Researchers Call to End Age Restrictions for Lynch Syndrome Testing

Many cases of Lynch syndrome might be going undetected under widely used testing methods and age restrictions for screening, warn authors of a new study published in the Journal of Clinical Oncology.

Tumor microsatellite instability (MSI) typing increases detection of Lynch syndrome among endometrial cancer patients by 12%, and should be used alongside other tools to screen for Lynch syndrome among all endometrial cancer patients, regardless of age, according to the researchers.

“Combined tumor MSI [microsatellite instability], methylation [MLH1], and IHC [immunohistochemistry] analysis may prove useful in Lynch screening in EC [endometrial cancer],” the researchers reported. “Restricting Lynch syndrome testing to women diagnosed at less than age 60 years or to women with IHC defects could result in missing a substantial fraction of genetic disease.”

Lynch syndrome, an inherited genetic disorder, increases patients’ risk of developing endometrial, ovarian, colon, gastric, gastrointestinal, and liver cancers. Optimal screening strategies for women diagnosed with endometrial cancer have not been identified, although it has been recommended that screening be limited to women younger than age 60 years at diagnosis with endometrial cancer.

The study coauthors “sought to determine whether MSI typing along with IHC and MLH1 methylation analysis can help identify women with Lynch syndrome,” analyzing 1,002 endometrial tumors.

“Analysis of 1,002 endometrial cancers suggested possible MMR [mismatch repair protein] mutation in 11.8% of tumors,” the researchers reported. “The number of patients with a family history suggestive of Lynch syndrome was highest among women whose tumors were classified as probable MMR mutation (P = .001).”

The researchers also found that 24% of patients who harbored Lynch syndrome gene mutations were diagnosed with endometrial cancer after age 60, “and one carrier had an MSI-positive tumor with no IHC defect.”

Testing for Lynch syndrome among only those patients who are diagnosed with endometrial cancer at age 60 or younger means many cases of the syndrome will go undetected.

“If we don’t identify patients who have these fundamental changes in their DNA structure then we also can’t use this information to help stop and detect these cancers in their at-risk relatives,” said coauthor Paul J. Goodfellow, PhD, a professor at The Ohio State University Comprehensive Cancer Center, Columbus, OH, in a news release.

The increased cancer risk for relatives of the Lynch endometrial cancer patients older than 60 would not be known or accounted for, so, the opportunity for early detection and intervention would be lost. We believe that all endometrial cancer patients should have tumor analysis to screen of Lynch syndrome should be for, irrespective of age,” Dr. Goodfellow concluded. “The benefit of earlier detection of cancers and pre-cancers in mutation carriers is well established.”