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. 2017 Apr 27;8(4):e91.
doi: 10.1038/ctg.2017.18.

Evaluation of PTGS2 Expression, PIK3CA Mutation, Aspirin Use and Colon Cancer Survival in a Population-Based Cohort Study

Ronan T Gray  1 , Marie M Cantwell  2 , Helen G Coleman  1 , Maurice B Loughrey  3   4 , Peter Bankhead  3 , Stephen McQuaid  3   5 , Roisin F O'Neill  1 , Kenneth Arthur  3 , Victoria Bingham  3 , Claire McGready  3 , Anna T Gavin  6 , Chris R Cardwell  1 , Brian T Johnston  7 , Jacqueline A James  3   4   5 , Peter W Hamilton  3 , Manuel Salto-Tellez  3   4 , Liam J Murray  1
Affiliations

Evaluation of PTGS2 Expression, PIK3CA Mutation, Aspirin Use and Colon Cancer Survival in a Population-Based Cohort Study

Ronan T Gray et al. Clin Transl Gastroenterol. .

Abstract

Objectives: The association between aspirin use and improved survival after colorectal cancer diagnosis may be more pronounced in tumors that have PIK3CA mutations or high PTGS2 expression. However, the evidence of a difference in association by biomarker status lacks consistency. In this population-based colon cancer cohort study the interaction between these biomarkers, aspirin use, and survival was assessed.

Methods: The cohort consisted of 740 stage II and III colon cancer patients diagnosed between 2004 and 2008. Aspirin use was determined through clinical note review. Tissue blocks were retrieved to determine immunohistochemical assessment of PTGS2 expression and the presence of PIK3CA mutations. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for colorectal cancer-specific and overall survival.

Results: In this cohort aspirin use was associated with a 31% improvement in cancer-specific survival compared to non-use (adjusted HR=0.69, 95% CI 0.47-0.98). This effect was more pronounced in tumors with high PTGS2 expression (PTGS2-high adjusted HR=0.55, 95% CI 0.32-0.96) compared to those with low PTGS2 expression (PTGS2-low adjusted HR=1.19, 95% CI 0.68-2.07, P for interaction=0.09). The aspirin by PTGS2 interaction was significant for overall survival (PTGS2-high adjusted HR=0.64, 95% CI 0.42-0.98 vs. PTGS2-low adjusted HR=1.28, 95% CI 0.80-2.03, P for interaction=0.04). However, no interaction was observed between aspirin use and PIK3CA mutation status for colorectal cancer-specific or overall survival.

Conclusions: Aspirin use was associated with improved survival outcomes in this population-based cohort of colon cancer patients. This association differed according to PTGS2 expression but not PIK3CA mutation status. Limiting adjuvant aspirin trials to PIK3CA-mutant colorectal cancer may be too restrictive.

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Conflict of interest statement

Guarantor of the article: Ronan T. Gray, MB BCh (Hons), MSc, MRCS.

Specific author contributions: Study conception and design: Marie M. Cantwell, Helen G. Coleman, Maurice B. Loughrey, Stephen McQuaid, Chris R. Cardwell, Jacqueline A. James, Brian T. Johnston, Manuel Salto-Tellez, and Liam J. Murray; Data acquisition: Ronan T. Gray, Helen G. Coleman, Maurice B. Loughrey, Peter Bankhead, Stephen McQuaid, Roisin F O’Neill, Kenneth Arthur, Victoria Bingham, Claire McGready, and Jacqueline A. James; Data analysis and interpretation: Ronan T. Gray, Helen G. Coleman, Chris R. Cardwell, and Liam J. Murray; Drafting manuscript: Ronan T. Gray, Helen G. Coleman, Stephen McQuaid, Chris R. Cardwell and Liam J. Murray. Manuscript revision: All. Final approval: All.

Financial support: This project was supported by a Health and Social Care (HSC) Research & Development Division of the Public Health Agency Doctoral Fellowship (EAT/4905/13—RTG), a Cancer Research UK (CRUK) Research Bursary (C50104/A17592—RTG), and a CRUK Population Health Postdoctoral Fellowship (C37703/A15333–H.G.C.). H.G.C., M.M.C., L.J.M., R.T.G. and R.F.O’N are all co-investigators or affiliated members of the UKCRC Centre of Excellence for Public Health Northern Ireland. The Northern Ireland Cancer Registry is funded by the Public Health Agency, Northern Ireland. The Northern Ireland Biobank is funded by the HSC Research and Development Division of the Public Health Agency in Northern Ireland and CRUK through the Belfast CRUK Centre, the Northern Ireland Experimental Cancer Medicine Centre and Friends of the Cancer Centre. The Northern Ireland Molecular Pathology Laboratory has received funding from CRUK, the Friends of the Cancer Centre, and the Sean Crummey Foundation. The study funders played no role in the study design or collection, analysis, and interpretation of data.

Potential competing interests: Peter W. Hamilton is Founder and Director in PathXL Ltd. Manuel Salto-Tellez is a senior advisor to PathXL. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Selection of stage II and III colon cancer (adenocarcinoma) patients and samples. NIB, Northern Ireland Biobank.
Figure 2
Figure 2
PTGS2 immunohistochemistry in colon cancer tissue microarrays (TMAs) and associated mark-up for digital immunoscoring using QuPath image analysis software. Detected cells are color-coded according to their classification: green, non-tumor; blue, negatively staining tumor; yellow, weakly staining tumor; orange, moderately staining tumor; red, strongly staining tumor. (a) Original core from a tumor weakly expressing PTGS2 (PTGS2-low). (b) Original core from a tumor strongly expressing PTGS2 (PTGS2-high). (c) QuPath cellular mark-up in the PTGS2-low core (H-score 30.3). (d) QuPath cellular mark-up in the PTGS2-high core (H-score 243.4).
See this image and copyright information in PMC

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