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Molecular Oncology, Markers, Clinical Correlates |
Department of Urology, Niigata University School of Medicine, Niigata 951, Japan
Loss of normal ß-catenin expression and the ß-catenin gene mutations have been shown to contribute to the malignant character of various cancers. Using PCR-single-strand conformation polymorphism and DNA direct sequencing, we examined the presence of genetic alterations within the third exon of ß-catenin, which are frequently observed in other tumors, in transitional cell cancer (TCC) and renal cell cancer (RCC) cell lines, and in tumor specimens. The degrees of expression and intracellular distribution of ß-catenin were detected by immunohistochemical staining in 77 primary and 12 metastatic RCCs and in 81 primary TCCs. Western blot analysis was also applied to confirm the degree of ß-catenin expression in the cell lines and some tumor samples. We failed to reveal any genetic alterations, at least in the third exon of the ß-catenin gene, in RCC and TCC. Reduced membranous immunoreactivity of ß-catenin was observed in portions of RCC (15.5%) and TCC (24.7%) and was correlated with advanced stages and nodal involvement in RCC and with advanced stages and multiple tumors in TCC. Within the power limitations of this small study, ß-catenin abnormal expression was not correlated with recurrence or survival in either RCC or TCC. Interstitial deletions and mutations in the third exon of ß-catenin do not play a significant role in RCC or TCC tumorigenesis. Down-regulation of normal ß-catenin expression might contribute to the malignant character of RCC and TCC and result in tumor progression. However, this event is not an independent prognostic factor for recurrence or tumor specific survival.
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