Possible alternative carcinogenesis pathway featuring microsatellite instability in colorectal cancer stroma.
Differential microsatellite instability (MSI) in tumour epithelial and stromal compartments has not been well examined for colorectal cancers. Using laser-captured microdissection, separate specimens of these compartments of 40 sporadic colorectal cancers were sampled and MSI was tested with four markers. To examine the relation between the MSI phenotype in the stroma and other genetic events and histopathological features, p53 and K-ras gene mutations were analysed, and the expression of p53, hMLH1, and hMSH2 protein was determined by immunohistochemistry. Microsatellite instability positive results were obtained for both epithelium (34%) and stromal tissue (41%). While MSI in epithelium correlated with differentiation and Dukes' stage, that in stroma demonstrated an inverse relation, being particularly frequent in well-differentiated adenocarcinomas (54%) and Dukes' A lesions (55%). Further, a significant inverse correlation between p53 protein overexpression in the epithelium and MSI in the stroma was found (P=0.02475). The results suggest an alternative pathway of carcinogenesis involving stromal genetic instability in the development of colorectal cancers.
Matsumoto
N
N
Department of Pathology, Kitasato University School of Medicine, Kitasato 1-15-1, Sagamihara, Kanagawa 228-8555, Japan.
Yoshida
T
T
Yamashita
K
K
Numata
Y
Y
Okayasu
I
I
D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020137:Base Pair Mismatch; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D004847:Epithelial Cells; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D017154:Stromal Cells / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein