Abstract 353P
Background
Lack of expression of the tumor suppressor CDX2 is associated with stage II/III colorectal cancer (CRC) poor outcomes. Its potential prognostic and predictive values in metastatic CRC (mCRC), and correlation with other potential biomarkers are of great interest. Overexpression of the PTGS2 gene encoding cyclooxygenase 2 (COX2) has shown a significantly direct association with advanced CRC stages. Reduced CDX2 in CRC has been suggested to enhance NF-κB-mediated inflammatory response, upregulating COX2 expression. However, the relationship between both markers in mCRC pathogenesis remains undetermined. We aimed to assess CDX2 and COX2 expression in mCRC tumor samples from a clinically characterized cohort.
Methods
346 out of 720 patients with mCRC between Jan. 2010 and Dec. 2019 had primary tumor and/or metastasis tumor tissues appropriate for analysis. Tissue microarrays (TMA) were assembled and analyzed by IHC with anti-CDX2 and -COX2 antibodies. Negative CDX2 (CDX2-) samples were defined as complete lack of the CDX2 protein staining and/or scattered faint nuclear labelling in few cancer cells. COX2 intensity and extent staining was positive (COX2+) if the final score was ≥3 (0-7). Retrospective demographic, clinical and survival data were analyzed. Comparisons of overall survival (OS) between groups were performed by log rank.
Results
CDX2 loss was found in 27 (7.8%) samples and was significantly enriched among poorly differentiated tumors (26.1% vs 8.1%; p = 0.009) and those with the BRAF p.V600E variant (42.9% vs 5.4%; p = 0.0002). CDX2- was not associated with age, gender, tumor sidedness, RAS mutation or presence of microsatellite instability. COX2+ tumors were the majority (93.4%) and not associated with CDX2 IHC expression. Median OS for CDX2- and CDX2+ mCRC patients was 30 and 53 months, respectively (p < 0.0008), and not significant for the COX2 comparison (p < 0.152). The median PFS in first-line chemotherapy was significantly lower for those with CDX2- tumors (6 vs. 10 months; p < 0.026).
Conclusions
Loss of CDX2 expression in mCRC was associated with a higher risk of death and progression after first-line treatment, poor differentiated tumors and the BRAF p.V600E variant. COX2 was highly expressed in mCRC. Further analyses may be warranted.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
A.M.D.C. Caldas.
Funding
Amgen Inc.(IHC, TMA).
Disclosure
All authors have declared no conflicts of interest.