Advertisement

Standardization in Immunohistology

  • Anthony S.-Y. LeongEmail author
  • Trishe Y.-M. Leong
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 724)

Abstract

The rapid acceptance of immunohistology as an invaluable adjunct to morphologic diagnosis has been possible because of the development of new and more sensitive antibodies and detection systems that allow its application to formalin-fixed, paraffin-embedded tissue (FFPT). More importantly, antigen-retrieval techniques have resulted in some degree of consistency allowing immunohistology to be used reliably as a diagnostic tool. The advent of prognostic and predictive biomarkers, and the desire for individualized therapy has resulted in mounting pressure to employ the immunohistological assay in a quantitative manner. While it was not a major issue when the technique was employed in a qualitative manner, the numerous variables in the preanalytical and analytical phases of the test procedure that influence the immunoexpression of proteins in FFPT become critical to standardization. Tissue fixation is pivotal to antigen preservation but exposure to fixative prior to accessioning by the laboratory is not controlled. Antigen retrieval, crucial in the analytical phase, continues to be employed in an empirical manner with the actual mechanism of action remaining elusive. There is great variation in reagents, methodology, and duration of tissue processing and immunostaining procedure, and the detection systems employed are not standardized between laboratories. While many of these variables are offset by the application of antigen retrieval, which enables the detection of a wide range of antigens in FFPT, the method itself is not standardized. This myriad of variables makes it inappropriate to provide meaningful comparisons of results obtained in different laboratories and even in the same laboratory, as in current practice, each specimen experiences different preanalytical variables. Furthermore, variables in interpretation exist and cutoff thresholds for positivity differ. Failure to recognize false-positive and false-negative stains leads to further errors of quantitative measurement. Many of the problems relating to the technology and interpretation of immunostaining originate from failure to recognize that this procedure is different from other histological stains and involves many more steps that cannot be monitored until the end result is attained. While several remedial measures can be suggested to address some of these problems, accurate and reproducible quantitative assessment of immunostains presently remains elusive as important variables that impact on antigen preservation in the paraffin-embedded biopsy ­cannot be standardized.

Key words

Immunohistochemistry Variables Antibodies Controls Quantitation Pitfalls Validation 

References

  1. 1.
    Leong, A.S.-Y., Wick, M.R., and Swanson, P.E. (1997) Immunohistology and Electron Microscopy of Anaplastic and Pleomorphic Tumours. Cambridge: Cambridge University Press; 2–35.Google Scholar
  2. 2.
    Elias, J.M. (2003) Immunohistopathology. A Practical Approach to Diagnosis. Chicago: ASCP Press.Google Scholar
  3. 3.
    Taylor, C.R. and Cote, R.J. (2005) Immunomicroscopy, A Tool for the Surgical Pathology, 3rd Edition. Edinburgh: Elsevier.Google Scholar
  4. 4.
    Leong, A.S.-Y. and Wright, J. (1987) The contributions of immunohistochemical staining in tumour diagnosis. Histopathology 11, 1295–1305.PubMedCrossRefGoogle Scholar
  5. 5.
    Leong, A.S.-Y. and Leong, F.J. (1997) Immunohistochemistry in the Diagnosis of Solid Tumours. IN: Nakamura, R., ed. Manual of Clinical Laboratory Immunology, 5th Edition. Washington, DC: ASM Press; 380–387.Google Scholar
  6. 6.
    Leong, A.S.-Y. (1992) New vistas in the histopathological assessment of cancer. Med J Aust. 157, 699–701.PubMedGoogle Scholar
  7. 7.
    Leong, A.S.-Y., Vinyuvat, S., Suthipintawong, C., and Leong, F.J. (1997) Patterns of basal lamina immunostaining in soft tissue tumours. Appl Immunohistochem. 5, 1–7.CrossRefGoogle Scholar
  8. 8.
    Leong, A.S.-Y., Parkinson, R., and Milios, J. (1990) ‘Thick’ cell membranes revealed by immunocytochemical staining. A clue to the diagnosis of malignant mesothelioma. Diagn Cytopathol. 6, 9–13.PubMedCrossRefGoogle Scholar
  9. 9.
