New Blood Tests Offer Noninvasive Method of Detecting GI Cancers
By Roxanne Nelson
Medscape Medical News
September 28, 2009 (Berlin, Germany) — Two new blood tests might enhance the diagnosis of gastrointestinal cancers, researchers reported here at the 15th Congress of the European CanCer Organization and the 34th European Society for Medical Oncology Multidisciplinary Congress.
Although the results of the studies are still early, the tests could potentially offer a noninvasive, simpler, and more cost-effective means of diagnosing early gastrointestinal tumors.
When approached by Medscape Oncology for independent comment, Josep Tabernero, MD, from Vall d'Hebron University Hospital in Barcelona, Spain, said that although the papers were interesting, there were "several caveats to the studies."
"Right now, they are not specific enough for diagnosis," he said, "or for general screening."
SYNE1 and FOXE1
One of the 2 tests is a methylation test, developed by Joost Louwagie, PhD, vice president of product development at OncoMethylome Sciences in Leuven, Belgium, and colleagues. Research has demonstrated that DNA methylation is involved in the regulation of protein expression, and methylation of key genes has been associated with both initiation and proliferation of tumors.
The researchers tested 2 groups of blood samples, each obtained from a single blood draw, using varying amounts of plasma volume. In the first test, samples were obtained from 124 patients with colorectal cancer and 444 control subjects.
The extraction of DNA and bisulfite conversion methods resulted in recovery of about 40% of the input DNA. They found that 2 newly reported methylation markers, SYNE1 and FOXE1, had a high frequency in patients at all stages of colorectal cancer. These methylation genes occur infrequently in individuals without cancer.
In the first cohort tested, plasma volumes ranged from 0.8?mL to 4.3?mL; the sensitivity for the combination of SYNE1 and FOXE1 was 58% and specificity was 90%.
Testing was conducted in a second independent cohort of 69 patients with colorectal cancer and 242 control subjects. The results showed that sensitivity for the combined markers was 58% and the specificity was 91%. But in samples with at least 3.3?mL of plasma, the sensitivity increased to 77%.
"Increasing the volume did seem to give better sensitivity, and this effect was seen most strongly in patients with early-stage disease," said Dr. Louwagie.
On the basis of these results, the researchers are now preparing to conduct a large validation study and are currently enrolling participants in a prospective colorectal cancer screening study. The goal is to have 7000 people enrolled by the end of 2009.
Dr. Louwagie pointed out that this test is not meant to replace colonoscopy, but once it is validated, it can serve as an option for individuals who are either unable or who decline to undergo colonoscopy screening. The methylation test can be performed during routine physical exams and can help identify patients who should then be referred for colonoscopy.
S100A4 mRNA
The second new test is an assay that detects transcription levels of S100A4 messenger (m)RNA in plasma, which was developed by Ulrike Stein, MD, and colleagues, from Charite University Medicine Berlin and Max Delbruck Center for Molecular Medicine in Berlin, Germany.
The test might help diagnose colon, rectal, and gastric cancers, and might help predict the likelihood of metastatic disease in patients who have already been diagnosed. Dr. Stein explained that S100A4 is known to be a metastasis progressor, and the detection of S100A4 mRNA in several primary tumors is of diagnostic and prognostic relevance.
"S100A4 was cloned as one of the first markers associated with metastasis," said Dr. Stein. "It is a marker for advanced disease and poor prognosis for several tumors."
The goal of this study, explained Dr. Stein, was to define the diagnostic and prognostic power of S100A4 transcripts detected in plasma samples from colon, rectal, and gastric cancer patients. Daily blood samples were collected from patients with colon cancer (n?= 185), rectal cancer (n?= 190), and gastric cancer (n?= 91). Samples were also obtained from 51 healthy volunteers who served as control subjects. Levels of S100A4 mRNA were determined by quantitative gene-specific 2-step real-time reverse-transcriptase PCR.
The researchers detected S100A4 mRNA in all plasma samples that were analyzed, and levels were significantly higher in colon, rectal, and gastric cancer patients than in the control subjects (P?< .0001, respectively). Higher levels were also detected in colon cancer patients with metastatic disease than in those with nonmetastasized disease.
Higher levels of S100A4 were associated with the future development of metastases, according to Dr. Stein. "On follow-up, patients who had gone on to develop metastatic disease had higher levels of S100A4 on their initial blood samples," she said.
The S100A4 transcript can conceivably be used as a screening tool for gastrointestinal cancers, but larger prospective studies are needed, Dr. Stein said.
Dr. Louwagie's study was sponsored by Signature Diagnostics in collaboration with OncoMethylome Sciences. Dr. Stein's study was supported by a grant from the Berlin Cancer Society.
15th Congress of the European CanCer Organization (ECCO 15) and the 34th European Society for Medical Oncology (34th ESMO) Multidisciplinary Congress: Abstracts 12 LBA and 13LBA. Presented September 21, 2009.
