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RAS Plus Panel

RAS panel (KRAS + NRAS + BRAF)

  • Clinical Implications
    • Colorectal Cancer
      • Recommendations for colorectal cancer by (NCCN)
        • All individuals with metastatic colorectal cancer should have tumor tissue genotyped for RAS (KRAS and NRAS) and BRAF mutations.
        • Individuals with any known KRAS mutation (exon 2, 3, 4) or NRAS mutation (exon 2, 3, 4) should not be treated with either cetuximab or panitumumab.
        • BRAF V600E mutation makes response to cetuximab or panitumumab highly unlikely unless given with a BRAF inhibitor.
      • Mutations in KRAS and NRAS are seen in approximately 52% of colorectal cancers, commonly involving codons 12, 13 and 61.
      • KRAS and NRAS mutations are frequently encountered in approximately 44.7% and 7.5% of cases, respectively

  • Test Description
  • Real-Time Polymerase Chain Reaction (qPCR).

  • Test approach
    • DNA was isolated and amplified by quantitative polymerase chain reaction (qPCR) using NRAS and KRAS CE-IVD kits according to manufacture protocol. Results interpreted according to the manufacture user guide.
    • DNA was isolated and amplified by quantitative polymerase chain reaction (qPCR) using BRAF V600E, D, R and K CE-IVD kit. according to manufacture protocol. Results interpreted according to the manufacture user guide.

  • Reporting name
  • RAS Plus Panel

  • Test prerequisites (To ensure timely results)
    • Patient’s demographic data.
    • Clinicopathologic information:
      • Pathology report (final or preliminary) including anatomic location.
      • History of any given therapy for cancer and its date and relation to sample sent for molecular study (i.e. pre & post therapy). Therapy includes chemo and radiotherapy, hormonal or targeted therapy.
      • Any other relevant clinical data or history.
    • Type of sample:
      • Preferred: Formalin-fixed, paraffin-embedded (FFPE) tumor tissue block or cell block.
      • Acceptable:
        • Section in Eppendorf: Up to 4 sections, each with a thickness of up to 10 μm and a surface area of up to 250 mm2 + good H&E slide for assessment.
        • Five unstained slides + one good H&E slide.
      • Specimen Minimum Volume: Two 10-micron sections of FFPE.

  • Quality Control measures
  • All samples are subject to stringent quality control measures that include:

    • From your side:
      • Double check you are fulfilling all required data before sending your sample.
      • Check that your pathologist has selected the best block in terms of tumor cellularity, with least presence of necrosis and inflammation.
      • Pretherapy sample is preferred (if underwent any cancer therapy).
    • In our lab:
      • Assessment of tissue for adequacy & tumor cellularity before any molecular analysis.
      • Matching block ID with the report ID and demographic data.
      • Matching the submitted block with the data reported in the pathology report.
    • N.B.
      • If the sample sent in Eppendorf, it is your pathology lab’s responsibility to ensure the sample in Eppendorf is corresponding to the submitted H&E slide (we can’t prepare slide from Eppendorf).
      • This test does not include a pathology consultation.

  • Test Time
  • From 3 days to 5 working days.

  • Retention of the sample
  • Client provided paraffin blocks, Whole Blood EDTA and unstained slides (if provided) will be returned after testing is complete.

  • Selected References
    1. Lindeman NI et al: Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: guideline from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. J Mol Diagn. 20(2):129-59, 2018
    2. Wiesweg M et al: Impact of RAS mutation subtype on clinical outcome-a cross-entity comparison of patients with advanced non-small cell lung cancer and colorectal cancer. Oncogene. ePub, 2018
    3. Tímár J: The clinical relevance of KRAS of gene mutation in non-small-cell lung cancer. Curr Opin Oncol. 26(2):138-44, 2014
    4. di Magliano MP et al: Roles for KRAS in pancreatic tumor development and progression. Gastroenterology. 144(6):1220-9, 2013
    5. Plowman SJ et al: K-ras 4A and 4B are co-expressed widely in human tissues, and their ratio is altered in sporadic colorectal cancer. J Exp Clin Cancer Res. 25(2):259-67, 2006
    6. Tannapfel A et al: Frequency of p16(INK4A) alterations and K-ras mutations in intrahepatic cholangiocarcinoma of the liver. Gut. 47(5):721-7, 2000
    7. Cox, Adrienne D et al. “Drugging the undruggable RAS: Mission possible?.” Nature reviews. Drug discovery vol. 13,1: 828-51, (2014).
    8. Sepulveda, A. R., et al. “Biomarkers for the evaluation of colorectal cancer: guideline summary from the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology.” J Clin Oncol 35: 1453-86, 2017.
    9. Van Krieken, J. Han JM, et al. “RAS testing in metastatic colorectal cancer: advances in Europe.” Virchows Archiv 468.4: 383-396, 2016