Unusual tumors associated with the hereditary nonpolyposis colorectal cancer syndrome
Open accessAbstract
The molecular pathogenesis of tumors outside the usual tumor spectrum for hereditary nonpolyposis colorectal cancer (HNPCC) is currently controversial. Specifically, it is not known whether these tumors are related to defects in DNA mismatch repair or arise independently of this defect in these patients. Here, we report two young patients, each with a known MSH2 mutation in the family, who developed rare tumors (adrenal cortical carcinoma and anaplastic carcinoma of the thyroid) that are not usually associated with HNPCC. Both of these patients were members of families that fulfilled modified Amsterdam (Amsterdam II) criteria for this familial cancer syndrome. Both the adrenal tumor and the thyroid tumor showed complete loss of immunohistochemical expression for MSH2 protein. Neither tumor was considered microsatellite instability-high following microsatellite instability analysis using the established National Cancer Institute panel of five microsatellite markers. To our knowledge, MSH2 defects in these types of tumors have not been previously reported in patients with the HNPCC syndrome. Our results suggest that microsatellite instability analysis using the National Cancer Institute panel of five microsatellite markers may not detect microsatellite instability in tumors that fall outside the usual tumor spectrum of this syndrome. Therefore, when analyzing unusual tumors in patients with known or suspected HNPCC syndrome, we advocate the performance of immunohistochemistry for mismatch repair gene products in addition to microsatellite instability analysis.
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ACC has been reported in patients with Lynch syndrome.
“ACC has also been reported in patients with Lynch syndrome (53–56).”
From Adrenocortical carcinoma (2014) · cites this paper as [56]
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- Authors
- Broaddus, R. R., Lynch, P. M., Lu, K. H., Luthra, R., & Michelson, S. J.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Broaddus, Russell R
- ORCID
- Broaddus, Russell R
- Venue
- Modern Pathology
- Publisher
- Elsevier BV
- Published
- 2004-08
- Volume
- 17
- Issue
- 8
- Pages
- 981-989
- ISSN
- 0893-3952 (ISSN-L)
- OpenAlex
- W2093733641
- Cited by
- 69
- References
- 31
- Citations by year
- 2026: 1 · 2024: 4 · 2022: 2 · 2021: 5 · 2020: 2 · 2019: 6 · 2018: 5 · 2017: 7 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 8 · 2012: 5
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Modern Pathology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- Lynch syndrome, MSH2 mutation, DNA mismatch repair, adrenocortical carcinoma, anaplastic thyroid carcinoma, microsatellite instability, Amsterdam criteria, tumor spectrum, molecular pathogenesis
- MeSH terms
- MutL Protein Homolog 1, Adrenal Cortex Neoplasms, Adult, Carrier Proteins, Colorectal Neoplasms, Hereditary Nonpolyposis, DNA Mutational Analysis, DNA-Binding Proteins, DNA, Neoplasm, Female, Humans, Immunohistochemistry, Male, Neoplasm Proteins, Nuclear Proteins, Proto-Oncogene Proteins, Syndrome, Thyroid Neoplasms, Microsatellite Repeats, DNA Methylation, Adaptor Proteins, Signal Transducing, MutS Homolog 2 Protein
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