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β‐Catenin expression and mutational analysis in renal cell carcinomas
Author(s) -
Kim YoungSik,
Kang Yong Koo,
Kim Jung Bun,
Han Seon Ae,
Kim Kwang Il,
Paik Seung R.
Publication year - 2000
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1046/j.1440-1827.2000.01111.x
Subject(s) - adenomatous polyposis coli , beta catenin , biology , cancer research , catenin , carcinogenesis , wnt signaling pathway , exon , missense mutation , microbiology and biotechnology , gene mutation , tumor suppressor gene , mutation , pathology , signal transduction , gene , cancer , genetics , medicine , colorectal cancer
β ‐Catenin acts as a downstream transcriptional activator of the Wingless‐Wnt signaling pathway. The β ‐catenin‐Tcf complex transactivates the downstream genes that regulate cell proliferation or inhibit apoptosis. The activation of this pathway through stabilization of β ‐catenin is caused either by inactivating mutations of adenomatous polyposis coli (APC) tumor suppressor gene or by activating mutations in β ‐catenin exon 3. To determine whether the abnormal expression and activating mutations in exon 3 of the β ‐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 β ‐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 β ‐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 β ‐catenin mutations are a relatively rare event in RCC and that cytoplasmic accumulations of β ‐catenin protein are found only in conventional (clear cell) renal carcinomas. These data suggest that the activation of the β ‐catenin signaling pathway may partly play a role in the development of conventional RCC.