Beta-catenin expression is altered in human colonic aberrant crypt foci.
The aberrant expression of beta-catenin in colon tumors and the discovery of beta-catenin mutations in small adenomas suggest that alterations of beta-catenin are early events in human colorectal carcinogenesis. Here, we describe the expression of beta-catenin in human aberrant crypt foci (ACF), the earliest identified neoplastic lesions in the colon. Paraffin-embedded sections of 94 ACF, 12 adenomas, and 10 carcinomas were evaluated for beta-catenin expression by immunohistochemistry. Normal colonic epithelial cells adjacent to these lesions showed strong membranous expression of beta-catenin and lacked cytoplasmic and nuclear expression. Cytoplasmic expression of beta-catenin was seen in 25 of 46 ACF with dysplasia and in 2 of 48 ACF with atypia. In ACF with dysplasia, reduced membranous expression of beta-catenin was associated with increased nuclear (P = 0.0013) and cytoplasmic (P = 0.0247) expression. The membranous (P = 0.0003) expression of beta-catenin was reduced, and the cytoplasmic (P = 0.0016) and nuclear (P = 0.0266) expressions increased in ACF according to their degree of dysplasia. Likewise, membranous (P = 0.0007) expression of beta-catenin was reduced, and the cytoplasmic (P = 0.0050) and nuclear (P = 0.0001) expressions increased from ACF to adenoma to carcinoma. These data suggest that ACF and their aberrant expression of beta-catenin play a role in colon tumorigenesis.
Hao
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XP
Department of Pathology, Case Western Reserve University School of Medicine and Cancer Center, 2085 Adelbert Road, Cleveland, Ohio 44106, USA.
Pretlow
T G
TG
Rao
J S
JS
Pretlow
T P
TP
D000236:Adenoma / Q000378:metabolism; D011125:Adenomatous Polyposis Coli / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D011230:Precancerous Conditions / Q000378:metabolism*; D015534:Trans-Activators; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin