Microsatellite instability and intratumoural heterogeneity in 100 right-sided sporadic colon carcinomas.
Microsatellite instability has been proposed as an alternative pathway of colorectal carcinogenesis. The aim of this study was to evaluate the interest of immunohistochemistry as a new tool for highlighting mismatch repair deficiency and to compare the results with a PCR-based microsatellite assay. A total of 100 sporadic proximal colon adenocarcinomas were analysed. The expression of hMLH1, hMSH2 and hMSH6 proteins evaluated by immunohistochemistry was altered in 39% of the cancers, whereas microsatellite instability assessed by PCR was detected in 43%. There was discordance between the two methods in eight cases. After further analyses performed on other tumoural areas for these eight cases, total concordance between the two techniques was observed (Kappa=100%). Our results demonstrate that immunohistochemistry may be as efficient as microsatellite amplification in the detection of unstable phenotype provided that at least two samples of each carcinoma are screened, because of intratumoural heterogeneity.
Service d'Anatomie Pathologique CHU Dijon, 21079 Dijon, France, and INSERM EPI 01-06, IFR 100 Faculté de Médecine, 21079 Dijon, France.
C
C
Chapusot
L
L
Martin
A M
AM
Bouvier
C
C
Bonithon-Kopp
A
A
Ecarnot-Laubriet
D
D
Rageot
T
T
Ponnelle
P
P
Laurent Puig
J
J
Faivre
F
F
Piard
D048868:Adaptor Proteins, Signal Transducing; D000241:Adenosine / Q000235:genetics*; D020137:Base Pair Mismatch; D002352:Carrier Proteins; D003110:Colonic Neoplasms / Q000235:genetics*; D004260:DNA Repair; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018895:Microsatellite Repeats; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D000241:Adenosine