Scientific evidence is mounting that warrants screening all patients with endometrial cancer for Lynch syndrome. Next to colorectal cancer, endometrial cancer is the most common form of cancer in women with Lynch syndrome.
Currently, colon cancer specimens are screened for Lynch syndrome via specialized tumor testing. This tumor testing, known as immunohistochemistry (IHC) and microsatellite instability (MSI), gives clinicians some preliminary information to see if Lynch syndrome plays a role in the development of their patients’ cancer.
Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, is an inherited genetic disorder that increases the risk for many types of cancers but, in particular, colon and endometrial cancer. Lynch syndrome is passed down to a child from a parent who has the genetic traits that make up the disease. The inherited gene is abnormal, or mutated, which leads to increased cancer risk. Variation occurs in one of four mismatch repair (MMR) genes (ie, mutL homolog 1 [MLH1], mutS homolog 2 [MSH2] including epithelial cell adhesion molecule [EPCAM], mutS homolog 6 [MSH6], or postmeiotic segregation increased 2 [PMS2]). This mutation leads to instability in the ability of DNA to repair mismatches and ultimately increases an individual’s risk for certain cancers. However, not all people who inherit the genetic mutation will develop cancer.
“While not all women with endometrial cancer have Lynch syndrome, endometrial cancer is the second most common type of cancer that women with Lynch syndrome develop. The importance of screening women with endometrial cancer for Lynch syndrome is based on their risk of developing other forms of cancer for which screening and early detection can have an enormous impact on the patient and their family,” said Gregory J. Tsongalis, PhD, professor of pathology at Geisel School of Medicine at Dartmouth-Hitchcock Norris Cotton Cancer Center in Lebanon, New Hampshire. He was corresponding author on a recent review of evidence for screening patients with endometrial cancer for Lynch syndrome, which appeared in Clinical Chemistry (2013; doi:10.1373/clinchem.2013.206888).
The genetic mutations of Lynch syndrome are associated with a 40% to 80% risk of colon cancer, a 25% to 60% risk of endometrial cancers, and a 10% to 12% risk of ovarian cancer. Depending on the specific gene altered, the risks can be even greater. For example, mutations in the MSH6 gene translate into a lifetime risk of 70% for endometrial cancer. A smaller—but still elevated—risk of urinary tract, small bowel, stomach, pancreas, biliary tract, and brain tumors also exists.
“In 40% to 60% of women with Lynch syndrome, endometrial cancer is their first malignancy and up to 14% of women with Lynch syndrome presenting with cancer have both a gynecologic and colonic cancer simultaneously. Raising awareness of endometrial cancer’s association with Lynch syndrome will lead to identification of more patients and families who may benefit from screening. Screening tumors with IHC and MSI [microsatellite instability] helps identify tumors that may be associated with Lynch syndrome and also guides subsequent genetic testing for specific MMR gene sequencing,” said Laura J. Tafe, MD, also of Dartmouth.