Advertisement

Overview of Methods Used in Predictive Biomarker Studies in a Molecular Anatomic Pathology Laboratory

  • Perry Maxwell
  • Manuel Salto-Tellez
Chapter

Abstract

The development of predictive biomarkers is a multifactorial laboratory exercise. In this chapter, we address some of these determinants: the pre-analytical factors that may influence downstream molecular tests; the types of sample and the essential use of the morphomolecular aspects in order to evaluate tumors as part of analytical variable management; the use of biorepositories; and the choice of most appropriate technologies for predictive biomarker medicine. Together, these represent the laboratory milieu that requires management for the successful analysis, and effective delivery of a predictive biomarker, from sample collection to test interpretation, including the potential for circulating tumor, cell-free DNA as a biomarker of discovery or profiling. We emphasize the need for effective and robust validation of tests and the recording of clear and concise management throughout the process of biomarker development. In doing so, we propose that morphological analysis remains the cornerstone of tissue-based diagnostics, and we propose a morphomolecular paradigm to modern pathology and modern diagnostics in the era of molecular medicine.

Keywords

Surgical pathology Tissue pathology Molecular pathology Morphomolecular pathology Biomarker development Test validation Pre-analyticals 

References

  1. 1.
    Yildiz-Aktas IZ, Dabbs DJ, Cooper KL, Chivukula M, McManus K, Bhargava R. The effect of 96-hour formalin fixation on the immunohistochemical evaluation of estrogen receptor, progesterone receptor, and Her2 expression in invasive breast carcinoma. Am J Clin Pathol. 2012;137:691–8.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Babic A, Loftin IR, Stanislaw S, Wang M, Miller R, Warren SM, et al. Methods. 2010;52:287–300.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Pang B, Dettmer M, Ong CW, Dhewar AN, Gupta S, Lim GL, et al. The positive impact of cytological specimens for EGFR mutation testing in non-small cell lung cancer: a single South East Asian Laboratory’s analysis of 670 cases. Cytopathology. 2012;23:229–36.CrossRefPubMedGoogle Scholar
  4. 4.
    Mattocks CJ, Morris MA, Mathijs G, Swinnen E, Corveleyn A, Dequeker E, et al. A standardized framework for the validation and verification of clinical molecular genetic tests. Eur J Hum Genet. 2010;18:1276–88.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Maxwell P, Salto-Tellez M. Validation of immunocytochemistry as a morphological technique. Cancer Cytopathol. 2016;124:540–5.Google Scholar
  6. 6.
    Lewis C, McQuaid S, Hamilton PW, Salto-Tellez M, McArt D, James JA. Building a “repository of science”: the importance of integrating biobanks within molecular pathology programmes. Eur J Cancer. 2016;67:191–9.CrossRefPubMedGoogle Scholar
  7. 7.
    McCourt CM, Boyle D, James J, Salto-Tellez M. Immunohistochemistry in the era of personalised medicine. J Clin Pathol. 2013;66:58–61.CrossRefPubMedGoogle Scholar
  8. 8.
    Hynes S, Pang B, james J, Maxwell P, Salto-Tellez M. Tissue-based next generation sequencing: application in a universal healthcare system. Br J Cancer. 2017;116:553–60.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Salto Tellez M, Gonzalez de Castro D. Next-generation sequencing: a change in paradigm in molecular diagnostic validation. J Pathol. 2014;234:5–10.CrossRefPubMedGoogle Scholar
  10. 10.
    Wong SQ, Li J, AY-C T. Sequence artefacts in a prospective series of formalin-fixed tumours tested for mutations in hotspot regions by massively parallel sequencing. BMC Med Genet. 2014;7:23–33.Google Scholar
  11. 11.
    Tan SP, Natrajan R, Reis-Filho JS. Microarray-based comparative genomic hybridization. In: Hannon-Fletcher M, Maxwell P, editors. Advanced techniques in diagnostic cellular pathology. Oxford: Wiley-Blackwell; 2009.Google Scholar
  12. 12.
    Turajlic S, Swanton C. Metastasis as an evolutionary process. Science. 2016;352:169–75.CrossRefPubMedGoogle Scholar
  13. 13.
    Geiss GK, Bumgarner RE, Birditt B, et al. Direct multiplexed measurement of gene expression with color-coded probe pairs. Nat Biotechnol. 2008;26:317–25.CrossRefPubMedGoogle Scholar
  14. 14.
    Hindson CM, Chevillet JR, Briggs HA, et al. Absolute quantification by droplet digital PCR versus analog real-time PCR. Nat Methods. 2013;10:1003–5.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Brown SD, Warren RL, Gibb EA, et al. Neo-antigens predicted by tumor genome meta-analysis correlate with increased patient survival. Genome Res. 2014;24:743–50.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Salto-Tellez M. A case for integrated morphomolecular diagnostic pathologists. Clin Chem. 2007;53:1188–90.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Precision Medicine Centre of ExcellenceQueen’s University BelfastBelfastUK
  2. 2.Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research, Department of Cell BiologyQueens University BelfastBelfastUK

Personalised recommendations