    Leong, A.S.-Y., Stevens, M.W., and Mukherjee, T.M. (1992) Malignant ­mesothelioma: cytologic diagnosis with histologic, immunohistochemical and ultrastructural correlation. Semin Diagn Pathol. 9, 141–150.PubMedGoogle Scholar
  10. 10.
    Leong, A.S.-Y. and Lee, A.K.C. (1995) Biological indices in the assessment of breast cancer. Clin Mol Pathol. 48, M221–M238.PubMedCrossRefGoogle Scholar
  11. 11.
    Leong, A.S.-Y. (2001) Immunohistological markers for tumor prognostication. Curr Diagn Pathol. 7, 176–186CrossRefGoogle Scholar
  12. 12.
    Bratthauer, G.L., Moinfar, F., Stamatakos, M.D., et al. (2002) Combined E-cadherin and high molecular weight cytokeratin immunoprofile differentiates lobular, ductal, and hybrid mammary intraepithelial neoplasias. Hum Pathol. 33, 620–627.PubMedCrossRefGoogle Scholar
  13. 13.
    Wood, B. and Leong, A.S.-Y. (2003) Cell adhesion proteins – biology, detection and applications. Pathology 35, 101–105.PubMedGoogle Scholar
  14. 14.
    Ribic, C.M., Sargent, D.J., Moore, M.J., et al. (2003) Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med. 349, 247–257.PubMedCrossRefGoogle Scholar
  15. 15.
    Popat, S., Hubner, R., and Houlston, R.S. (2005) Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol. 23, 609–618.PubMedCrossRefGoogle Scholar
  16. 16.
    Acs, G., Lawton, T.J., Rebbeck, T.R., et al. (2001) Differential expression of E-cadherin in lobular and ductal neoplasms of the breast and its biologic and diagnostic implications. Am J Clin Pathol. 115, 85–98.PubMedCrossRefGoogle Scholar
  17. 17.
    Fletcher, C.D., Berman, J.J., Corless, C., et al. (2003) Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol. 33, 459–465.CrossRefGoogle Scholar
  18. 18.
    Stein, H., Foss H.D., Durkop, H., et al. (2000) CD30+ anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features. Blood 96, 3681–3695.PubMedGoogle Scholar
  19. 19.
    Leong, A.S.-Y. and Leong, T.Y.-M. (2006) Invited review: newer developments in immunohistology. J Clin Pathol. 59, 1117–1126.PubMedCrossRefGoogle Scholar
  20. 20.
    Taylor, C.R. (1994) An exaltation of experts: concerted efforts in the standardization of immunohistochemistry. Hum Pathol. 25, 2–4.PubMedCrossRefGoogle Scholar
  21. 21.
    O’Leary, T.J. (2001) Standardization in immunohistochemistry. Appl Immunohis­tochem Mol Morphol. 9, 3–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Taylor, C.R. and Levenson, R.M. (2006) Quantification of immunohistochemical – issues concerning methods, utility and semi-quantitative assessment II. Histopathology 49, 411–424.PubMedCrossRefGoogle Scholar
  23. 23.
    Goldstein, N.S., Hewitt, S.M., Taylor, C.R., et al. (2007) Recommendations for improved standardization of immunohistochemistry. Appl Immunohistochem Mol Morphol. 15, 124–133.PubMedCrossRefGoogle Scholar
  24. 24.
    Pelstring, R.J., Allred, D.C., Esther, R.J., et al. (1991) Differential antigen preservation during autolysis. Hum Pathol. 22, 237–241.PubMedCrossRefGoogle Scholar
  25. 25.
    Pearse, A.G.E. (1980) Histochemistry. Theoretical and Applied, 4th Edition, vol 1. Edinburgh: Churchill Livingstone; 95.Google Scholar
  26. 26.
    Leong, A.S.-Y. and Gilham, P.N. (1989) The effects of progressive formaldehyde fixation on the preservation of tissue antigens. Pathology 21, 81–89.Google Scholar
  27. 27.
