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Microsatellite instability and DNA mismatch repair deficiency testing in hereditary and sporadic gastrointestinal cancers.
Clin Lab Med. 2005 Mar; 25(1):179-96.CL

Abstract

The reference cancers associated with DNA mismatch repair (MMR)deficiency are the adenocarcinomas of patients with hereditary nonpolyposis colorectal cancer, also known as Lynch syndrome. Sporadic gastrointestinal (GI) carcinomas, most commonly colorectal and gastric carcinomas, may also be associated with deficiencies of DNA mismatch repair. Deficiency in cellular MMR leads to wide-spread mutagenesis and neoplastic development and progression. An important diagnostic feature of MMR-deficient tumors is the high rate of mutations that accumulate in repetitive nucleotide regions, and these mutations are known as microsatellite instability(MSI). A standard panel of markers to test for MSI in tumors has been recommended and efficiently separates tumors into those with high, low, or no microsatellite instability (MSI-H, MSI-L, or MSS). Tumors characterized by MSI-H characteristically show loss of one of the main DNA MMR proteins, mLH1 or MSH2, and rarely MSH6 and PMS2, detected by immunohistochemistry (IHC). The combination of MSI testing and IHC for MMR proteins in tumors tissues is used to identify underlying DNA MMR deficiency andis clinically relevant screen patients who might have hereditary non-polyposis colorectal cancer for DNA repair gene germline testing. Increasing evidence demonstrates that tumors with a positive MSI status have lower lymph node metastases burden, and these patients have an overall improved survival, suggesting that the MSI and MMR status may contribute to decision making regarding treatment approaches. Updated guidelines for MSI and IHC for DNAMMR testing, and the biological and potential clinical implications of MMR deficiency and microsatellite instability in GI polyps and cancers are reviewed.

Authors+Show Affiliations

Department of Pathology, University of Pittsburgh, PUH-A610, 100 Lothrop Street, Pittsburgh, PA 15213-2582, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.
Review

Language

eng

PubMed ID

15749237

Citation

Gologan, Adrian, and Antonia R. Sepulveda. "Microsatellite Instability and DNA Mismatch Repair Deficiency Testing in Hereditary and Sporadic Gastrointestinal Cancers." Clinics in Laboratory Medicine, vol. 25, no. 1, 2005, pp. 179-96.
Gologan A, Sepulveda AR. Microsatellite instability and DNA mismatch repair deficiency testing in hereditary and sporadic gastrointestinal cancers. Clin Lab Med. 2005;25(1):179-96.
Gologan, A., & Sepulveda, A. R. (2005). Microsatellite instability and DNA mismatch repair deficiency testing in hereditary and sporadic gastrointestinal cancers. Clinics in Laboratory Medicine, 25(1), 179-96.
Gologan A, Sepulveda AR. Microsatellite Instability and DNA Mismatch Repair Deficiency Testing in Hereditary and Sporadic Gastrointestinal Cancers. Clin Lab Med. 2005;25(1):179-96. PubMed PMID: 15749237.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Microsatellite instability and DNA mismatch repair deficiency testing in hereditary and sporadic gastrointestinal cancers. AU - Gologan,Adrian, AU - Sepulveda,Antonia R, PY - 2005/3/8/pubmed PY - 2005/5/5/medline PY - 2005/3/8/entrez SP - 179 EP - 96 JF - Clinics in laboratory medicine JO - Clin. Lab. Med. VL - 25 IS - 1 N2 - The reference cancers associated with DNA mismatch repair (MMR)deficiency are the adenocarcinomas of patients with hereditary nonpolyposis colorectal cancer, also known as Lynch syndrome. Sporadic gastrointestinal (GI) carcinomas, most commonly colorectal and gastric carcinomas, may also be associated with deficiencies of DNA mismatch repair. Deficiency in cellular MMR leads to wide-spread mutagenesis and neoplastic development and progression. An important diagnostic feature of MMR-deficient tumors is the high rate of mutations that accumulate in repetitive nucleotide regions, and these mutations are known as microsatellite instability(MSI). A standard panel of markers to test for MSI in tumors has been recommended and efficiently separates tumors into those with high, low, or no microsatellite instability (MSI-H, MSI-L, or MSS). Tumors characterized by MSI-H characteristically show loss of one of the main DNA MMR proteins, mLH1 or MSH2, and rarely MSH6 and PMS2, detected by immunohistochemistry (IHC). The combination of MSI testing and IHC for MMR proteins in tumors tissues is used to identify underlying DNA MMR deficiency andis clinically relevant screen patients who might have hereditary non-polyposis colorectal cancer for DNA repair gene germline testing. Increasing evidence demonstrates that tumors with a positive MSI status have lower lymph node metastases burden, and these patients have an overall improved survival, suggesting that the MSI and MMR status may contribute to decision making regarding treatment approaches. Updated guidelines for MSI and IHC for DNAMMR testing, and the biological and potential clinical implications of MMR deficiency and microsatellite instability in GI polyps and cancers are reviewed. SN - 0272-2712 UR - https://www.unboundmedicine.com/medline/citation/15749237/Microsatellite_instability_and_DNA_mismatch_repair_deficiency_testing_in_hereditary_and_sporadic_gastrointestinal_cancers_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0272-2712(04)00110-6 DB - PRIME DP - Unbound Medicine ER -