Value of microsatellite instability typing in detecting hereditary non-polyposis colorectal cancer. A prospective multicentric study by the Association Aquitaine Gastro.
OBJECTIVE
To detect hereditary non-polyposis colorectal cancer (HNPCC) patients with a strategy combining clinical selection (patient age at onset of cancer less than 50 years or family history of HNPCC tumors) and microsatellite instability typing plus immunohistochemistry, leading to mismatch repair (MMR) germline mutation analysis.


METHODS
Tumors were screened for microsatellite instability (MSI) and for hmlh1 and hmsh2 immunohistochemical expression. Germline mutation analysis was performed to search for MLH1 and MSH2 mutations in patients with MSI-High and MSI-Low tumors.


RESULTS
197 adenocarcinomas were studied: 164 patients were< or =50 years old, 33 were older than 50 years but had a family history of HNPCC tumors. Fifty tumors (25.4%) were MSI-High, 10 were MSI-Low (5.1%), and 130 were MS-Stable (66%). MSI typing was inconclusive in 7 (3.5%). Immunohistochemistry screening was performed on 165 tumors: sensitivity was 63.6%, specificity was 99%. Germline mutation analysis was performed in 33/60 MSI-High or Low tumors: 23 mutations were noted (70% of the tested patients).


CONCLUSIONS
This proposed strategy of determining microsatellite instability in young colorectal cancer patients or in patients with a family history of HNPCC tumors led to an increased frequency in the detection of MMR germline mutations.
Bécouarn
Yves
Y
Département d'Oncologie Digestive, Institut Bergonié, Bordeaux, France. becouarn@bergonie.org
Rullier
Anne
A
Gorry
Philippe
P
Smith
Denis
D
Richard-Molard
Bruno
B
Echinard
Emmanuel
E
Texereau
Patrick
P
Beyssac
Richard
R
Legoux
Jean-Louis
JL
Lamouliatte
Hervé
H
Frebourg
Thierry
T
Olschwang
Sylviane
S
Gilbert
Brigitte
B
Venat
Laurence
L
Picot
Véronique
V
Paraf
François
F
Longy
Michel
M
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D020137:Base Pair Mismatch / Q000235:genetics; D043171:Chromosomal Instability; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics*; D004260:DNA Repair; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D010375:Pedigree; D011446:Prospective Studies