Evidence Warrants Endometrial Cancer Tumor Testing to Identify Women with Lynch Syndrome

This is the conclusion by the authors, from Norris Cotton Cancer Center (Lebanon, NH, USA), of an evidence-review to be published in the journal Clinical Chemistry, January 2014. Various testing algorithms, along with genetic-counseling efforts, can lead to a cost-efficient and beneficial screening program. Tumor testing using immunohistochemistry (IHC) and microsatellite instability (MSI) gives preliminary information to check if Lynch syndrome played a role in the development of the cancer.

In Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer (HNPCC) syndrome) mutant variation occurs in one among four mismatch repair (MMR) genes. Not all people who inherit the mutation will develop cancer, and not all women with endometrial cancer have LS. However, endometrial cancer is the second most common type of cancer that women with LS develop. “The importance of screening women with endometrial cancer for LS is based on their risk of developing other forms of cancer," said Gregory J. Tsongalis, PhD, professor of pathology at Geisel School of Medicine at Dartmouth (Lebanon, NH, USA). The genetic mutations of LS are associated with a 40%-80% risk of colon cancer, 25%–60% risk of endometrial cancers, and 10%–12% risk of ovarian cancer. Depending on the specific gene altered, the risks can be even greater. A smaller, but still elevated risk of urinary tract, small bowel, stomach, pancreas, biliary tract, and brain tumors also exists.

"In 40%–60% of women with LS, endometrial cancer is their first malignancy and up to 14% of women with LS presenting with cancer have both a gynecologic and colonic cancer simultaneously. Raising awareness of endometrial cancer's association with LS will lead to identification of more patients, and families, who may benefit from screening. Screening tumors with IHC and MSI helps identify tumors that may be associated with LS and also guides subsequent genetic testing for specific MMR gene sequencing," said Laura J. Tafe, MD, assistant professor of pathology at Geisel School of Medicine at Dartmouth.

For individuals at high risk for LS, sequencing of the LS-associated MMR genes effectively tests for the condition. In women who have been identified to have LS, screening for endometrial cancer can be considered. "Those individuals with a mutation can increase cancer surveillance to manage their elevated risks; those individuals who test negative for a familial mutation are considered to have the general population's risks for cancer and do not need a special screening protocol," said Eleanor Riggs, MS, CGC, certified genetic counselor at the Norris Cotton Cancer Center.

Related Links:
Norris Cotton Cancer Center
Geisel School of Medicine at Dartmouth