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Chapter 8 - Current Status of Immunohistochemistry

Published online by Cambridge University Press:  16 June 2022

By
Trung Nguyen
Edited by
Trung Nguyen
Trung Nguyen
Affiliation:
Peter MacCallum Cancer Centre, Australia
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Summary

The current utilization of immunohistochemistry (IHC) in a diagnostic context is discussed. The modern facility requirements, the various roles IHC is tasked with and the key concept of standardization are covered. Common terminologies are addressed and explained within an IHC context. The terms 'validation' and 'verification' provide one example of words which may cause confusion. The present status in terms of protocol set-up, antibody clones and epitope retrieval are offered to emphasize current best practice. A treatise is given concerning IHC’s special relationship with emerging molecular technologies and how these two analytical devices are shaping diagnoses and treatment strategies for patients. Specific examples are taken from melanoma, breast, lung and bowel cancers. The reader should be able to ascertain the role of IHC in today’s pathology laboratories.

Keywords

personalized medicinemolecular techniquesin situ hybridizationcompanion diagnosticscheckpoint inhibitorsmutationbiomarkerstandardizationhistopathology
Type
Chapter
Information
Immunohistochemistry
A Technical Guide to Current Practices
 , pp. 210 - 252
Publisher: Cambridge University Press
Print publication year: 2022

