LYNCH SYNDROME DETECTED WITH SIMPLE IMMUNOHISTOCHEMISTRY

Lynch Syndrome Detectable Using Microsatellite Instability

NEW YORK (Reuters Health) Apr 08 - Lynch syndrome - also called hereditary non-polyposis colorectal cancer (HNPCC) -- can be detected in young colorectal cancer patients using microsatellite instability (MSI) as the initial test, according to a report in the March 1st International Journal of Cancer.

"A relatively simple lab test will allow the identification of younger colorectal cancer patients who are likely to have Lynch syndrome," Dr. Barry Iacopetta from University of Western Australia, Nedlands, told Reuters Health. "If this is confirmed by further genetic tests, it will allow other affected family members who have the mutant gene to undergo regular surveillance."

Dr. Iacopetta and colleagues used MSI as the initial screen to ascertain previously unrecognized cases of Lynch syndrome out of all patients diagnosed with colorectal cancer in Western Australia between 2000 and 2006.

MSI was found in 8.7% of colorectal tumors from patients under age 60 years, the authors report, but the frequency of MSI was higher (15.7%) among patients under 45 years old.

In 97 cases evaluated using immunohistochemistry, 95 (98%) showed loss of expression in at least one mismatch repair protein.

Similarly, among 35 patients for whom germline mutation data could be obtained, likely pathogenic mutations were found in 11 cases and unclassified variants in 2 cases.

Using all the available data, the total number of germline mutation carriers in the entire cohort of 1344 patients under 60 years old was estimated at 48 (3.6%), including 25 already known, 11 newly discovered, and 12 extrapolated to exist in patients who were not tested.

"Thanks to this test, there is no reason why Lynch syndrome families should go undetected in the population," Dr. Iacopetta said. "We recommend that all colorectal cancer patients aged less than 55 years should undergo MSI testing."

"This strategy avoids the reliance on clinicians to routinely obtain a family history of cancer as the screening method for determining referral to familial cancer clinics," the investigators explain. "Although this MSI-based approach cannot identify 100% of Lynch syndrome cases, and further comparisons with an immunohistochemistry-based approach are required, we believe it represents an effective strategy for detecting the maximum number of cases with minimal use of resources."

"In the state of Western Australia this test is now being offered to all younger patients at no cost," Dr. Iacopetta added.