DNA synthesis and repair genes linked to survival in early lung cancer
NEW YORK (Reuters Health) - Elevated expression of two genes -- one involved in DNA synthesis (RRM1) and the other in DNA repair (ERCC1) -- are associated with prolonged survival among patients with completely resected, stage 1 non-small-cell lung cancer, investigators report in the New England Journal of Medicine for Feb. 22.
However, translating this knowledge into development of practical markers for cancer outcomes "has not been possible ... because of technical limitations," the authors note.
So Dr. Gerold Bepler and his team at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla., developed an automated, quantifiable, immunohistochemical technique, which they used to determine levels of RRM1 (ribonucleotide reductase M1) and ERCC1 (excision repair cross-complementation group 1).
They tested their system using tissue samples from 187 patients who had undergone complete surgical resection for stage 1 non-small-cell lung cancer at their institution. None of the patients had been treated with chemotherapy or radiotherapy.
For patients whose tumors had levels of RRM1 below the median, the median disease-free survival was 54.5 months. For those with higher levels, disease-free survival was 120 months (p = 0.004). The median overall survival was 60.2 months and > 120 months, respectively (p = 0.02).
The investigators observed that ERCC1 expression was significantly associated with overall survival, but not disease-free survival.
Bepler and his group then stratified patients according to level of expression of each gene. Results showed that, for those with high expression of one protein and those with low expression of both, overall survival ranged from 56.8 months to 80 months. For those with high levels of both proteins, disease-free and overall survival were > 120 months, significantly longer than in the other three groups.
"Although high expression of either protein alone was associated with a good prognosis, co-expression of the two proteins characterized the group with an excellent outcome," the investigators write.
Bepler and his associates point out that RRM1 and ERCC1 expression is associated with poor response to gemcitabine and platinum chemotherapy. So it is possible that gene expression profiles could be used to determine treatment for patients with cancer.
N Engl J Med 2007;356:800-808.