Pathologist Seeks Earlier Answers for Families with Lynch Syndrome

Lynch syndrome is one of the most common inherited conditions that raises a person’s risk of colorectal cancer. It can also raise the risk of developing other gastrointestinal and gynecologic cancers, often at younger ages than average.

Until recently, diagnosis of Lynch syndrome has relied on family history — at least three relatives with a Lynch-associated cancer, among other criteria — or on tumor testing, if a physician indicated a patient might be at risk. Without those pieces, individuals are not referred for the genetic testing that would confirm Lynch syndrome.

As families have gotten smaller and knowledge about relatives’ health history has become more limited, applying those criteria have been less effective in identifying people at risk for Lynch syndrome.

Pathologist Jennifer Findeis-Hosey, M.D., is trying to improve that process. Her goal is to identify clinical and pathological features of colon polyps that may indicate the condition before an individual at risk has developed cancer. An estimated 3 percent to 5 percent of new colorectal cancers are associated with Lynch syndrome, and the presence of the condition can affect treatment options for those who already have cancer. Many people, however, are diagnosed after they have not only developed cancer but also after they have had surgery.

“This would shift the clock back,” says Findeis-Hosey, who specializes in identifying gastrointestinal cancers. “We could identify patients at an earlier age and earlier stage.”

Her work aligns with the national public health objective of increasing the proportion of people who receive genetic testing to identify Lynch or other familial colorectal cancer syndromes. She is also collaborating with colleagues across the University of Rochester Medical Center to develop a system that ensures patients with Lynch syndrome and their families get the genetic testing, counseling and follow-up care they need.

Four years ago, Findeis-Hosey began performing immunohistochemistry (IHC) testing on all colorectal cancer resections performed at Strong and Highland hospitals — regardless of whether they had been flagged for possible Lynch syndrome. She used special dyes to stain the tissue and determine whether certain proteins were absent. The absence of those proteins indicates that an individual may have Lynch syndrome, and that person is then referred for genetic testing.

But that was still identifying people after they had already undergone surgery.

“For some patients, if they are identified early, this could alter their disease management and treatment options,” says Chin-To Fong, M.D., who leads the Genetics team at URMC and works with Findeis-Hosey. “They may be at higher risk of other cancers and would benefit from other surveillance options.”

Their families also need to be screened for Lynch syndrome, and those who are identified could also benefit from more aggressive surveillance.

“For every affected person, there are about five or six at-risk people who are invisible to us without screening,” Fong says. First-degree relatives of individuals with Lynch syndrome — parents, siblings and children — have a 50 percent chance of also having the condition.

Findeis-Hosey and her team then began to explore whether using IHC on biopsied tissue would be just as effective. After verifying that this technique produced comparable results, they began routinely staining all colorectal cancer biopsies, allowing patients and their families to be referred for genetic testing and counseling before surgery.

Findeis-Hosey is now conducting a study that uses the same technique on large, advanced polyps that are removed during a colonoscopy — before cancer has developed. She is collaborating with UR Medicine gastroenterologists Danielle Marino, M.D., and Arthur DeCross, M.D., who work closely with a community group called Strollin’ for the Colon, which was started by a family with Lynch syndrome and which is funding some of Findeis-Hosey’s research.

“This is the type of research that will have an impact on national guidelines,” DeCross says. “The old clinical guidelines of identifying Lynch families are hard to apply today where nuclear families are smaller.”

Earlier identification means that individuals with Lynch syndrome may begin cancer screenings at younger ages and more frequently than the national recommendations. That means that their cancers may be caught earlier, giving them more treatment options.

“Early detection is so important,” says Tina Cottone, who started Strollin’ for the Colon. “It saves lives.”

It also requires a system that ensures these individuals have genetic testing in a timely manner and that meets their ongoing needs, a feat proving more complicated than the science.

“The science is straightforward,” Findeis-Hosey says. “But you need a multimodal process to make sure people get the genetic testing.”

Once a person is identified as a candidate for testing, they have to be referred to Genetics by their primary care provider, surgeon or other physician. Because the pathologists can’t make that connection directly, Findeis-Hosey is working with DeCross and involving their colleagues from Gastroenterology, Gynecologic Oncology and Hematology/Oncology to close that gap. They are also collaborating to create a multidisciplinary clinic for individuals at high risk for certain cancers because of genetic predisposition.

“We are pulling in other disease areas because Lynch syndrome isn’t just colorectal cancers,” Findeis-Hosey says. It can also lead to endometrial, ovarian, urinary tract, stomach and liver/bile duct cancers, among others.

They are also working to educate community physicians — including primary care physicians and gastroenterologists — about Lynch syndrome and the importance of testing patients who are at risk.

“Community education is key,” Marino says. “Hopefully we can identify families earlier and ultimately prevent some cancers.”