    Goldstein, N.S., Ferkowicz, M., Odish, E., et al. (2003) Minimum formalin fixation time for consistent estrogen receptor immunohistochemical staining of invasive breast carcinoma. Am J Clin Pathol. 120, 86–92.PubMedCrossRefGoogle Scholar
  28. 28.
    Raymond, W. and Leong, A.S.-Y. (1990) Oestrogen receptor staining of paraffin-embedded breast carcinomas following short fixation in formalin: a comparison with ­cytosolic and frozen section receptor analyses. J Pathol. 160, 295–303.PubMedCrossRefGoogle Scholar
  29. 29.
    Leong, A.S.-Y. and Milios, J. (1993) An assessment of the efficacy of the microwave-antigen retrieval procedure on a range of ­tissue antigens. Appl Immunohistochem. 1, 267–274.Google Scholar
  30. 30.
    Leong, A.S.-Y. and Milios, J. (1993) Comparison of antibodies to oestrogen and progesterone receptors and the influence on microwave-antigen retrieval. Appl Immunohistochem. 1, 2–88.Google Scholar
  31. 31.
    Leong, A.S.-Y., Milios, J., and Duncis, C.G. (1988) Antigen preservation in microwave-irradiated tissues. A comparison with routine formalin fixation. J Pathol. 156, 275–282.PubMedCrossRefGoogle Scholar
  32. 32.
    Suthipintawong, C., Vinyuvat, S., and Leong, A.S.-Y. (1996) Immunostaining of cell preparations: a comparative evaluation of common fixatives and protocols. Diagn Cytopathol. 15, 167–174.PubMedCrossRefGoogle Scholar
  33. 33.
    Larsson, L. (1993) Tissue preparation methods for light microscopic immunohistochemistry. Appl Immunohistochem. 1, 2–16.Google Scholar
  34. 34.
    Leong, A.S.-Y. (1994) Fixation and Fixatives. IN: Woods, A.E., Ellis, R.C., eds. Laboratory Histopathology – A Complete Reference. London: Churchill Livingstone; 1–26.Google Scholar
  35. 35.
    Gown, A.M. and Vogel, A.M. (1984) Monoclonal antibodies to human intermediate filament proteins. II. Distribution of filament proteins in normal human tissues. Am J Pathol. 114, 309–321.PubMedGoogle Scholar
  36. 36.
    Shi, S.R., Liu, C., Pootrakul, L., et al. (2006) Evaluation of the value of frozen tissue section used as ‘gold standard’ for immunohistochemistry. Am J Clin Pathol. 129, 358–366.CrossRefGoogle Scholar
  37. 37.
    Kakimoto, K., Takekoshi, S., Miyajima, K., and Osamura, R.Y. (2008) Hypothesis for the mechanism for heat-induced antigen retrieval occurring on fresh frozen sections without formalin fixation in immunohistochemistry. J Mol Histol. 39, 389–399.PubMedCrossRefGoogle Scholar
  38. 38.
    Visinoni, F., Milios, J., Leong, A.S.-Y., et al. (1998) Ultra-rapid microwave/variable pressure induced histoprocessing: description of a new tissue processor. J Histotechnol. 21, 219–224.Google Scholar
  39. 39.
    Morales, A.R., Nassiri, M., Kanhoush, R., et al. (2004) Experience with an automated microwave assisted rapid tissue processing method: effect on histology and timeliness of diagnostic surgical pathology. Am J Clin Pathol. 121, 528–536.PubMedCrossRefGoogle Scholar
  40. 40.
    Jacobs, T.W., Prioleau, J.E., Stillman, I.E., et al. (1996) Loss of tumor marker-immunostaining intensity on stored paraffin slides of breast cancer. J Natl Cancer Inst. 88, 1054–1060.PubMedCrossRefGoogle Scholar
  41. 41.
    Wester, K., Wahlund, E., Sundstrom, C., et al. (2000) Paraffin section storage and immunohistochemistry. Effects of time, temperature, fixation, and retrieval protocol with emphasis on p53 protein and MIB1 antigen. Appl Immunohistochem Mol Morphol. 8, 61–70.PubMedCrossRefGoogle Scholar
  42. 42.
