Key Points
➤ Molecular testing to select targeted and conventional therapies for patients with
colorectal cancer (CRC) has been the focus of a number of recent studies and is
becoming standard practice for management of patients with CRC.
➤ Current evidence-based recommendations for the molecular testing of CRC
tissues to guide EGFR-targeted therapies and conventional chemotherapy
regimens were developed through collaboration of four societies: American
Society for Clinical Pathology (ASCP), College of American Pathologists (CAP),
Association for Molecular Pathology (AMP), and American Society of Clinical
Oncology (ASCO).
Diagnosis
➤ Colorectal carcinoma patients being considered for anti-EGFR therapy must
receive RAS mutational testing. Mutational analysis should include KRAS and
NRAS codons 12, 13 of exon 2; 59, 61 of exon 3; and 117 and 146 of exon 4
("expanded" or "extended" RAS). (R-C/A-B-H/I)
➤ BRAF p.V600 (BRAF c. 1799 (p.V600) mutational analysis should be performed
in colorectal cancer tissue in patients with colorectal carcinoma for prognostic
stratification. (R-A/Ina-B/H-I/L)
➤ BRAF p.V600 mutational analysis should be performed in deficient MMR
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. (R-A/Ina-B/H-I/L)
➤ Clinicians should order mismatch repair status testing in patients with colorectal
cancers for the identification of patients at high risk for Lynch syndrome and/or
prognostic stratification. (R-A/I-B/H-I/L)
➤ There is insufficient evidence to recommend BRAF c.1799 p.V600 mutational
status as a predictive molecular biomarker for response
to anti-EGFR inhibitors. (NR-Ins-U-Ins)
➤ There is insufficient evidence to recommend PIK3CA mutational analysis of
colorectal carcinoma tissue for therapy selection outside of a clinical trial. (NR-
Ins-U-Ins)
Note: Retrospective studies have suggested improved survival with post-operative aspirin use in
patients whose colorectal carcinoma harbors a PIK3CA mutation.
