Gastroenterology

Gastroenterology

Volume 121, Issue 4, October 2001, Pages 1005-1008
Gastroenterology

Editorials
HNPCC: An uncommon but important diagnosis

https://doi.org/10.1053/gast.2001.28634Get rights and content

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How common is HNPCC?

In this issue of GASTROENTEROLOGY, Samowitz et al.9 make a valuable contribution to our understanding of the frequency of HNPCC in the general population of the United States. They determined by genetic criteria the burden of colon cancer associated with HNPCC in a population-based sample of 1066 individuals from Utah and California. Microsatellite instability was present in 16% of the 1066 tumors. Individuals with MSI tumors then underwent germline genetic testing. Pathogenic mutations in MSH2

When should HNPCC be suspected, and how should the diagnosis be made?

The data indicate that MSH2 or MLH1 gene carriers account for a small fraction of CRC cases. This does not mean that HNPCC is an unimportant diagnosis to establish. Unlike familial adenomatous polyposis, HNPCC does not have a characteristic phenotype. Obtaining a personal and family cancer history from all patients is critical, and a high index of suspicion needs to be maintained if individuals with HNPCC are to be detected. Many diagnostic criteria have been proposed for HNPCC, the best known

Population-based screening for HNPCC?

Is it time to advocate population-based molecular detection of HNPCC? Such an approach to the diagnosis of HNPCC appears feasible. Salovaara et al.13 have proposed MSI testing of all colorectal tumors from individuals younger than 50 years of age who were diagnosed, those with multiple primary cancers of the colorectum and/or endometrium, or those with a first-degree relative with colorectal or endometrial cancer. Individuals found to have MSI-H tumors would then undergo germline MSH2 and MLH1

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  • Cited by (12)

    • Molecular basis of diseases of the gastrointestinal tract

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    • Hereditary cancer syndromes as model systems for chemopreventive agent development

      2016, Seminars in Oncology
      Citation Excerpt :

      MSH2/MLH1 mutation-associated colorectal cancers account for about 50% of the excess colorectal cancers observed in first-degree relatives of a familial colorectal cancer case [111]. Estimated carrier frequency of germline mutations in these genes in the population range from about 1 in 300 to 1 in 3,000 [110,112–116]. Nearly 90% of the mutations in MMR genes in LS are located in MLH1 and MSH2 and approximately 10% in MSH6 and PMS2 [117].

    • Molecular Basis of Diseases of the Gastrointestinal Tract

      2009, Molecular Pathology: The Molecular Basis of Human Disease
    • Microsatellite instability and DNA mismatch repair deficiency testing in hereditary and sporadic gastrointestinal cancers

      2005, Clinics in Laboratory Medicine
      Citation Excerpt :

      MSH2 and MLH1 protein immunostaining showed loss of protein expression in 94% of tumors from probands with germline mutations or variants. These data indicate that detection of high-frequency MSI or loss of MSH2 or MLH1 immunostaining in colorectal adenocarcinomas are useful criteria for selecting high-risk patients who should be tested for germline mutations in MSH2 or MLH1 [53,54]. Another study by Halversson et al [55] evaluated MSI status and expression of MLH1, MSH2, and MSH6 by IHC stains in colon cancers of patients suspected of having HNPCC.

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    Address requests for reprints to: Jonathan P. Terdiman, M.D., Box 1623, University of California, San Francisco, San Francisco, California 94143. e-mail: [email protected]; fax: (415) 502-2249.

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