Relevance of the mammalian target of rapamycin pathway in the prognosis of patients with high-risk non-muscle invasive bladder cancer

Mona Fahmy, Jose Joao Mansure, Fadi Brimo, Faysal A. Yafi, Robert Segal, Abdulaziz Althunayan, Jessica Hicks, Alan Keith Meeker, George Netto, Wassim Kassouf

Research output: Contribution to journalArticle

Abstract

High-risk non-muscle invasive bladder cancer (NMIBC) is associated with higher rates of recurrence and progression. Molecular markers within aberrant signaling pathways in cancer need further evaluation of their role as prognostic indicators and potential future targets for prevention of recurrence. Our objective was to investigate the role of the mammalian target of rapamycin (mTOR) signaling pathway on the stage and outcome of patients with high-risk NMIBC. Tissue microarrays were built from archival bladder tumor specimens (n = 142). Various clinicopathologic variables were collected retrospectively from patients treated with transurethral resection. Immunohistochemical staining was performed for phosphatase and tensin homolog, phosphorylated Akt, phosphorylated mTOR, phosphorylated S6 (p-S6), eukaryotic translation initiation factor 4E-binding protein-1, and p27. Multivariate analysis using Cox regression models addressed recurrence-free survival (RFS), progression-free survival, and worsening-free survival. In multivariate analysis, p-S6 was an independent predictor of shorter RFS (hazard ratio, 3.55; 95% CI, 1.31-9.64). Expression of p27 was inversely correlated with RFS (hazard ratio, 0.27; 95% CI, 0.10-0.74). Low levels of phosphatase and tensin homolog expression were associated with worsening-free survival (P

Original languageEnglish (US)
Pages (from-to)1766-1772
Number of pages7
JournalHuman Pathology
Volume44
Issue number9
DOIs
StatePublished - Sep 2013

Fingerprint

Sirolimus
Urinary Bladder Neoplasms
Recurrence
S 6
Survival
Phosphoric Monoester Hydrolases
Multivariate Analysis
Eukaryotic Initiation Factor-4E
Eukaryotic Initiation Factors
Proportional Hazards Models
Disease-Free Survival
Carrier Proteins
Staining and Labeling
Neoplasms
Tensins

Keywords

  • High-risk non-muscle invasive bladder cancer
  • mTOR pathway
  • Prognosis
  • Tissue microarray

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Relevance of the mammalian target of rapamycin pathway in the prognosis of patients with high-risk non-muscle invasive bladder cancer. / Fahmy, Mona; Mansure, Jose Joao; Brimo, Fadi; Yafi, Faysal A.; Segal, Robert; Althunayan, Abdulaziz; Hicks, Jessica; Meeker, Alan Keith; Netto, George; Kassouf, Wassim.

In: Human Pathology, Vol. 44, No. 9, 09.2013, p. 1766-1772.

Research output: Contribution to journalArticle

Fahmy, M, Mansure, JJ, Brimo, F, Yafi, FA, Segal, R, Althunayan, A, Hicks, J, Meeker, AK, Netto, G & Kassouf, W 2013, 'Relevance of the mammalian target of rapamycin pathway in the prognosis of patients with high-risk non-muscle invasive bladder cancer', Human Pathology, vol. 44, no. 9, pp. 1766-1772. https://doi.org/10.1016/j.humpath.2012.11.026
Fahmy, Mona ; Mansure, Jose Joao ; Brimo, Fadi ; Yafi, Faysal A. ; Segal, Robert ; Althunayan, Abdulaziz ; Hicks, Jessica ; Meeker, Alan Keith ; Netto, George ; Kassouf, Wassim. / Relevance of the mammalian target of rapamycin pathway in the prognosis of patients with high-risk non-muscle invasive bladder cancer. In: Human Pathology. 2013 ; Vol. 44, No. 9. pp. 1766-1772.
@article{5aeab8ac3e484247806e21efe9c8901b,
title = "Relevance of the mammalian target of rapamycin pathway in the prognosis of patients with high-risk non-muscle invasive bladder cancer",
abstract = "High-risk non-muscle invasive bladder cancer (NMIBC) is associated with higher rates of recurrence and progression. Molecular markers within aberrant signaling pathways in cancer need further evaluation of their role as prognostic indicators and potential future targets for prevention of recurrence. Our objective was to investigate the role of the mammalian target of rapamycin (mTOR) signaling pathway on the stage and outcome of patients with high-risk NMIBC. Tissue microarrays were built from archival bladder tumor specimens (n = 142). Various clinicopathologic variables were collected retrospectively from patients treated with transurethral resection. Immunohistochemical staining was performed for phosphatase and tensin homolog, phosphorylated Akt, phosphorylated mTOR, phosphorylated S6 (p-S6), eukaryotic translation initiation factor 4E-binding protein-1, and p27. Multivariate analysis using Cox regression models addressed recurrence-free survival (RFS), progression-free survival, and worsening-free survival. In multivariate analysis, p-S6 was an independent predictor of shorter RFS (hazard ratio, 3.55; 95{\%} CI, 1.31-9.64). Expression of p27 was inversely correlated with RFS (hazard ratio, 0.27; 95{\%} CI, 0.10-0.74). Low levels of phosphatase and tensin homolog expression were associated with worsening-free survival (P",
keywords = "High-risk non-muscle invasive bladder cancer, mTOR pathway, Prognosis, Tissue microarray",
author = "Mona Fahmy and Mansure, {Jose Joao} and Fadi Brimo and Yafi, {Faysal A.} and Robert Segal and Abdulaziz Althunayan and Jessica Hicks and Meeker, {Alan Keith} and George Netto and Wassim Kassouf",
year = "2013",
month = "9",
doi = "10.1016/j.humpath.2012.11.026",
language = "English (US)",
volume = "44",
pages = "1766--1772",
journal = "Human Pathology",
issn = "0046-8177",
publisher = "W.B. Saunders Ltd",
number = "9",

