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KRAS Mutation Detection

Test Code

KRAS

CPT Codes

83896 x 8 ; 83898 x 8 ; 83907 x 1 ; 83912 x 1 ; 83912-26 x 1

Specimen

Formalin-fixed paraffin-embedded tissue curls or non-stained mounted tissue sections originating from colorectal cancer (CRC) or metastatic CRC (mCRC) biopsies. All tissue sections (slides or tubes with curls) should be clearly labeled with correct sample identifiers. A detailed pathology report including % tumor load is required to accompany the patient sample and at least 20% tumor cells must be present. All sections for KRAS testing should contain representative tumor cells as determined by the pathologist.

Volume

3-5 non-stained slides with 10um mounted sections (no cover slip), OR 3 pre-cut non-mounted sections at 10um are acceptable. If non-mounted tissue curls are to be sent, the sample must be freshly cut and placed into a sterile tube immediately to prevent further drying.

Minimum Volume

3 non-stained slides with 10um mounted sections (no cover slip), OR 3 pre-cut non-mounted sections at 10um each.

Container

Untreated slides (for mounted sections) or sterile tubes (for pre-cut, non-mounted sections)

Storage Instructions

Maintain at room temperature, protect from extreme heat or cold

Cause for Rejection

Insufficient quantity (<3) of tissue sections Sections unaccompanied by pathology report containing required information Sections with < 20% tumor load Improperly labeled sections Improperly fixed sections (e.g., alternative fixatives other than FFPE, stained slides, cover slipped, etc)

Use

This assay detects seven known mutations in the KRAS gene. Any of the seven KRAS gene mutations result in a constitutively activated KRAS protein, which can lead to tumor growth and progression. Presence of a KRAS mutation predicts tumor resistance, or lack of response, to EGFR-targeted therapies including cetuximab and panitumumab. Only those patients whose tumors harbor the wild-type (non-mutated) KRAS gene may respond to the addition of such EGFR-targeted therapies to their chemotherapy regimens.

Limitations

The assay detects six known mutations in codon 12 and one mutation in codon 13 of the KRAS gene. Any other known or unknown mutations of KRAS or other genes are not detected. Samples must contain at least 20% tumor as determined by the pathologist. Samples with <20% tumor may harbor particularly low levels of KRAS mutation that are undetectable by this assay. Absence of KRAS mutation (a negative test result) does not definitively predict positive response to EGFR-targeted therapies. Physicians should continue to monitor patients accordingly.

Methodology

Real-time polymerase chain reaction combined with ARMS and SCORPION technology (DxS Diagnostic Innovations).

Turnaround Time

Five business days after receipt of specimen.

References

DxS K-RAS Mutation Kit package insert, version RU003e, date July 2009. DxS Diagnostic Innovations, Manchester, UK Jimeno A et al. J Clin Oncol 2009;27(7):1130-6. Amado RG et al. J Clin Oncol 2008;26(10):1626-1634. Van Cutsem E et al. J Clin Oncol 2008;26 (May 20 suppl; abstr 2). CRYSTAL Bokemeyer C et al. J Clin Oncol 2008;26 (May 20 suppl; abst 4000). OPUS Lievre. J Clin Onocol 2008;26(3):374-9. Van Custem E et al. J Clin Oncol 2007;25(13):1658-64.