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High Levels of Phosphatase and Tensin Homolog Expression Are Associated With Tumor Progression, Tumor Recurrence, and Systemic Metastases in pT1 Urothelial Carcinoma of the Bladder: A Tissue Microarray Study of 156 Patients Treated by Transurethral Resection.
MedLine Citation:
PMID:  23273076     Owner:  NLM     Status:  In-Data-Review    
OBJECTIVE: To evaluate immunohistochemical expression of phosphatase and tensin homolog (PTEN) and mammalian target of rapamycin (mTOR) pathway members in pT1 urothelial carcinomas treated by transurethral resection and to determine if immunohistochemistry can be used to predict prognosis.
METHODS: Formalin-fixed, paraffin-embedded tissue samples from 156 patients with pT1 urothelial carcinoma treated by transurethral resection were used to build 5 tissue microarrays. Tissue microarray sections were stained for PTEN, phosphorylated (phos)-AKT, phos-mTOR, phos-S6, eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), and phos-4EBP1. Patients were monitored after initial treatment (mean, 22.5; median, 16; range, 3-108 months) to detect tumor recurrence, tumor progression, or systemic metastases.
RESULTS: During follow-up, 101 patients (65%) showed tumor recurrence, 57 showed tumor progression (37%), and 18 showed systemic metastases (12%). Patients with ≥2 lesions at the initial workup had higher proportions and higher hazard ratios of tumor recurrence, tumor progression, and systemic metastases. Complete loss of PTEN expression was observed in 6 patients (4%), and >80% of the mTOR pathway members showed at least focal positivity. Proportions of tumors with higher levels of PTEN immunohistochemical expression were higher in patients with tumor recurrence (P = .001), tumor progression (P = .05), and systemic metastases (P = .001). Proportions of tumors with lower phos-S6 and low phos-4EBP1 levels were higher in patients with tumor recurrence (P ≤ .05). Proportions were similar for the remaining biomarkers.
CONCLUSION: Higher levels of PTEN immunohistochemical expression were associated with higher rates of tumor recurrence, tumor progression, and systemic metastases in patients with pT1 urothelial carcinomas treated by transurethral resection.
Alcides Chaux; Eva Compérat; Justine Varinot; Jessica Hicks; Kristen Lecksell; Jason Solus; George J Netto
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Urology     Volume:  81     ISSN:  1527-9995     ISO Abbreviation:  Urology     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0366151     Medline TA:  Urology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  116-22     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Elsevier Inc. All rights reserved.
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland; Norte University School of Medicine, Asunción, Paraguay.
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