Two new blood tests help identify GI cancers, predict risk for metastases

ECCO 15 – ESMO 34 Multidisciplinary Congress

According to data from two studies presented today at the ECCO 15 – ESMO 34 Multidisciplinary Congress in Berlin, two new blood tests have been developed that will simplify gastrointestinal cancer detection while improving cost-effectiveness and increasing patient compliance.

The advent of the two new blood tests — a methylation test for colorectal cancer screening and a blood test for the detection of colon, rectal or gastric cancers — may improve patient compliance and reduce costs associated with screening.

“Once validated in a prospective colorectal screening trial, the new methylation test could be used as a noninvasive screening option for patients who decline or do not have access to colonoscopy or do not wish to undertake the fecal occult blood test,” Joost Louwagie, PhD, vice president of OncoMethylome Sciences in Belgium and study researcher, said in a press release.

SYNE1 and FOXE1

Researchers from the first study, a multicenter feasibility trial, aimed to identify and provide a sensitive, specific and patient-friendly option for colorectal cancer screening. Using blood from 193 patients with known colorectal cancer and 688 controls undergoing colonoscopy for cancer screening, the researchers extracted DNA from the blood plasma and tested for the presence of DNA methylation of specific genes. They chose methylated genes capable of discriminating between cancerous and normal tissues and evaluated the best-performing genes in blood samples.

“We optimized the methods of DNA extraction and methylation detection so that we could detect low levels of methylated genes in people with colorectal cancer,” Louwagie said in a press release. “And we were able to find a high frequency of two newly reported methylation genes, SYNE1 and FOXE1, in patients with colorectal cancer. The same methylation genes occurred infrequently in non-cancerous individuals.”

The researchers tested the marker — the combination of SYNE1 and FOXE1 — in 444 controls and 124 patients with colorectal cancer who had plasma volumes between 0.8 mL and 4.3 mL. They reported 58% sensitivity and 90% specificity. When tested in 242 controls and 69 cases, the sensitivity of the marker was 56% and the specificity was 91%. Sensitivity was 41% for stage I disease and 80% for stage II disease.

By the end of 2009, Louwagie and colleagues plan to enroll 7,000 people into a prospective colorectal screening study in several German colonoscopy centers. According to Louwagie, the researchers are currently speaking with partners about distribution rights.

With the new methylation test, nurses or primary care physicians can take blood samples without special equipment or training, which would increase patient compliance rates and help to identify those patients who qualify for colonoscopy, according to Louwagie. In addition, providing a blood sample could be part of the regular physical exams performed as part of health insurance packages in several countries.

S100A4 mRNA

In a second study, researchers from Germany developed a blood test to aid in tumor diagnosis among patients with colon, rectal or gastric cancers. According to researchers, the test can also predict the likelihood of metastatic disease after diagnosis.

Ulrike Stein, PhD, professor at the Experimental and Clinical Research Center at the Charité University of Medicine and the Max-Delbrueck-Center for Molecular Medicine in Berlin, and colleagues isolated RNA from blood plasma samples from patients with gastrointestinal tumors to identify the presence of an S100A4 transcript. The researchers obtained 185 blood samples from patients with colon cancer, 190 with rectal cancer and 91 with gastric cancer. The samples were matched with blood from 51 age-matched, tumor-free controls.

“We found that S100A4 mRNA was present at significantly higher levels in the group of patients with cancer, no matter whether they had colorectal or gastric cancer, than in the tumor-free control group,” Stein said in a press release. “And there were yet higher levels in the patients with metastases than in those where the disease had not yet metastasized.”

More importantly, according to Stein, are the data from a prospective analysis, demonstrating that patients who later developed metastases had higher levels of S100A4 at initial analysis compared with those who did not experience disease metastases.

“This means that in the future we might be able to identify those patients who are likely to develop metastases,” she said.

The test may also be useful in screening for gastrointestinal cancers in the general population because it is able to identify tumors in patients showing no signs of disease. According to researchers, however, this capability needs to be validated in a large, prospective trial. Researchers have known that the S100A4 transcript is able to promote the increased metastatic capability of cancer cells; however, until now the test to establish S100A4’s existence in a tumor has been expensive and complicated.

The researchers are currently examining the correlation of S100A4 transcript levels in blood and the survival of individual patients after a minimum three years of follow-up.

“We are hoping that, by enabling the identification of those patients whose disease is likely to progress more quickly, we will be able to treat them in the future accordingly by tailoring therapy to their individual needs,” Stein said.

For more information:

• Louwagie J. #12LBA.
• Stein U. #13LBA. Both presented at: ECCO 15 and 34th ESMO Multidisciplinary Congress; Sept. 20-24, 2009; Berlin.