Hypoxia-inducible factor and mammalian target of rapamycin pathway markers in urothelial carcinoma of the bladder: possible therapeutic implications.
BJU Int
; 107(5): 844-849, 2011 Mar.
Article
en En
| MEDLINE
| ID: mdl-20707797
ABSTRACT
OBJECTIVE:
To investigate the rationale for using targeted therapies against hypoxia-inducible factor (HIF) and mammalian target of rapamycin (mTOR) pathways in urothelial carcinoma of the bladder, by studying the immunohistochemical expression of molecules of these pathways in urothelial carcinoma, as recent pre-clinical studies and clinical trials have shown the potential utility of such targeted therapies. PATIENTS ANDMETHODS:
Immunohistochemical stains were performed on a tissue microarray prepared from 92 cases of ≥ pT2 urothelial (transitional cell) carcinoma of bladder, using antibodies against HIF-1α and VEGF-R2, and phospho-S6 and phospho-4E BP1, molecules of HIF and activated mTOR pathways, respectively. Immunoreactivity was graded from 0 to 3+ (0, 0-5%; 1+, 6-25%; 2+, 26-50%; 3+, > 50% tumour cells positive).RESULTS:
In all, 58, 34, 35 and 17% of the tumours showed grade 2-3+ expression of phospho-4E BP1, phospho-S6, HIF-1α and VEGF-R2, respectively. Moderate correlation for immunoreactivity was observed between molecules within the same pathway [(phospho-4E BP1 with phospho-S6 (rho = 0.411), and HIF-1α with VEGF-R2 (rho = 0.265)], but not between molecules across pathways.CONCLUSIONS:
Urothelial carcinomas of the bladder express molecules of the HIF and mTOR pathways, providing a rationale for clinical trials evaluating agents targeting these pathways. Correlation between molecules within the same pathway, and not across pathways, suggests that investigating the usefulness of a specific targeted agent might benefit from pre-treatment evaluation of pathway marker expression.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Vejiga Urinaria
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Carcinoma de Células Transicionales
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Sirolimus
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Subunidad alfa del Factor 1 Inducible por Hipoxia
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Serina-Treonina Quinasas TOR
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Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
BJU Int
Asunto de la revista:
UROLOGIA
Año:
2011
Tipo del documento:
Article