Tissue Microarrays in Cancer Research

Part of the Applied Bioinformatics and Biostatistics in Cancer Research book series (ABB)


Tissue microarrays (TMAs) are composite tissue blocks capable of accommodating over 1,000 unique tissue cores on a single glass slide. TMAs have become widely adopted in pathology and biomarker research. This chapter briefly discusses the design and construction of TMAs, the state of TMA imaging, and current methods for the analysis and management of TMA data. A significant portion of the chapter highlights the technical challenges of using formalin-fixed, paraffin embedded tissue and analyzing tissue stained using immunohistochemistry (IHC).


FFPE Tissue Slide Scanner Whole Slide Imaging Tyramide Signal Amplification Donor Block 
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  1. Adams EJ, Green JA, Clark AH, Youngson JH (1999) Comparison of different scoring systems for immunohistochemical staining. J Clin Pathol 52:75–77.PubMedCrossRefGoogle Scholar
  2. Ahram M, Flaig MJ, Gillespie JW, Duray PH, Linehan WM, Ornstein DK, Niu S, Zhao Y, Petricoin EF 3rd, Emmert-Buck MR (2003) Evaluation of ethanol-fixed, paraffin-embedded tissues for proteomic applications. Proteomics 3:413–421.PubMedCrossRefGoogle Scholar
  3. Arber DA (2002) Effect of prolonged formalin fixation on the immunohistochemical reactivity of breast markers. Appl Immunohistochem Mol Morphol 10:183–186.PubMedCrossRefGoogle Scholar
  4. Battifora H (1986) The multitumor (sausage) tissue block: novel method for immunohistochemical antibody testing. Lab Invest 55:244–248.PubMedGoogle Scholar
  5. Battifora H, Mehta P (1990) The checkerboard tissue block. An improved multitissue control block. Lab Invest 63:722–724.PubMedGoogle Scholar
  6. Berez CG, Hicks JL, Lecksell K, Southerland M, Fedor H, De Marzo AM (2010) A simple storage approach for biomarker preservation in precut tissue microarray slides. Manuscript in preparation.Google Scholar
  7. Bertheau P, Cazals-Hatem D, Meignin V, de Roquancourt A, Verola O, Lesourd A, Sene C, Brocheriou C, Janin A (1998) Variability of immunohistochemical reactivity on stored paraffin slides. J Clin Pathol 51:370–374.PubMedCrossRefGoogle Scholar
  8. Bilgin C, Demir C, Nagi C, Yener B (2007) Cell-graph mining for breast tissue modeling and classification. Conference proceedings. Conf Proc IEEE Eng Med Biol Soc 2007:5311–5314.PubMedGoogle Scholar
  9. Blind C, Koepenik A, Pacyna-Gengelbach M, Fernahl G, Deutschmann N, Dietel M, Krenn V, Petersen I (2008) Antigenicity testing by immunohistochemistry after tissue oxidation. J Clin Pathol 61:79–83.PubMedCrossRefGoogle Scholar
  10. Bobrow MN, Harris TD, Shaughnessy KJ, Litt GJ (1989) Catalyzed reporter deposition, a novel method of signal amplification. Application to immunoassays. J Immunol Meth 125:279–285.CrossRefGoogle Scholar
  11. Bobrow MN, Shaughnessy KJ, Litt GJ (1991) Catalyzed reporter deposition, a novel method of signal amplification. II. Application to membrane immunoassays. J Immunol Meth 137:103–112.CrossRefGoogle Scholar
  12. Brown LA, Huntsman D (2007) Fluorescent in situ hybridization on tissue microarrays: challenges and solutions. J Mol Histol 38:151–157.PubMedCrossRefGoogle Scholar
  13. Brumby SP, Theiler J, Perkins SJ, Harvey NR, Szymanski JJ, Bloch JJ, Mitchell M (1999) Investigation of Feature Extraction by a Genetic Algorithm. Proc SPIE. 3812:24–31.CrossRefGoogle Scholar
  14. Burnett MG (1982) The mechanism of the formaldehyde clock reaction. J Chem Educ 59:160–162.CrossRefGoogle Scholar
