Screening Colorectal Tumors for Lynch Syndrome: Who Gets Missed?

Identifying colorectal cancer patients with Lynch syndrome (also known as hereditary non-polyposis colon cancer or HNPCC) makes an important difference  in preventing further cancers for them and also for their family members.  However, family or personal medical histories don’t always find everyone at risk.

One of every 35 patients with colorectal cancer has Lynch syndrome, and each one has at least three family members who carry a Lynch gene and will need more intensive polyp and cancer surveillance beginning when they are young adults.

Researchers at Ohio State University compared methods of testing colon tumors to screen for Lynch syndrome and predict those patients who need further genetic testing.  They also looked at more traditional ways of finding potential Lynch syndrome, including family histories and age at diagnosis.

Studying 500 colorectal cancer patients, they found 18 (3.6 percent) had Lynch syndrome based on mutations found during genetic analysis.

  • All 18 had tumors that were microsatellite-high (MSI-H).
  • Immunohistochemical tumor testing (IHC) found  17 of 18 cases.
  • Less than half of identified patients were under the age of 50 — 8 of 18 or 44 percent.
  • Fewer than 3 out of 4 met revised Bethesda guidelines connecting family and personal history to Lynch syndrome or 72 percent.

The bottom line is that depending on only family history or young age to spot colorectal cancer patients with Lynch syndrome may miss a quarter to one half of patients who will eventually test positive for a mutation.  Tumor testing for MSI or loss of gene expression in an IHC test is more reliable to screen for patients who need more extensive genetic testing.

Heather Hampel and her team from the Human Cancer Genetics Program at Ohio State concluded,

One of every 35 patients with colorectal cancer has Lynch syndrome, and each has at least three relatives with LS; all of whom can benefit from increased cancer surveillance. For screening, IHC is almost equally sensitive as MSI, but IHC is more readily available and helps to direct gene testing. Limiting tumor analysis to patients who fulfill Bethesda criteria would fail to identify 28% (or one in four) cases of LS.

Lynch syndrome or hereditary non-polyposis colon cancer (HNPCC) is inherited directly from parent to child.  A child of a person with Lynch syndrome has a 50 percent chance of carrying a gene that causes colorectal cancer as well as other associated cancers.  People who have one of the Lynch genes (MLH1, MSH2, or MSH6) are at very high risk of colon or rectal cancer, and women are at greatly increased risk for endometrial and ovarian cancer.  Lynch cancers are often diagnosed at a young age and develop more rapidly than the usual sporadic colorectal cancers.

When Lynch syndrome is found, both patients and their families should receive early and frequent colonoscopies to find and remove precancerous polyps or diagnosis colorectal cancer early.  Women should be screened to find endometrial or ovarian cancer early when it can be treated successfully.  But, family members who don’t carry the gene can be spared intensive testing.

SOURCE: Hampel et al., Journal of Clinical Oncology, Early online ahead of print, September 22, 2008.


  1. Robert Mardock says

    My wife was diagnosed with Colon Cancer in 2003. She meets the revised Bethesda Guidelines with a Grandfather dying of Colon Cancer, a brother Dying of Glioblastoma Multiforme, and her own diagnosis at 49. She originally received IHC testing for MLH1 and MSH2 which were normal, but not MSH6 or PMS2. Should these newer test be added?

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