    DiVito, K.A., Charette, L.A., Rimm, D.L., and Camp, R.L. (2004) Long-term preservation of antigenicity on tissue microarrays. Lab Invest. 84, 1071–1078.PubMedCrossRefGoogle Scholar
  43. 43.
    Blind, C., Koepenik, A., Pacyna-Gengelbach, M., et al. (2008) Antigenicity testing by immunohistochemistry after tissue oxidation. J Clin Pathol. 61, 79–83.PubMedCrossRefGoogle Scholar
  44. 44.
    Leong, A.S.-Y. (1993) Immunohistochemistry – Theoretical and Practical Aspects. IN: Leong, A.S.-Y., ed. Applied Immunohis­tochemistry for the Surgical Pathologist. London: Edward Arnold; 1–22.Google Scholar
  45. 45.
    Sabattini, E., Bisgaard, K., Ascani, S., et al. (1998) The EnVision system. A new immunohistochemical method for diagnostics and research: critical comparison with the APAAP, ChemMate, CSA, LABC, and SABC techniques. J Clin Pathol. 51, 506–510.PubMedCrossRefGoogle Scholar
  46. 46.
    King, G., Payne, S., Walker, F., et al. (1998) A highly sensitive detection method for immunohistochemistry using biotinylated tyramine. J Pathol. 183, 237–241.CrossRefGoogle Scholar
  47. 47.
    Shi, S.R., Key, M.E., and Kalra, K.L. (1991) Antigen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem. 39, 741–748.PubMedGoogle Scholar
  48. 48.
    Gown, A.M., de Wever, N., and Battifora, H. (1993) Microwave-based antigenic ­unmasking: a revolutionary new technique for routine immunohistochemistry. Appl Immunohistochem. 1, 256–266.Google Scholar
  49. 49.
    Miller, R.T., Swanson, P.E., and Wick, M.R. (2000) Fixation and epitope retrieval in diagnostic immunohistochemistry: a concise review with practical considerations. Appl Immunohistochem Mol Morphol. 8, 228–235.PubMedCrossRefGoogle Scholar
  50. 50.
    Leong, A.S-Y., Milios, J., and Leong, F.J. (1996) Epitope retrieval with microwaves: a comparison of citrate buffer and EDTA with three commercial retrieval solutions. Appl Immunohistochem. 4, 201–207.Google Scholar
  51. 51.
    Chaiwun, B., Shi, S.R., Cote, R.J., and Taylor, C.R. (2000) Major Factors Influencing the Effectiveness of Antigen Retrieval Immunohistochemistry. IN: Shi, S.R., Gu, J., Taylor, C.R., eds. Antigen Retrieval Techniques. Natick, MA: Eaton Publishing; 41–53.Google Scholar
  52. 52.
    Leong, A.S.-Y., Lee, E.S., Yin, H., et al. (2002) Superheating antigen retrieval. Appl Immunohistochem. 10, 263–268.CrossRefGoogle Scholar
  53. 53.
    Fraenkel-Conrat, H., Brandon, B., and Olcott, H. (1947) The reaction of formaldehyde with proteins. IV: Participation of indole groups: gramicidin. J Biol Chem. 168, 99–118.PubMedGoogle Scholar
  54. 54.
    Fraenkel-Conrat, H. and Olcott, H. (1948) Reaction of formaldehyde with proteins. VI: Crosslinking between amino groups with phenol, imidazole, or indole groups. J Biol Chem. 174, 827–843.PubMedGoogle Scholar
  55. 55.
    Fraenkel-Conrat, H. and Olcott, H. (1948) The reaction of formaldehyde with proteins. V: Crosslinking between amino and primary amide or guanidyl groups. J Am Chem Soc. 70, 2673–2684.PubMedCrossRefGoogle Scholar
  56. 56.
    Shi, S.-R., Gu, J., Turrens, J., et al. (2000) Development of the Antigen Retrieval Technique: Philosophical and Theoretical Bases. IN: Shi, S.-R., Gu, J., Taylor, C.R., eds. Antigen Retrieval Techniques: Immuno­histochemical and Molecular Morphology. Natick, MA: Eaton Publishing; 17–40.Google Scholar
  57. 57.