  15. Camp RL, Chung GG, Rimm DL (2002) Automated subcellular localization and quantification of protein expression in tissue microarrays. Nat Med 8:1323–1327.PubMedCrossRefGoogle Scholar
  16. Cattoretti G, Becker MH, Key G, Duchrow M, Schluter C, Galle J, Gerdes J (1992) Monoclonal antibodies against recombinant parts of the Ki-67 antigen (MIB 1 and MIB 3) detect proliferating cells in microwave-processed formalin-fixed paraffin sections. J Pathol 168:357–363.PubMedCrossRefGoogle Scholar
  17. Chubb C, Inagaki Y, Sheu P, Cummings B, Wasserman A, Head E, Cotman C (2006) BioVision: an application for the automated image analysis of histological sections. Neurobiol Aging 27:1462–1476.PubMedCrossRefGoogle Scholar
  18. Compton CC (2009) The surgical specimen is the personalized part of personalized cancer medicine. Ann Surg Oncol 16:2079–2080.PubMedCrossRefGoogle Scholar
  19. Coons AH, Creech HJ, Jones RN, Berliner E (1942) The Demonstration of Pneumococcal Antigen in Tissues by the Use of Fluorescent Antibody. J Immunol. 45:159–170.Google Scholar
  20. Cordell JL, Falini B, Erber WN, Ghosh AK, Abdulaziz Z, MacDonald S, Pulford KA, Stein H, Mason DY (1984) Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem 32:219–229.PubMedCrossRefGoogle Scholar
  21. Dash A, Maine IP, Varambally S, Shen R, Chinnaiyan AM, Rubin MA (2002) Changes in differential gene expression because of warm ischemia time of radical prostatectomy specimens. Am J Pathol 161:1743–1748.PubMedCrossRefGoogle Scholar
  22. D’Amico F, Skarmoutsou E, Stivala F (2009) State of the art in antigen retrieval for immunohistochemistry. J Immunol Methods. Feb 28;341(1–2):1–18.Google Scholar
  23. de Jong D, Rosenwald A, Chhanabhai M, Gaulard P, Klapper W, Lee A, Sander B, Thorns C, Campo E, Molina T, Norton A, Hagenbeek A, Horning S, Lister A, Raemaekers J, Gascoyne RD, Salles G, Weller E, Lunenburg Lymphoma Biomarker C (2007) Immunohistochemical prognostic markers in diffuse large B-cell lymphoma: validation of tissue microarray as a prerequisite for broad clinical applications – a study from the Lunenburg Lymphoma Biomarker Consortium. J Clin Oncol 25:805–812.PubMedCrossRefGoogle Scholar
  24. De Marzo AM, Fedor HH, Gage WR, Rubin MA (2002) Inadequate formalin fixation decreases reliability of p27 immunohistochemical staining: probing optimal fixation time using high-density tissue microarrays. Hum Pathol 33:756–760.PubMedCrossRefGoogle Scholar
  25. De Marzo AM, Morgan JD, Iacobuzio-Donahue C, Razzaque B, Faith DA (2004) TMAJ: open source software to manage a tissue microarray database. Arch Pathol Lab Med 128:1094.Google Scholar
  26. Del Castillo P, Llorente AR, Stockert JC (1989) Influence of fixation, exciting light and section thickness on the primary fluorescence of samples for microfluorometric analysis. Basic Appl Histochem 33:251–257.PubMedGoogle Scholar
  27. DiVito KA, Charette LA, Rimm DL, Camp RL (2004) Long-term preservation of antigenicity on tissue microarrays. Lab Invest 84:1071–1078.PubMedCrossRefGoogle Scholar
  28. Doyle S, Rodriguez C, Madabhushi A, Tomaszeweski J, Feldman M (2006) Detecting prostatic adenocarcinoma from digitized histology using a multi-scale hierarchical classification approach. Conf Proc IEEE Eng Med Biol Soc 1:4759–4762.PubMedGoogle Scholar
  29. Faith DA, Ertoy-Baydar D, Spolter YS, Platz EA, Rubin MA, Ayala G, De Marzo AM (2005) Multi-institution automated image analysis of PTEN protein in prostatic adenocarcinoma. Mod Pathol 18:140A.Google Scholar
