TY - JOUR
T1 - Use of microsatellite instability and immunohistochemistry testing for the identification of individuals at risk for Lynch syndrome
AU - Baudhuin, Linnea M.
AU - Burgart, Lawrence J.
AU - Leontovich, Olga
AU - Thibodeau, Stephen N.
PY - 2005/9
Y1 - 2005/9
N2 - It is now generally recognized that a specific subset of those patients clinically defined as having hereditary non polyposis colon cancer (HNPCC) have germline mutations in any one of several genes involved in DNA mismatch repair (MMR). This important subset of HNPCC families is now defined as having Lynch syndrome. A considerable amount of data has shown that tumors from patients with Lynch syndrome have characteristic features resulting from the underlying molecular involvement of defective MMR, that is, the presence of microsatellite instability (MSI) and the absence of MMR protein expression by immunohistochemistry (IHC). As a result, identifying patients with Lynch syndrome can now be accomplished by testing tumors for these tumor-related changes. Together, MSI and IHC are powerful tools that help identify individuals at risk for having Lynch syndrome and to distinguish these cases from HNPCC cases with other hereditary gene defects. Furthermore, IHC analysis provides valuable clues as to which MMR gene is mutated, allowing for comprehensive mutational analyses of that gene. Here, we discuss the current and historical perspectives regarding MSI and IHC analyses in tumors from sporadic colon cancer and from patients with Lynch syndrome. Given this background, we also provide a testing strategy for the identification of patients at risk for Lynch syndrome and subsequent gene testing.
AB - It is now generally recognized that a specific subset of those patients clinically defined as having hereditary non polyposis colon cancer (HNPCC) have germline mutations in any one of several genes involved in DNA mismatch repair (MMR). This important subset of HNPCC families is now defined as having Lynch syndrome. A considerable amount of data has shown that tumors from patients with Lynch syndrome have characteristic features resulting from the underlying molecular involvement of defective MMR, that is, the presence of microsatellite instability (MSI) and the absence of MMR protein expression by immunohistochemistry (IHC). As a result, identifying patients with Lynch syndrome can now be accomplished by testing tumors for these tumor-related changes. Together, MSI and IHC are powerful tools that help identify individuals at risk for having Lynch syndrome and to distinguish these cases from HNPCC cases with other hereditary gene defects. Furthermore, IHC analysis provides valuable clues as to which MMR gene is mutated, allowing for comprehensive mutational analyses of that gene. Here, we discuss the current and historical perspectives regarding MSI and IHC analyses in tumors from sporadic colon cancer and from patients with Lynch syndrome. Given this background, we also provide a testing strategy for the identification of patients at risk for Lynch syndrome and subsequent gene testing.
KW - HNPCC
KW - Immunohistochemistry
KW - Lynch syndrome
KW - Microsatellite instability
KW - Mismatch repair
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U2 - 10.1007/s10689-004-1447-6
DO - 10.1007/s10689-004-1447-6
M3 - Review article
C2 - 16136387
AN - SCOPUS:24144493178
SN - 1389-9600
VL - 4
SP - 255
EP - 265
JO - Familial Cancer
JF - Familial Cancer
IS - 3
ER -