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

Background. Platinum resistance is a dominant cause of poor outcomes in advanced ovarian cancer (DC). 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. Patients and methods. 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. Results. 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 5561 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) <1 cm or >= 1 cm), with a numerically superior PFS in patients with high PTEN (23.5 vs 14.9 m) only when RD < 1 cm (p = 0.19). There was no association between PTEN levels and overall survival. Conclusions. AQUA is a,novel method to measure PTEN expression. Further study of PTEN as a biomarker in OC is warranted. (C) 2016 Elsevier Inc. All rights reserved.