SET complex in serous epithelial ovarian cancer

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With low cure rates but increasing diverse treatment options that provide variable remission times, ovarian cancer is increasingly being recognized as a chronic disease. This reality indicates the need for a better understanding of factors influencing disease progression. In a previous global analysis of gene expression, we identified genes differentially expressed when comparing serous epithelial ovarian tumors of low and high malignant potential (grade 0vsgrade 3). In this analysis, 4 out of 5 members of the SET complex, SET, APE1, NM23 and HMGB2, were highly expressed in invasive grade 3 tumors. To further investigate the expression of these genes and the fifth member of the SET complex (pp32), we performed immunohistochemistry, on a tissue array composed of 235 serous tumors of different grades and disease stages. A significant correlation between expression of all SET complex proteins and the tumor differentiation was observed (p< 0.05). When combining all tumors, overexpression of Nm23 (p= 0.04), Set (p= 0.004) and Ape1 (p= 0.004) was associated with the clinical stage of the disease. No marker by itself was associated with prognosis. The combination of a high level of Nm23 in the context of a low level of Set compared to all other combinations of these markers did confer a better prognosis (p= 0.03). When combined, high expression of Hmgb2 and low expression of Ape1 was also associated with patient prognosis (p= 0.05). These findings suggest that a strategy that sums the activities of different partners within a pathway may be more appropriate in designing nomograms for patient stratification.

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