Bethesda criteria
The Bethesda criteria are a standardized set of guidelines designed to identify individuals who may have hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome. This autosomal dominant condition is characterized by an early onset of colorectal cancer, typically before the age of 45, and can lead to tumors in various other tissues, including endometrial and ovarian cancers. The Bethesda criteria were established in 1997 and expanded in 2002 to incorporate additional factors such as the presence of extracolonic tumors and specific histological characteristics. They help differentiate hereditary cases from sporadic colorectal cancer, which is crucial given that HNPCC accounts for a small percentage of colorectal cancer cases.
Key elements of the criteria include early-onset colorectal cancer, a family history of HNPCC-related tumors, and high microsatellite instability (MSI). If individuals meet these criteria, they are recommended to undergo genetic and molecular testing to assess the condition more thoroughly. Testing typically involves evaluating MSI status and may include sequencing specific genes like MSH2 and MLH1, which, when mutated, indicate a higher risk for cancer. The Bethesda criteria serve as an important tool for healthcare providers in identifying at-risk patients and guiding appropriate screening and preventive measures.
Bethesda criteria
DEFINITION: Bethesda criteria are a standardized set of criteria used to identify potential cases of hereditary nonpolyposis colorectal cancer (also known as Lynch syndrome) (HNPCC), or Lynch syndrome.
Hereditary nonpolyposis colorectal cancer: HNPCC is an autosomal dominant disease that is characterized by early age of onset (average is before the age of forty-five), tumor formation in a variety of tissues (endometrial, gastric, renal, ovarian, and skin), and microsatellite instability. HNPCC accounts for only about 2 to 7 percent of the cases of colorectal cancer, and the molecular and genetic testing that is required to diagnose this form of cancer can be quite time-consuming and costly. Therefore, it became important to set down a standardized set of criteria for identifying potential cases of HNPCC and to separate them from sporadic, noninherited forms of colorectal cancer.
History: In 1997, a group of experts met at the National Institutes of Health to discuss the state of research on HNPCC. They produced a set of criteria, the Bethesda criteria, which expanded the previous Amsterdam criteria to include extracolonic tumor formation as well as more specific histological characterization. In 2002, the criteria were further revised to define tumors that should be tested for microsatellite instability (MSI), which is the frequent mutation of repetitive deoxyribonucleic acid (DNA) sequences due to defects in the mismatch repair machinery in the cell.
Criteria: The criteria for identifying a potential case of HNPCC are as follows:
- Colorectal cancer diagnosed prior to age fifty
- Presence of synchronous or metachronous HNPCC-associated tumors
- High microsatellite instability (MSI-H) histology diagnosed prior to age sixty
- One or more first-degree relatives diagnosed with an HNPCC-related tumor prior to age fifty
- Colorectal cancer diagnosed in two or more first- or second-degree relatives
Testing: Several molecular and genetic tests are recommended if a patient meets the Bethesda criteria. The ideal set of tests would include evaluating microsatellite instability status and immunohistochemical analysis of tumors. In patients with high levels of microsatellite instability and loss of expression of one or more DNA mismatch repair proteins, DNA sequencing of MSH2 and MLH1, the two genes most commonly mutated in HNPCC, should be performed. Patients who have mutations in either of these genes show an increased risk of developing cancer, and they should, therefore, undergo frequent screening.
Bibliography
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