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


MATERIAL AND METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
['Berus|Tomasz|T|0000-0002-4615-3446', 'Markiewicz|Anna|A|', 'Kobylinska|Katarzyna|K|', 'Biecek|Przemyslaw|P|', 'Orlowska-Heitzman|Jolanta|J|', 'Romanowska-Dixon|Bozena|B|', 'Donizy|Piotr|P|']
D000368:Aged D018797:Cell Cycle Proteins D015536:Down-Regulation D005260:Female D006801:Humans D053208:Kaplan-Meier Estimate D008297:Male D008545:Melanoma D008875:Middle Aged D011379:Prognosis D017346:Protein Serine-Threonine Kinases D011518:Proto-Oncogene Proteins D014604:Uveal Neoplasms
polo-like kinase-1 uveal melanoma prognostic factor IHC