A cost-effective algorithm for hereditary nonpolyposis colorectal cancer detection.
Colorectal cancer with microsatellite instability (MSI) may occur sporadically or be inherited in cases of hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. However, there is no consensus as to which patients must be tested and how to test MSI. In this study, MSI was tested by immunohistochemical analysis and by polymerase chain reaction in 148 cases of colorectal cancer, and methylation of the hMLH1 promoter was examined. MSI status was correlated with tumor phenotype. We found that localization, tumor infiltrating lymphocytes, and mucinous differentiation were predictive of high-frequency MSI (MSI-H) colorectal cancer and might be used to select cases for MSI analysis. Immunohistochemical analysis detected most MSI-H colorectal cancer and might constitute the first step in MSI detection. Absence of hMLH1 promoter methylation in MSI-H colorectal cancer could be predictive of hereditary colorectal cancer, and, hence, methylation analysis might constitute the second step in the identification of patients with HNPCC.
Bouzourene
Hanifa
H
Institute of Pathology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Taminelli
Lorenzo
L
Chaubert
Pascal
P
Monnerat
Christian
C
Seelentag
Walter
W
Sandmeier
Dominique
D
Andrejevic
Snejana
S
Matter
Maurice
M
Bosman
Fred
F
Benhattar
Jean
J
D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000465:Algorithms; D002352:Carrier Proteins / Q000235:genetics*; D015331:Cohort Studies; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics; D003362:Cost-Benefit Analysis; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000191:economics / Q000379:methods*; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1