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Cancer Health Center

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Genetics of Colorectal Cancer (PDQ®): Genetics - Health Professional Information [NCI] - Major Genetic Syndromes

Table 10. Clinical Practice Guidelines for Colon Surveillance of BiallelicMYH-Associated Polyposis (MAP) continued...

The research criteria for defining LS families were established by the International Collaborative Group (ICG) meeting in Amsterdam in 1990 and are known as the Amsterdam criteria.[257] These criteria were limited to CRC. In 1999, the Amsterdam criteria were revised to include some extracolonic cancers.[258] These criteria provide a general approach to identifying LS families, but they are not considered comprehensive; a number of families who do not meet these criteria, but have germline MMR gene mutations, have been reported.

Amsterdam criteria I (1990):

  1. One member diagnosed with CRC before age 50 years.
  2. Two affected generations.
  3. Three affected relatives, one of them a first-degree relative of the other two.
  4. FAP should be excluded.
  5. Tumors should be verified by pathological examination.

Amsterdam criteria II (1999):

  • Same as Amsterdam criteria I, but tumors of the endometrium, small bowel, ureter, or renal pelvis can be used to substitute an otherwise qualifying CRC.

Although these criteria are the most stringent used to identify potential candidates for microsatellite and germline testing, it must be cautioned that by definition, FCCX includes families meeting Amsterdam criteria but in whom there is no evidence of MSI. (Refer to the Familial colorectal cancer type X (FCCX) section in the Major Genetic Syndromes section of this summary for more information.)

Recognizing both the relative insensitivity of the Amsterdam criteria and the increasing importance of tumor-based testing for detecting LS, the Bethesda guidelines were developed. The Bethesda guidelines and a subsequent revision were formulated to improve sensitivity by targeting patients whose tumors would be most likely to show MSI.[259,260] (Refer to the Genetic/molecular Testing for LS section in the Major Genetic Syndromes section of this summary for more information about testing for MSI and IHC.)

Bethesda guidelines (1997):

  1. Cancer in families that meet the Amsterdam criteria.
  2. The presence of two LS-related cancers, including synchronous and metachronous CRCs or associated extracolonic cancers. Endometrial, ovarian, gastric, hepatobiliary, or small-bowel cancer or transitional cell carcinoma of the renal pelvis or ureter.
  3. The presence of CRC and a first-degree relative with CRC and/or LS-related extracolonic cancer and/or a colorectal adenoma; one of the cancers diagnosed before age 45 years, and the adenoma diagnosed before age 40 years.
  4. CRC or endometrial cancer diagnosed before age 45 years.
  5. Right-sided CRC with an undifferentiated pattern (solid/cribriform) on histopathology diagnosed before age 45 years. Solid/cribriform defined as poorly differentiated or undifferentiated carcinoma composed of irregular, solid sheets of large eosinophilic cells and containing small gland-like spaces.
  6. Signet-ring-cell-type CRC diagnosed before age 45 years. Composed of more than 50% signet ring cells.
  7. Adenomas diagnosed before age 40 years.
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