Oncogene status predicts patterns of metastatic spread in treatment-naive nonsmall cell lung cancer.
Cancer
; 118(18): 4502-11, 2012 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-22282022
ABSTRACT
BACKGROUND:
The discovery of distinct subsets of nonsmall cell lung cancer (NSCLC) characterized by activation of driver oncogenes has greatly affected personalized therapy. It is hypothesized that the dominant oncogene in NSCLC would be associated with distinct patterns of metastatic spread in NSCLC at the time of diagnosis.METHODS:
A total of 209 consecutive patients with stage IV nonsquamous NSCLC with an EGFR (epidermal growth factor receptor) mutation (N = 39), KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutation (N = 49), ALK (anaplastic lymphoma receptor tyrosine kinase) gene rearrangement (N = 41), or wild-type for all 3 (triple negative, N = 80) were included. The percentage of patients with metastatic disease at a given site was compared between each molecular cohort (EGFR, KRAS, or ALK) and the triple negative cohort.RESULTS:
ALK gene rearrangement was significantly associated with pericardial disease (odds ratio [OR] = 4.61; 95% confidence interval [CI] = 1.30, 16.37; P = .02) and pleural disease (OR = 4.80; 95% CI = 2.10, 10.97; P < .001). Patients with ALK gene rearrangements (OR = 5.50; 95% CI = 1.76, 17.18; P = .003) and patients with EGFR mutations (OR = 5.17; 95% CI = 1.63, 16.43; P = .006) were predisposed to liver metastasis compared to the triple negative cohort. No molecular cohort had a predisposition to pulmonary nodules, or adrenal, bone, or brain metastasis compared to the triple negative cohort. The mean number of metastatic disease sites in patients within the ALK rearranged cohort was significantly greater than that of the triple negative cohort (mean = 3.6 sites vs 2.5 sites, P < .0001).CONCLUSIONS:
The results support the hypothesis that the dominant molecular oncogenes in NSCLC are associated with different biological behaviors manifesting as distinct patterns of metastatic spread at the time of diagnosis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oncogenes
/
Proteínas Proto-Oncogênicas
/
Receptores Proteína Tirosina Quinases
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Carcinoma Pulmonar de Células não Pequenas
/
Proteínas ras
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Receptores ErbB
/
Neoplasias Pulmonares
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article