Academic Unit of Surgery, Glasgow Royal Infirmary, Glasgow, United Kingdom;
Mark Scott Johnstone , Sara SF Al-Badran , Reiss Stoops , Jennifer Hay , Jakub Jawny , Gerard Lynch , Stephen T McSorley , Joanne Edwards
Background: Following colorectal polypectomy, 20-50% develop metachronous polyps, and some have increased colorectal cancer (CRC) risk. Surveillance colonoscopy is recommended to high-risk patients, based on index polyp number, histology and size. We aimed to assess if COX2, p53 and beta-catenin expression could predict metachronous polyp/ CRC risk. Methods: Tissue microarrays (TMA’s) were constructed for 339 patients from the INCISE study, a retrospective analysis of all patients undergoing screening polypectomy (Apr’09-Dec’16) followed by surveillance (6months-6years) in Glasgow, UK. Epithelial COX2, p53 and beta-catenin expression were assessed for each patient’s most advanced index polyp using immunohistochemistry, quantified by QuPath software. Kaplan-Meier analysis, log-rank tests and univariate/ multivariate cox regression assessed the association between marker expression and time to metachronous polyp/ CRC detection. Results: Low nuclear p53 expression was associated with shorter time to metachronous polyp/ CRC detection (p=0.024). Low nuclear (p=0.012) and membranous (p=0.046) beta-catenin expression was associated with shorter time to metachronous polyp/ CRC detection. There was no association between cytoplasmic COX2 expression and time to metachronous polyp/ CRC detection overall (p=0.309), but high cytoplasmic COX2 expression was associated with shorter time to detection of advanced metachronous lesions (advanced colorectal polyps/ CRC) (p=0.011). A combined score using the two most powerful biomarkers (nuclear p53 and nuclear beta-catenin – both high/ one low/ both low) was also associated with shorter time to metachronous polyp/ CRC detection (p=0.011). Univariate and multivariate cox regression are shown. Conclusions: Index polyp number and combined nuclear p53/beta-catenin expression independently predicted time to metachronous polyp/ CRC detection.
Univariate | Multivariate | ||||||
---|---|---|---|---|---|---|---|
Variable | HR | 95% CI | P | HR | 95% CI | P | |
Sex | Male | 1.0 | |||||
Female | 0.703 | 0.490-1.009 | 0.056 | ||||
Age (Years) | <65 | 1.0 | |||||
≥65 | 1.034 | 0.761-1.405 | 0.831 | ||||
No. of Index Polyps | 1 | 1.0 | 1.0 | ||||
2-4 | 1.955 | 1.303-2.933 | 0.001 | 1.995 | 1.321-3.011 | 0.001 | |
5+ | 4.255 | 2.728-6.639 | <0.001 | 4.252 | 2.707-6.681 | <0.001 | |
HGD | No | 1.0 | |||||
Yes | 1.075 | 0.701-1.648 | 0.741 | ||||
Villous Features | No | 1.0 | |||||
Yes | 0.753 | 0.552-1.025 | 0.072 | ||||
Cytoplasmic COX2 Expression | Low | 1.0 | |||||
High | 0.760 | 0.446-1.293 | 0.311 | ||||
Nuclear p53 Expression | High | 1.0 | |||||
Low | 1.475 | 1.051-2.069 | 0.025 | ||||
Nuclear Beta-Catenin Expression | High | 1.0 | |||||
Low | 1.485 | 1.089-2.026 | 0.013 | ||||
Membranous Beta-Catenin Expression | High | 1.0 | |||||
Low | 1.374 | 1.004-1.879 | 0.047 | ||||
Combined Nuclear p53/Beta-Catenin Expression | Both High | 1.0 | 1.0 | ||||
One Low | 1.487 | 0.945-2.339 | 0.086 | 1.306 | 0.824-2.068 | 0.256 | |
Both Low | 1.970 | 1.250-3.103 | 0.003 | 1.725 | 1.089-2.734 | 0.02 |
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