June 8, 2011 — Colon cancer presenting in a patient younger than 50 years of age raises the suspicion that the patient has Lynch syndrome, a genetic hereditary disorder that increases susceptibility to cancer. These individuals have an increased risk for colorectal cancer, and women have an increased risk for uterine and ovarian cancer. Identifying these individuals is important because they can benefit from increased surveillance and possibly other interventions.
However, screening for Lynch syndrome is still somewhat controversial, and there is ongoing discussion about what criteria should be met before such screening is carried out. "Personally, I think that if an individual presents with colon cancer before the age of 50, that is sufficient by itself to warrant screening for Lynch syndrome," said Eric Dozois, MD, from the division of colon and rectal surgery at the Mayo Clinic in Rochester, Minnesota. "But this is not set in stone," he added.
Preoperative screening of such patients is the best approach, because individuals who are found to have Lynch syndrome can be treated differently (e.g., with more extensive surgery), Dr. Dozois explained in an interview with Medscape Medical News.
If such individuals are not screened preoperatively, there is another chance to catch them after surgery. To do this, Dr. Dozois and colleagues developed a protocol for reflex testing of tumor tissue removed during surgery.
The team reported 5-year data for this protocol at the recent American Society of Colon and Rectal Surgeons Annual Meeting, held in Vancouver, British Columbia, Canada.
Initial testing was carried out using microsatellite instability (MSI), and patients who were categorized as high for MSI were offered additional testing, which can identify germline mutations that confirm Lynch syndrome, and genetic counseling.
In the case series that Dr. Dozois and colleagues report, the MSI test was carried out in 210 of 258 newly diagnosed patients younger than 50 years of age. It was done preoperatively in 128 patients and postoperatively in 82 patients.
In total, 13% (n = 28) of patients were found to have high MSI tumors — 15% of those tested preoperatively and 11% of those tested postoperatively.
Of these 28 patients with high MSI tumors, 16 agreed to undergo germline mutation testing; 9 patients tested preoperatively and 1 tested postoperatively were found to have Lynch syndrome.
The researchers conclude that adding reflex testing after surgery was useful. It increased the testing rate to 88%, and in their series, such testing found 1 extra patient with Lynch syndrome. Without this reflex testing protocol in place, 32% of tumors with high MSI would have been missed, they report.
Nevertheless, even though this protocol captured most of the missed patients, the ideal approach is to screen high-risk patients for Lynch syndrome preoperatively, they note, because it has an impact on surgical recommendations.
"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 high risk to providers experienced with the management of Lynch syndrome," Dr. Dozois said in a statement. He has organized such a team at the Mayo Clinic, known as the Young Onset Working Group. Working together, the team can ensure that patients who are identified as having Lynch syndrome receive appropriate evaluation and genetic and surgical counseling before critical treatment decisions are made.
"The benefit of this testing to the patient and his/her family is huge," said Rajesh Pendlimari, MBBS, a research fellow and first author of the abstract. "If they have Lynch syndrome, they will, therefore, be more prone to getting cancer, and they can get screened more regularly. Plus, with it being a hereditary condition, family members can also get tested," he said in the statement.
Recommendations Already Published
When approached for comment on this study. Heather Hampel, MS, CGC, associate director of the division of human genetics at Ohio State University (OSU) Comprehensive Cancer Center in Columbus, said it was not clear what exactly is new.
MSI is one method of screening for Lynch syndrome, but immunohistochemistry (IHC) can also be used, she explained, adding that her center prefers IHC because it is more cost-effective.
"Many centers screen all patients with colorectal cancer for Lynch syndrome, as we do at OSU," she explained; others use an age cut-off, as was done in the Mayo Clinic study (below 50 years). She also noted that the Evaluation of Genomic Applications in Prevention and Practice (EGAPP) group recommended in 2009 that all colorectal cancer patients be screened for Lynch syndrome (Genet Med. 2009;11:35-41).
American Society of Colon and Rectal Surgeons Annual Meeting. Abstract S24 presented May 17, 2011.
However, screening for Lynch syndrome is still somewhat controversial, and there is ongoing discussion about what criteria should be met before such screening is carried out. "Personally, I think that if an individual presents with colon cancer before the age of 50, that is sufficient by itself to warrant screening for Lynch syndrome," said Eric Dozois, MD, from the division of colon and rectal surgery at the Mayo Clinic in Rochester, Minnesota. "But this is not set in stone," he added.
Preoperative screening of such patients is the best approach, because individuals who are found to have Lynch syndrome can be treated differently (e.g., with more extensive surgery), Dr. Dozois explained in an interview with Medscape Medical News.
If such individuals are not screened preoperatively, there is another chance to catch them after surgery. To do this, Dr. Dozois and colleagues developed a protocol for reflex testing of tumor tissue removed during surgery.
The team reported 5-year data for this protocol at the recent American Society of Colon and Rectal Surgeons Annual Meeting, held in Vancouver, British Columbia, Canada.
Initial testing was carried out using microsatellite instability (MSI), and patients who were categorized as high for MSI were offered additional testing, which can identify germline mutations that confirm Lynch syndrome, and genetic counseling.
In the case series that Dr. Dozois and colleagues report, the MSI test was carried out in 210 of 258 newly diagnosed patients younger than 50 years of age. It was done preoperatively in 128 patients and postoperatively in 82 patients.
In total, 13% (n = 28) of patients were found to have high MSI tumors — 15% of those tested preoperatively and 11% of those tested postoperatively.
Of these 28 patients with high MSI tumors, 16 agreed to undergo germline mutation testing; 9 patients tested preoperatively and 1 tested postoperatively were found to have Lynch syndrome.
The researchers conclude that adding reflex testing after surgery was useful. It increased the testing rate to 88%, and in their series, such testing found 1 extra patient with Lynch syndrome. Without this reflex testing protocol in place, 32% of tumors with high MSI would have been missed, they report.
Nevertheless, even though this protocol captured most of the missed patients, the ideal approach is to screen high-risk patients for Lynch syndrome preoperatively, they note, because it has an impact on surgical recommendations.
"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 high risk to providers experienced with the management of Lynch syndrome," Dr. Dozois said in a statement. He has organized such a team at the Mayo Clinic, known as the Young Onset Working Group. Working together, the team can ensure that patients who are identified as having Lynch syndrome receive appropriate evaluation and genetic and surgical counseling before critical treatment decisions are made.
"The benefit of this testing to the patient and his/her family is huge," said Rajesh Pendlimari, MBBS, a research fellow and first author of the abstract. "If they have Lynch syndrome, they will, therefore, be more prone to getting cancer, and they can get screened more regularly. Plus, with it being a hereditary condition, family members can also get tested," he said in the statement.
Recommendations Already Published
When approached for comment on this study. Heather Hampel, MS, CGC, associate director of the division of human genetics at Ohio State University (OSU) Comprehensive Cancer Center in Columbus, said it was not clear what exactly is new.
MSI is one method of screening for Lynch syndrome, but immunohistochemistry (IHC) can also be used, she explained, adding that her center prefers IHC because it is more cost-effective.
"Many centers screen all patients with colorectal cancer for Lynch syndrome, as we do at OSU," she explained; others use an age cut-off, as was done in the Mayo Clinic study (below 50 years). She also noted that the Evaluation of Genomic Applications in Prevention and Practice (EGAPP) group recommended in 2009 that all colorectal cancer patients be screened for Lynch syndrome (Genet Med. 2009;11:35-41).
American Society of Colon and Rectal Surgeons Annual Meeting. Abstract S24 presented May 17, 2011.
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I always hope that there is better answer.
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