A new study reveals that thousands of patients with colorectal and endometrial cancer could benefit from immunotherapy than currently being offered. Researchers emphasize the importance of considering DNA mismatch repair deficiency (MMR-D) as a diagnostic marker for treatment decisions with immunotherapy. MMR-D is associated with an increased risk for developing various types of cancer and is the most common cause of hereditary endometrial cancer.
The study, published in Cancer Cell on December 28, compared two laboratory methods for diagnosing cancer: Traditional immunohistochemistry (IHC) – a laboratory technique using antibodies to detect antigens in tissues; and Next Generation Sequencing (NGS) – a novel technology for DNA sequencing that can identify specific mutation patterns. The researchers found that NGS enables a more accurate assessment of MMR status.
We found that 1% of patients with colorectal cancer and 6% of patients with endometrial cancer have a mismatch repair deficiency that is still undetected by IHC, the current standard for diagnostic tests. However, these are detected by NGS. Importantly, we have shown that these patients, who are overlooked by IHC and detected by NGS, benefit from long-term immunotherapy. We recommend reviewing mismatch repair testing guidelines and incorporating both NGS and IHC.
Amin Nassar, MD, senior author of the study and member of the Yale Cancer Center
Researchers estimate that the implementation of NGS along with IHC could identify an additional 6,000 patients in the United States annually who could benefit from life-prolonging immunotherapy. These patients would not be offered immunotherapy if IHC alone were used.
The researchers call for larger studies to further validate these findings in patients with colorectal and endometrial cancer, as well as to investigate the application of NGS in other types of cancer.
Nassar is a clinical fellow at the Yale Cancer Center and completed much of the work while serving as a resident at Brigham and Women’s Hospital. He was joined by first author Dr. Elias Bou Farhat from Brigham and Women’s Hospital.
Bou Farhat, E., et al. (2023). Benchmarking DNA mismatch repair testing for cancer patients receiving immunotherapy. Cancer Cell. doi.org/10.1016/j.ccell.2023.12.001.