  30. Fedor HL, De Marzo AM (2005) Practical methods for tissue microarray construction. Meth Mol Med 103:89–101.Google Scholar
  31. Fox CH, Johnson FB, Whiting J, Roller PP (1985) Formaldehyde fixation. J Histochem Cytochem 33:845–853.PubMedCrossRefGoogle Scholar
  32. Fraenkel-Conrat H, Olcott HS (1948) Reaction of formaldehyde with proteins; cross-linking of amino groups with phenol, imidazole, or indole groups. J Biol Chem 174:827–843.PubMedGoogle Scholar
  33. Giorno R (1984) A comparison of two immunoperoxidase staining methods based on the avidin–biotin interaction. Diagn Immunol 2:161–166.PubMedGoogle Scholar
  34. Goldstein NS, Ferkowicz M, Odish E, Mani A, Hastah F (2003) Minimum formalin fixation time for consistent estrogen receptor immunohistochemical staining of invasive breast carcinoma. Am J Clin Pathol 120:86–92.PubMedCrossRefGoogle Scholar
  35. Goto M, Nagatomo Y, Hasui K, Yamanaka H, Murashima S, Sato E (1992) Chromaticity analysis of immunostained tumor specimens. Pathol Res Pract 188:433–437.PubMedCrossRefGoogle Scholar
  36. Grizzle W (2009) Special symposium: fixation and tissue processing models. Biotechnic and histochemistry: official publication of the Biological Stain Commission, 1–9.Google Scholar
  37. Guesdon JL, Ternynck T, Avrameas S (1979) The use of avidin–biotin interaction in immunoenzymatic techniques. J Histochem Cytochem 27:1131–1139.PubMedCrossRefGoogle Scholar
  38. Gurel B, Iwata T, Koh CM, Jenkins RB, Lan F, Van Dang C, Hicks JL, Morgan J, Cornish TC, Sutcliffe S, Isaacs WB, Luo J, De Marzo AM (2008) Nuclear MYC protein overexpression is an early alteration in human prostate carcinogenesis. Mod Pathol 21:1156–1167.PubMedCrossRefGoogle Scholar
  39. Halushka MK, Cornish TC, Lu J, Selvin S, Selvin E (2010) Creation, validation, and quantitative analysis of protein expression in vascular tissue microarrays. Cardiovasc Pathol 19(3):136–146.PubMedCrossRefGoogle Scholar
  40. Hammes LS, Korte JE, Tekmal RR, Naud P, Edelweiss MI, Valente PT, Longatto-Filho A, Kirma N, Cunha-Filho JS (2007) Computer-assisted immunohistochemical analysis of cervical cancer biomarkers using low-cost and simple software. Appl Immunohistochem Mol Morphol 15:456–462.PubMedCrossRefGoogle Scholar
  41. Harvey JM, Clark GM, Osborne CK, Allred DC (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.PubMedGoogle Scholar
  42. Heras A, Roach CM (1995) Enhanced polymer detection system for immunohistochemistry. Mod Pathol 8:165A.Google Scholar
  43. Howat WJ, Warford A, Mitchell JN, Clarke KF, Conquer JS, McCafferty J (2005) Resin tissue microarrays: a universal format for immunohistochemistry. J Histochem Cytochem 53:1189–1197.PubMedCrossRefGoogle Scholar
  44. Hsu SM, Raine L, Fanger H (1981) Use of avidin–biotin–peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29:577–580.PubMedCrossRefGoogle Scholar
  45. Huang SN (1975) Immunohistochemical demonstration of hepatitis B core and surface antigens in paraffin sections. Lab Invest 33:88–95.PubMedGoogle Scholar
  46. Jacobs TW, Prioleau JE, Stillman IE, Schnitt SJ (1996) Loss of tumor marker-immunostaining intensity on stored paraffin slides of breast cancer. J Natl Cancer Inst 88:1054–1059.PubMedCrossRefGoogle Scholar
  47. Kajdacsy-Balla A, Geynisman JM, Macias V, Setty S, Nanaji NM, Berman JJ, Dobbin K, Melamed J, Kong X, Bosland M, Orenstein J, Bayerl J, Becich MJ, Dhir R, Datta MW, Cooperative Prostate Cancer Tissue R (2007) Practical aspects of planning, building, and interpreting tissue microarrays: the cooperative prostate cancer tissue resource experience. J Mol Histol 38:113–121.PubMedCrossRefGoogle Scholar
