Gene expression in fixed tissues and outcome in hepatocellular carcinoma.
N Engl J Med
; 359(19): 1995-2004, 2008 Nov 06.
Article
em En
| MEDLINE
| ID: mdl-18923165
ABSTRACT
BACKGROUND:
It is a challenge to identify patients who, after undergoing potentially curative treatment for hepatocellular carcinoma, are at greatest risk for recurrence. Such high-risk patients could receive novel interventional measures. An obstacle to the development of genome-based predictors of outcome in patients with hepatocellular carcinoma has been the lack of a means to carry out genomewide expression profiling of fixed, as opposed to frozen, tissue.METHODS:
We aimed to demonstrate the feasibility of gene-expression profiling of more than 6000 human genes in formalin-fixed, paraffin-embedded tissues. We applied the method to tissues from 307 patients with hepatocellular carcinoma, from four series of patients, to discover and validate a gene-expression signature associated with survival.RESULTS:
The expression-profiling method for formalin-fixed, paraffin-embedded tissue was highly effective samples from 90% of the patients yielded data of high quality, including samples that had been archived for more than 24 years. Gene-expression profiles of tumor tissue failed to yield a significant association with survival. In contrast, profiles of the surrounding nontumoral liver tissue were highly correlated with survival in a training set of tissue samples from 82 Japanese patients, and the signature was validated in tissues from an independent group of 225 patients from the United States and Europe (P=0.04).CONCLUSIONS:
We have demonstrated the feasibility of genomewide expression profiling of formalin-fixed, paraffin-embedded tissues and have shown that a reproducible gene-expression signature correlated with survival is present in liver tissue adjacent to the tumor in patients with hepatocellular carcinoma.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Hepatocelular
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Perfilação da Expressão Gênica
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Neoplasias Hepáticas
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Recidiva Local de Neoplasia
Tipo de estudo:
Prognostic_studies
Limite:
Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
N Engl J Med
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos