Expression of DNA Damage Checkpoint Protein Hus1 in Epithelial Ovarian Tumors Correlates With Prognostic Markers

Abstract

Hus1 and Rad9 are proteins involved in DNA damage checkpoint regulation, which is required for the maintenance of genomic stability. In addition to checkpoint activation, mammalian cells also use apoptosis to eliminate cells with severe DNA damage. Interestingly, Rad9 was shown to be directly involved in apoptosis as well. Despite the knowledge of molecular mechanisms on how Hus1 and Rad9 act in response to DNA damage, little is known about the role of these 2 proteins in cancer progression. In this study, we analyzed the expression of Rad9 and Hus1 in epithelial ovarian tumors and correlated them to clinopathological parameters and apoptotic biomarkers (p53, Bcl-2, and Bax). Histological sections from 114 primary ovarian epithelial tumors were stained with antibodies using the streptavidin-biotin method. In addition, mitotic and apoptotic indices (both hematoxylin-eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling assay) were also measured. We found that Rad9 expression correlated closely to significance only with the apoptotic and mitotic indices (P = 0.056 and 0.059, respectively). Hus1 levels correlated significantly with the clinicopathologic factors of bad prognosis, including FIGO (International Federation of Gynecology and Obstetrics) stage (P < 0.002) and with the p53 expression (P < 0.001), Bax expression (P < 0.008), mitotic index (P < 0.001), and apoptotic index (P < 0.003).