Molecular Markers Predict Prognosis in Colorectal Cancer

Douglas K. Rex, MD, FASGE, reviewing Phipps AI, et al. Gastroenterology 2020 Feb 20.

Current recommendations from the U.S. Multi-Society Task Force recommend that all colorectal cancers (CRCs) undergo testing for either microsatellite instability (MSI) or immunohistochemistry (IHC) for mismatch repair gene products. In addition, clinical laboratories commonly report mutations in BRAF and KRAS oncogenes. BRAF and KRAS are in the same signaling pathway, and most CRCs are mutated in one or the other but not in both. CpG island methylator phenotype (CIMP) refers to the methylation status of the tumor, and CIMP positivity is generally interpreted as a tumor that developed through the serrated pathway. 

This study is an extension of previous studies that have examined survival in association with various combinations of these tumor markers. This report pooled data from 7 international studies involving 5010 CRCs. 

In this study, the reference subtype was microsatellite stable (MSS), CIMP negative, and no mutations in BRAF or KRAS (type 4). Compared to this, the worst survival was associated with type 2 (MSS, CIMP positive, mutated BRAF). The hazard ratio for death with type 2 compared to type 4 was 1.65. The addition of a KRAS mutation to type 4 makes type 3, which was associated with a 1.33 hazard ratio for death compared to type 4. Both types associated with MSI, whether type 1 (through the serrated pathway) or type 5 (through Lynch syndrome), were associated with improved survival compared to type 4.

Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.

Douglas K. Rex, MD, FASGE

CITATION(S)

Phipps AI, Alwers E, Harrison T, et al. Association between molecular subtypes of colorectal tumors and patient survival, based on pooled analysis of 7 international studies. Gastroenterology 2020 Feb 20. (Epub ahead of print) (https://doi.org/10.1053/j.gastro.2020.02.029)