}

TY - JOUR

T1 - Relevance of the mammalian target of rapamycin pathway in the prognosis of patients with high-risk non-muscle invasive bladder cancer

AU - Fahmy, Mona

AU - Mansure, Jose Joao

AU - Brimo, Fadi

AU - Yafi, Faysal A.

AU - Segal, Robert

AU - Althunayan, Abdulaziz

AU - Hicks, Jessica

AU - Meeker, Alan Keith

AU - Netto, George

AU - Kassouf, Wassim

PY - 2013/9

Y1 - 2013/9

N2 - High-risk non-muscle invasive bladder cancer (NMIBC) is associated with higher rates of recurrence and progression. Molecular markers within aberrant signaling pathways in cancer need further evaluation of their role as prognostic indicators and potential future targets for prevention of recurrence. Our objective was to investigate the role of the mammalian target of rapamycin (mTOR) signaling pathway on the stage and outcome of patients with high-risk NMIBC. Tissue microarrays were built from archival bladder tumor specimens (n = 142). Various clinicopathologic variables were collected retrospectively from patients treated with transurethral resection. Immunohistochemical staining was performed for phosphatase and tensin homolog, phosphorylated Akt, phosphorylated mTOR, phosphorylated S6 (p-S6), eukaryotic translation initiation factor 4E-binding protein-1, and p27. Multivariate analysis using Cox regression models addressed recurrence-free survival (RFS), progression-free survival, and worsening-free survival. In multivariate analysis, p-S6 was an independent predictor of shorter RFS (hazard ratio, 3.55; 95% CI, 1.31-9.64). Expression of p27 was inversely correlated with RFS (hazard ratio, 0.27; 95% CI, 0.10-0.74). Low levels of phosphatase and tensin homolog expression were associated with worsening-free survival (P

AB - High-risk non-muscle invasive bladder cancer (NMIBC) is associated with higher rates of recurrence and progression. Molecular markers within aberrant signaling pathways in cancer need further evaluation of their role as prognostic indicators and potential future targets for prevention of recurrence. Our objective was to investigate the role of the mammalian target of rapamycin (mTOR) signaling pathway on the stage and outcome of patients with high-risk NMIBC. Tissue microarrays were built from archival bladder tumor specimens (n = 142). Various clinicopathologic variables were collected retrospectively from patients treated with transurethral resection. Immunohistochemical staining was performed for phosphatase and tensin homolog, phosphorylated Akt, phosphorylated mTOR, phosphorylated S6 (p-S6), eukaryotic translation initiation factor 4E-binding protein-1, and p27. Multivariate analysis using Cox regression models addressed recurrence-free survival (RFS), progression-free survival, and worsening-free survival. In multivariate analysis, p-S6 was an independent predictor of shorter RFS (hazard ratio, 3.55; 95% CI, 1.31-9.64). Expression of p27 was inversely correlated with RFS (hazard ratio, 0.27; 95% CI, 0.10-0.74). Low levels of phosphatase and tensin homolog expression were associated with worsening-free survival (P

KW - High-risk non-muscle invasive bladder cancer

KW - mTOR pathway

KW - Prognosis

KW - Tissue microarray

UR - http://www.scopus.com/inward/record.url?scp=84883465705&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84883465705&partnerID=8YFLogxK

U2 - 10.1016/j.humpath.2012.11.026

DO - 10.1016/j.humpath.2012.11.026

M3 - Article

VL - 44

SP - 1766

EP - 1772

JO - Human Pathology

JF - Human Pathology

SN - 0046-8177

IS - 9

ER -