What is the Septin9 test Epi proColon?
The “Epi proColon” test is a CE-marked test that detects methylated DNA from the Septin9 gene, a DNA modification specific to colorectal cancer in blood plasma. The presence of circulating methylated cell-free Septin9 DNA in blood plasma is strongly correlated with the occurrence of colorectal cancer.

How will this test help me care for my patients?
It is believed that this blood-based test will be accepted by many subjects that reject conventional screening methods such as colonoscopy or Fecal Occult Blood Tests (FOBT). The Epi proColon test, may help a population who would not otherwise get screened. The more people screened, the higher the chance to reduce the mortality rate from colorectal cancer.

What is the science behind the Septin9 test?
The test detects a specific cell-free colorectal tumor-derived DNA in blood plasma, i.e. methylated DNA of the Septin 9 gene or ^mSEPT9. DNA methylation is a biological process that turns genes on or off. As different cells make use of different genes, every cell type has a unique DNA methylation fingerprint. In cancer, the methylation fingerprint shows changes that are specific to the disease, i.e. genes that are normally unmethylated become methylated and vice versa. Epigenomics discovered that the Septin9 gene is aberrantly methylated in colorectal cancer but not in normal cells of the colon and rectum. They developed techniques to detect cell-free tumor-derived methylated Septin9 DNA as a biomarker for the presence of colorectal cancer. We coined this biomarker ^mSEPT9 where “SEPT9” is the official symbol for the Septin9 gene and “^m” indicates the methylation of the gene.

Which studies have been done to validate the clinical effectiveness of the test?
The biomarker ^mSEPT9 has been successfully tested in several case-control studies with more than 3,000 participants, showing consistently high performance in colorectal cancer detection. The results of two clinical case-control studies completed in 2008 have recently been published in Clinical Chemistry (issue 55/ 7, July 1st, 2009) titled “Circulating Methylated Septin 9 DNA in Plasma is a Biomarker for Colorectal Cancer”.
^mSEPT9 is currently being evaluated for its utility in population-wide colorectal cancer screening in the ongoing prospective PRESEPT study, which is one of the largest privately sponsored studies ever in colorectal cancer screening (for more information click here: www.presept.net).

What is the function of the Septin9 gene?
The gene SEPT9 codes for the Septin 9 protein, a member of a conserved family of GTP-binding proteins. Septins are multifunctional proteins, involved in vesicle trafficking, apoptosis, cytoskeletal remodelling, infection, neurodegeneration, neoplasia (i.e. cancer), among other important cellular processes.

Who developed the Septin9 test?
The test was developed by Epigenomics AG, a molecular diagnostics company with a focus on the development of novel products for cancer. The Septin9 test is marketed by Epigenomics in Europe as a CE-marked IVD test under the Brand name “Epi proColon”.
Using DNA methylation biomarkers, Epigenomics’ tests aim at detecting cancer at an early stage, before symptoms occur and thereby may reduce mortality from this disease.

Eligible Patients

Which patients may benefit from the Septin9 test
The test is for average risk individuals who want to get tested for colorectal cancer in the absence of symptoms. In particular it can be used as an alternative test for patients who should comply with the recommended regular colorectal cancer screening guidelines but reject methods that are currently recommended in these guidelines such as FOBTs and colonoscopy. Depending on the country regular screening for colorectal cancer is in general recommended from the age of 50 year, however, younger patients can also undergo the test. The test is not intended to replace colonoscopy but provide an alternative to patients not willing or able to undergo colonoscopy as a first step in colorectal cancer screening. Patients tested positive with the Epi proColon test should in any case get a colonoscopy for confirmation.

Should any patients be excluded from undergoing the test?
Patients with a history of colorectal cancer, familiar adenomatous polyposis and hereditary nonpolyposis colon cancer have an increased risk for colorectal cancer. For those patients, special screening guidelines apply.

What about patients with Crohn´s disease? Can they get the test?
For patients with inflammatory bowel disease like ulcerative colitis and Crohn´s disease, special screening programs are recommended. Patients with these diseases can be tested with the Epi proColon test, but a higher rate of false positive results has been reported in this patient population.

