Immunohistochemical detection of ZAP70 in chronic lymphocytic leukemia predicts immunoglobulin heavy chain gene mutation status and time to progression.
Mod Pathol
; 23(11): 1518-23, 2010 Nov.
Article
em En
| MEDLINE
| ID: mdl-20657554
ABSTRACT
Zeta-associated protein-70 (ZAP70) expression measured by flow cytometry has been proposed as a surrogate marker of the somatic mutation status of the immunoglobulin heavy chain variable region (IGHV) genes in chronic lymphocytic leukemia. However, attempts to implement this approach in clinical flow cytometry laboratories have been problematic; many commercially available antibodies give unreliable results. Assessment of ZAP70 protein expression by immunohistochemistry in chronic lymphocytic leukemia tissue sections is an easy, alternative approach, although lack of quantitation and subjective interpretation of results are potential pitfalls. In this study, we correlated ZAP70 protein expression, assessed by immunohistochemistry, with ZAP70 messenger RNA (mRNA) transcript expression, assessed by semi-quantitative real-time reverse transcriptase-polymerase chain reaction assay, with the somatic mutation status of the IGHV genes in previously untreated patients with chronic lymphocytic leukemia. Expression of ZAP70 protein and mRNA transcripts correlated strongly (P=8.238 × 10(-12)). Expression of ZAP70 protein and mRNA transcripts also correlated strongly with the somatic mutation status of the IGHV genes (P=0.000071 and P=0.00076, respectively). Further, ZAP70 positivity by immunohistochemistry was associated with an increased risk of progression to therapy requirement (3-year risk 83% vs 31% for ZAP70 negative by immunohistochemistry, P=0.03). These results show that ZAP70 expression assessed by immunohistochemistry is a reliable surrogate marker of the somatic mutation status of the IGHV genes, and predicts time to progression.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Imuno-Histoquímica
/
Leucemia Linfocítica Crônica de Células B
/
Biomarcadores Tumorais
/
Proteína-Tirosina Quinase ZAP-70
/
Genes de Cadeia Pesada de Imunoglobulina
/
Mutação
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
America do norte
Idioma:
En
Revista:
Mod Pathol
Assunto da revista:
PATOLOGIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos