NEW YORK (Reuters Health) - Revised Bethesda Guidelines specify criteria for testing colorectal tumors for microsatellite instability (MSI), and for testing patients with hereditary nonpolyposis colorectal cancer (HNPCC) and their relatives, according to a report in the February 18th Journal of the National Cancer Institute.
At least three DNA mismatch repair genes (MSH2, MLH1, and MSH6) have been linked to HNPCC, a common syndrome characterized by the development of neoplastic lesions in a variety of tissues at an early age (younger than 45 years), the authors explain. This syndrome is marked by microsatellite instability, which is also apparent in 15% of all colorectal cancers.
Dr. Asad Umar from National Cancer Institute (NCI), Bethesda, Maryland and colleagues developed revised Bethesda Guidelines for identifying individuals with NHPCC and recommended criteria for MSI testing in a 2002 HNPCC workshop conducted by NCI.
“Recent advances in genomics and proteomics are bringing promising new approaches for the early diagnosis of cancer,” Dr. Umar commented to Reuters Health. “However, our main challenge remains with the implementation of existing screening and surveillance strategies that have already been shown to reduce mortality from colorectal cancer, and are currently recommended in standard clinical practice.”
HNPCC requires particularly close attention. “People with Lynch syndrome (HNPCC) are recommended by AGA to have a colonoscopy every 1-2 years, ten years earlier than the youngest age of colon cancer diagnosis in the family or beginning at age 20-25 years - whichever comes first,” Dr. Umar explained,
“Genetic testing for HNPCC should be offered to first-degree relatives of persons with a known inherited gene mutation,” he continued. “The revised Bethesda guidelines try to simplify approaches to the decision process for genetic testing among high-risk individuals.”
The Revised Bethesda Guidelines recommend testing tumors for MSI in five settings:
(1) colorectal cancer diagnosed in a patient younger than 50 years;
(2) presence of synchronous, metachronous colorectal, or HNPCC-associated tumors, regardless of age;
(3) colorectal cancer with high-MSI histology in a patient younger than 60 years;
(4) colorectal cancer diagnosed in at least one first-degree relative with an HNPCC-related tumor, with one of the cancers being diagnosed under age 50 years;
(5) colorectal cancer diagnosed in at least 2 first- or second-degree relatives with HNPCC-related tumors, regardless of age.
Although the Bethesda Guidelines may be the most efficient strategy for identifying HNPCC patients, workshop presenter Dr. Scott Ramsey from Fred Hutchinson Cancer Research Center, Seattle, Washington said, “the cost-effectiveness of this method depends on locating, testing, and screening first-degree relatives of patients identified with mismatch repair gene mutations.”
Because the original NCI 5-marker microsatellite panel for evaluation of MSI might underestimate the number of high-MSI tumors and overestimate the number of low-MSI tumors, the participants suggested that a pentaplex panel of 5 quasi-monomorphic mononucleotide markers should be included in the evaluation of MSI.
Once an individual is identified as having a mutation responsible for HNPCC, the participants recommend referral of at-risk relatives for genetic counseling and possible testing. Even if no such mutation is found, patients whose tumors show high MSI should be counseled as if HNPCC was confirmed and high-risk surveillance should be undertaken.
Summing up, Dr. Umar said the main message from this report ought to be to underscore the importance of microsatellite instability (i.e., defects in mismatch repair) in colorectal cancer development, and its implications for family members.
“Specifically, the bar to initial testing for this pathogenesis has been lowered a bit in hopes of identifying more individuals - and family members - with this disease; screening and surveillance helps to improve quality and duration of life.”
Source: J Natl Cancer Inst 2004;96:261-268. [ Google search on this article ]
MeSH Headings:Colonic Diseases: Colorectal Neoplasms, Hereditary Nonpolyposis: Digestive System Neoplasms: Gastrointestinal Neoplasms: Health Occupations: Health Services Administration: Intestinal Neoplasms: Neoplasms: Neoplasms by Site: Neoplastic Syndromes, Hereditary: Quality Assurance, Health Care: Quality of Health Care: Colorectal Neoplasms: Guidelines: Health Care Quality, Access, and Evaluation: Biological Sciences: Diseases: Health CareCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
