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Ancillary Studies: Contribution to Error and Error Prevention

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Abstract

Ancillary tests, including histochemical analyses, immunohistochemistry (IHC), in situ hybridization, and a panoply of established and emerging molecular techniques, are designed with the hope that results generated by these tests will improve diagnostic accuracy, provide for better prediction of response to targeted therapies, and lead to overall better patient management. Using IHC as an example, the attendant risks to better practice through ancillary testing can be discussed. While understanding how the specificity of a reagent for its analyte forms a solid foundation for the development and implementation of clinically useful ancillary tests, mitigation of potential error in these testing systems can only be achieved through careful development of appropriate controls on which optimization/calibration and validation of the method can be based. However, even within the framework of a validated assay, errors in diagnosis and clinical management may emerge. Proper use of evidence may diminish the likelihood of error in the use and interpretation of ancillary tests, but some level of error is implicit in the system, and the risk of error may increase with the use of ancillary tests if not properly mitigated.

Gown’s Law: With sufficient manipulation of tissue or test conditions, any antibody can be made to stain any tissue [1].

Murphy’s Corollary to Gown’s Law: Anything that can be done intentionally can be done accidently.

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References

  1. http://medical-dictionary.thefreedictionary.com/Gown%e2%80%99s+Law.

  2. Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor w testing in breast cancer. J Clin Oncol. 2007;25:118–45.

    Article  CAS  PubMed  Google Scholar 

  3. Swanson PE. Foundations of immunohistochemistry. A practical review. Am J Clin Pathol. 1988;90:333–9.

    CAS  PubMed  Google Scholar 

  4. Raybould T, Takahashi M. Production of stable rabbit-mouse hybridomas that secrete rabbit mAb of defined specificity. Science. 1988;240:1788–90.

    Article  CAS  PubMed  Google Scholar 

  5. Parnes O. From interception to incorporation: degeneracy and promiscuous recognition as precursors of a paradigm shift in immunology. Mol Immunol. 2004;40:985–91.

    Article  CAS  PubMed  Google Scholar 

  6. Cohn M. Degeneracy, mimicry and crossreactivity in immune recognition. Mol Immunol. 2005;42:651–5.

    Article  CAS  PubMed  Google Scholar 

  7. Morsi HM, Leers MPG, Jaeger W, et al. The patterns of expression of an apoptosis-related CK18 neoepitope, the bcl-2 proto-oncogene, and the Ki67 proliferation marker in normal, hyperplastic, and malignant endometrium. Int J Gynecol Pathol. 2000;19:118–26.

    Article  CAS  PubMed  Google Scholar 

  8. Willingham MC. Conditional epitopes: is your antibody always specific? J Histochem Cytochem. 1999;47:1233–5.

    Article  CAS  PubMed  Google Scholar 

  9. Shi SR, Cote RJ, Taylor CR. Antigen retrieval immunohistochemistry: past, present and future. J Histochem Cytochem. 1997;45:327–43.

    Article  CAS  PubMed  Google Scholar 

  10. True LD. Quality control in molecular immunohistochemistry. Histochem Cell Biol. 2008;130:473–80.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Eisen RN. Quality management in immunohistochemistry. Diagn Histopathol. 2008;14:299–307.

    Article  Google Scholar 

  12. Miller K, Ibrahim M, Barnett S, Jasani B. Technical aspects of predictive and prognostic markers in breast cancer: what UK NEQAS data shows. Curr Diagn Pathol. 2007;13:135–49.

    Article  Google Scholar 

  13. Taylor CR. The total test approach to standardization of immunohistochemistry. Arch Pathol Lab Med. 2000;124:945–51.

    CAS  PubMed  Google Scholar 

  14. Anagnostou VK, Welsh AW, Giltnane JM, Siddiqui S, Liceaga C, et al. Analytic variability in immunohistochemistry biomarker studies. Cancer Epidemiol Biomarkers Prev. 2010;19:982–91.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Dyhdalo KS, Fitzgibbons PL, Goldmsith JD, Souers RJ, Nakhleh RE. Laboratory compliance with the American Society of Clinical Oncology/College of American Pathologists human epidermal growth factor receptor 2 testing guidelines: a 3-year comparison of validation procedures. Arch Pathol Lab Med. 2014;138:876–84.

