[Microsatellite instability and relative gene expressions in sporadic and familial adenomatous polyposis adenomas].
In order to understand the role of mismatch repair (MMR) gene in colorectal carcinogenesis,microsatellite instability (MSI) status of 16 microsatellite loci of 62 adenomas from 59 patients, including sporadic and familial adeonmatous polyposis (FAP) adenomas were detected by microdissection-PCR-SSLP, and protein expressions of beta-catenin, P53, and BAX, etc. were assayed by immunohistochemistry. Results were as following: (1)The overall MSI alteration rate of the 16 loci was 14.4%. Different adenomas from the same patient showed different microsatellite alterations at the same loci; (2)All of the five FAP patients were MSI-L, three of which showed MSI at the locus of hMSH3; (3)The membrane expression rate of beta-catenin in adenomas and accompanied carcinomas was 42.9% and 11.4%, respectively (P<0.001); (4)Microsatellite alterations of the microsatellite loci of TP53, D5S346, TCF4(A)(9), TGFbetaRII(GT)(3) and TGFbetaRII(A)(10) were associated with the changes of their protein expressions. It could be concluded the following: (1)Microsatellite instability existed even in the early stage (adenomas) of colorectal tumorigenesis. The alterations of chromosome 1p, APC genes, and the TGFbeta signal transduction pathway could also be deduced; (2)In the progression of adenoma to carcinoma, the staining of beta-catenin would be transferred from membrane to cytoplasm and then nucleus, and the cytoplasm stain was stronger in carcinoma than that in adenomas. The abnormality of the signal transduction pathway of APC-beta-catenin-TCF4 could be concluded.
Cheng
Lei
L
Department of Pathology, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, P.R.China. Chenglei1107@hotmail.com
Wang
Hui-Ping
HP
Huang
Qiong
Q
Lai
Mao-De
MD
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011125:Adenomatous Polyposis Coli / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053843:DNA Mismatch Repair; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012004:Rectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051176:beta Catenin