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References

Asch-Kendrick, RJ, Samols, MA, Lilo, MT, Subhawong, AP, Sharma, R, Illei, PB, Argani, P, Cimino-Mathews, A 2014. NKX3.1 is expressed in ER-positive and AR-positive primary breast carcinomas. J Clin Pathol 67(9):768–71.CrossRefGoogle ScholarPubMed
Bartlett, EK, Karakousis, GC 2015. Current staging and prognostic factors in melanoma. Surg Oncol Clin N Am 24(2):215–27.CrossRefGoogle ScholarPubMed
Brevet, M, Arcila, M, Ladanyi, M 2010. Assessment of EGFR mutation status in lung adenocarcinoma by immunohistochemistry using antibodies specific to the two major forms of mutant EGFR. J Mol Diagn 12(2):169–76.Google Scholar
Browne, MA, Howard, CV, Jolleys, GD 1995. Principles of stereology. In Wootton, R, Springall, DR, Polak, JM, eds. Image analysis in histology: Conventional and confocal microscopy. Cambridge University Press; 96–120.Google Scholar
Bubendorf, L, Büttner, R, Al-Dayel, F, Dietel, M, Elmberger, G, Kerr, K, López-Ríos, F, Marchetti, A, Öz, B, Pauwels, P, Penault-Llorca, F, Rossi, G, Ryška, A, Thunnissen, E 2016. Testing for ROS1 in non-small cell lung cancer: A review with recommendations. Virchows Arch 469(5):489–503.CrossRefGoogle ScholarPubMed
Cai, SJ, Xu, Y, Cai, GX, Lian, P, Guan, ZQ, Mo, SJ, Sun, MH, Cai, Q, Shi, DR 2003. Clinical characteristics and diagnosis of patients with hereditary nonpolyposis colorectal cancer. World J Gastroenterol 9(2):284–7.Google Scholar
Cao, J, Chen, D, Yang, F, Yao, J, Zhu, W, Zhao, C 2017. NUT midline carcinoma as a primary lung tumor: A case report. J Thorac Dis 9(12):e1045–9.Google Scholar
Chapman, PB, Hauschild, A, Robert, C, Haanen, JB, Ascierto, P, Larkin, J, Dummer, R, Garbe, C, Testori, A, Maio, M, Hogg, D, Lorigan, P, Lebbe, C, Jouary, T, Schadendorf, D, Ribas, A, O’Day, SJ, Sosman, JA, Kirkwood, JM, Eggermont, AMM, Dreno, B, Nolop, K, Li, J, Nelson, B, Hou, J, Lee, RJ, Flaherty, KT, McArthur, GA 2011. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 26(364):2507–16.Google Scholar
Compton, LA, Murphy, GF, Lian, CG 2015. Diagnostic immunohistochemistry in cutaneous neoplasia: An update. Dermatopathology (Basel) 2(1):15–42.CrossRefGoogle ScholarPubMed
Conde, E, Hernandez, S, Martinez, R, Angulo, B, De Castro, J, Collazo-Lorduy, A, Jimenez, B, Muriel, A, Mate, JL, Moran, T, Aranda, I, Massuti, B, Rojo, F, Domine, M, Sansano, I, Garcia, F, Felip, E, Mancheño, N, Juan, O, Sanz, J, Gonzalez-Larriba, JL, Atienza-Cuevas, L, Arriola-Arellano, E, Abdulkader, I, Garcia-Gonzalez, J, Camacho, C, Rodriguez-Abreu, D, Teixido, C, Reguart, N, Gonzalez-Piñeiro, A, Lazaro-Quintela, M, Lozano, MD, Gurpide, A, Gomez-Roman, J, Lopez-Brea, M, Pijuan, L, Salido, M, Arriola, E, Company, A, Insa, A, Esteban-Rodriguez, I, Saiz, M, Azkona, E, Alvarez, R, Artal, A, Luz Plaza, M, Aguiar, D, Enguita, AB, Benito, A, Paz-Ares, L, Garrido, P, Lopez-Rios, F 2019. Assessment of a new ROS1 immunohistochemistry clone (SP384) for the identification of ROS1 rearrangements in patients with non–small cell lung carcinoma: The ROSING Study. J Thorac Onco 14(12):2120–32.Google Scholar
Conklin, CMJ, Craddock, KJ, Have, C, Laskin, J, Couture, C, Ionescu, DN 2013. Immunohistochemistry is a reliable screening tool for identification of ALK rearrangement in non-small cell lung carcinoma and is antibody dependent. J Thorac Oncol 8(1):45–51.Google Scholar
Dako 2020. Omnis EnVision Flex, High pH GV800 Instructions for use. Agilent Technologies (online). Available at www.agilent.com/cs/library/packageinsert/public/PD04120EFG_02.pdf (Accessed 16 June 2021).Google Scholar
Davis, LE, Shalin, SC, Tackett, AJ 2019. Current state of melanoma diagnosis and treatment. Cancer Biol Ther 20(11):1366–79.Google Scholar
Dyck, L, Mills, KHG 2017. Immune checkpoints and their inhibition in cancer and infectious diseases. Eur J Immunol 47(5):765–79.Google Scholar
Engel, P, Boumsell, L, Balderas, R, Bensussan, A, Gattei, V, Horejsi, V, Jin, BQ, Malavasi, F, Mortari, F, Schwartz-Albiez, R, Stockinger, H, Van Zelm, MC, Zola, H, Clark, G 2015. CD nomenclature 2015: Human leukocyte differentiation antigen workshops as a driving force in immunology. J Immunol 195(10):4555–63.CrossRefGoogle ScholarPubMed
Franklin, WA, Veve, R, Hirsch, FR, Helfrich, BA, Bunn, PA Jr 2002. Epidermal growth factor receptor family in lung cancer and premalignancy. Semin Oncol 29(1 Suppl 4):3–14.Google Scholar