  48. Kay EW, Walsh CJ, Cassidy M, Curran B, Leader M (1994) C-erbB-2 immunostaining: problems with interpretation. J Clin Pathol 47:816–822.PubMedCrossRefGoogle Scholar
  49. Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP (1998) Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 4:844–847.PubMedCrossRefGoogle Scholar
  50. Kyndi M, Sorensen FB, Knudsen H, Overgaard M, Nielsen HM, Andersen J, Overgaard J (2008) Tissue microarrays compared with whole sections and biochemical analyses.. A subgroup analysis of DBCG 82 b&c. Acta Oncol (Stockholm, Sweden 47:591–599.CrossRefGoogle Scholar
  51. Lamaziere JM, Lavallee J, Zunino C, Larrue J (1993) Semiquantitative study of the distribution of two cellular antigens by computer-directed color analysis. Lab Invest 68:248–252.PubMedGoogle Scholar
  52. Latson L, Sebek B, Powell KA, Latson L, Sebek B, Powell KA (2003) Automated cell nuclear segmentation in color images of hematoxylin and eosin-stained breast biopsy. Anal Quant Cytol Histol 25:321–331.PubMedGoogle Scholar
  53. Levenson RM, Bearman GH, Mahadevan-Jansen A (2003) Spectral imaging: instrumentation, applications, and analysis II. Proc SPIE 4959:27–33.CrossRefGoogle Scholar
  54. Luo J, Zha S, Gage WR, Dunn TA, Hicks JL, Bennett CJ, Ewing CM, Platz EA, Ferdinandusse S, Wanders RJ, Trent JM, Isaacs WB, De Marzo AM (2002) Alpha-methylacyl-CoA racemase: a new molecular marker for prostate cancer. Cancer Res 62:2220–2226.PubMedGoogle Scholar
  55. Marinelli RJ, Montgomery K, Liu CL, Shah NH, Prapong W, Nitzberg M, Zachariah ZK, Sherlock GJ, Natkunam Y, West RB, van de Rijn M, Brown PO, Ball CA (2008) The Stanford tissue microarray database. Nucleic Acids Res 36:D871–D877.PubMedCrossRefGoogle Scholar
  56. Marrack J (1934) The nature of antibodies. Nature 133:292–293.CrossRefGoogle Scholar
  57. McCabe A, Dolled-Filhart M, Camp RL, Rimm DL (2005) Automated quantitative analysis (AQUA) of in situ protein expression, antibody concentration, and prognosis. J Natl Cancer Inst 97:1808–1815.PubMedCrossRefGoogle Scholar
  58. McCarty KS Jr, Szabo E, Flowers JL, Cox EB, Leight GS, Miller L, Konrath J, Soper JT, Budwit DA, Creasman WT (1986) Use of a monoclonal anti-estrogen receptor antibody in the immunohistochemical evaluation of human tumors. Cancer Res 46:4244s–4248s.PubMedGoogle Scholar
  59. Mete M, Xu X, Fan CY, Shafirstein G (2007) Automatic delineation of malignancy in histopathological head and neck slides. BMC Bioinformatics 8(Suppl 7):S17.PubMedCrossRefGoogle Scholar
  60. Morgan JM, Navabi H, Schmid KW, Jasani B (1994) Possible role of tissue-bound calcium ions in citrate-mediated high-temperature antigen retrieval. J Pathol 174:301–307.PubMedCrossRefGoogle Scholar
  61. Mulrane L, Rexhepaj E, Penney S, Callanan JJ, Gallagher WM (2008) Automated image analysis in histopathology: a valuable tool in medical diagnostics. Expert Rev Mol Diagn 8:707–725.PubMedCrossRefGoogle Scholar
  62. Nakane PK, Pierce GB Jr (1966) Enzyme-labeled antibodies: preparation and application for the localization of antigens. J Histochem Cytochem 14:929–931.PubMedCrossRefGoogle Scholar
  63. National Cancer Institute Best Practices for Biospecimen Resources (2007) US Department of Health and Human Services, Bethesda, MD.Google Scholar
  64. Olapade-Olaopa EO, Ogunbiyi JO, MacKay EH, Muronda CA, Alonge TO, Danso AP, Moscatello DK, Sandhu DP, Shittu OB, Terry TR, Wong AJ, Habib FK (2001) Further characterization of storage-related alterations in immunoreactivity of archival tissue sections and its implications for collaborative multicenter immunohistochemical studies. Appl Immunohistochem Mol Morphol 9:261–266.PubMedCrossRefGoogle Scholar