    Article  PubMed  Google Scholar 

  16. Goldstein NS, Hewitt SM, Taylor CR, et al. Members of the ad hoc committee on immunohistochemistry standardization. Recommendations for improved standardization of immunohistochemistry. Appl Immunohistochem Mol Morphol. 2007;15:124–33.

    Article  CAS  PubMed  Google Scholar 

  17. Torlakovic EE, Riddell R, Banerjee D, et al. Canadian Association of Pathologists-Association canadienne des pathologists National Standards Committee/Immunohistochemistry: best practices recommendation for standardization of immunohistochemistry tests. Am J Clin Pathol. 2010;133:354–65.

    Article  PubMed  Google Scholar 

  18. Clinical and Laboratory Standards Institute. Quality assurance for design control and implementation of immunohistochemical assays; approved guideline—second edition. CLSI document I/LA28-A2, 2011;31(4).

    Google Scholar 

  19. www.nordiqc.org.

  20. www.ciqc.ca.

  21. www.ukneqasicc.ucl.ac.uk.

  22. Reiner-Concin A. External quality assurance in immunohistochemistry—is it the solution to a complex problem? Breast Care (Basel). 2008;3:78–9.

    Google Scholar 

  23. Cheung CC, Banerjee D, Barnes PJ, et al. Canadian Association of Pathologists-Association canadienne des pathologists National Standards Committee for High Complexity Testing/Immunohistochemistry: guidelines for the preparation, release and storage of unstained archived diagnostic tissue sections for immunohistochemistry. Am J Clin Pathol. 2014 (in press).

    Google Scholar 

  24. Sato M, Kojima M, Nagatsuma AK, et al. Optimal fixation for total preanalytic phase evaluation in pathology laboratories. A comprehensive study including immunohistochemistry, DNA and mRNA assays. Pathol Int. 2014;64:209–16.

    Article  CAS  PubMed  Google Scholar 

  25. Goldstein NS, Ferkowicz M, Odish E, Mani A, Hastah F. Minimum formalin fixation time for consistent estrogen receptor immunohistochemical staining of invasive breast carcinoma. Am J Clin Pathol. 2003;120:86–92.

    Article  PubMed  Google Scholar 

  26. Werner M, Chott A, Fabiano A, Battifora H. Effect of formalin tissue fixation and processing on immunohistochemistry. Am J Surg Pathol. 2000;24:1016–9.

    Article  CAS  PubMed  Google Scholar 

  27. Ostrowski K, Komender J, Kwarecki K. Quantitative investigations on the solubility of proteins extracted from tissues fixed by different chemical and physical methods. Ann Histochim. 1961;6:502–6.

    Google Scholar 

  28. Helander KG. Kinetic studies of formaldehyde binding in tissue. Biotech Histochem. 1994;69:177–9.

    Article  CAS  PubMed  Google Scholar 

  29. Fitzgibbons PL, Murphy DA, Hammond ME, Allred DC, Valenstein PN. Recommendation for validating estrogen and progesterone receptor immunohistochemistry assays. Arch Pathol Lab Med. 2010;134:930–5.

    CAS  PubMed  Google Scholar 

  30. Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen receptors and progesteronereceptors in breast cancer. J Clin Oncol. 2010;28:2784–95.

    Article  PubMed Central  PubMed  Google Scholar 

  31. Apple S, Pucci R, Lowe AC, et al. The effect of delay in fixation, different fixatives and duration of fixation in estrogen and progesterone receptor results in breast carcinoma. Am J Clin Pathol. 2011;135:592–8.

