Panel Establishes Biomarker Guidelines for CRC Diagnostics

After reviewing more than 4,000 articles, an expert panel has issued recommendations for testing diagnostic biomarkers in patients with early and advanced colorectal cancer.

The multi-disciplinary panel was established by The American Society for Clinical Pathology (ASCP), the College of American Pathologists (CAP), the Association for Molecular Pathology (AMP), and the American Society of Clinical Oncology (ASCO) with the objective of establishing standard molecular biomarker testing of colorectal cancer (CRC) tissues to guide epidermal growth factor receptor (EGFR) therapies and conventional chemotherapy regimens.


To accomplish this goal, the panel conducted a comprehensive literature search that included more than 4,000 articles. The members of the panel focused on the following list of key questions: (1) What biomarkers are useful to select patients with CRC for targeted and conventional therapies? (2) How should tissue specimens be processed for biomarker testing for CRC management? (3) How should biomarker testing for CRC management be performed? (4) How should molecular testing of CRC be implemented and operationalized? (5) Are there emerging genes/biomarkers that should be routinely tested in CRC?

Following their review, the panel published its findings in the February 6, 2017, online editions of the American Journal of Clinical Pathology, Archives of Pathology & Laboratory Medicine, the Journal of Molecular Diagnostics and the Journal of Clinical Oncology, from each collaborating organization, respectively.

The panel established 21 guideline statements (eight recommendations, 10 expert consensus opinions, and three "no recommendation") and concluded that the evidence supported mutational testing of specific genes in the EGFR signaling pathway, since they provide clinically actionable information for targeted therapy of CRC with anti-EGFR monoclonal antibodies. Mutations in some of the biomarkers have clear prognostic value (BRAF, MMR), and at least two (KRAS and NRAS) have relatively strong evidence as negative predictors of benefit to anti-EGFR therapies and should be used to guide the use of these agents. BRAF mutations are consistently associated with poor outcomes in patients with metastatic CRC, including those who relapse after adjuvant therapy.

"While many existing recommendations cover the application of individual molecular biomarkers in colorectal cancer, this guideline fills the need for an overarching set of recommendations spanning the breadth of current knowledge,” said contributing author Dr. Wayne W. Grody, professor of medicine at the University of California, Los Angeles and project co-chair on behalf of ASCP. "This comprehensive guideline will prove useful for pathologists and oncologists to support decision-making on what molecular tests to order for patients with colorectal cancer."