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Genetic alterations predict lung cancer reccurrence
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Early recurrence in patients with non–small cell lung cancer who are treated with curative surgery is linked to methylation of the promoter region of four genes, according to data published in The New England Journal of Medicine.
Researchers from Johns Hopkins Hospital in Baltimore and the Lovelace Respiratory Research Institute in Albuquerque, N.M. evaluated 51 patients who underwent curative resection for stage I non–small cell lung cancer, but had a recurrence within the following 40 months. They matched these patients with 116 patients with stage I non–small cell lung cancer who underwent curative surgery, but did not experience recurrence within 40 months.
The following were associated with tumor recurrence: promoter methylation of the cyclin-dependent kinase inhibitor 2A gene p16, the H-cadherin gene CDH13, the Ras association domain family 1 gene RASSF1A and the adenomatous polyposis coli gene APC in tumors and in histologically tumor-negative lymph nodes. These findings were independent of NSCLC stage, age, sex, race, smoking history and histological characteristics of the tumor.
In both tumor and mediastinal lymph nodes, methylation of the promoter regions of p16 and CDH13 was linked to an odds ratio of recurrent cancer of 15.50 in the original group and OR of 25.25 when the original group was joined by an independent validation group of 20 patients with stage I NSCLC, according to the study. – by Stacey L. Adams
N Engl J Med. 2008;358:1118-1128.
This is a very interesting article that is likely to eventually have an enormous impact. Finding methods to predict the cases of early lung cancer that are most likely to suffer disease recurrence could be of enormous value, both for prognosis and for selection of subpopulations in whom adjuvant therapies would best be tested (and the risk of toxicities justified). As such, this very preliminary study identified four possible target methylated genes for validation of results. Given the small numbers of cases (and controls), the retrospective nature of the data and the multiple variables studied in this closed data set (otherwise often referred to as multiple data set incursions), the current study, while suggestive, cannot come to definitive conclusions about the role of these methylated gene assays in predicting recurrence, as suggested by the authors. Nevertheless, the findings are important and this is an area to watch closely for prospective validation.
– Joseph Aisner, MD
HemOnc Today Editorial Board member