    Article  PubMed  Google Scholar 

  32. Moatamed NA, Nanjangud G, Pucci R, et al. Effect of ischemic time, fixation time and fixative type on Her2/neu immunohistochemical and fluorescence I situ hybridization results in breast cancer. Am J Clin Pathol. 2011;136:754–61.

    Article  PubMed  Google Scholar 

  33. Rimm DL. What brown cannot do for you. Nature Biotechnol. 2006;24:914–6.

    Article  CAS  Google Scholar 

  34. Jaziji H, Taylor CR, Goldstain NS, et al. Consensus recommendations on estrogen receptor testing in breast cancer by immunohistochemistry. Appl Immunohistochem Mol Morphol. 2008;16:513–20.

    Article  Google Scholar 

  35. True LD. Methodologic requirements for valid tissue-based biomarker studies that can be used in clinical practice. Virchows Arch. 2014;464:257–63.

    Article  CAS  PubMed  Google Scholar 

  36. Deutsch EW, Ball CA, Berman JJ, et al. Minimum information specification for in situ hybridization and immunohistochemistry experiments (MISFISHIE). Nature Biotech. 2008 doi:10.1038/nbt1391.

    Google Scholar 

  37. Taylor CR. An exaltation of experts: concerted efforts in the standardization of immunohistochemistry. Hum Pathol. 1994; 25:2–11.

    Article  CAS  PubMed  Google Scholar 

  38. Lipton J. An exaltation of larks: the ultimate edition. New York: Penguin Books; 1993.

    Google Scholar 

  39. Torlakovic EE, Francis G, Garratt J, et al. Standardization of negative controls in diagnostic immunohistochemistry: recommendations from the international ad hoc expert panel. Appl Immunohistochem Mol Morphol. 2014;22:241–52.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Torlakovic EE, Nielsen S, Francis G, et al. Standardization of positive controls in diagnostic immunohistochemistry: recommendations from the international ad hoc expert committee. Appl Immunohistochem Mol Morphol. 2015;23:1–18.

    Google Scholar 

  41. Cutz JC, Craddock KJ, Torlakovic EE, et al. Canadian anaplastic lymphoma kinase study: a model for multicenter standardization and optimization of ALK testing in lung cancer. J Thorac Oncol. 2013;8:45–51.

    Google Scholar 

  42. Burry RW. Controls for immunohistochemistry: an update. J Histochem Cytochem. 2011;59:6–12.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Medical Devices; Classification/Reclassification of Immunohistochemistry Reagents and Kits, final rule, Federal Register, 63(105):30132–42, June 3, 1998. FDA final rule.

    Google Scholar 

  44. Kaur P, Ward B, Saha B, et al. Human breast cancer histoid: an in vitro 3-dimensional co-culture model that mimics breast cancer tissue. J Histochem Cytochem. 2011;59:1087–100.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Toriyama A, Mori T, Sekine S, et al. Utility of PAX8 monoclonal antibody in the diagnosis of thyroid, thymic, pleural and lung tumours: a comparison with polyclonal PAX8 antibody. Histopathology. 2014. doi:10.111/his.12405.

    Google Scholar 

  46. Swanson PE. Heffalumps, jagulars and cheshire cats. A commentary on cytokeratins and soft tissue sarcomas. Am J Clin Pathol. 1991;95(Suppl 1):S2–7.

    CAS  PubMed  Google Scholar 

  47. Miettinin M. Immunoreactivity for cytokeratin and epithelial membrane antigen in leiomyosarcoma. Arch Pathol Lab Med. 1988;112:637–40.

    Google Scholar 

  48. Mentzel T, Beham A, Calonje E, Katenkamp D, Fletcher CD. Epithelioid hemangioendothelioma of skin and soft tissues: clinicopathologic and immunohistochemical study of 30 cases. Am J Surg Pathol. 1997;21:363–74.

