What are the ASCP-CAP-AMP-ASCO guidelines on molecular biomarker testing for the evaluation of colorectal cancer?

Updated: Mar 18, 2021
  • Author: Elwyn C Cabebe, MD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Guidelines on molecular biomarker testing for the evaluation of colorectal cancer (CRC) from the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology include the following recommendations [29] :

  • Patients with CRC who are being considered for anti–epidermal growth factor receptor (EGFR) therapy must receive RAS mutational testing, which should include KRAS and NRAS codons 12 and 13 of exon 2, 59 and 61 of exon 3, and 117 and 146 of exon 4 (“expanded” or “extended” RAS).
  • BRAF p.V600 ( BRAF c.1799 [p.V600]) position mutational analysis should be performed in CRC tissue in selected patients for prognostic stratification.
  • BRAF p.V600 mutational analysis should be performed in deficient mismatch repair (dMMR) tumors with loss of MLH1 to evaluate for Lynch syndrome risk. Presence of a BRAF mutation strongly favors a sporadic pathogenesis. The absence of BRAF mutation does not exclude risk of Lynch syndrome.
  • Clinicians should order mismatch repair status testing in patients with CRC to identify patients at high risk for Lynch syndrome and/or for prognostic stratification.
  • Tissues from metastatic or recurrent CRC tumors are the preferred specimens for treatment-predictive biomarker testing and should be used if such specimens are available and adequate. In their absence, primary tumor tissue is an acceptable alternative and should be used.
  • Formalin-fixed, paraffin-embedded (FFPE) tissue is an acceptable specimen for molecular biomarker mutational testing in colorectal carcinoma. Use of other specimens (eg, cytology specimens) will require additional adequate validation, as would any changes in tissue-processing protocols.
  • Laboratories must validate the performance of immunohistochemistry (IHC) testing for CRC molecular biomarkers (currently IHC testing for MLH1, MSH2, MSH6, and PMS2) in accordance with best laboratory practices.
  • Laboratories should use CRC molecular biomarker testing methods that are able to detect mutations in specimens with at least 5% mutant allele frequency, taking into account the analytical sensitivity of the assay (limit of detection [LOD]) and tumor enrichment (eg, microdissection).

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