beta-catenin expression and mutational analysis in renal cell carcinomas.
beta-Catenin acts as a downstream transcriptional activator of the Wingless-Wnt signaling pathway. The beta-catenin-Tcf complex transactivates the downstream genes that regulate cell proliferation or inhibit apoptosis. The activation of this pathway through stabilization of beta-catenin is caused either by inactivating mutations of adenomatous polyposis coli (APC) tumor suppressor gene or by activating mutations in beta-catenin exon 3. To determine whether the abnormal expression and activating mutations in exon 3 of the beta-catenin gene are implicated in renal cell carcinogenesis, 52 renal cell carcinomas (RCC) were analyzed by immunohistochemistry, polymerase chain reaction-single-strand conformational polymorphism analysis (PCR-SSCP), and direct DNA sequencing. Immunohistochemically, all cases, as well as normal kidneys, showed membranous and/or cytoplasmic staining patterns without nuclear localization. However, the cytoplasmic accumulations of beta-catenin were observed in five (22.7%) of 22 cases of conventional (clear cell) renal carcinoma, but not in papillary or chromophobe renal carcinomas. The beta-catenin mutation was identified in only one case of conventional renal carcinoma and was a single-base missense mutation on codon 61, leading to substitution of glutamine by arginine. In conclusion, this study demonstrates that beta-catenin mutations are a relatively rare event in RCC and that cytoplasmic accumulations of beta-catenin protein are found only in conventional (clear cell) renal carcinomas. These data suggest that the activation of the beta-catenin signaling pathway may partly play a role in the development of conventional RCC.
Kim
Y S
YS
Department of Pathology, College of Medicine, Korea University, Gojan-Dong, Ansan, Korea. apysk@yahoo.com
Kang
Y K
YK
Kim
J B
JB
Han
S A
SA
Kim
K I
KI
Paik
S R
SR
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D015534:Trans-Activators; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D004273:DNA, Neoplasm; D015534:Trans-Activators; D051176:beta Catenin