    Article  CAS  PubMed  Google Scholar 

  49. Fletcher CD, Beham A, Bekir S, Clarke AM, Marley NJ. Epithelioid angiosarcoma of deep soft tissue: a distinctive tumor readily mistaken for an epithelial neoplasm. Am J Surg Pathol. 1991;15:915–24.

    Article  CAS  PubMed  Google Scholar 

  50. Harvey JM, Clark GM, Osborne CK, Allred DC. Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast carcinoma. J Clin Oncol. 1999;17:1474–81.

    CAS  PubMed  Google Scholar 

  51. Collins LC, Botero ML, Schnitt SJ. Bimodal frequency distribution of estrogen receptor immunohistochemical staining results in breast cancer: an analysis of 825 cases. Am J Clin Pathol. 2005;123:16–20.

    Article  PubMed  Google Scholar 

  52. Nadji M, Gomez-Fernandez C, Ganjei-Azar P, Morales AR. Immunohistochemistry of estrogen and progesterone receptors reconsidered: experience with 5,993 breast cancers. Am J Clin Pathol. 2005;123:21–7.

    Article  PubMed  Google Scholar 

  53. Wick MR, Swanson PE, Marchevsky AM. Evidence-based practices in applied immunohistochemistry: dilemma caused by cross-purposes. In: Marchevsky AM, Wick MR, editors. Evidence based pathology and laboratory medicine. New York: Springer; 2011. p 261–98.

    Chapter  Google Scholar 

  54. Swanson PE. Schmidt RA: beneath the surface of the mud, part II: the dichotomization of continuous biologic variables by maximizing immunohistochemical method sensitivity. Am J Clin Pathol. 2005;123:9–12.

    Article  PubMed  Google Scholar 

  55. Cheang MC, Treaba DO, Speers CH, et al. Immunohistochemical detection using the new rabbit monoclonal antibody SP1 of estrogen receptor in breast cancer is superior to mouse monoclonal antibody 1D5 in predicting survival. J Clin Oncol. 2006;20:5637–44.

    Article  Google Scholar 

  56. Fitzgibbon PL, Bradley LA, Fatheree LA, et al. Principles of analytic validation of immunohistochemical assays. Guideline from the College of American Pathologists Pathology and Laboratory Quality Center. Arch Pathol Lab Med. 2014;138:1432–43. doi:10.5858/arpa.2013-0610-CP.

    Google Scholar 

  57. Marchio C, Dowsett M, Reis-Filho JS. Revisiting the technical validation of tumour biomarker assays: how to open a Pandora’s box. BMC Med. 2011;9:41–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Wolff AC, Hammond ME, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013;31:3997–4013.

    Article  PubMed  Google Scholar 

  59. Bordeaux J, Welsh AW, Agarwal S, et al. Antibody validation. Biotechniques. 2010;48:197–209.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  60. Hardy LB, Fitzgibbons PL, Goldsmith JD, et al. Immunohistochemistry validation procedures and practices. A College of American Pathologists survey of 727 laboratories. Arch Pathol Lab Med. 2013;137:19–25.

    Article  PubMed  Google Scholar 

  61. http://www.antibodypedia.com.

  62. Bjorling E, Uhlen M. Antibodypedia, a portal; for sharing antibody and antigen validation data. Mol Cell Proteomics. 2008;7:2028–37.

    Article  PubMed  Google Scholar 

  63. Dunstan RW, Wharton KA Jr, Quigley C, Lowe A. The use of immunohistochemistry for biomarker assessment—can it compete with other technologies? Toxicol Pathol. 2011;39:988–1002.

    Article  PubMed  Google Scholar 

  64. http://en.wikipedia.org/wiki/Wikipedia:Josh_Billings.

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Correspondence to Paul E. Swanson MD .

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Swanson, P. (2015). Ancillary Studies: Contribution to Error and Error Prevention. In: Nakhleh, R. (eds) Error Reduction and Prevention in Surgical Pathology. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2339-7_9

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  • DOI: https://doi.org/10.1007/978-1-4939-2339-7_9

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