RGD Reference Report - Expression status and prognostic significance of mammalian target of rapamycin pathway members in urothelial carcinoma of urinary bladder after cystectomy. - Rat Genome Database

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Expression status and prognostic significance of mammalian target of rapamycin pathway members in urothelial carcinoma of urinary bladder after cystectomy.

Authors: Schultz, L  Albadine, R  Hicks, J  Jadallah, S  Demarzo, AM  Chen, YB  Nielsen, ME  Gonzalgo, ML  Sidransky, D  Schoenberg, M  Netto, GJ 
Citation: Schultz L, etal., Cancer. 2010 Dec 1;116(23):5517-26. doi: 10.1002/cncr.25502. Epub 2010 Oct 11.
RGD ID: 7207427
Pubmed: PMID:20939013   (View Abstract at PubMed)
PMCID: PMC3568488   (View Article at PubMed Central)
DOI: DOI:10.1002/cncr.25502   (Journal Full-text)

BACKGROUND: Bladder urothelial carcinoma has high rates of mortality and morbidity. Identifying novel molecular prognostic factors and targets of therapy is crucial. Mammalian target of rapamycin (mTOR) pathway plays a pivotal role in establishing cell shape, migration, and proliferation. METHODS: Tissue microarrays were constructed from 132 cystectomies (1994-2002). Immunohistochemistry was performed for Pten, c-myc, p27, phosphorylated (phos)Akt, phosS6, and 4E-BP1. Markers were evaluated for pattern, percentage, and intensity of staining. RESULTS: Mean length of follow-up was 62.6 months (range, 1-182 months). 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 bladder urothelial carcinoma. All markers showed lower expression in invasive bladder urothelial carcinoma compared with benign urothelium with the exception of 4E-BP1. Pten, p27, phosAkt, phosS6, and 4E-BP1 expression correlated with pathologic stage (pathological stage; P<.03). Pten, 4E-BP1, and phosAkt expression correlated with divergent aggressive histology and invasion. phosS6 expression inversely predicted OS (P=.01), DSS (P=.001), and progression (P=.05). c-myc expression inversely predicted progression (P=.01). In a multivariate analysis model that included TNM stage grouping, divergent aggressive histology, concomitant carcinoma in situ, phosS6, and c-myc expression, phosS6 was an independent predictor of DSS (P=.03; hazard ratio [HR], -0.19), whereas c-myc was an independent predictor of progression (P=.02; HR, -0.38). 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=.03; HR, -0.21) and progression (P=.03; HR, -0.34), respectively. CONCLUSIONS: We found an overall down-regulation of mTOR pathway in bladder urothelial carcinoma. phosS6 independently predicted DSS, and c-myc independently predicted progression.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
urinary bladder cancer disease_progressionIEP 7207427protein:decreased expression:urinary bladder urothelium (human)RGD 
urinary bladder cancer disease_progressionISOMYC (Homo sapiens)7207427; 7207427protein:decreased expression:urinary bladder urothelium (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Myc  (MYC proto-oncogene, bHLH transcription factor)

Genes (Mus musculus)
Myc  (myelocytomatosis oncogene)

Genes (Homo sapiens)
MYC  (MYC proto-oncogene, bHLH transcription factor)


Additional Information