  65. Pan CC, Chen PC, Chiang H (2004) An easy method for manual construction of high-density ­tissue arrays. Appl Immunohistochem Mol Morphol 12:370–372.PubMedCrossRefGoogle Scholar
  66. Perkins S, Theiler J, Brumby SP, Harvey NR, Porter RB, Szymanski JJ, Bloch JJ (2000) GENIE – A Hybrid Genetic Algorithm for Feature Classification in Multi-Spectral Images. Proc SPIE. 4120:52–62.Google Scholar
  67. Pham NA, Morrison A, Schwock J, Aviel-Ronen S, Iakovlev V, Tsao MS, Ho J, Hedley DW (2007) Quantitative image analysis of immunohistochemical stains using a CMYK color model. Diagnos Pathol 2:8.CrossRefGoogle Scholar
  68. Pires AR, Andreiuolo Fda M, de Souza SR (2006) TMA for all: a new method for the construction of tissue microarrays without recipient paraffin block using custom-built needles. Diagnost Pathol 1:14.CrossRefGoogle Scholar
  69. Poston RN, Gall NP (1990) Hue-saturation-intensity color image analysis for the quantitation of immunoperoxidase staining. Acto Histochem Cytochem 23:730.Google Scholar
  70. Rabinovich A, Krajewski S, Krajewska M, Shabaik A, Hewitt SM, Belongie S, Reed JC, Price JH (2006) Framework for parsing, visualizing and scoring tissue microarray images. IEEE Trans Inf Technol Biomed 10:209–219.PubMedCrossRefGoogle Scholar
  71. Ramos-Vara JA, Miller MA (2006) Comparison of two polymer-based immunohistochemical detection systems: ENVISION+ and ImmPRESS. J Microsc 224:135–139.PubMedCrossRefGoogle Scholar
  72. Riera J, Simpson JF, Tamayo R, Battifora H (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 111:329–335.PubMedGoogle Scholar
  73. Rimm DL (2006) What brown cannot do for you. Nat Biotechnol 24:914–916.PubMedCrossRefGoogle Scholar
  74. Rojo MG, Garcia GB, Mateos CP, Garcia JG, Vicente MC (2006) Critical comparison of 31 ­commercially available digital slide systems in pathology. Int J Surg Pathol 14:285–305.PubMedCrossRefGoogle Scholar
  75. Rubin MA, Zhou M, Dhanasekaran SM, Varambally S, Barrette TR, Sanda MG, Pienta KJ, Ghosh D, Chinnaiyan AM (2002) Alpha-Methylacyl coenzyme A racemase as a tissue biomarker for prostate cancer. JAMA: J Am Med Assoc 287:1662–1670.CrossRefGoogle Scholar
  76. Ruifrok AC, Johnston DA (2001) Quantification of histochemical staining by color deconvolution. Anal Quant Cytol Histol 23:291–299.PubMedGoogle Scholar
  77. Ruifrok AC, Katz RL, Johnston DA (2003) Comparison of quantification of histochemical staining by hue-saturation-intensity (HSI) transformation and color-deconvolution. Appl Immu­nohistochem Mol Morphol 11:85–91.PubMedGoogle Scholar
  78. Russ JC (2007) The image processing handbook. CRC Press/Taylor & Francis, Boca Raton.Google Scholar
  79. Sabattini E, Bisgaard K, Ascani S, Poggi S, Piccioli M, Ceccarelli C, Pieri F, Fraternali-Orcioni G, Pileri SA (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 51:506–511.PubMedCrossRefGoogle Scholar
  80. Schlomm T, Nakel E, Lubke A, Buness A, Chun FK, Steuber T, Graefen M, Simon R, Sauter G, Poustka A, Huland H, Erbersdobler A, Sultmann H, Hellwinkel OJ (2008) Marked gene ­transcript level alterations occur early during radical prostatectomy. Eur Urol 53:333–344.PubMedCrossRefGoogle Scholar
  81. Schoenberg Fejzo M, Slamon DJ (2001) Frozen tumor tissue microarray technology for analysis of tumor RNA, DNA, and proteins. Am J Pathol 159:1645–1650.PubMedCrossRefGoogle Scholar
