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Practicing Pathology in the Post-genomic Era: Challenges and Opportunities

  • Karen L. Kaul
Chapter

Abstract

The rapid implementation of new molecular methods in support of precision medicine has been both exciting and challenging to pathology. Next-generation sequencing is coming to maturity as a clinical procedure, with concomitant development of guidelines for assay validation and performance, quality standards, and proficiency programs. Evolving issues include the type, target, and timing of genomic analysis of tumors and regulatory and reimbursement issues. Additionally, educational needs for pathology trainees, practicing pathologists, and clinical colleagues should be addressed.

Keywords

Genomics Anatomic pathology Next-generation sequencing Molecular pathology Informatics pipeline Quality control Education Regulation Reimbursement 

References

  1. 1.
    Vogelstein B, et al. Cancer genome landscapes. Science. 2013;339(6127):1546–58.CrossRefGoogle Scholar
  2. 2.
    The cancer genome atlas. Available at cancergenome.nih.gov.
  3. 3.
    Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Weistler OD, Kleihues P, Ellison DW. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131:803–20.CrossRefGoogle Scholar
  4. 4.
    Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA, Zelenetz AD, Jaffe ES. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127:2375–90.  https://doi.org/10.1182/blood-2016-01-643569.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Wang HL, Lopategui J, Amin MB, et al. KRAS mutation testing in human cancers: the pathologist’s role in the era of personalized medicine. Adv Anat Pathol. 2010;17:23–32.PubMedGoogle Scholar
  6. 6.
    Lièvre A, Bachet JB, Le Corre D, Boige V, Landi B, Emile JF, Côté JF, Tomasic G, Penna C, Ducreux M, Rougier P, Penault-Llorca F, Laurent-Puig P. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res. 2006;66(8):3992–5.  https://doi.org/10.1158/0008-5472.CAN-06-0191. PMID16618717.CrossRefPubMedGoogle Scholar
  7. 7.
    Di Fiore F, Le Pessot F, Lamy A, et al. KRAS mutation is highly predictive of cetuximab resistance in metastatic colorectal cancer. J Clin Oncol. 2007 ASCO Annual Meeting Proc. 2007;25(18S (June 20 Supplement)):10502.Google Scholar
  8. 8.
    Weichart W, Schewe C, Lehmann A, et al. KRAS genotyping of paraffin-embedded colorectal cancer tissue in routine diagnostics: comparison of methods and impact of histology. J Mol Diagn. 2010;12:35–42.CrossRefGoogle Scholar
  9. 9.
    Kamel-Reid S, Zhang T, Persons DL, et al. (Molecular Oncology Resource Committee of the College of American Pathologists). Validation of KRAS testing for anti-EGFR therapeutic decisions for patients with metastatic colorectal carcinoma. Arch Pathol Lab Med. 2012;136:26–32.  https://doi.org/10.5858/arpa.2011-0220-OA. http://www.ncbi.nlm.nih.gov/pubmed/22208484.
  10. 10.
    Allegra CJ, Jessup JM, Somerfield MR, et al. American Society of Clinical Oncology Provisional Clinical Opinion: testing for KRAS mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol. 2009;27:2091–5.CrossRefGoogle Scholar
  11. 11.
    National Comprehensive Cancer Network Guidelines on Colon and Rectal Cancers. Practice guidelines established for KRAS mutation testing in colorectal cancer. NCCN; 2008.Google Scholar
  12. 12.
    Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. Recommendations from the EGAPP Working Group: can testing of tumor tissue for mutations in EGFR pathway downstream effector genes in patients with metastatic colorectal cancer improve health outcomes by guiding decisions regarding anti-EGFR therapy? Genet Med. 2013;15(7):517–27.  https://doi.org/10.1038/gim.2012.184.CrossRefGoogle Scholar
  13. 13.
    Allegra CJ, Rumble RB, Hamilton SR, Roach N, Hantel A, Schilsky RL. Extended RAS gene mutation testing in metastatic colorectal carcinoma to predict response to anti–epidermal growth factor receptor monoclonal antibody therapy: ASCO provisional clinical opinion update 2015. J Oncol Pract. 2015;  https://doi.org/10.1200/JCO.2015.63.9674.
  14. 14.
    Kaul KL, Sabatini LM, Tsongalis GJ, et al. The case for laboratory developed procedures: quality and positive impact on patient care. Acad Pathol. 2017;4:1–21.CrossRefGoogle Scholar
  15. 15.
    Tang W, Hu Z, Muallem H, Gulley ML. Quality assurance of RNA expression profiling in clinical laboratories. J Mol Diagn. 2012;14:1–11.  https://doi.org/10.1016/j.jmoldx.2011.09.003.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Mortensen MM, Høyer S, Lynnerup A-S, Ørntoft TF, Sørensen KD, Borre M, Dyrskjøt L. Expression profiling of prostate cancer tissue delineates genes associated with recurrence after prostatectomy. Nat Sci Rep. 2015;5:16018.  https://doi.org/10.1038/srep16018.CrossRefGoogle Scholar
  17. 17.
    Nielsen T, Wallden B, Schaper C, Ferree S, Liu S, Gao D, Barry G, Dowidar N, Maysuria M, Storhoff J. Analytic validation of the PAM50-based Prosigna Breast Cancer Prognostic Gene Signature Assay and nCounter Analysis System using formalin-fixed paraffin embedded breast tumor specimens. BMC Cancer. 2014;14:177. http://www.biomedcentral.com/1471-2407/14/177CrossRefGoogle Scholar
