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Updated: Mar 27, 2026
Heterogeneity Mapping of Protein Expression in Tumors using Quantitative Immunofluorescence
Published on: October 25, 2011
First application of the Automated QUantitative Analysis (AQUA) technique to quantify PTEN protein expression in
J I Weberpals1, M S Amin2, B E Chen3
1Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Canada; Division of Gynecologic Oncology, The Ottawa Hospital, Ottawa, Ontario, Canada.
Background:
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.
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 ≤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.
Conclusions:
AQUA is a novel method to measure PTEN expression. Further study of PTEN as a biomarker in OC is warranted.
Insights
Quantitative analysis of phosphatase and tensin homolog (PTEN) expression using AQUA shows potential as a biomarker for predicting progression-free survival in ovarian cancer patients, particularly those with minimal residual disease after surgery.
Area of Science:
- Oncology
- Biomarker Discovery
- Cancer Therapeutics
Background:
- Platinum resistance significantly impacts outcomes in advanced ovarian cancer (OC).
- Phosphatidylinositol 3 kinase (PI3K) pathway activation contributes to platinum resistance by inhibiting apoptosis.
- The role of phosphatase and tensin homolog (PTEN), a PI3K pathway inhibitor, as an ovarian cancer biomarker remains unclear.
Purpose of the Study:
- To quantitatively analyze PTEN protein expression using Automated QUantitative Analysis (AQUA) in ovarian cancer patients.
- To investigate the association between PTEN expression levels and clinical outcomes, including progression-free survival (PFS) and overall survival (OS).
- To explore PTEN as a potential predictive biomarker for treatment response in ovarian cancer.
Main Methods:
- PTEN protein expression was quantified using AQUA in 202 patient tumors from the NCIC-CTG trial OV.16.
- Cox regression models were employed for univariate and multivariate analyses to assess the relationship between PTEN expression and clinical outcomes.
- The study utilized a minimum p-value approach and interaction analysis to evaluate PTEN's association with PFS, considering the extent of surgical debulking.
Main Results:
- Quantitative PTEN expression analysis revealed a trend towards association with improved PFS in univariate analysis (HR=0.77, p=0.083) and approached significance in multivariate analysis (HR=0.74, p=0.059).
- A significant interaction (p=0.01) was observed between PTEN expression and residual disease (RD) extent, with high PTEN correlating with superior PFS (23.5 vs 14.9 months) only in patients with RD <1cm.
- No significant association was found between PTEN expression levels and overall survival.
Conclusions:
- Automated QUantitative Analysis (AQUA) provides a novel and quantitative method for assessing PTEN protein expression in ovarian cancer.
- PTEN expression, particularly when quantified by AQUA, shows promise as a predictive biomarker for progression-free survival in ovarian cancer patients.
- Further research into PTEN as a biomarker is warranted to optimize its clinical utility in managing ovarian cancer.
