Newswise — Northfield, IL — Recognizing a need for evidence-based recommendations to guide molecular testing in the management of patients with cancer, the College of American Pathologists (CAP) and three collaborating societies are developing a clinical guideline for testing DNA mismatch repair (MMR) and microsatellite instability (MSI) status in patients with a range of cancer types.

Today, the groups open the public comment period for the guideline “MMR and MSI Testing in Patients Being Considered for Checkpoint Inhibitor Therapy.”  All stakeholders—including pathologists who refer and perform molecular testing, oncologists, laboratory personnel, and allied health professionals—should provide feedback on the draft recommendations before March 13 to ensure final recommendations are clinically practical.

“This guideline is the first to address testing based more on the methodology status of a biomarker and less on the cancer type or tumor origin,” explains guideline developer, pathologist Russell Broaddus, MD, PhD, FCAP. “As we’ve learned more about patient response to checkpoint inhibitor therapy, we’ve seen that patients whose cancers had high levels of MSI or defective MMR would respond well, specifically to a checkpoint inhibitor drug such as pembrolizumab.” 

Dr. Broaddus chairs the panel of experts representing the societies collaborating on the guideline: the American Society of Clinical Oncology (ASCO), the Association for Molecular Pathology (AMP), and Fight Colorectal Cancer (Fight CRC). The panel will consider all comments garnered during the comment period prior to finalizing the recommendations and submitting the guideline for publication.

“For patients, knowing your MSI status is extremely important prior to selecting a treatment,” according to experts at Fight CRC. “Many patients with MSI-high tumors have had a positive response to immunotherapy treatments, also known as immune-checkpoint therapies.”

And while the FDA approved a drug for patients with MSI-high or MMR-deficient tumor status, regardless of cancer type, it did not detail how to test for that status. This new CAP guideline aims to fill that gap and provide oncologists, pathologists, and laboratories of all sizes with evidence-based recommendations to efficiently deploy specific assays and accurately identify patients eligible for treatment.

In particular, the panel developing the guideline sought evidence to answer these questions: 

  • Which test modality best predicts DNA MMR?
  • Does cancer type matter when choosing a testing modality?
  • Does MMR by immunohistochemistry, MSI by polymerase chain reaction, or MSI by next generation sequencing results predict improved clinical outcomes in patients treated with checkpoint inhibitors?
  • Does tumor mutation burden predict improved clinical outcomes in patients treated with checkpoint inhibitors?

As drafted, the guideline includes six recommendations and three “good practice statements” that impact testing for patients with colorectal, endometrial, gastroesophageal and small bowel, and other types of cancer. In addition, the recommendations provide guidance on the role of tumor mutational burden in MMR testing and the evaluation of Lynch Syndrome.

To read and comment on the draft guideline, visit until March 13, 2020.

About the College of American Pathologists

As the world's largest organization of board-certified pathologists and leading provider of laboratory accreditation and proficiency testing programs, the College of American Pathologists (CAP) serves patients, pathologists, and the public by fostering and advocating excellence in the practice of pathology and laboratory medicine worldwide. For more information, read the CAP Annual Report at

Journal Link: “MMR and MSI Testing in Patients Being Considered for Checkpoint Inhibitor Therapy” Guideline