For many malignant cancers - cancers that are potentially deadly - a common treatment is surgical removal of the tumor. Surgery has a fairly high success rate for treating many cancers.
However, for patients with one kind of lung cancer, surgical treatment fails in 30 to 40 percent of cases, and many of those patients die.
Malcolm Block and colleagues at Hopkins Hospital looked for clues to this problem in the DNA of patients with early stage non-small-cell lung cancer.
One factor that might contribute to the high recurrence rate after surgery is the methylation of cancer genes involved in the progression of lung cancer.
Methylation is a type of epigenetic modification, a kind of regulation in which DNA is altered during an organism's lifetime without changing its base sequence.
By methylating a DNA sequence, the cell can silence a gene - prevent it from becoming a protein - without permanently changing the strand.
A laboratory technique called methylation-specific PCR was used to define patterns of DNA methylation in these patients to better characterize the behavior of cancerous tumors, as well as to detect small, hidden metastases, or spreading cancers, in benign tumors and healthy lymph nodes. Lymph nodes are common places to find tumor cells that are spreading throughout the body.
Patients who underwent surgery without lapsing back into cancer were matched with patients who did relapse on the basis of age, stage of the disease, gender and date of treatment.
Blind tissue specimens were taken from all patients and DNA samples were extracted from them. A small amount of DNA was purified.
A total of 889 samples of DNA from tumor and lymph-node tissue were examined through gel electrophoresis of the methylation-specific PCR product, which allowed researchers to determine the length of the DNA fragment.
The death of all of the patients were found to be cancer-related, with frequent recurrences of cancer in the lungs, followed by metastasis to bones and brains.
The methylation profiles of seven genes were obtained, and four genes in particular were observed to have large differences in distribution of methylation in the tissue samples. Of these four genes, p16 and CDH13 were associated with a significant chance of recurrence.
The survival rate of patients without methylation in any of the four genes was 27.3 percent. Methylation of both p16 and CDH13 in the tumor and the mediastinal lymph nodes, which are located in the chest between the two lungs, yielded a low survival rate of 14.3 percent.
The study indicated that modification of certain genes in specific tissues is associated with recurrence of a tumor.
This study also demonstrates that patients could have microscopic disease in apparently normal lymph nodes and not have any clinical symptoms until it's too late.
Furthermore, success in this research provides a new assay for evaluation of disease recurrence and survival rate in non-small-cell lung cancer patients.