    Cattoretti, G., Peleri, S., Parravicini, C., et al. (1993) Antigen unmasking on formalin-fixed, paraffin-embedded tissue sections. J Pathol. 171, 83–98.PubMedCrossRefGoogle Scholar
  58. 58.
    Suurmeijer, A.J.H. and Boon, M.E. (1993) Notes on the application of microwaves for antigen retrieval in paraffin and plastic tissue sections. Eur J Morphol. 31, 144–150.PubMedGoogle Scholar
  59. 59.
    Morgan, J.M., Navabi, H., and Jasani, B. (1997) Role of calcium chelation in high-temperature antigen retrieval at different pH values. J Pathol. 182, 233–237.PubMedCrossRefGoogle Scholar
  60. 60.
    Hjerpe, A., Boon, M.E., and Kok, L.P. (1988) Microwave stimulation of an immunological reaction (CEA/anti-CEA) and its use in immunohistochemistry. Histochem J. 20, 388–396.PubMedCrossRefGoogle Scholar
  61. 61.
    Choi, T.-S., Whittlesey, M., Slap, S.E., et al. (1997) Microwave Immunocytochemistry: Advances in Temperature Control. IN: Gu, J., ed. Analytical Morphology: Theory, Applica­tions, and Protocols. Natick, MA: Eaton Publishing; 91–114.Google Scholar
  62. 62.
    Takes, P.A., Kohrs, J., Krug, R., and Kewley, S. (1999) Microwave technology in ­immunohistochemistry: application to avidin-biotin staining of diverse antigens. J Histotechnol. 12, 95–98.Google Scholar
  63. 63.
    Hopwood, D., Yeaman, G., and Milne, G. (1988) Differentiating the effects of microwave and heat on tissue proteins and their cross linking by formaldehyde. Histochem J. 20, 341–346.PubMedCrossRefGoogle Scholar
  64. 64.
    Porcelli, M., Cacciapuoti, G., Fusco, S., et al. (1997) Non-thermal effects of microwaves on proteins: thermophilic enzymes as model system. FEBS Lett. 402, 102–106.PubMedCrossRefGoogle Scholar
  65. 65.
    Sompuram, S.R., Vani, K., and Bogen, S.A. (2006) A molecular model of antigen retrieval using a peptide array. Am J Clin Pathol. 25, 91–98.Google Scholar
  66. 66.
    Sompuram, S.R., Vani, K., Messana, E., and Bogen, S.A. (2004) A molecular mechanism of formalin fixation and antigen retrieval. Am J Clin Pathol. 121, 190–199.PubMedCrossRefGoogle Scholar
  67. 67.
    Leong, A.S.-Y., Haffajee, Z., and Clark, M. (2007) Microwave enhancement of CISH for Her2 oncogene. Appl Immunohistochem Mol Morphol. 15, 88–93.PubMedCrossRefGoogle Scholar
  68. 68.
    Portiansky, E.L. and Gimeno, E.J. (1996) A new epitope retrieval method for the detection of structural cytokeratins in the bovine prostate tissue. Appl Immunohistochem. 4, 208–214.Google Scholar
  69. 69.
    Leong, A.S.-Y. (2005) Microwave Technology for Light Microscopy and Ultrastructural Studies. Bangkok: Amarin Printing and Publishing Company Ltd.Google Scholar
  70. 70.
    Leong, A.S.-Y., Yin, H., and Haffajee, Z. (2002) Patterns of immunostaining of immunoglobulin in formalin-fixed, paraffin-embedded sections. Appl Immunohistochem Mol Morphol. 10, 110–114.PubMedCrossRefGoogle Scholar
  71. 71.
    Taylor, C.R., Shi, S.R., Chen, C., et al. (1996) Comparative study of antigen retrieval heating methods: microwave, microwave and pressure cooker, autoclave and steamer. Biotech Histochem. 71, 263–270.PubMedCrossRefGoogle Scholar
  72. 72.
