Evidence mounts for endometrial cancer tumor testing to identify women with Lynch syndrome

December 11, 2013

A recent article by Norris Cotton Cancer Center researchers published in the January 2014 issue of the journal Clinical Chemistry reviews the scientific evidence that warrants screening all endometrial cancers for Lynch syndrome. Next to colorectal cancer, endometrial cancer is the most common form of cancer in women with Lynch syndrome. Currently at Dartmouth-Hitchcock Medical Center, every colon cancer specimen is screened for Lynch syndrome via specialized tumor testing. There is mounting evidence that this special tumor testing should also be done on every endometrial cancer specimen. This tumor testing, known as immunohistochemistry (IHC) and microsatellite instability (MSI), gives clinicians some preliminary information to see if Lynch syndrome played a role in the development of their patient's cancer.

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, is an inherited 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 disease. The inherited gene is abnormal, or mutated, which leads to increased cancer risk. Variation occurs in one of four mismatch repair (MMR) genes (i.e., MLH1, MSH2 including EPCAM, MSH6, or PMS2). This mutation leads to instability in the DNA's ability to repair mismatches and ultimately increases an individual's risk for certain cancers. However, it is important to keep in mind that 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 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 and Director of Molecular Pathology.

The genetic mutations of Lynch syndrome are associated with a 40-80 percent risk of colon cancer, 25-60 percent risk of , and 10-12 percent 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 percent for endometrial cancer. A smaller, but still elevated risk of urinary tract, small bowel, stomach, pancreas, biliary tract, and brain tumors also exists.

"In 40-60% of women with Lynch syndrome, endometrial cancer is their first malignancy and up to 14 percent 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 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, assistant professor of Pathology Geisel School of Medicine at Dartmouth and assistant director of Molecular Pathology.

For individuals at high risk for Lynch syndrome, DNA sequencing effectively tests for the condition by examining a DNA sample for genetic mutations within the MMR genes. In women who have been identified to have Lynch syndrome, screening for endometrial cancer can be considered. This often involves a transvaginal ultrasound and/or endometrial biopsy. The early signs of endometrial can include abnormal vaginal bleeding, so women with Lynch syndrome should be educated about these symptoms and seek prompt medical attention if they present. For colorectal cancer screening, frequent colonoscopy screening is the recommended surveillance method.

"Genetic testing for Lynch syndrome can be a powerful tool for families. Genetic testing can tell us who in a family are at an increased risk for cancer and who are not, allowing for more personalized screening and prevention recommendations. 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 and do not need a special screening protocol," said Eleanor Riggs, MS, CGC, certified genetic counselor in Norris Cotton Cancer Center's Familial Cancer Program.

Explore further: Prostate cancer risk rises in men with inherited genetic condition

Related Stories

Prostate cancer risk rises in men with inherited genetic condition

April 1, 2013
Men with an inherited genetic condition called Lynch syndrome face a higher lifetime risk of developing prostate cancer and appear to develop the disease at an earlier age, according to a new study led by researchers at the ...

Study revises colorectal cancer risk down and other cancer risks up for women with Lynch Syndrome

February 26, 2013
Lynch Syndrome is a heritable genetic mutation that causes colorectal, endometrial and other cancers. A cooperative study that included the University of Colorado Cancer Center, published in this month's issue of the Journal ...

Study identifies genetic mutations associated with cancer risk for hereditary cancer syndrome

June 5, 2011
(Medical Xpress) -- Among various genetic mutations for individuals with Lynch syndrome, a hereditary cancer syndrome that carries a high risk of colon cancer and an above-normal risk of other cancers, researchers have identified ...

Snack attack: Eating unhealthy snack foods may affect cancer risk in patients with Lynch syndrome

December 17, 2012
A new analysis has found that loading up on snack foods may increase cancer risk in individuals with an inborn susceptibility to colorectal and other cancers. Published early online in CANCER, a peer-reviewed journal of the ...

Health of entire families at risk through under-use of genetic testing

June 7, 2013
A new study of the use of genetic testing for cancer-causing mutations in affected families in France has found that its take-up is very low. Professor Pascal Pujol, Head of the Cancer Genetics Department, Montpellier University ...

Recommended for you

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.