Ca(2+)/calmodulin-dependent protein kinase IV (CaMKIV) is a multifunctional
protein kinase expressed abundantly in the central nervous system. Because changes in intracellular Ca(2+) concentrations affect progression through the mitotic cell cycle, enhanced expression of CaMKIV has been reported in
small cell lung carcinoma and
hepatocellular carcinoma. To elucidate the involvement of CaMKIV in epithelial ovarian
carcinogenesis, we analyzed serial frozen sections for CaMKIV
protein expression in 26 patients with
ovarian epithelial carcinoma and ten patients with benign
cystadenoma of the ovary by fluorescent immunohistochemistry. We analyzed the relationship between the percentages of CaMKIV-stained cells and the patient's characteristics, including histological classification, clinical stage, histological grade, and clinical outcome. In the benign ovarian
cystadenoma, CaMKIV was detected in none of the cases examined. Most of the CaMKIV
proteins were found in the nucleus of
epithelial ovarian cancer tissue. CaMKIV expression was significantly associated with clinical stage (P<0.01), histological grade (P<0.01), and clinical outcome (P<0.01). Survival data were available for all patients, and univariate Cox regression analysis showed that CaMKIV expression was significantly associated with poor prognosis (P<0.05). Our results demonstrate that CaMKIV expression in
epithelial ovarian cancer correlates with the malignant potential of this
tumor.