  82. Selvarajan S, Bay BH, Choo A, Chuah KL, Sivaswaren CR, Tien SL, Wong CY, Tan PH (2002) Effect of fixation period on HER2/neu gene amplification detected by fluorescence in situ hybridization in invasive breast carcinoma. J Histochem Cytochem 50:1693–1696.PubMedCrossRefGoogle Scholar
  83. Selvarajan S, Bay BH, Mamat SB, Choo A, Chuah KL, Sivaswaren CR, Tien SL, Wong CY, Tan PH (2003) Detection of HER2/neu gene amplification in archival paraffin-embedded breast cancer tissues by fluorescence in situ hybridization. Histochem Cell Biol 120:251–255.PubMedCrossRefGoogle Scholar
  84. Shi SR, Imam SA, Young L, Cote RJ, Taylor CR (1995) Antigen retrieval immunohistochem­istry under the influence of pH using monoclonal antibodies. J Histochem Cytochem 43:193–201.PubMedCrossRefGoogle Scholar
  85. Shi SR, Cote RJ, Taylor CR (1997) Antigen retrieval immunohistochemistry: past, present, and future. J Histochem Cytochem 45:327–343.PubMedCrossRefGoogle Scholar
  86. Shi SR, Guo J, Cote RJ, Young LL, Hawes D, Shi Y, Thu S, Taylor CR (1999) Sensitivity and detection efficiency of a novel two-step detection system (power vision) for immunohistochemistry. Appl Immunohistochem Mol Morphol 7:201–208.CrossRefGoogle Scholar
  87. Shi SR, Liu C, Perez J, Taylor CR (2005) Protein-embedding technique: a potential approach to standardization of immunohistochemistry for formalin-fixed, paraffin-embedded tissue sections. J Histochem Cytochem 53:1167–1170.PubMedCrossRefGoogle Scholar
  88. Simon R, Sauter G (2003) Tissue microarray (TMA) applications: implications for molecular medicine. Expert Rev Mol Med 5:1–12.PubMedCrossRefGoogle Scholar
  89. Spruessel A, Steimann G, Jung M, Lee SA, Carr T, Fentz AK, Spangenberg J, Zornig C, Juhl HH, David KA (2004) Tissue ischemia time affects gene and protein expression patterns within minutes following surgical tumor excision. Biotechniques 36:1030–1037.PubMedGoogle Scholar
  90. Sternberger LA, Hardy PH Jr, Cuculis JJ, Meyer HG (1970) The unlabeled antibody enzyme method of immunohistochemistry: preparation and properties of soluble antigen–antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in identification of spirochetes. J Histochem Cytochem 18:315–333.PubMedCrossRefGoogle Scholar
  91. Summersgill B, Clark J, Shipley J (2008) Fluorescence and chromogenic in situ hybridization to detect genetic aberrations in formalin-fixed paraffin embedded material, including tissue microarrays. Nat Protoc 3:220–234.PubMedCrossRefGoogle Scholar
  92. Tanner M, Gancberg D, Di Leo A, Larsimont D, Rouas G, Piccart MJ, Isola J (2000) Chromogenic in situ hybridization: a practical alternative for fluorescence in situ hybridization to detect HER-2/neu oncogene amplification in archival breast cancer samples. Am J Pathol 157:1467–1472.PubMedCrossRefGoogle Scholar
  93. Tawfik OW, Kimler BF, Davis M, Donahue JK, Persons DL, Fan F, Hagemeister S, Thomas P, Connor C, Jewell W, Fabian CJ (2006) Comparison of immunohistochemistry by automated cellular imaging system (ACIS) versus fluorescence in-situ hybridization in the evaluation of HER-2/neu expression in primary breast carcinoma. Histopathology 48:258–267.PubMedCrossRefGoogle Scholar
  94. Taylor CR, Levenson RM (2006) Quantification of immunohistochemistry – issues concerning methods, utility and semiquantitative assessment II. Histopathology 49:411–424.PubMedCrossRefGoogle Scholar
  95. Thallinger GG, Baumgartner K, Pirklbauer M, Uray M, Pauritsch E, Mehes G, Buck CR, Zatloukal K, Trajanoski Z (2007) TAMEE: data management and analysis for tissue microarrays. BMC Bioinform 8:81.CrossRefGoogle Scholar
