TABLE II.

Summary of recommendations

Recommendation		Level of consensus
1.	Indications and funding for KRAS testing
	KRAS is a predictive biomarker for anti–epidermal growth factor receptor (egfr) therapy and tumour KRAS status should be determined whenever anti-egfr therapy is considered in the treatment of metastatic colorectal cancer (mcrc).	1
	Funding of the drug should be linked to funding of the requisite predictive test.	2A
2.	Timing of KRAS testing
	When possible, it is recommended that KRAS testing be requested when mcrc patients start second-line therapy.	2B
3.	Sample requirements
	Formalin-fixed paraffin-embedded tissue blocks are typically available for mutational analysis. Tumour cell enrichment by micro- or macro-dissection or selective sampling of the paraffin block by needle core should be used to increase the sensitivity of tumour testing.
	Mutational analysis should use the primary resection specimen, if available.
	An endoscopic core biopsy of the primary tumour is preferred over a core biopsy of a distant metastasis. If core biopsy of the primary is not possible, core biopsy of a distant metastasis should be obtained. Fine-needle aspiration of a metastasis should be avoided.	2A
	If every reasonable effort has been made to ascertain KRAS status, but that status remains unknown, it would be reasonable to speak with the patient and to offer the benefit of consideration for anti-egfr therapy.
4.	Optimal test for KRAS mutational analysis
	KRAS testing strategies are deemed acceptable if they satisfy these minimal requirements: a mutation-detection sensitivity between 95% and 99%, and a specificity of 100%.
	KRAS testing must be reproducible and should be performed by an accredited laboratory that conforms to quality guidelines for KRAS testing and routinely participates in proficiency testing such as that offered by the College of American Pathologists, with external validation.	2A
5.	Testing beyond KRAS: BRAF status
	BRAF is a negative prognostic factor, but does not appear to be predictive. Routine testing of BRAF mutation status before anti-egfr therapy is not currently recommended.
	Similarly, data are currently insufficient to recommend testing of other potential biomarkers (PTEN, amphiregulin, epiregulin, and PIK3CA mutations, among others).	2A
6.	Test reporting requirements
	The absence or presence of KRAS mutation must be reported.
	At a minimum, if a mutation is identified, the affected codon should be specified, and if available, the specific change should be indicated.
	Appropriate nomenclature should be used in reporting results.	2A
	Report should specify the assay used.
	Reports should conform to existing reporting guidelines (American College of Medical Genetics, College of American Pathologists, Canadian College of Medical Geneticists).
7.	Acceptable turnaround times
	Once the specimen is received by the testing laboratory, 10 working days is an acceptable turnaround time for reporting the result to the ordering physician.	2A