    Shi, S.R., Imam, S.A., Young, L., Cote, R.J., and Taylor, C.R. (1995) Antigen retrieval immunohistochemistry under the influence of pH using monoclonal antibodies. J Histochem Cytochem. 43, 193–201.PubMedGoogle Scholar
  73. 73.
    Lan, H.Y., Mu, W., Nikolic-Paterson, D.J., and Atkins, R.C. (1995) A novel, simple, reliable, and sensitive method for multiple immunoenzyme staining: use of microwave oven heating to block antibody cross reactivity and retrieve antigens. J Histochem Cytochem. 43, 97–102.PubMedGoogle Scholar
  74. 74.
    Gao, C., Wang, A.Y., and Han, Y.J. (2008) Microwave antigen retrieval blocks endogenous peroxidase activity in immunohistochemistry. Appl Immunohistochem Mol Morphol. 16, 393–399.PubMedCrossRefGoogle Scholar
  75. 75.
    Leong, A.S.-Y., Milios, J., and Tang, S.K. (1993) Is immunolocalisation of proliferating cell nuclear antigen (PCNA) in paraffin sections a valid index of cell proliferation? Appl Immunohistochem. 1, 27–35.Google Scholar
  76. 76.
    Leong, A.S.-Y., Vinyuvat, S., Suthipintawong, C., and Milios, J. (1995) A comparative study of cell proliferation markers in breast carcinomas. Clin Mol Pathol. 48, M83–M87.PubMedCrossRefGoogle Scholar
  77. 77.
    Willingham, M.C. (1999) Conditional epitopes: is your antibody always specific? J Histochem Cytochem. 47, 1233–1239.PubMedGoogle Scholar
  78. 78.
    Burry, R.W. (2000) Specificity controls for immunocytochemical methods. J Histochem Cytochem. 48, 163–168.PubMedGoogle Scholar
  79. 79.
    Riera, J., Simpson, J.F., Tamayo, R., et al. (1999) Use of cultured cells as a control for quantitative immunocytochemical analysis of estrogen receptor in breast cancer. The Quicgel method. Am J Clin Pathol. 111, 329–332.PubMedGoogle Scholar
  80. 80.
    Taylor, C.R. (2006) Personal communication.Google Scholar
  81. 81.
    McGuire, W.L. (1991) Breast cancer prognostic factors: evaluation guidelines. J Natl Cancer Inst. 83, 154–155.PubMedCrossRefGoogle Scholar
  82. 82.
    Wolff, A.C., Hammond, M.E., Schwartz, J.N., et al. (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 25, 118–145.PubMedCrossRefGoogle Scholar
  83. 83.
    Vogel, C.L., Cobleigh, M.A., Tripathy, D., et al. (2002) Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol. 20, 719–726.PubMedCrossRefGoogle Scholar
  84. 84.
    Leong, T.Y.-M. and Leong, A.S.-Y. (2006) Controversies in the assessment of HER-2. More questions than answers. Adv Anat Pathol. 13, 263–269.PubMedCrossRefGoogle Scholar
  85. 85.
    Dybdal, N., Leiberman, G., Anderson, S., et al. (2005) Determination of HER2 gene amplification by fluorescence in situ hybridization and concordance with the clinical trials immunohistochemical assay in women with metastatic breast cancer evaluated for treatment with trastuzumab. Breast Cancer Res Treat. 93, 3–11.PubMedCrossRefGoogle Scholar
  86. 86.
    Perez, E.A., Suman, V.J., Davidson, N.E., et al. (2006) HER2 testing by local, central, and reference laboratories in specimens from the North Central Cancer Treatment Group N9831 intergroup adjuvant trial. J Clin Oncol. 24, 3032–3038.PubMedCrossRefGoogle Scholar
  87. 87.
    Rhodes, A., Jasani, B., Balaton, A.J., et al. (2001) Study of interlaboratory reliability and reproducibility of estrogen and progesterone receptor assays in Europe. Documentation of poor reliability and identification of ­insufficient microwave antigen retrieval time as a major contributory element of unreliable results. Am J Clin Pathol. 115, 44–58.PubMedCrossRefGoogle Scholar
  88. 88.
