First application of the Automated QUantitative Analysis (AQUA) technique to quantify PTEN protein expression in ovarian cancer: A correlative study of NCIC CTG OV.16.

J I Weberpals, M S Amin, B E Chen, D Tu, J N Spaans, J A Squire, E A Eisenhauer, S Virk, D Ma, M Duciaume, P Hoskins, D P LeBrun

Gynecologic oncology 2016 Mar

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Platinum resistance is a dominant cause of poor outcomes in advanced ovarian cancer (OC). A mechanism of platinum resistance is the inhibition of apoptosis through phosphatidylinositol 3 kinase (PI3K) pathway activation. The role of phosphatase and tensin homolog (PTEN), a negative regulator of this pathway, as a tumor biomarker is unclear. Quantitative analysis of PTEN expression as an alternative to immunohistochemistry has not been considered. In 238 patient tumors from the NCIC-CTG trial OV.16, PTEN protein expression was quantified by Automated QUantitative Analysis (AQUA). Cox model was used to study the association between PTEN expression and clinical outcomes using a minimum p-value approach in univariate analysis. Multivariate analysis was used to adjust for clinical and pathological parameters. PTEN scores (range 13.9-192.3) of the 202 samples that passed quality control were analyzed. In univariate analysis, there was a trend suggesting an association between PTEN expression by AQUA as a binary variable (low ≤61 vs high >61) and progression free survival (HR=0.77, p=0.083), and in multivariate analysis, this association approached significance (HR=0.74, p=0.059). The relationship between quantitative PTEN expression and PFS differed (p=0.01 for interaction) by the extent of surgical debulking (residual disease (RD) <1cm or ≥1cm), with a numerically superior PFS in patients with high PTEN (23.5 vs 14.9m) only when RD<1cm (p=0.19). There was no association between PTEN levels and overall survival. AQUA is a novel method to measure PTEN expression. Further study of PTEN as a biomarker in OC is warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

Citation

J I Weberpals, M S Amin, B E Chen, D Tu, J N Spaans, J A Squire, E A Eisenhauer, S Virk, D Ma, M Duciaume, P Hoskins, D P LeBrun. First application of the Automated QUantitative Analysis (AQUA) technique to quantify PTEN protein expression in ovarian cancer: A correlative study of NCIC CTG OV.16. Gynecologic oncology. 2016 Mar;140(3):486-93