Plasma Qualitative Methylated Septin 9 (mSEPT9): Optimal Testing Recommendations

  • The mSEPT9 test is not recommended for screening colorectal cancer (CRC);
  • It may be used for male and female patients > 50 years old who are at average risk for CRC and decline first-line screening tests such as colonoscopy and fecal immunochemical test (FIT).

Guidelines for Test Utilization

What does the test tell me?

SEPT9 gene methylation increases with the progression of CRC. When tumor apoptosis releases DNA into blood, the presence of methylated SEPT9 indicates a positive screening test for CRC. [back to top]

When should I order this test?

This test may be ordered for patients who decline first-line screening tests for CRC. [back to top]

When should I NOT order this test?

  • Do not order this test as first-line screening test for CRC.
  • Do not order this test to screen for hematological malignancies, solid tumors other than CRC.
  • Do not order this test for patients with a personal or family (first degree relatives) history of colorectal polyps (e.g., familial adenomatous polyposis), inherited colorectal cancers such as Lynch syndrome, inflammatory bowel disease, ulcerative colitis, or Crohn’s disease.

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How should I interpret the result?

A positive mSETP9 test result should be referred for diagnostic colonoscopy. A negative mSETP9 test does not rule out CRC.[back to top]

Is the test result diagnostic/confirmatory of the condition?

The mSEPT9 test is not a diagnostic/confirmatory test for CRC. [back to top]

Are there factors that can affect the lab result?

  • Tumor apoptosis and sampling time in relation to the onset of CRC, may result in a false negative test.
  • Individual testing labs also may have different testing parameters (e.g., Ct values) that may lead to variable results around levels of mSEPT9 that would be identified as either positive or negative in different patients.

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Are there considerations for special populations?

The testing population is limited to both sexes > 50 years old who are at average risk for CRC and have declined first-line screening tests for CRC. [back to top]

What other test(s) might be indicated?

Colonoscopy and fecal immunochemical test (FIT) are the first-line screening tests. [back to top]

References

Rex DK, Boland CR, Dominitz JA, Giardiello FM, Johnson DA, Kaltenbach T, et al. Colorectal cancer screening: Recommendations for physicians and patients from the U.S. Multi-Society Task Force on Colorectal Cancer. Gastrointest Endosc 2017; 86(1): 18-33.

Sun J, Zheng M-Y, Li Y-W, Zhang S-W. Structure and function of Septin 9 and its role in human malignant tumors. World J Gastrointest Oncol 2020; 12(6): 619-631.

Xie L, Jiang X, Li Q, Sun Z, Quan W, Duan Y, et al. Diagnostic value of methylated Septin9 for colorectal cancer detection. Front Oncol 2018;8(247): 1-8.

Church TR, Wandell M, Lofton C. Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer. Gut 2013; 63(2):317-25.


Last reviewed: March 2023. The content for Optimal Testing: the Association for Diagnostics & Laboratory Medicine’s (ADLM) Guide to Lab Test Utilization has been developed and approved by the Academy of Diagnostics & Laboratory Medicine and ADLM’s Science and Practice Core Committee.

As the fields of laboratory medicine and diagnostic testing continue to grow at an incredible rate, the knowledge and expertise of clinical laboratory professionals is essential to ensure that patients receive the highest quality and most useful laboratory tests. ADLM’s Academy and Science and Practice Core Committee have developed a test utilization resource focusing on commonly misused tests in hospitals and clinics. Improper test utilization can result in poor patient outcomes and waste in the healthcare system. This important resource geared toward medical professionals recommends better tests and diagnostic practices. Always consult your laboratory director to make sure these recommendations are appropriate for your patient population.