Polo-like kinase isoform expression is a prognostic factor in ovarian carcinoma

Abstract

The Polo-like kinase (PLK) family comprises three serine/threonine kinases, functionally involved in signal transduction pathways essential for the accomplishment of mitosis in both normal and malignant cells. Moreover, certain PLKs have been functionally linked to cytoskeletal reorganisation. In this study, the expression of PLK1 and PLK3 was determined immunohistochemically in tissue specimen of normal ovaries (n ¼ 9), cystadenomas (n ¼ 17), borderline tumours (n ¼ 13) and ovarian carcinomas (n ¼ 77). PLK 1 and PLK3 expression was low in normal ovarian surface epithelium and borderline tumours, with moderately higher expression levels in cystadenomas. In ovarian carcinomas, 26% of cases were PLK1 positive and 50.6% of cases were PLK3 positive. A positive correlation of both PLK1 and PLK3 expression with indicators of mitotic frequency could be established. The overexpression of either isoenzyme had an impact on patient prognosis with shortened survival time for patients with tumours positive for PLK1 (P ¼ 0.02) and PLK3 (P ¼ 0.02), but only PLK1 expression remained a prognostic factor in multivariate survival analysis (P ¼ 0.03). The results of this study, if interpreted in the context of recently published functional data, suggest that inhibition of PLKs might represent an interesting new targeted approach for chemotherapy of epithelial ovarian cancer. Furthermore, this study suggests that PLK1 is a novel independent prognostic marker in ovarian carcinomas.

High expression of RelA/p65 is associated with activation of nuclear factor-κB-dependent signaling in pancreatic cancer and marks a patient population with poor prognosis

“…Cytoplasmic as well as nuclear RelA staining was scored by applying a semiquantitative immunoreactivity scoring (IRS) system, which ranges from 0 to 12, as described (Weichert et al, 2004). For statistical analysis, cases exhibiting an IRS from 0 to 6 were considered as RelA 'negative', cases with an IRS of 8 or higher were considered as RelA 'positive'.…”

Polo-like kinases (Plks) and cancer

“…The overexpression of Plk1 had an impact on patient prognosis with shortened survival time for patients with tumors positive for Plk1 (P ¼ 0.02), and Plk1 expression remained a prognostic factor in multivariate survival analysis (P ¼ 0.03) (Weichert et al, 2004).…”

Differential regulation of polo-like kinase 1, 2, 3, and 4 gene expression in mammalian cells and tissues

“…Also, Plk3 mRNA downregulation has been detected in uterus (Ando et al, 2004), bladder (Ando et al, 2004), and head and neck squamous cell carcinoma (Dai et al, 2000) specimens. However, an increase in Plk3 mRNA levels has been found in some hepatoblastomas (Ando et al, 2004) and when Plk3 protein levels were compared in a panel of normal ovary and ovarian carcinoma samples using an immunohistochemical approach, moderately higher expression levels were noted in the tumor specimens (Weichert et al, 2004).…”

“…References: Plk1 (Lake and Jelinek, 1993;Lee et al, 1995); Plk2 (Simmons et al, 1992;Ma et al, 2003b); Plk3 (Donohue et al, 1995;Chase et al, 1998); and Plk4 (Fode et al, 1996) (Holtrich et al, 1994;Wolf et al, 1997;Wikman et al, 2002;Ando et al, 2004) tumor biopsies compared to corresponding adjacent normal tissue specimens. Also, high levels of Plk1 protein expression have been detected in breast (Yuan et al, 1997;Wolf et al, 2000), ovarian (Takai et al, 2001;Weichert et al, 2004), head and neck squamous cell carcinoma (Knecht et al, 2000), and melanoma tumor specimens using an immunohistochemical approach. In some of the studies described above, a statistically significant correlation was found between high Plk1 expression and low patient survival, suggesting that Plk1 may have utility as a negative prognostic indicator for some tumor types Knecht et al, 1999;Tokumitsu et al, 1999;Knecht et al, 2000;Strebhardt et al, 2000;Weichert et al, 2004).…”

“…Also, high levels of Plk1 protein expression have been detected in breast (Yuan et al, 1997;Wolf et al, 2000), ovarian (Takai et al, 2001;Weichert et al, 2004), head and neck squamous cell carcinoma (Knecht et al, 2000), and melanoma tumor specimens using an immunohistochemical approach. In some of the studies described above, a statistically significant correlation was found between high Plk1 expression and low patient survival, suggesting that Plk1 may have utility as a negative prognostic indicator for some tumor types Knecht et al, 1999;Tokumitsu et al, 1999;Knecht et al, 2000;Strebhardt et al, 2000;Weichert et al, 2004).…”