Abstract
Microsatellite instability (MSI) has been associated with colitic cancer. However, reported frequency of MSI was varied and the association of MSI with mismatch repair (MMR) deficiency was unclear. In addition, the occurrence of genetic alterations in stromal cells within ulcerative colitis (UC) is still controversial. We therefore sampled 164 microareas in various pathological lesions of UC with or without colitic cancer and studied the MSI status in relation to the DNA repair protein expressions. A total of 129 microfoci from colorectal tissue of 5 colitic cancer patients and 35 microfoci of 7 UC patients (without neoplasm) were carefully sampled by laser-capture microdissection. MSI was analyzed in each microsamples. The protein expression of MMR genes (MLH1, MSH2, MSH6), O 6-methylguanine-DNA methyltransferase and p53 were assessed by immunohistochemical analysis. Variety of di-nulcleotide microsatellite markers was altered in individual microfoci from different morphological epithelial lesions, in full range of nonneoplastic epithelium to colitic cancer. Interestingly, MSI was not observed in stromal cells at any sites, including those within colitic cancer/dysplasia lesions. Expression of the MMR proteins was not lost in any of the lesions examined. Microsatellite alterations rather seem to be related to the initiation than to the progression of colitic cancer.
| Original language | English |
|---|---|
| Pages (from-to) | 2513-2519 |
| Number of pages | 7 |
| Journal | International Journal of Cancer |
| Volume | 119 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Dec 1 2006 |
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Keywords
- Colitic cancer
- Microsatellite instability
- Mismatch repair
- Stroma
- Ulcerative colitis
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Heterogeneous microsatellite instability observed within epithelium of ulcerative colitis. / Ozaki, Kazuhide; Nagasaka, Takeshi; Notohara, Kenji; Kambara, Takeshi; Takeda, Masanori; Sasamoto, Hiromi; Jass, Jeremy R.; Tanaka, Noriaki; Matsubara, Nagahide.
In: International Journal of Cancer, Vol. 119, No. 11, 01.12.2006, p. 2513-2519.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Heterogeneous microsatellite instability observed within epithelium of ulcerative colitis
AU - Ozaki, Kazuhide
AU - Nagasaka, Takeshi
AU - Notohara, Kenji
AU - Kambara, Takeshi
AU - Takeda, Masanori
AU - Sasamoto, Hiromi
AU - Jass, Jeremy R.
AU - Tanaka, Noriaki
AU - Matsubara, Nagahide
PY - 2006/12/1
Y1 - 2006/12/1
N2 - Microsatellite instability (MSI) has been associated with colitic cancer. However, reported frequency of MSI was varied and the association of MSI with mismatch repair (MMR) deficiency was unclear. In addition, the occurrence of genetic alterations in stromal cells within ulcerative colitis (UC) is still controversial. We therefore sampled 164 microareas in various pathological lesions of UC with or without colitic cancer and studied the MSI status in relation to the DNA repair protein expressions. A total of 129 microfoci from colorectal tissue of 5 colitic cancer patients and 35 microfoci of 7 UC patients (without neoplasm) were carefully sampled by laser-capture microdissection. MSI was analyzed in each microsamples. The protein expression of MMR genes (MLH1, MSH2, MSH6), O 6-methylguanine-DNA methyltransferase and p53 were assessed by immunohistochemical analysis. Variety of di-nulcleotide microsatellite markers was altered in individual microfoci from different morphological epithelial lesions, in full range of nonneoplastic epithelium to colitic cancer. Interestingly, MSI was not observed in stromal cells at any sites, including those within colitic cancer/dysplasia lesions. Expression of the MMR proteins was not lost in any of the lesions examined. Microsatellite alterations rather seem to be related to the initiation than to the progression of colitic cancer.
AB - Microsatellite instability (MSI) has been associated with colitic cancer. However, reported frequency of MSI was varied and the association of MSI with mismatch repair (MMR) deficiency was unclear. In addition, the occurrence of genetic alterations in stromal cells within ulcerative colitis (UC) is still controversial. We therefore sampled 164 microareas in various pathological lesions of UC with or without colitic cancer and studied the MSI status in relation to the DNA repair protein expressions. A total of 129 microfoci from colorectal tissue of 5 colitic cancer patients and 35 microfoci of 7 UC patients (without neoplasm) were carefully sampled by laser-capture microdissection. MSI was analyzed in each microsamples. The protein expression of MMR genes (MLH1, MSH2, MSH6), O 6-methylguanine-DNA methyltransferase and p53 were assessed by immunohistochemical analysis. Variety of di-nulcleotide microsatellite markers was altered in individual microfoci from different morphological epithelial lesions, in full range of nonneoplastic epithelium to colitic cancer. Interestingly, MSI was not observed in stromal cells at any sites, including those within colitic cancer/dysplasia lesions. Expression of the MMR proteins was not lost in any of the lesions examined. Microsatellite alterations rather seem to be related to the initiation than to the progression of colitic cancer.
KW - Colitic cancer
KW - Microsatellite instability
KW - Mismatch repair
KW - Stroma
KW - Ulcerative colitis
UR - http://www.scopus.com/inward/record.url?scp=33750632505&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33750632505&partnerID=8YFLogxK
U2 - 10.1002/ijc.22095
DO - 10.1002/ijc.22095
M3 - Article
C2 - 16929496
AN - SCOPUS:33750632505
VL - 119
SP - 2513
EP - 2519
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 11
ER -