In checklists, new approach for predictive markers

Valerie Neff Newitt

November 2019—In the 2019 edition of the CAP accreditation program checklists, released in September, requirements for predictive marker testing were revised to make them general so they apply to all types of such testing performed by immunohistochemistry and in situ hybridization, wherever possible.

The revision will prevent an overload of new requirements as the number of new predictive markers grows, but still ensure the quality of the testing, say those who led the 18-month effort to, in effect, build a new system.

“HER2 was the first widely used predictive marker, so we used that experience as a foundation. And yet every marker has its own unique challenges, so we needed to figure out a system that would fit an ever-increasing list of predictive markers so as to avoid producing new requirements for each new marker,” says Raouf Nakhleh, MD, chair of the CAP Council on Scientific Affairs and professor of pathology, Mayo Clinic Jacksonville.

Until now, once a new predictive marker came into clinical use, “a CAP guideline would grow around it,” says Andrew Bellizzi, MD, chair of the CAP Immunohistochemistry Committee and clinical associate professor, Department of Pathology, University of Iowa Hospitals and Clinics. “Then each new CAP guideline was typically translated into one, two, or as many as five new checklist requirements. And because predictive markers can be done by different methodologies, the predictive marker requirements needed to be placed in several different checklists.”

Just when the Checklists Committee was considering adding checklist requirements about gastric HER2, “six or seven additional predictive markers moved into prime time. It was time for a rethink,” he says.

There were two ways to go, they say. “We could continue to add checklist requirements or we could reorganize around a common framework,” Dr. Bellizzi explains. The former created the risk of unwieldy checklists and difficult inspections. So the CAP chose the latter and assembled a team drawn from its Checklists, Cytogenetics, Surgical Pathology, Immunohistochemistry, Molecular Oncology, Cancer, and Center committees, led by Harris Goodman, MD, Checklists Committee chair. “He did it masterfully,” Dr. Bellizzi says of his leadership.

The team’s work culminated in revised or new requirements for the all common, anatomic pathology, cytogenetics, molecular pathology, and laboratory general checklists. While generalizing the requirements was the aim, some requirements that pertain only to breast cancer markers have been retained.

“Many committee members wanted to keep breast cancer specific requirements in place,” explains Dr. Goodman, of Alameda Health System’s Highland Hospital, Oakland, Calif. “The anatomic pathology checklist has a section on predictive markers that applies only to assays performed on breast cancer. So, at least at this time, it was felt that we would keep some checklist requirements specific to tumor types. But the goal to move toward more general checklist requirements as they apply to predictive markers remains.”

The more substantive revisions pertaining to predictive markers are found in the following checklist requirements:

• COM.01520 PT and Alternative Performance Assessment for IHC and ISH Predictive Marker Interpretation. “This is new and very important,” Dr. Bellizzi says. “In the past we’ve had Surveys pertaining to many predictive markers that provided a lab with tools to show how well they were doing with some tests. Participation was optional; now participation in something is required. So of all the checklist requirements this one is perhaps the most impactful for laboratories. It requires them to do something new—PT or alternative performance assessment, and evidence of compliance must be maintained.”

• ANP.22969/MOL.39295/CYG.47880 Report Elements. “If you do an IHC or ISH predictive marker test,” Dr. Goodman says, “your report has to include information on specimen processing, the antibody clone or probe used, and the scoring method used.”

It is not a new requirement, “but it has gotten more teeth,” Dr. Bellizzi says. “This is an excellent checklist requirement that is being used as a linchpin to capture all of the reporting requirements around a predictive marker. This was already the most general guideline in IHC regarding predictive markers, but now we have trimmed some of the fat and folded various other checklist requirements into this one requirement.”

• ANP.22978/MOL.39323/CYG.48399 Predictive Marker Testing—Validation/Verification. “In this requirement, assay validation and verification no longer refer only to HER2, but to all predictive marker test validations and verifications,” says Jeffrey Goldsmith, MD, CAP Center Guideline lead, associate professor of pathology at Harvard Medical School, and director of GI pathology, Boston Children’s Hospital.