Can the Septin9 test be positive in other diseases like Crohn’s disease?
^mSEPT9 was discovered as a biomarker specific for colorectal cancer. Based on Epigenomics’ research, a positive test result indicates a high likelihood of having colorectal cancer. However, positive results for the test have been occasionally observed in individuals with some inflammatory gastrointestinal or systemic diseases such as gastritis, inflammatory bowel disease, or rheumatoid arthritis.

Are there any other individuals for whom the Septin9 test is not recommended?
The test is intended for an asymptomatic colorectal cancer screening population. If there is a suspicion of colorectal cancer, the patient is strongly recommended to undergo a colonoscopy for diagnostic clarification.

How should a patient prepare for this test?
No bowel preparation or nutritional recommendations are required for Septin9 testing. Patients do not need to fast before having the test and no alterations in medication or diet are required.

Test Performance

What is the performance of the Septin9 test?
The performance of the biomarker ^mSEPT9 has been established in multiple independent studies with more than 3,000 individual plasma samples tested.
The Septin9 test consistently identified about 70% of cancers at a specificity of 90% in training and testing studies, making the Septin9 test more sensitive than
the widely used guaiac FOBT test. Moreover, the Septin9 test is a simple blood test, expected to enhance patients’ acceptance and thus significantly increase compliance.

Can the Septin9 test also detect other cancers in blood (e.g. lung cancer or breast cancer)?
The ^mSEPT9 biomarker was discovered as a biomarker specific for colorectal cancer. Based on Epigenomics’ research, a positive test result indicates a high likelihood of having colorectal cancer. To the extent studied, ^mSEPT9 is rarely found in plasma from patients with other malignancies and gives little indication of the presence of any other cancer in a typical asymptomatic colorectal cancer screening population.

Test Result

If the test result is positive, does that mean my patient has colorectal cancer?
A positive test result indicates an increased likelihood of having colorectal cancer. As with any other diagnostic test, there is a chance of false positive results. The Septin9 test has a specificity of about 90%. For confirmation of diagnosis, all patients testing positive should undergo colonoscopy.

If the test result is negative, does that mean that my patient has no colorectal cancer?
As with any other diagnostic test, there is a chance of false negative test results. The sensitivity of the Septin9 test is about 70%, meaning there are false negative results 30% of the time. Colorectal cancer develops over a time span of 10 to15 years, which means that regardless of the screening method, regular re-testing is highly recommended and helps reduce the risk of false negative results over time.

If a patient has this Septin9 test, does it mean he or she does not need a colonoscopy?
As with FOBT, the Septin9 test identifies those patients who have an increased likelihood of having colorectal cancer. The test is not intended to definitively diagnose colorectal cancer or replace colonoscopy.

What clinical actions can be taken as a result of the Septin9 test?
Patients having a positive test result should undergo a follow-up colonoscopy to confirm the diagnosis. For patients who have a negative Septin9 test result, the physician and patient can jointly decide what future screening is necessary, e.g. re-testing at regular intervals.

How frequently should a patient have a Septin9 test?
As with all screening tests, the Septin9 test is not a one-time test. It should be repeated at regular intervals for maximum effectiveness because a patient’s current test result has no bearing on their future risk of developing colorectal cancer.

Submitting a patient sample for testing

What needs to be done to submit a sample for Septin9 testing?
The test needs to be prescribed by a healthcare professional, who draws a 10 ml EDTA blood sample from the patient. The sample needs to be shipped at 2-8°C within 24 h to the analysing laboratory where the plasma is prepared and the Septin9 test is performed.

What is the turnaround time for the test?
In general, test results will be sent from the laboratory to the referring physician within five business days from date of receipt of the blood sample.

Which laboratories offer the test?
The test is currently offered by several laboratories in Germany and Switzerland. Please contact us for detailed information at Tel +49 30 24345-111 or sales@products.epigenomics.com

Reimbursement of the test

Is the cost of the Septin9 test covered by the government or by health insurance?
Currently, the Septin9 test is being offered only to self-payors and privately insured patients. Epigenomics is actively working with key opinion leaders in gastroenterology, oncology and health economics to advocate for coverage under public health care schemes for the test in the future. 

To find out where to get the test please click here