Abstract
Accurate frequencies of CpG island methylator phenotype (CIMP) have not been determined for laterally spreading tumors (LSTs) and other flat-type colorectal adenomas, and the role of JC virus T-antigen (T-Ag) in these tumors is unclear. We used MethyLight assay to analyze the relationship between CIMP status and clinicopathologic characteristics in tissue from 72 LST of granular-type (LST-G), 35 LST of nongranular-type (LST-NG), 54 protruded-type adenomas, and 89 colorectal cancers. We also investigated the relationship between CIMP status and T-Ag by immunohistochemistry. With the use of 5 markers for CIMP status, tumors were classified as CIMP-high (≥4/5 methylated promoters), CIMP-low (1/5 to 3/5 methylated promoters), or CIMP-0 (no methylated promoters). The proportion classified as CIMP-0 status was 5.6% for protruded-type adenoma, 17.1% for LST-NG, and 29.2% for LST-G (LST-G versus protruded-type adenoma, P = .001). CIMP-low status was established for 62.5% of LST-G, 74.3% of LST-NG, and 81.5% of protruded-type adenomas. CIMP-high status was established for 8.3% of LST-G, 8.6% of LST-NG, and 12.9% of protruded-type adenomas. The proportions of CIMP-low and CIMP-high status were not significantly different between the 3 groups. Multiple logistic analysis showed that LST-G appearance was the only significant factor for identifying CIMP-0 status. BRAF mutation was the only significant factor for identifying CIMP-high status. T-Ag expression increased with CIMP status and was not associated with macroscopic appearance. In conclusion, among colorectal adenomas, CIMP-high status was determined by BRAF mutation and not by macroscopic type, unlike CIMP-0. JC virus T-Ag may be important in determining methylator phenotype.
| Original language | English |
|---|---|
| Pages (from-to) | 767-775 |
| Number of pages | 9 |
| Journal | Human Pathology |
| Volume | 39 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2008 May |
| Externally published | Yes |
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Keywords
- BRAF
- CIMP
- Colorectal adenoma
- JC virus
- LST
ASJC Scopus subject areas
- Pathology and Forensic Medicine
Cite this
Correlation of laterally spreading type and JC virus with methylator phenotype status in colorectal adenoma. / Nosho, Katsuhiko; Yamamoto, Hiroyuki; Takahashi, Taiga; Mikami, Masashi; Hizaki, Keiichi; Maehata, Tadateru; Taniguchi, Hiroaki; Yamaoka, Satoshi; Adachi, Yasushi; Itoh, Fumio; Imai, Kohzoh; Shinomura, Yasuhisa.
In: Human Pathology, Vol. 39, No. 5, 05.2008, p. 767-775.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Correlation of laterally spreading type and JC virus with methylator phenotype status in colorectal adenoma
AU - Nosho, Katsuhiko
AU - Yamamoto, Hiroyuki
AU - Takahashi, Taiga
AU - Mikami, Masashi
AU - Hizaki, Keiichi
AU - Maehata, Tadateru
AU - Taniguchi, Hiroaki
AU - Yamaoka, Satoshi
AU - Adachi, Yasushi
AU - Itoh, Fumio
AU - Imai, Kohzoh
AU - Shinomura, Yasuhisa
PY - 2008/5
Y1 - 2008/5
N2 - Accurate frequencies of CpG island methylator phenotype (CIMP) have not been determined for laterally spreading tumors (LSTs) and other flat-type colorectal adenomas, and the role of JC virus T-antigen (T-Ag) in these tumors is unclear. We used MethyLight assay to analyze the relationship between CIMP status and clinicopathologic characteristics in tissue from 72 LST of granular-type (LST-G), 35 LST of nongranular-type (LST-NG), 54 protruded-type adenomas, and 89 colorectal cancers. We also investigated the relationship between CIMP status and T-Ag by immunohistochemistry. With the use of 5 markers for CIMP status, tumors were classified as CIMP-high (≥4/5 methylated promoters), CIMP-low (1/5 to 3/5 methylated promoters), or CIMP-0 (no methylated promoters). The proportion classified as CIMP-0 status was 5.6% for protruded-type adenoma, 17.1% for LST-NG, and 29.2% for LST-G (LST-G versus protruded-type adenoma, P = .001). CIMP-low status was established for 62.5% of LST-G, 74.3% of LST-NG, and 81.5% of protruded-type adenomas. CIMP-high status was established for 8.3% of LST-G, 8.6% of LST-NG, and 12.9% of protruded-type adenomas. The proportions of CIMP-low and CIMP-high status were not significantly different between the 3 groups. Multiple logistic analysis showed that LST-G appearance was the only significant factor for identifying CIMP-0 status. BRAF mutation was the only significant factor for identifying CIMP-high status. T-Ag expression increased with CIMP status and was not associated with macroscopic appearance. In conclusion, among colorectal adenomas, CIMP-high status was determined by BRAF mutation and not by macroscopic type, unlike CIMP-0. JC virus T-Ag may be important in determining methylator phenotype.
AB - Accurate frequencies of CpG island methylator phenotype (CIMP) have not been determined for laterally spreading tumors (LSTs) and other flat-type colorectal adenomas, and the role of JC virus T-antigen (T-Ag) in these tumors is unclear. We used MethyLight assay to analyze the relationship between CIMP status and clinicopathologic characteristics in tissue from 72 LST of granular-type (LST-G), 35 LST of nongranular-type (LST-NG), 54 protruded-type adenomas, and 89 colorectal cancers. We also investigated the relationship between CIMP status and T-Ag by immunohistochemistry. With the use of 5 markers for CIMP status, tumors were classified as CIMP-high (≥4/5 methylated promoters), CIMP-low (1/5 to 3/5 methylated promoters), or CIMP-0 (no methylated promoters). The proportion classified as CIMP-0 status was 5.6% for protruded-type adenoma, 17.1% for LST-NG, and 29.2% for LST-G (LST-G versus protruded-type adenoma, P = .001). CIMP-low status was established for 62.5% of LST-G, 74.3% of LST-NG, and 81.5% of protruded-type adenomas. CIMP-high status was established for 8.3% of LST-G, 8.6% of LST-NG, and 12.9% of protruded-type adenomas. The proportions of CIMP-low and CIMP-high status were not significantly different between the 3 groups. Multiple logistic analysis showed that LST-G appearance was the only significant factor for identifying CIMP-0 status. BRAF mutation was the only significant factor for identifying CIMP-high status. T-Ag expression increased with CIMP status and was not associated with macroscopic appearance. In conclusion, among colorectal adenomas, CIMP-high status was determined by BRAF mutation and not by macroscopic type, unlike CIMP-0. JC virus T-Ag may be important in determining methylator phenotype.
KW - BRAF
KW - CIMP
KW - Colorectal adenoma
KW - JC virus
KW - LST
UR - http://www.scopus.com/inward/record.url?scp=42649086015&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=42649086015&partnerID=8YFLogxK
U2 - 10.1016/j.humpath.2007.10.005
DO - 10.1016/j.humpath.2007.10.005
M3 - Article
C2 - 18284934
AN - SCOPUS:42649086015
VL - 39
SP - 767
EP - 775
JO - Human Pathology
JF - Human Pathology
SN - 0046-8177
IS - 5
ER -