Galimberti, V, Cole, BF, Zurrida, S, Viale, G, Luini, A, Veronesi, P, Baratella, P, Chifu, C, Sargenti, M, Intra, M, Gentilini, O, Mastropasqua, MG, Mazzarol, G, Massarut, S, Garbay, JR, Zgajnar, J, Galatius, H, Recalcati, A, Littlejohn, D, Bamert, M, Colleoni, M, Price, KN, Regan, MM, Goldhirsch, A, Coates, AS, Gelber, RD, Veronesi, U 2013. International Breast Cancer Study Group Trial 23–01 investigators. Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23–01): A phase 3 randomised controlled trial. Lancet Oncol 14(4):297–305.Google Scholar
Gelmann, EP, Bowen, C, Bubendorf, L 2003. Expression of NKX3.1 in normal and malignant tissues. Prostate 55:111–17.Google Scholar
Grenert, JP 2016. Hereditary nonpolyposis colorectal cancer and Lynch syndrome. In Leonard, DGB, ed. Molecular pathology in clinical practice. Springer; 339–50.Google Scholar
Gurel, B, Ali, TZ, Montgomery, EA, Begum, S, Hicks, J, Goggins, M, Eberhart, CG, Clark, DP, Bieberich, CJ, Epstein, JI, De Marzo, AM 2010. NKX3.1 as a marker of prostatic origin in metastatic tumors. Am J Surg Pathol 34(8):1097–105.Google Scholar
Haack, H, Johnson, LA, Fry, CJ, Crosby, K, Polakiewicz, RD, Stelow, EB, Hong, SM, Schwartz, BE, Cameron, MJ, Rubin, MA, Chang, MC, Aster, JC, French, CA 2009. Diagnosis of NUT midline carcinoma using a NUT-specific monoclonal antibody. Am J Surg Pathol 33(7):984–91.CrossRefGoogle ScholarPubMed
Hammond, ME, Hayes, DF, Dowsett, M, Allred, DC, Hagerty, KL, Badve, S, Fitzgibbons, PL, Francis, G, GoldsteinNS, , Hayes, M, Hicks, DG, Lester, S, Love, R, Mangu, PB, McShane, L, Miller, K, Osborne, CK, Paik, S, Perlmutter, J, Rhodes, A, Sasano, H, Schwartz, JN, Sweep, FC, Taube, S, Torlakovic, EE, Valenstein, P, Viale, G, Visscher, D, Wheeler, T, Williams, RB, Wittliff, JL, Wolff, AC, American Society of Clinical Oncology, College of American Pathologists 2010. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. Arch Pathol Lab Med 134(6):907–22.Google Scholar
Ilie, M, Khambata-Ford, S, Copie-Bergman, C, Huang, L, Juco, J, Hofman, V, Hofman, P 2017. Use of the 22C3 anti–PD-L1 antibody to determine PD-L1 expression in multiple automated immunohistochemistry platforms. PLoS One 12(8):e0183023.Google Scholar
Inamura, K 2018. Update on immunohistochemistry for the diagnosis of lung cancer. Cancers 10(3):72.Google Scholar
Kim, CH, Kim, SH, Park, SY, Yoo, J, Kim, SK, Kim, HK 2015. Identification of EGFR mutations by immunohistochemistry with EGFR mutation-specific antibodies in biopsy and resection specimens from pulmonary adenocarcinoma. Cancer Res Treat 47(4):653–60.Google Scholar
Kim, RH, Meehan, SA 2017. Immunostain use in the diagnosis of melanomas referred to a tertiary medical center: A 15‐year retrospective review (2001–2015). J Cutan Pathol 44: 221–7.Google Scholar
Koppel, C, Schwellenbach, H, Zielinski, D, Eckstein, S, Martin-Ortega, M, D’Arrigo, C, Schildhaus, HU, Rüschoff, J, Jasani, B 2018. Optimization and validation of PD-L1 immunohistochemistry staining protocols using the antibody clone 28–8 on different staining platforms. Mod Pathol 31(11):1630–44.Google Scholar
Koulis, C, Yap, R, Engel, R, Jardé, T, Wilkins, S, Solon, G, Shapiro, JD, Abud, H, McMurrick, P 2020. Personalized medicine: Current and emerging predictive and prognostic biomarkers in colorectal cancer. Cancers (Basel) 12(4):812.Google Scholar
Kővári, B, Turkevi-Nagy, S, Báthori, Á, Fekete, Z, Krenács, L 2020. Syntaxin 1: A novel robust immunophenotypic marker of neuroendocrine tumors. Int J Mol Sci 21(4):1213.Google Scholar
Lee, SJ, Jun, SY, Lee, IH, Kang, BW, Park, SY, Kim, HJ, Park, JS, Choi, GS, Yoon, G, Kim, JG 2018. CD274, LAG3, andIDO1 expressions in tumor-infiltrating immune cells as prognostic biomarker for patients with MSI-high colon cancer. J Cancer Res Clin Oncol 144(6):1005–14.Google Scholar
Leica 2019. Refine detection kit Cat#DS9800 Instructions for use. Leica Biosystems Newcastle Ltd.Google Scholar
Lezcano, C, Jungbluth, AA, Nehal, KS, Hollmann, TJ, Busam, KJ 2018. PRAME expression in melanocytic tumors. Am J Surg Pathol 42(11):1456–65.Google Scholar
Lynch, HT, Smyrk, T, Lynch, JF 1998. Molecular genetics and clinical-pathology features of hereditary nonpolyposis colorectal carcinoma (Lynch syndrome): Historical journey from pedigree anecdote to molecular genetic confirmation. Oncology 55(2):103–8.Google Scholar
Lynch, TJ, Bell, DW, Sordella, R, Gurubhagavatula, S, Okimoto, RA, Brannigan, BW, Harris, PL, Haserlat, SM, Supko, JG, Haluska, FG, Louis, DN, Christiani, DC, Settleman, J, Haber, DA 2004. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350(21):2129–39.CrossRefGoogle ScholarPubMed
Mies, C 2016. Breast cancer. In: Leonard, DGB, ed. Molecular pathology in clinical practice. Springer; 433–46.Google Scholar