  18. 18.
    Peck AR, Girondo MA, Liu C, et al. Validation of tumor protein marker quantification by two independent automated immunofluorescence image analysis platforms. Mod Pathol. 2016;29:1143–54.  https://doi.org/10.1038/modpathol.2016.112; published online 17 June 2016.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Wilhelm M, Schlegl J, Hahne H, Gholami AM, Lieberenz M, Savitski MM, Ziegler E, Butzmann L, Gessulat S, Marx H, Mathieson T, Lemeer S, Schnatbaum K, Reimer U, Wenschuh H, Mollenhauer M, Slotta-Huspenina J, Boese J-H, Bantscheff M, Gerstmair A, Faerber F, Kuster B. Mass-spectrometry-based draft of the human proteome. Nature. 2014;509:582–7.  https://doi.org/10.1038/nature13319.CrossRefPubMedGoogle Scholar
  20. 20.
  21. 21.
    Quail MA, Smith M, Copeland P, Otto TD, Harris SR, Connor TR, Bertoni A, Swerdlow HP, Gu Y. A tale of three next generation sequencing platforms: comparison of Ion Torrent, Pacific BioScidences and Illumina MiSeq sequencers. BMC Genomics. 2012;13:341–54.CrossRefGoogle Scholar
  22. 22.
    Corless CL. Next-generation sequencing in cancer diagnostics. J Mol Diagn. 2016;18:813–6.CrossRefGoogle Scholar
  23. 23.
    Misura M, Zhang T, Sukhai MA, Thomas M, Garg S, Kamel-Reid S, Stockley TL. Comparison of next generation sequencing panels and platforms for detection and verification of somatic tumor variants for clinical diagnostics. J Mol Diagn. 2016;18:842–50.CrossRefGoogle Scholar
  24. 24.
    Kaul KL. Preparing pathology for precision medicine: challenges and opportunities. Virchows Arch. 2017;471(2):141.  https://doi.org/10.1007/s00428-017-2141-z.CrossRefPubMedGoogle Scholar
  25. 25.
    Gargis AG, Kalman L, Bick DP, da Silva C, Dimmock DP, Funke BH, Gowrisankar S, Hegde MR, Kulkarni S, Mason CE, Nagarajan R, Voelkerding KV, Worthey EA, Aziz N, Barnes J, Bennett SF, Bisht H, Church DM, Dimitrova Z, Gargis SR, Hafez N, Hambuch T, Hyland FCL, Luna RA, MacCannell D. Good laboratory practice for clinical next-generation sequencing informatics pipelines. Nat Biotechnol. 2015;33:689–93.  https://doi.org/10.1038/nbt.3237.CrossRefPubMedGoogle Scholar
  26. 26.
    Lindeman NI, Cagle PT, Beasley MB, Chitale DA, Dacic S, Giaccone G, et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors. Guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. J Mol Diagn. 2013;15:415–53.CrossRefGoogle Scholar
  27. 27.
    NCCN clinical practice guidelines in oncology: non-small cell lung cancer v. 3.2017. www.nccn.org.
  28. 28.
    Simon R, Roychowdhury S. Implementing personalized cancer genomics in clinical trials. Nature. 2013;12:358–69.Google Scholar
  29. 29.
    Plunkett-Rondeau J, Hyland K, Dasgupta S. Training future physicians in the era of genomic medicine: trends in undergraduate medical genetics education. Genetics. 2015;17:927–34.  https://doi.org/10.1038/gim.2014.208.CrossRefGoogle Scholar
  30. 30.
    Training residents in genomics. 2012. www.pathologylearning.org/trig/resources.
  31. 31.
    Sireci AN, Aggarwal VS, Turk AT, et al. Clinical genomic profiling of a diverse array of oncology specimens at a large academic center: identification of targetable variants and experience with reimbursement. J Mol Diagn. 2017;19:277–87.  https://doi.org/10.1016/j.jmoldx.2016.10.008.CrossRefPubMedGoogle Scholar
  32. 32.
    Lih C-J, Harrington RD, Sims DJ, et al. Analytical validation of the next-generation sequencing assay for a nationwide signal-finding clinical trial: molecular analysis for therapy choice clinical trial. J Mol Diagn. 2017;19:313–27.  https://doi.org/10.1016/j.jmoldx.2016.10.007.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
  34. 34.
    Matthijs G, Souche E, Alders M, Corveleyn A, Eck S, Feensgra I, Race V, Sistermans E, Sturm M, Weiss M, Yntem H, Bakker E, Scheffer H, Bauer P. Guidelines for diagnostic next-generation sequencing. Eur J Hum Genet. 2016;24:2–5.CrossRefGoogle Scholar
  35. 35.
    Deans Z, Watson CM, Charlton R, et al. Practice guidelines for targeted next generation sequencing analysis and interpretation. http://www.acgs.uk.com/media/983872/bpg_for_targeted_next_generation_sequencing_-_approved_dec_2015.pdf.
  36. 36.
    Joseph L, Cankovic M, Caughron S, et al. The spectrum of clinical utilities in molecular pathology testing procedures for inherited conditions and cancer. J Mol Pathol. 2016;5:605–19.Google Scholar
  37. 37.
    Zehnbauer B, Lofton-Day C, Pfeifer J, Shaughnessy E, Goh L. Diagnostic quality assurance pilot: a model to demonstrate comparative laboratory test performance with an oncology companion device assay. J Mol Diagn. 2017;19:1–3.  https://doi.org/10.1016/j.jmoldx.2016.10.001.CrossRefPubMedGoogle Scholar
  38. 38.
  39. 39.
    Perkel JM, Fung PA. Next-gen sequencing 2016 update, www.biocompare.com.

Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pathology and Laboratory Medicine, NorthShore University HealthSystemClinical Professor of Pathology, University of Chicago Pritzker School of MedicineEvanstonUSA

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