NGS Outperforms IHC in Mismatch Repair Deficiency Testing

In a paper published in Cancer Cell, researchers at Brigham and Women’s Hospital propose a potential paradigm shift in cancer care, suggesting that revising existing testing guidelines could extend immunotherapy benefits to approximately 6,000 additional cancer patients annually in the U.S. The study also highlights the efficacy of immunotherapy for patients with mismatch repair deficiency, revealing that current testing methods may overlook eligible individuals.

The investigation focused on endometrial and colorectal cancers, prevalent in over 150,000 and 65,000 annual U.S. diagnoses, respectively. The standard immunohistochemistry test, used to identify mismatch repair deficiency, missed nearly six percent of endometrial cancer patients and one percent of colorectal cancer patients, as unveiled by next-generation sequencing. This more advanced technique, by researchers' estimates, could identify 6,000 more patients who could benefit from immunotherapy.

Dr. Elias Bou Farhat, the study's first author, emphasizes the significance of including next-generation sequencing as a complementary diagnostic tool. Even in late-stage cancers, patients with mismatch repair deficiency responding to immunotherapy exhibit prolonged survival and potential cures. The study suggests that this additional testing practice could be valuable at all stages of cancer treatment.

The research cohort, consisting of 1,655 patients from Brigham and Women’s Hospital and Dana-Farber Cancer Institute, underwent both immunohistochemistry and next-generation sequencing tests. Patients identified as mismatch repair deficient by sequencing but not by immunohistochemistry demonstrated comparable treatment outcomes and survival rates to those identified by both methods.

While the study indicates the heightened sensitivity of next-generation sequencing in detecting mutations, further research is essential for confirmation and generalization of the findings. The data underscore the potential negative impact of missing eligible patients, leading to suboptimal treatments and outcomes. Moving forward, researchers aim to explore the applicability of these findings to different sequencing panels and cancer types, with a focus on uncovering additional genetic deficiencies associated with mismatch repair deficiency.