Journal article
Evaluation of the prognostic significance of altered mammalian target of rapamycin pathway biomarkers in upper tract urothelial carcinoma
Urology (Ridgewood, N.J.), Vol.84(5), pp.1134-1140
11/2014
DOI: 10.1016/j.urology.2014.07.050
PMID: 25443916
Abstract
To evaluate the prognostic value of altered mammalian target of rapamycin (mTOR) pathway biomarkers in upper tract urothelial carcinoma (UTUC). We performed a multi-institutional review of clinical and pathologic information on patients receiving extirpative surgery for UTUC from 1990 to 2008. Immunohistochemistry for phosphorylated-S6, mTOR, phosphorylated-mTOR, PI3K, phosphorylated-4EBP1, phosphorylated-AKT, PTEN, HIF-1a, raptor, and cyclin D was performed on tissue microarrays from radical nephroureterectomy (RNU) specimens. Prognostic markers were identified and the significance of altered markers was assessed with the Kaplan-Meier analysis and the Cox regression analysis. Six hundred twenty patients were included. Over a median follow-up of 27.3 months, 24.6% of patients recurred and 21.8% died of UTUC. On multivariate analysis, PI3K (odds ratio, 1.28; P = .001) and cyclin D (odds ratio, 3.45; P = .05) were significant predictors of clinical outcomes. Cumulative marker score was defined as low risk (no altered markers or 1 altered marker) or high risk (cyclin D and PI3K altered). Patients with high-risk marker score had a significantly higher proportion of high-grade disease (91% vs 71%; P <.001), non-organ-confined disease (61% vs 33%; P <.001), and lymphovascular invasion (35% vs 20%; P = .001). The Kaplan-Meier analysis demonstrated a significant difference in cancer-specific mortality (CSM) based on the risk groups. On Cox regression multivariate analysis for CSM incorporating non-organ-confined disease, grade, lymphovascular invasion, tumor architecture, and marker score, high-risk biomarker score was an independent predictor of CSM (hazard ratio, 1.5; 95% confidence interval, 1.04-2.3; P = .03). Alterations in mTOR pathway correlate with established adverse pathologic features and independently predict inferior oncologic outcomes. Incorporation of mTOR-based marker profiles may allow for enhanced patient counseling, risk stratification, and individualized treatment regimens.
Details
- Title: Subtitle
- Evaluation of the prognostic significance of altered mammalian target of rapamycin pathway biomarkers in upper tract urothelial carcinoma
- Creators
- Aditya Bagrodia - Department of Urology, University of Texas Southwestern Medical Center, Dallas, TXLaura-Maria Krabbe - Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX; Department of Urology, University of Muenster Medical Center, Muenster, GermanyBishoy A Gayed - Department of Urology, University of Texas Southwestern Medical Center, Dallas, TXPayal Kapur - Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TXIra Bernstein - Division of Biostatistics, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TXXian-Jin Xie - Division of Biostatistics, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TXChristopher G Wood - Department of Urology, MD Anderson Cancer Center, Houston, TXJose A Karam - Department of Urology, MD Anderson Cancer Center, Houston, TXAlon Z Weizer - Department of Urology, University of Michigan Cancer Center, Ann Arbor, MIJay D Raman - Department of Urology, Penn State Hershey Medical Center, Hershey, PAMesut Remzi - Department of Urology, Medical University of Vienna, Vienna, AustriaNathalie Rioux-Leclerq - Department of Pathology, Centre Hospitalier Universitaire de Rennes, Rennes, FranceAndrea Haitel - Department of Pathology, Medical University Vienna, Vienna, AustriaMarco Roscigno - Department of Urology, Ospedali Riuniti of Bergamo, Bergamo, ItalyChristian Bolenz - Department of Urology, Mannheim Medical Center, University of Heidelberg, Mannheim, GermanyKarim Bensalah - Department of Urology, Centre Hospitalier Universitaire de Rennes, Rennes, FranceArthur I Sagalowsky - Department of Urology, University of Texas Southwestern Medical Center, Dallas, TXShahrokh F Shariat - Department of Urology, Medical University of Vienna, Vienna, AustriaYair Lotan - Department of Urology, University of Texas Southwestern Medical Center, Dallas, TXVitaly Margulis - Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX. Electronic address: Vitaly.margulis@utsouthwestern.edu
- Resource Type
- Journal article
- Publication Details
- Urology (Ridgewood, N.J.), Vol.84(5), pp.1134-1140
- Publisher
- United States
- DOI
- 10.1016/j.urology.2014.07.050
- PMID
- 25443916
- ISSN
- 0090-4295
- eISSN
- 1527-9995
- Language
- English
- Date published
- 11/2014
- Academic Unit
- Preventive and Community Dentistry; Biostatistics; Dental Research
- Record Identifier
- 9983917767402771
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