    Fitzgibbons, P.L., Murphy, D.A., Dorfman, D.M., et al. (2006) Interlaboratory ­comparison of immunohistochemical testing for HER2: results of the 2004 and 2005 College of American Pathologists HER2 Immunohistochemistry Tissue Microarray Survey. Arch Pathol Lab Med. 130, 1440–1445.PubMedGoogle Scholar
  89. 89.
    Leong, A.S.-Y. (2004) Pitfalls in diagnostic immunohistology. Adv Anat Pathol. 11, 86–93.PubMedCrossRefGoogle Scholar
  90. 90.
    Smith, P.S., Parkinson, I.H., and Leong, A.S.-Y. (1996) Principles of ploidy analysis by static cytometry. Clin Mol Pathol. 49, M104–M111.PubMedCrossRefGoogle Scholar
  91. 91.
    Seidal, T., Balaton, A.J., and Battifora, H. (2001) Interpretation and quantification of immunostains. Am J Surg Pathol. 25, 1204–1207.PubMedCrossRefGoogle Scholar
  92. 92.
    Leong, A.S.-Y. (2004) Quantitation in immunohistology: fact or fiction? A discussion of variables that influence results. Appl Immunohistochem Mol Morphol. 12, 1–7.PubMedGoogle Scholar
  93. 93.
    Cooper, K., Haffajee, Z., and Taylor, L. (1997) Comparative analysis of biotin intranuclear inclusions of gestational endometrium using the APAAP, ABC and PAP immunodetection systems. J Clin Pathol. 50, 153–156.PubMedCrossRefGoogle Scholar
  94. 94.
    Penault-Llorca, F., Cayre, A., Arnould, L., et al. (2006) Is there an immunohistochemical technique definitely valid in epidermal growth factor assessment? Oncol Rep. 16, 1173–1179.PubMedGoogle Scholar
  95. 95.
    Hirsch, F.R., Dziadziuszko, R., Thacher, N., et al. (2008) Epidermal growth factor receptor immunohistochemistry: comparison of antibodies and cutoff points to predict benefit from gefitinib in a phase 3 placebo-controlled study in advanced nonsmall-cell lung cancer. Cancer 112, 1114–1121.PubMedCrossRefGoogle Scholar
  96. 96.
    Cappuzzo, F., Finocchiaro, G., Rossi, E., et al. (2008) EGFR FISH assay predicts for response to cetuximab in chemotherapy refractory colorectal cancer patients. Ann Oncol. 19, 717–723.PubMedCrossRefGoogle Scholar
  97. 97.
    Cunningham, D., Humblet, Y., Siena, S., et al. (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 351, 337–345.PubMedCrossRefGoogle Scholar
  98. 98.
    Saltz, L.B., Meropol, N.J., Loehrer, P.J., et al. (2004) Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol. 22, 1201–1208.PubMedCrossRefGoogle Scholar
  99. 99.
    Goldstein, N.S. and Amin, M. (2001) Epidermal growth factor receptor immunohistochemical reactivity in patients with American Joint Committee on Cancer Stage IV colon adenocarcinoma: implications for a standardized scoring system. Cancer 92, 1331–1346.PubMedCrossRefGoogle Scholar
  100. 100.
    Tos, A.P. and Ellis, I. (2005) Assessing epidermal growth factor receptor expression in tumours: what is the value of current test methods? Eur J Cancer. 41, 1383–1392.CrossRefGoogle Scholar
  101. 101.
    Sabourin, J.C., Cayre, A., Arnould, L., et al. (2005) Comparison of three commercially available immunohistochemical tests for EGFR expression in clorectal cancers. Is immunohistochemistry (IHC) reliable? J Clin Oncol. 23(June Suppl), 9705–9710.Google Scholar
  102. 102.
    Barnes, D.M., Harris, W.H., Smith, P., et al. (1996) Immunohistochemical determination of oestrogen receptor: comparison of ­different methods of assessment of staining and correlation with clinical outcome of breast cancer patients. Br J Cancer 74, 1445–1451.PubMedCrossRefGoogle Scholar
  103. 103.
    Allred, D.C., Harvey, J.M., Berardo, M., et al. (1998) Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 11, 155–168.PubMedGoogle Scholar
  104. 104.
