Amplification/overexpression of a mitotic kinase gene in XXXX @entity150 .

@entity1 @entity2007 @entity146 @entity5 @entity406 @entity875 @entity150 @entity982 @entity3
BACKGROUND: The mitotic kinase-encoding gene @entity875 / @entity875 / @entity875 is associated with @entity2007 and transformation when overexpressed in @entity1 cells. @entity875 overexpression activates an unknown oncogenic pathway that involves centrosome amplification and results in missegregation of chromosomes. Because clinical prognosis and @entity5 @entity2007 are tightly linked in @entity1 @entity150 , we examined whether increased @entity875 copy number and protein levels are linked to @entity2007 in @entity150 . METHODS: @entity875 protein was visualized by immunohistochemistry in 205 @entity406 -fixed, @entity982 -embedded @entity1 @entity150 . @entity875 gene copy number was evaluated in 61 @entity5 by Southern blot hybridization and in 21 of these 61 @entity5 by fluorescence in situ hybridization (FISH). Copy numbers of chromosomes 3, 17, 20, and 21 were evaluated by FISH with chromosome-specific probes. @entity875 expression levels were related to histologic grade, stage, and DNA ploidy of the @entity5 and to the @entity1 ' follow-up data. The chi-square test for association was used to analyze the relationship between @entity875 expression and pathologic features. All statistical tests were two-sided. RESULTS: @entity5 with low levels of @entity875 amplification (3-4 copies) showed minimal deviation in their chromosome copy number and diploid or near-diploid total nuclear DNA content. @entity5 with higher levels of @entity875 amplification (>4 copies) had a major increase of chromosome copy number and of their total nuclear DNA content, i.e., exhibited pronounced @entity2007 . Elevated expression of @entity875 was strongly associated with parameters of clinical @entity146 including high histologic grade (P<.001), invasion (P<.001), increased rate of @entity3 (P<.001), and decreased @entity3 -free (P<.001) and overall (P<.001) survival of @entity1 with @entity150 . CONCLUSION: @entity875 gene amplification and associated increased expression of the mitotic kinase it encodes are associated with @entity2007 and @entity146 clinical behavior in @entity1 @entity150 .
