Abstract 1797P
Background
Polo-Like Kinase-1 (PLK1) exerts its influence by affecting the progression of the cell through G2/M checkpoint. Higher levels of PLK1 promote transition of the cell phase to mitosis, thereby promoting cell proliferation. Overexpression of PLK1 mRNA has been shown to be associated with worse clinico-pathological features and patient outcomes in various cancer types, including non-small cell lung cancer (NSCLC). Reports of protein expression of PLK1 by immunohistochemistry in tumour tissue has suggested a similar trend whereby higher expression of PLK1 is associated with aggressive tumour behaviour.
Methods
Eighty-eight patients with resected early-stage NSCLC treated with adjuvant platinum-based chemotherapy were identified. These blocks were retrieved, reviewed by a pathologist and two cores from each block taken to form a tumour microarray (TMA). A PLK1 antibody was optimised for use in lung tumour tissue and sections of the TMA stained with the PLK1 antibody. Nuclear expression of PLK1, percentage expression and intensity (0-3), was derived by computer training using the Qupath software. A H-score was calculated for each core and the average score across the 2 cores calculated. Regression tree analysis determined the optimal H-score cut point for high and low groups for two analyses, relapse free survival (RFS) and overall survival (OS).
Results
The optimal H-score cut point was found to be 5.99 for RFS (P: 0.032) and 9.29 for OS (P: 0.026). The optimal cut point divided patients into 2 group, high and low. The median RFS was 1.9 years in the high group compared 6.25 years in the low group. This represents an improvement of over 4 years for patients with a low PLK1 H-score. At 5 years, the RFS was 53% versus 30% respectively. The median OS for patients in the high group was 6.75 years and was not reached in the low group. At 5 years, the OS was 78% versus 57% respectively.
Conclusions
The H-score is a meaningful measure of PLK1 expression in lung tumour tissue. Using the optimal cut point of 5.99 we identified a group of patients with early-stage NSCLC at high risk of relapse. This translated across to OS whereby those with a score of 9.29 and above were at increased risk of death. PLK1 H-score should be developed further as a biomarker of relapse and survival in high risk resected NSCLC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Connor O'Leary.
Funding
1. Queensland University of Technology; 2. Metro South Research Support Scheme.
Disclosure
All authors have declared no conflicts of interest.