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Oesophageal II
PWE-014 Polo-like kinase 1 expression predicts aneuploidy in the Barrett's metaplasia-dysplasia-carcinoma sequence
  1. M A Butt1,2,
  2. R J Haidry1,2,
  3. D Oukrif3,
  4. J M Dunn4,
  5. A Gupta2,
  6. M Bhatt2,
  7. L Hrynkiewicz3,
  8. A Waheed3,
  9. C Owen3,
  10. A Machhada3,
  11. M Rodriguez-Justo2,
  12. M R Banks1,2,
  13. L B Lovat1,2,
  14. M R Novelli2,3
  1. 1National Medical Laser Centre, University College London, London, UK
  2. 2University College Hospital, London, UK
  3. 3University College London, London, UK
  4. 4University Hospital Lewisham, London, UK

Abstract

Introduction Finding an accurate and convenient biomarker for cancer progression in Barrett's (BE) is of high clinical importance. DNA ploidy abnormalities (DNA-PA) are a reliable predictor of cancer risk in BE, but measurement is expensive and scarcely available. We have shown polo-like kinase-1 (PLK1) may act as a surrogate marker of DNA-PA in oesophageal adenocarcinoma (OA) resection specimens. This study aimed to examine the potential of PLK1 in predicting DNA-PA in the metaplasia-dysplasia-OA sequence.

Methods 36 paraffin embedded oesophageal tissue specimens were selected from patients with non-dysplastic BE (NDBE, n=5), low grade dysplasia (LGD, n=5), high grade dysplasia (HGD, n=12), intramucosal cancer (IMC, n=5) and invasive OA (IOA, n=9). Sections were mounted and immunostained with 2 PLK-1 antibodies PLK1-M and PLK1-L using an automated system (BOND-MAX, Leica) for consistency. Results were reported by two independent expert pathologists blinded to patient status with the Allred scoring system, a composite of the percentage and intensity of staining.

Results Aneuploidy was present in LGD (20%), HGD (75%), IMC (20%) and IOA (56%) samples. Using linear regression analysis, Pearson coefficient was calculated for the correlation between DNA-PA and mean Allred expression scores for each PLK1 antibody. PLK1-M had a higher degree of correlation (r2=0.26, p=0.001) then PLK1-L (r2=0.22, p=0.004). Inter-observer analysis with linear κ scores confirmed good correlation of PLK1-M (κ=0.72, 95% CI 0.60 to 0.83) and PLK1-L (κ=0.53, 95% CI 0.38 to 0.68), but a Bland–Altman plot found pathologist 2 had a trend to score PLK-L more highly. However, intra-observer analysis confirmed both PLK1-L scores correlated with ploidy status (r2=0.14, p=0.023 and r2=0.27, p=0.0016). Pathologists took 90.3 s/slide (mean) to review and score with the Allred method. Using a mean Allred cut off score of 3.5, the sensitivity and specificity for the detection of aneuploidy were 81.3% and 75% for PLK1-M, 93.8% and 45% for PLK1-L.

Conclusion This pilot study demonstrated a significant correlation between Allred reporting of PLK1 staining and DNA-PA. PLK1-L appears more sensitive and PLK1-M more specific. PLK1 immunostaining is relatively inexpensive, less work intensive and is more available than current methods to predict DNA-PA. Scoring staining with Allred is rapid and reproducible. In future, PLK1 staining may provide the basis of a more durable biomarker panel to predict DNA ploidy.

Competing interests None declared.

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