  96. van den Broek LJ, van de Vijver MJ (2000) Assessment of problems in diagnostic and research immunohistochemistry associated with epitope instability in stored paraffin sections. Appl Immunohistochem Mol Morphol 8:316–321.PubMedCrossRefGoogle Scholar
  97. van Der Laak JA, Pahlplatz MM, Hanselaar AG, de Wilde PC (2000) Hue-saturation-density (HSD) model for stain recognition in digital images from transmitted light microscopy. Cytometry 39:275–284.CrossRefGoogle Scholar
  98. van der Loos CM (2008) Multiple immunoenzyme staining: methods and visualizations for the observation with spectral imaging. J Histochem Cytochem 56:313–328.PubMedCrossRefGoogle Scholar
  99. Vincek V, Nassiri M, Nadji M, Morales AR (2003) A tissue fixative that protects macromolecules (DNA, RNA, and protein) and histomorphology in clinical samples. Lab Invest 83:1427–1435.PubMedCrossRefGoogle Scholar
  100. Vogel UF (2008) Simple, inexpensive and precise paraffin tissue microarrays constructed with predrilled ordinary steel embedding moulds. Histopathology 52:255–256.PubMedGoogle Scholar
  101. Wan WH, Fortuna MB, Furmanski P (1987) A rapid and efficient method for testing immunohistochemical reactivity of monoclonal antibodies against multiple tissue samples simultaneously. J Immunol Meth 103:121–129.CrossRefGoogle Scholar
  102. Watanabe A, Cornelison R, Hostetter G (2005) Tissue microarrays: applications in genomic research. Expert Rev Mol Diagn 5:171–181.PubMedCrossRefGoogle Scholar
  103. Weller TH, Coons AH (1954) Fluorescent antibody studies with agents of varicella and herpes zoster propagated in vitro. Proc Soc Exp Biol Med 86:789–794.PubMedGoogle Scholar
  104. Werner M, Chott A, Fabiano A, Battifora H (2000) Effect of formalin tissue fixation and processing on immunohistochemistry. Am J Surg Pathol 24:1016–1019.PubMedCrossRefGoogle Scholar
  105. Wester K, Wahlund E, Sundstrom C, Ranefall P, Bengtsson E, Russell PJ, Ow KT, Malmstrom PU, Busch C (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
  106. Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF, American Society of Clinical Oncology/College of American Pathology (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med 131:18–43.PubMedGoogle Scholar
  107. Yaziji H, Taylor CR, Goldstein NS, Dabbs DJ, Hammond EH, Hewlett B, Floyd AD, Barry TS, Martin AW, Badve S, Baehner F, Cartun RW, Eisen RN, Swanson PE, Hewitt SM, Vyberg M, Hicks DG, Members of the Standardization Ad-Hoc Consensus C (2008) Consensus recommendations on estrogen receptor testing in breast cancer by immunohistochemistry. Appl Immunohistochem Mol Morphol 16:513–520.PubMedCrossRefGoogle Scholar
  108. Zha S, Gage WR, Sauvageot J, Saria EA, Putzi MJ, Ewing CM, Faith DA, Nelson WG, De Marzo AM, Isaacs WB (2001) Cyclooxygenase-2 is up-regulated in proliferative inflammatory atrophy of the prostate, but not in prostate carcinoma. Cancer Res 61:8617–8623.PubMedGoogle Scholar
  109. Zhou L, Hodeib M, Abad JD, Mendoza L, Kore AR, Hu Z (2007) New tissue microarray technology for analyses of gene expression in frozen pathological samples. Biotechniques 43:101–105.PubMedCrossRefGoogle Scholar
  110. Zimmermann T, Rietdorf J, Pepperkok R (2003) Spectral imaging and its applications in live cell microscopy. FEBS Lett 546:87–92.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of PathologyJohns Hopkins University School of MedicineBaltimoreUSA

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