Immunotherapy, a highly effective treatment for patients whose cancers harbour mismatch repair deficiency, can also benefit endometrial and colon cancer patients.
Endometrial and colon cancer patients often have high rates of mismatch repair deficiency -- a genetic state where errors in DNA occur due to a lack of certain repair proteins. This state impairs DNA's ability to repair itself and can lead to many types of cancer.
These patients were missed by immunohistochemistry -- the current standard of care test for this condition -- but were caught by next-generation sequencing.
Previous research has shown that cancer patients with this condition typically respond well to immunotherapy treatment, which uses a person's own immune system to fight cancer.
"In colorectal cancer and endometrial cancer, which are the two types of cancer where mismatch repair deficiency is most commonly seen, immunotherapy is not the standard treatment unless a patient has this condition," said Elias Bou Farhat, MD, a postdoctoral research fellow in the division of Pulmonary and Clinical Care Medicine at Brigham and Women's Hospital in the US.
"But in patients with this condition, even in late-stage cancer, those who receive immunotherapy can live for years and in some cases be potentially cured. Including next-generation sequencing as a complementary testing practice could benefit patients in all phases of cancer, from pre-treatment to advanced stages," Farhat added.
In this study, published in the journal Cancer Cell, the researchers looked at a cohort of 1,655 patients who either had colorectal or endometrial cancer and who received both immunohistochemistry and next-generation sequencing tests.
The researchers observed that nearly six per cent of the patients with endometrial cancer and one per cent of the patients with colorectal cancer were missed as being mismatch repair deficient by immunohistochemistry. These patients responded better to immunotherapy than other treatments and their survival and treatment outcomes were the same as those who were found deficient by both tests.
Immunohistochemistry only detects mutations that affect the antigen; next-generation sequencing is a more sensitive test because it looks for more mutation characteristics.
While the current work suggests that next-generation sequencing will be a more sensitive diagnostic tool in these cases, further studies are needed to confirm and generalise this study's findings.
The study's data also showed that in patients with the same cancer type at the same stage, those who did not receive immunotherapy had worse outcomes than those who did.
Next, the researchers would like to see if these findings apply to other sequencing panels and other cancer types. They also plan to investigate the potential role of other genetic deficiencies involved in the condition of mismatch repair deficiency.