    Hervey, J.M., Clark, G.M., Osborne, C.K., et al. (1999) Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol. 17, 1474–1481.Google Scholar
  105. 105.
    Collins, L.C., Botero, M.L., and Schnitt, S.J. (2005) Bimodal frequency distribution of estrogen receptor immunohistochemical staining results in breast cancer: an analysis of 825 cases. Am J Clin Pathol. 123, 16–20.PubMedCrossRefGoogle Scholar
  106. 106.
    Nadji, M. (2006) Quantitative immunohistochemistry of estrogen receptor in breast cancer. Much ado about nothing. Appl Immunohistochem Mol Morphol. 16, 105–107.Google Scholar
  107. 107.
    Jacobs, T.W., Gown, A.M., Yazji, H., et al. (1999) Specificity of HercepTest in determining HER-2/neu status of breast cancers using the United States Food and Drug Administration-approved scoring system. J Clin Oncol. 17, 1983–1987.PubMedGoogle Scholar
  108. 108.
    Allred, D.C. and Swanson, P.E. (2000) Testing for erbB-2 by immunohistochemistry in breast cancer. Am J Clin Pathol. 113, 171–175.PubMedCrossRefGoogle Scholar
  109. 109.
    Vincent-Salomon, A., MacGrogan, G., Couturier, J., et al. (2003) Calibration of immunohistochemistry for assessment of Her2/neu in breast cancer: results of the French Multicentre GEFPICS Study. Histopathology 42, 337–347.PubMedCrossRefGoogle Scholar
  110. 110.
    Paik, S., Bryant, J., and Tan-Chiu, E., et al. (2002) Real-world performance of HER2 testing – National Surgical Adjuvant Breast and Bowel Project experience. J Natl Cancer Inst. 94, 852–854.PubMedGoogle Scholar
  111. 111.
    Roche, P.C., Suman, V.J., Jenkins, R.B., et al. (2002) Concordance between local and central laboratory HER2 testing in the Breast Intergroup Trial N9831. J Natl Cancer Inst. 94, 855–857.PubMedGoogle Scholar
  112. 112.
    Miller, K. and Ibrahim, M. (2004) The breast HER-2 module. Immunocytochemistry 3, 147–150.Google Scholar
  113. 113.
    Leong, A.S.-Y., Formby, M., Haffajee, Z., and Morey, A. (2006) Refinement of immunohistological parameters for Her2/neu scoring. Validation by FISH and CISH. Appl Immunohistochem Mol Morphol. 14, 384–389.PubMedCrossRefGoogle Scholar
  114. 114.
    Nagy, P., Jenei, A., Kirsch, A.K., et al. (1999) Activation-dependent clustering of the erbB2 receptor tyrosine kinase detected by scanning near-field optical microscopy. J Cell Sci. 112, 1733–1741.PubMedGoogle Scholar
  115. 115.
    Zlobec, I., Steele, R., Michel, R.P., et al. (2006) Scoring of p53, VEGF, Bcl-2 and APAF-1 immunohistochemistry and interobserver reliability in colorectal cancer. Mod Pathol. 19, 1236–1242.PubMedCrossRefGoogle Scholar
  116. 116.
    Zlobec, I., Terracciano, L., Jass, J.R., and Lugli, A. (2007) Value of staining intensity in the interpretation of immunohistochemistry for tumor markers in colorectal cancer. Virchows Arch. 451, 763–769.PubMedCrossRefGoogle Scholar
  117. 117.
    Kay, E.W., Walsh, C.J., Whelan, D., et al. (1996) Interobserver variation of p53 immunohistochemistry – an assessment of a practical problem and comparison with other studies. Br J Biomed Sci. 53, 101–107.PubMedGoogle Scholar
  118. 118.
    Leong, T.Y.-M. and Leong, A.S.-Y. (2007) Variables that influence outcomes in immunohistology. Aust J Med Sci. 28, 47–59.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.University of NewcastleNewcastleAustralia
  2. 2.Peking UniversityBeijingChina
  3. 3.Victorian Cytology ServiceMelbourneAustralia

Personalised recommendations