Downregulation of Polo-like kinase-1 (PLK-1) expression is associated with poor clinical outcome in uveal melanoma patients

• Published in: Folia histochemica et cytobiologica 2020-01, Vol.58 (2), p.108-116
• Main Authors: Berus, Tomasz, Markiewicz, Anna, Kobylinska, Katarzyna, Biecek, Przemyslaw, Orlowska-Heitzman, Jolanta, Romanowska-Dixon, Bozena, Donizy, Piotr
• Format: Article
• Language: English
• Subjects: Aged; Automation; Cancer; Cell cycle; Cell Cycle Proteins - metabolism; Cell division; Clinical outcomes; Correlation; Cytokinesis; Down-Regulation; Enucleation; Eye cancer; Eye diseases; Female; Health services; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Kinases; Male; Medical prognosis; Medical records; Melanoma; Melanoma - diagnosis; Metastases; Metastasis; Middle Aged; Mortality; Parameters; Patients; Polo-like kinase; Polo-Like Kinase 1; Prognosis; Protein Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins - metabolism; Retinal detachment; Skin cancer; Statistical analysis; Survival; Tumors; Uveal Neoplasms - diagnosis
• ISSN: 0239-8508; 1897-5631
• DOI: 10.5603/FHC.a2020.0017

Uveal melanoma (UM) is the most common primary eye tumour in adults. Distant metastases are seen in 50% of cases regardless of treatment, which contributes to high mortality rates. Polo-like kinase-1 (PLK-1) is a protein regulator of mitotic entry and cytokinesis. Increased PLK-1 expression has been shown in different tumours, which makes its inhibition a potential treatment target. To date, no study has been published to discuss the prognostic role of PLK-1 expression in patients with uveal melanoma. We assessed by immunohistochemistry PLK-1 expression in uveal melanoma cells collected in 158 patients treated by primary enucleation. We determined the correlation between PLK-1 levels evaluated by the immunoreactivity scale (IRS) method and detailed clinical as well as histological parameters. Additionally, we determined the association between PLK-1 expression levels and long-term prognosis. Elevated PLK-1 expression in tumour cells, defined as IRS > 2, was observed in 70% (111/158) of cases, whereas low expression or no expression was seen in the remaining 30% (47/158) of patients. There was a significant correlation between low PLK-1 expression and a higher clinical tumour stage (pT, p = 0.04) as well as a higher AJCC prognostic stage group (p = 0.037). We observed an inverse correlation between PLK-1 expression and tumour cell pigment content (p = 0.0019). There was no correlation between PLK-1 expression and other histological parameters such as mitotic rate or histological subtype. The Kaplan-Meier's analysis demonstrated that low PLK-1 expression was associated with significantly reduced overall survival (p = 0.0058). A similar trend, albeit not significant, was observed for disease-free survival (p = 0.088). Downregulated PLK-1 expression is a negative prognostic factor in uveal melanoma. It warrants further, multicentre research on prognostic role of PLK-1 expression and possibility of PLK-1 inhibition in uveal melanoma.