rate of 58.3%. On Univariate analysis, expression levels of p-mTOR and p-4E-BP1, in addition to the C-reactive protein level, pathological stage, and microvascular invasion, were identified as significant predictors for disease recurrence. Of these factors, the expression of p-4E-BP1, C-reactive protein level, and pathological T stage appeared to be independently related to recurrence-free survival on multivariate analysis. Moreover, significant differences were observed in recurrence-free survival according to the positive numbers of these 3 independent factors; that is, disease recurrence developed in 5 of 42 patients with negative results for any risk factor (11.9%), 23 of 50 patients with positive results for a single risk factor (46.0%), and 31 of 45 patients with positive results for 2 or 3 risk factors (68.8%). CONCLUSIONS: The combined evaluation of the expression levels of potential markers in the mTOR signaling pathway, particularly p-4E-BP1, in RCC specimens with conventional prognostic parameters would contribute to the accurate prediction of disease recurrence following radical nephrectomy for nonmetastatic RCC. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Nishikawa, Masatomo AU - Nishikawa M AD - Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan. FAU - Miyake, Hideaki AU - Miyake H AD - Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan. Electronic address: hideakimiyake@hotmail.com. FAU - Harada, Ken-ichi AU - Harada K AD - Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan. FAU - Fujisawa, Masato AU - Fujisawa M AD - Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan. LA - eng PT - Journal Article DEP - 20131113 PL - United States TA - Urol Oncol JT - Urologic oncology JID - 9805460 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Biomarkers, Tumor) RN - 0 (Cell Cycle Proteins) RN - 0 (EIF4EBP1 protein, human) RN - 0 (Phosphoproteins) RN - 9007-41-4 (C-Reactive Protein) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 3.1.3.67 (PTEN Phosphohydrolase) RN - EC 3.1.3.67 (PTEN protein, human) SB - IM MH - Adaptor Proteins, Signal Transducing/biosynthesis MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/*biosynthesis MH - C-Reactive Protein/biosynthesis MH - Carcinoma, Renal Cell/diagnosis/*metabolism/surgery MH - Cell Cycle Proteins MH - Female MH - Humans MH - Immunohistochemistry MH - Kaplan-Meier Estimate MH - Kidney Neoplasms/diagnosis/*metabolism/surgery MH - Male MH - Middle Aged MH - Multivariate Analysis MH - Neoplasm Recurrence, Local MH - Neoplasm Staging MH - Nephrectomy/methods MH - Outcome Assessment, Health Care MH - PTEN Phosphohydrolase/biosynthesis MH - Phosphoproteins/biosynthesis MH - Prognosis MH - Proto-Oncogene Proteins c-akt/biosynthesis MH - Ribosomal Protein S6 Kinases, 70-kDa/biosynthesis MH - *Signal Transduction MH - TOR Serine-Threonine Kinases/*biosynthesis OTO - NOTNLM OT - 4E-BP1 OT - Prognosis OT - Radical nephrectomy OT - Renal cell carcinoma OT - mTOR pathway EDAT- 2013/11/19 06:00 MHDA- 2014/09/27 06:00 CRDT- 2013/11/19 06:00 PHST- 2013/06/19 00:00 [received] PHST- 2013/07/24 00:00 [revised] PHST- 2013/07/24 00:00 [accepted] PHST- 2013/11/19 06:00 [entrez] PHST- 2013/11/19 06:00 [pubmed] PHST- 2014/09/27 06:00 [medline] AID - S1078-1439(13)00305-0 [pii] AID - 10.1016/j.urolonc.2013.07.014 [doi] PST - ppublish SO - Urol Oncol. 2014 Jan;32(1):49.e15-21. doi: 10.1016/j.urolonc.2013.07.014. Epub 2013 Nov 13.