Information for Health Professionals, Lynch Syndrome

Preoperative Testing For Lynch Syndrome Yields ‘Huge’ Benefit


Preoperative Testing For Lynch Syndrome Yields ‘Huge’ Benefit

Vancouver, British Columbia—Mayo Clinic researchers are calling for all young patients with colorectal cancer (CRC) to undergo preoperative testing for Lynch syndrome as the results can significantly alter surgical management.

“The benefit of this testing to the patient and their family is huge,” said Rajesh Pendlimari, MBBS, a research fellow at Mayo Clinic in Rochester, Minn., and a study investigator.

“If they have Lynch syndrome and will, therefore, be more prone to getting cancer, they can get screened more regularly. The knowledge gleaned can change the course of surgical treatment.”

At the 2011 annual meeting of the American Society of Colon and Rectal Surgeons, the Mayo team presented two studies examining the benefit of pre- and postoperative microsatellite instability (MSI) testing for Lynch syndrome.

In the first study, 210 of 258 newly diagnosed patients younger than age 50 years who underwent colorectal surgery at Mayo Clinic had MSI testing between 2003 and 2008. Of these, 82 underwent testing postoperatively, according to the hospital’s protocol requiring pathologists to complete MSI testing on operative specimens for all young patients who did not have the tests done prior to surgery. Overall, 13% of patients were found to have high levels of MSI and 33% of these would have been missed without the testing protocol.

The second, complementary paper retrospectively compared the surgical management of 210 patients who were tested pre- and postoperatively for MSI (n=103, n=107, respectively). (The number of patients in the postoperative group differs in the two studies: It is listed as 82 in the first study and 107 in the second because 25 patients underwent preoperative testing on the day of surgery; their results were not available to surgeons before operating.)

Results showed that the MSI test results significantly influenced surgical recommendations for total colectomy. Of patients with positive preoperative MSI tests (MSI-H), 94% underwent total colectomy, compared with 8% of patients whose status was not known until after surgery (P<0.0001). Moreover, there appears to be an increased rate of hysterectomy among women with MSI-H. Eight of 10 MSI-H women had a hysterectomy. There was only one female patient who was tested postoperatively and she did not have a hysterectomy.

“Probably the most significant result of this research is that it has stimulated our multidisciplinary team of geneticists, pathologists, gastroenterologists and surgeons to develop new clinical pathways that will direct patients at risk to providers experienced with management of Lynch syndrome,” said Eric Dozois, MD, professor of surgery at Mayo Clinic and lead researcher on the project.

Other gastroenterologists and surgeons applauded the paper, saying that preoperative testing for Lynch syndrome is easy to do and can dramatically affect surgical treatment.

“Virtually everybody [who] gets an operation for colorectal cancer has a colonoscopy or biopsy of the tumor before they go on to surgery. In my opinion, that is a golden opportunity, since you are taking a biopsy anyway, to get the cascade of evaluation going for the possible presence of HNPCC [hereditary nonpolyposis colorectal cancer],” said Patrick Lynch, MD, professor of medicine in the Department of Gastroenterology, Hepatology and Nutrition at the University of Texas MD Anderson Cancer Center in Houston.

He added that endoscopists should not skip the opportunity for testing during colonoscopic biopsy.

“It doesn’t take that much material, it’s easy to do and you’re doing it at the front end of a window of opportunity that exists between that time and when the patient goes to surgery. The surgeon and the patient can use that information to decide if they want to expand the surgery from a simple segmental resection to a subtotal colectomy.”

Preoperative testing could improve treatment for younger patients, a group that is showing increased incidence of CRC, said Michael Stamos, MD, professor and chair of surgery at the University of California, Irvine, where surgeons and gastroenterologists routinely do immunohistochemistry (IHC) staining testing prior to surgery.

The Mayo Clinic team has developed a new clinical pathway (Figure) for testing and treatment of patients at high risk for CRC. The protocol requires all high-risk patients to undergo either MSI or IHC to test for Lynch syndrome prior to surgery.

It’s still unclear which test is best to start with. Although MSI is the gold standard test for the DNA mismatch repair, it does have some disadvantages such as a slow turnaround time and it requires an advanced and experienced lab as well as more testing than IHC. Individuals with positive results still need to undergo IHC. On the other hand, IHC requires an experienced pathologist and detects abnormalities of only four major genes.

The best test depends on the local expertise, said Dr. Stamos.

Of every 35 patients with CRC, one has Lynch syndrome, the most common hereditary cause of colorectal and endometrial cancers.

The last guideline on screening was the 2004 Revised Bethesda Guideline, which calls for MSI screening for anyone with young-onset (<50 years old) CRC, synchronous or metachronous CRC or HNPCC-associated cancer at any age, CRC in a patient under age 60 years with tumor-infiltrating T lymphocytes, mucinous/signet ring differentiation or Crohn’s-like lymphocytic reaction, or for patients of any age with a first-degree relative with an HNPCC-related tumor before age 50, or two first- or second-degree relatives with HNPCC tumors at any age.

“Since those guidelines, we’ve discovered a new gene,” said Dr. Pendlimari. “Our understanding of this disease is changing considerably.”

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About kjmonahan

Service lead for Family History of Bowel Cancer Clinic

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