2013 Fiscal Year Research-status Report
Ｓｅｒｒａｔｅｄ ｐａｔｈｗａｙ大腸癌関連マイクロＲＮＡの同定と治療への展開
| Project/Area Number |
24590429
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| Research Institution | Dokkyo Medical University |
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Principal Investigator |
三富 弘之 獨協医科大学, 医学部, 教授 (90181940)
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| Co-Investigator(Kenkyū-buntansha) |
齋藤 剛 順天堂大学, 医学部, 准教授 (80439736)
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| Keywords | 広基性鋸歯状腺腫/ポリープ / 大腸 / Wntシグナル |
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| Research Abstract |
We performed β-catenin immunostaining, methylation specific PCR for Wnt signaling associated genes such as AXIN2, APC, MCC and secreted frizzled-related proteins (SFRPs) in 27 Sessile serrated adenoma/polyps (SSA/Ps), 14 SSA/Ps with high grade dysplasia (SSA/P-HDs) and 9 SSA/Ps with submucosal carcinoma (SSA/P-CAs), as well as 19 conventional tubular adenomas (ADs), 26 ADs with high grade dysplasia (AD-HDs) and 25 ADs with submucosal carcinoma (AD-CAs). Nuclear β-catenin labeling was significantly lower in the SSA/P series than in their AD counterparts whereas a significant increment was found from SSA/Ps to SSA/P-HDs or SSA/P-CAs. The frequency of SFRP4 methylation was significantly higher in SSA/Ps, SSA/P-HDs and SSA/P-CAs, as compared to corresponding AD series. Although APC was only rarely methylated in all groups, AXIN2 and MCC were more frequently methylated in SSA/P-HDs and SSA/P-CAs than in AD counterparts. Stepwise increment of AXIN2 and MCC methylation was identified from SSA/Ps through SSA/P-HDs to SSA/P-CAs. A significant correlation was seen between nuclear β-catenin expression and methylation of AXIN2 or MCC in the SSA/P series. In conclusion, Wnt/β-catenin signal activation mediated by methylation of SFRP4, MCC and AXIN2 may make different contributions to colorectal neoplasia between the serrated and conventional routes.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
広基性鋸歯状腺腫早期癌合併例23病変のWntシグナルの関連する遺伝子のメチル化解析にかなりのDNAを使ったため、microRNA 20, 21, 93, 181b発現の検討に用いる残りのDNA量がきわめて少なくなり、その解析が進んでいない状況である．
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| Strategy for Future Research Activity |
1) 広基性鋸歯状腺腫の早期癌化例あるい鋸歯状腺癌例を他施設も含めて当たって症例を再度蒐集する予定である．
2）現時点で、解析可能なDNAが残っている広基性鋸歯状腺腫癌合併例のmicroRNA 20, 21, 93, 181b発現の検討を進める．
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Research Products
(13 results)
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[Journal Article] Protein expression and methylation of DNA repair genes hMLH1, hMSH2, MGMT and BRCA1 and their correlation with clinicopathological parameters and prognosis in basal-like breast cancer.2013
Author(s)
Alkam Y, Mitomi H, Nakai K, Himuro T, Saito T, Takahashi M, Arakawa A, Yao T, Saito M:
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Journal Title
Histopathology
Volume: 63
Pages: 713-725
DOI
Peer Reviewed
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[Journal Article] Immunohistochemical analysis of chromogranin A and p53 expressions in ulcerative colitis-associated neoplasia: neuroendocrine differentiation as an early event in the colitis-neoplasia sequence.2013
Author(s)
Shigaki K, Mitomi H, Fujimori T, Ichikawa K, Tomita S, Imura J, Fujii S, Itabashi M, Kameoka S, Sahara R, Takenoshita S:
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Journal Title
Hum Pathol
Volume: 44
Pages: 2393-2399
DOI
Peer Reviewed
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