Overexpression of the Mitotic Spindle Assembly Checkpoint Genes hBUB1, hBUBR1 and hMAD2 in Thyroid Carcinomas with Aggressive Nature

Background: The mitotic spindle assembly checkpoint (MSAC) genes are responsible for preventing chromosome missegregation. MSAC gene expressions have been reported to be associated with tumor cell proliferation or unfavorable cancer behavior. The present study was conducted to preliminary investigate the MSAC gene expressions in thyroid neoplasms. Materials and Methods: Expression levels of MSAC genes (hBUB1, hBUBR1, hBUB3 and hMAD2) were evaluated in 9 follicular thyroid adenomas (FAs), 9 follicular thyroid carcinomas (FTCs), 21 papillary thyroid carcinomas (PTCs), 5 anaplastic (undifferentiated) thyroid carcinomas (ATCs) and 3 adjacent normal thyroid tissues (NTs) by real-time quantitative RT-PCR. These gene expressions were compared between undifferentiated thyroid carcinomas (ATCs) and differentiated thyroid carcinomas (DTCs) and between advanced DTCs and non-advanced DTCs. DTCs included PTCs and FTCs. Advanced DTCs were defined as carcinoma with aggressive nature such as extrathyroid extension, distant metastasis, recurrence or death from the disease. Results: MSAC gene expressions varied in different thyroid tumors and fell in the order of ATC, DTC (PTC and FTC), FA and NT. Carcinomas had higher expression compared to adenoma or normal tissue. hBUB1, hBUBR1 and hMAD2 expressions in ATCs were significantly higher than those in DTCs (p<0.005). hBUBR1 and hMAD2 expressions in advanced DTCs were significantly higher than those in non-advanced DTCs (p<0.05). Conclusion: The MSAC genes were overexpressed in thyroid carcinomas with aggressive nature. Further studies are required to clarify the relationship between the MSAC gene expressions and thyroid cancer behavior. The mitotic spindle assembly checkpoint (MSAC) delays the onset of anaphase initiation in mitotic cells with inappropriately aligned chromosomes to prevent chromosome missegregation. Consequently, activation of this checkpoint ensures each daughter cell has a euploid chromosome set successfully. Therefore, any defect of the MSAC has been considered to be associated with chromosome instability. Cahill et al. found (1) that mutational inactivation of MSAC genes was the key event