Reduced level of the spindle checkpoint protein BUB1B is associated with aneuploidy in colorectal cancers

Objectives: The majority of solid human malignancies demonstrate DNA aneuploidy as a consequence of chromosomal instability. We wanted to investigate whether Aurora A, Aurora B, BUB1B and Mad2 were associated with the development of aneuploidy in colorectal adenocarcinomas as suggested by several in vitro studies, and if their protein levels were related to alterations at the corresponding chromosomal loci. Materials and methods: Expression levels of these spindle proteins were investigated by immunohistochemistry using tissue micro-arrays in a series of DNA aneuploid and diploid colorectal adenocarcinomas previously examined for genomic aberrations by comparative genomic hybridization. Results: All proteins were overexpressed in malignant tissues compared to controls (P < 0.001 for all). BUB1B level was significantly reduced in aneuploid compared to diploid cancers (P = 0.001), whereas expression of the other proteins was not associated with DNA ploidy status. High levels of Aurora A (P = 0.049) and low levels of Aurora B (P = 0.031) were associated with poor prognosis, but no associations were revealed between protein expression and genomic aberration. Conclusions: A significant reduction of BUB1B level was detected in aneuploid compared to diploid colorectal cancers, consistent with earlier studies showing that loss of spindle checkpoint function may be involved in development of DNA aneuploidy. Our data also show that spindle proteins are overexpressed in colorectal cancers, and that expression of the Aurora kinases is associated with prognosis in colorectal cancer.