Ano de Publicação: 2010
AUTORIA
Luciana Schultz1, Roula Albadine1, Jessica Hicks1, Sana Jadallah1, Angelo M DeMarzo1,2,3,
Ying-Bei Chen1, Matthew E Neilsen2, Mark L Gonzalgo2,3, David Sidransky1,2,3,4, Mark
Schoenberg2,3, and George J Netto1,2,3
1 Department of Pathology, Johns Hopkins University, Baltimore, MD
2 Department of Urology, Johns Hopkins University, Baltimore, MD
3 Department of Oncology, Johns Hopkins University, Baltimore, MD
4 Department of Head and Neck Surgery, Johns Hopkins University, Baltimore, MD
RESUMO
Background—Bladder urothelial carcinoma (UrCa) proclaims high rates of mortality and
morbidity. Identifying novel molecular prognostic factors and targets of therapy is crucial. mTOR
pathway plays a pivotal role in establishing cell shape, migration and proliferation.
Design—TMA were constructed from 132 cystectomies (1994-2002). IHC was performed for
Pten, c-Myc, p27, phosAkt, phosS6, and 4E-BP1. Markers were evaluated for pattern, percent and
intensity of staining.
Results—Mean length of F/U was 62.6 months (1-182). Disease progression, overall survival
(OS) and disease specific survival (DSS) rates were 42%, 60% and 68%, respectively.
Pten showed loss of expression in 35% of UrCa. All markers showed lower expression in invasive
UrCa compared to benign urothelium with the exception of 4E-BP1. Pten, p27, phosAkt, phosS6
and 4E-BP1 expression correlated with pathologic stage (pT; p<0.03). Pten, 4E-BP1, and phosAkt
expression correlated with divergent aggressive histology and invasion.
PhosS6 expression inversely predicted OS (p=0.01), DSS (p=0.001) and progression (p=0.05). c-
Myc expression inversely predicted progression (p=0.01).
In a multivariate analysis model that included: TNM stage grouping, divergent aggressive
histology, concomitant CIS, phosS6 and c-Myc expression; phosS6 was an independent predictor
of DSS (p=0.03; HR: -.19) while c-Myc was an independent predictor of progression (p=0.02;
HR:-.38). In a second model substituting organ confined disease and lymph node status for TNM
stage grouping, phosS6 and c-Myc remained independent predictors of DSS (p=0.03; HR: -.21)
and progression (p=0.03; HR:-.34), respectively.
Conclusions—We found an overall downregulation of mTOR pathway in UrCa. PhosS6
independently predicted DSS and c-Myc independently predicted progression.