Augmented expression of Polo-like kinase 1 is a strong predictor of shorter cancer-specific overall survival in early stage breast cancer at 15-year follow-up

Abstract

Polo-like kinase 1 (PLK1) is a serine-threonine kinase that plays a crucial role in the regulation of cell division. In addition, it acts as a modulator of the DNA damage response and as a novel factor in the maintenance of genome stability during DNA replication. The present study aimed to reveal the associations between PLK1 expression and clinicopathological features of patients with breast cancer (BC), particularly patient survival at 5-, 10- and 15-year follow-up. PLK1 expression was evaluated immunohistochemically in routine diagnostic tissue specimens from 83 patients treated radically for stage II BC. Kaplan-Meier analysis revealed a correlation between PLK1 overexpression and long-term survival. High PLK1 immunoreactivity was associated with shorter cancer-specific overall survival (CSOS) and disease-free survival (P=0.00001 and 0.00013, respectively). Multivariate analysis confirmed the negative prognostic significance of PLK1 overexpression for CSOS in all 83 patients (P=0.00030). Furthermore, analogous correlations were observed in both subgroups with and without nodal metastases (P=0.01400 and 0.01200, respectively). The present results indicate that PLK1 expression has a prognostic role in early BC. Immunohistochemical assessment of PLK1 reactivity may potentially become a qualifier for inclusion of PLK1 inhibitor therapy.

Keywords: Polo-like kinase 1; breast cancer; prognosis; survival analysis.

Figure 1.

Immunohistochemical analysis of PLK1 expression in BC cells. (A) Lack of PLK-1 expression in BC cells (IRS=0; magnification, ×400; hematoxylin staining). (B) Intermediate level of cytoplasmic PLK1 expression in BC cells (IRS=6; magnification, ×200; hematoxylin staining). (C and D) High expression of PLK1 in BC cells of two different tumors (IRS=12; magnification, ×600; hematoxylin staining). PLK1, polo-like kinase 1; BC, breast cancer; IRS, immunoreactive score.

Figure 2.

PLK1 immunoreactivity and patient survival. High PLK1 immunoreactivity (IRS ≥8) was associated with shorter (A) CSOS (P=0.00001) and (B) DFS (P=0.00013). High PLK1 immunoreactivity was associated with shorter (C) CSOS (P=0.00110) and (D) DFS (P=0.00900) in patients without regional lymph node metastases. High PLK1 immunoreactivity was associated with shorter (E) CSOS (P=0.00900) and (F) DFS (P=0.03000) in patients with diagnosed nodal metastatic foci. PLK1, polo-like kinase 1; N, lymph nose metastasis; gr., group; CSOS, cancer-specific overall survival; DFS, disease-free survival.