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Antibody‐based screening for hereditary nonpolyposis colorectal carcinoma compared with microsatellite analysis and sequencing
Author(s) -
Christensen Mariann,
Katballe Niels,
Wikman Friedrik,
Primdahl Hanne,
Sørensen Flemming B.,
Laurberg Søren,
Ørntoft Torben F.
Publication year - 2002
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.10979
Subject(s) - msh2 , mlh1 , microsatellite instability , dna mismatch repair , microsatellite , lynch syndrome , medicine , immunohistochemistry , germline mutation , colorectal cancer , carcinoma , concordance , pathology , cancer , genetics , mutation , biology , gene , allele
BACKGROUND Germline mutations in the DNA mismatch repair genes, MSH2 , MLH1 , and others are associated with hereditary nonpolyposis colorectal cancer (HNPCC). Due to the high costs of sequencing, cheaper screening methods are needed to identify HNPCC cases. Ideally, these methods should have a high sensitivity and identify all mutated cases without too many false‐positive cases. METHODS Sequencing was compared with microsatellite analysis and immunohistochemistry to detect the presence or absence of the mismatch repair proteins. In the current study, the authors examined 42 patients with colorectal carcinoma of whom 11 met the Amsterdam criteria and 31 were suspected to belong to HNPCC families. Thirty‐five patients were examined by microsatellite analysis, 40 by immunohistochemical staining, and in 31 patients both the MLH1 and MSH2 genes were sequenced. RESULTS Ninety‐two percent of patients with germ line mutations were detected by either immunohistochemistry or microsatellite instability, indicating that a combination of these methods may be suitable for HNPCC screening. Microsatellite instability and abnormal immunohistochemical staining were found in 73% of the tumors. Concordance among the three methods was found in 74 % of the tumors. CONCLUSIONS The authors suggest that immunohistochemistry should be used in combination with microsatellite analysis to prescreen suspected HNPCC patients for the selection of cases where sequencing of the MLH1 and MSH2 mismatch repair genes is indicated. Cancer 2002;95:2422–30. © 2002 American Cancer Society. DOI 10.1002/cncr.10979