Thymidylate synthase gene amplification predicts pemetrexed resistance in patients with advanced non-small cell lung cancer.
Clin Transl Oncol
; 18(1): 107-12, 2016 Jan.
Article
em En
| MEDLINE
| ID: mdl-26220094
BACKGROUND: Thymidylate synthase (TYMS) expression in lung cancer tissue affects the therapeutic efficacy of pemetrexed (PMT). TYMS protein expression is primarily assessed using immunohistochemistry (IHC), but this method is not suitable for accurate quantitative analysis. It is not known whether the analysis of TYMS gene copy number using fluorescence in situ hybridization (FISH) is a useful method for assessment of TYMS expression. PATIENTS AND METHODS: The participants were patients with chemo-naïve advanced NSCLC treated with PMT plus carboplatin (CBDCA) in prospective clinical phase II study. TYMS expression was evaluated in 40 patients by gene copy number and protein expression using FISH and IHC. Therapeutic efficacy was evaluated by investigating the response rate (RR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). RESULTS: TYMS gene amplification was detected in 8 patients (32 %) among 25 patients who could be evaluated for TYMS gene copy number. There were no patients with complete or partial response in the TYMS amplified group. RR and DCR were lower in the TYMS amplified group compared with the TYMS unamplified group (0 versus 35.3 %, p = 0.0539, 62.5 versus 94.1 %, p = 0.0443). PFS and OS were reduced in the TYMS amplified group. The analysis of TYMS gene copy number had higher sensitivity and specificity compared with TYMS protein expression (76.2 versus 50.0 %, 75.0 versus 66.7 %). CONCLUSION: The analysis of TYMS gene copy number is more suitable than TYMS protein expression for assessment of TYMS expression. TYMS gene amplification predicts outcome of patients receiving PMT with advanced NSCLC.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Timidilato Sintase
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Amplificação de Genes
/
Carcinoma Pulmonar de Células não Pequenas
/
Resistencia a Medicamentos Antineoplásicos
/
Pemetrexede
/
Neoplasias Pulmonares
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Clin Transl Oncol
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Japão
País de publicação:
Itália