Moelans, CB, Kibbelaar, RE, Van den Heuvel, MC, Castigliego, D, De Weger, RA, Van Diest, PJ 2010. Validation of a fully automated HER2 staining kit in breast cancer. Cell Oncol 32(1–2):149–55.Google Scholar
Moll, R, Franke, WW, Schiller, DL, Geiger, B, Krepler, R 1982. The catalog of human cytokeratins: Patterns of expression in normal epithelia, tumors and cultured cells. Cell 31(1):11–24.Google Scholar
National Breast and Ovarian Cancer Centre and Australian Cancer Network 2008. The pathology reporting of breast cancer. A guide for pathologists, surgeons, radiologists and oncologists (3rd edition). National Breast and Ovarian Cancer Centre.Google Scholar
Nguyen, T 2011. Oracle HER2 Bond immunohistochemistry system validation. Journal of Histotechnology 34(2):79–87.Google Scholar
Nielsen, PS, Riber-Hansen, R, Jensen, TO, Schmidt, H, Steiniche, T 2013. Proliferation indices of phosphohistoneH3 and Ki67: Strong prognostic markers in a consecutive cohort with stage I/II melanoma. Mod Pathol 26(3):404–13.Google Scholar
NordiQC, 2020. Assessment run B29. NordiQC (online). Available at www.nordiqc.org/downloads/assessments/132_2.pdf (Accessed 1 July 2021).Google Scholar
Ordonez, NG 2003. The immunohistochemical diagnosis of mesothelioma: A comparative study of epithelioid mesothelioma and lung adenocarcinoma. Am J Surg Pathol 27(8):1031–51.Google Scholar
Paez, JG, Jänne, PA, Lee, JC, Tracy, S, Greulich, H, Gabriel, S, Herman, P, Kaye, FJ, Lindeman, N, Boggon, TJ, Naoki, K, Sasaki, H, Fujii, Y, Eck, MJ, Sellers, WR, Johnson, BE, Meyerson, M 2004. EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science 304(5676):1497–500.CrossRefGoogle ScholarPubMed
Parra, ER, Villalobos, P, Mino, B, Rodriguez-Canales, J 2018. Comparison of different antibody clones for immunohistochemistry detection of programmed cell death ligand 1 (PD-L1) on non-small cell lung carcinoma. Appl Immunohistochem Mol Morphol 26(2):83–93.Google Scholar
Ruszkiewicz, A, Bennett, G, Moore, J, Manavis, J, Rudzki, B, Shen, L, Suthers, G 2002. Correlation of mismatch repair genes immunohistochemistry and microsatellite instability status in HNPCC-associated tumours. Pathology 34(6):541–7.CrossRefGoogle ScholarPubMed
Roach, C, Zhang, N, Corigliano, E, Jansson, M, Toland, G, Ponto, G, Dolled-Filhart, M, Emancipator, K, Stanforth, D, Kulangara, K 2016. Development of a companion diagnostic PD-L1 immunohistochemistry assay for pembrolizumab therapy in non-small-cell lung cancer. Appl Immunohistochem Mol Morphol. 24(6):392–7.Google Scholar
Rolls, G 2021. Fixation and fixatives (2): Factors influencing chemical fixation, formaldehyde and glutaraldehyde. Leica Biosystems (online). Available at www.leicabiosystems.com/knowledge-pathway/fixation-and-fixatives-2-factors-influencing-chemical-fixation-formaldehyde-and-glutaraldehyde (Accessed 29 July 2021).Google Scholar
Rooper, LM, Sharma, R, Li, QK, Illei, PB, Westra, WH 2017. INSM1 demonstrates superior performance to the individual and combined use of synaptophysin, chromogranin and CD56 for diagnosing neuroendocrine tumors of the thoracic cavity. Am J Surg Pathol 41(11):1561–9.Google Scholar
Schweizer, J, Bowden, PE, Coulombe, PA, Langbein, L, Lane, EB, Magin, TM, Maltais, L, Omary, MB, Parry, DA, Rogers, MA, Wright, MW 2006. New consensus nomenclature for mammalian keratins. J Cell Biol 174(2):169–74.Google Scholar
Scolyer, RA, Long, GV, Thompson, JF 2011. Evolving concepts in melanoma classification and their relevance to multidisciplinary melanoma patient care. Mol Oncol 5(2):124–36.CrossRefGoogle ScholarPubMed
Shia, J 2008. Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome. Part I. The utility of immunohistochemistry. J Mol Diagn 10(4):293–300.Google Scholar
Silva, AP, Coelho, PV, Anazetti, M, Simioni, PU 2017. Targeted therapies for the treatment of non-small-cell lung cancer: Monoclonal antibodies and biological inhibitors. Hum Vaccin Immunother 13(4):843–53.Google Scholar
Soda, M, Lim Choi, Y, Enomoto, M, Takada, S, Yamashita, Y, Ishikawa, S, Fujiwara, SI, Watanabe, H, Kurashina, K, Hatanaka, H, Bando, M, Ohno, S, Ishikawa, Y, Aburatani, H, Niki, T, Sohara, Y, Sugiyama, Y, Mano, H 2007. Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer. Nature 448 (7153):561–6.Google Scholar
Takeuchi, K, Choi, YL, Togashi, Y, Soda, M, Hatano, S, Inamura, K, Takada, S, Ueno, T, Yamashita, Y, Satoh, Y, Okumura, S, Nakagawa, K, Ishikawa, Y, Mano, H 2009. KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based diagnostic system for ALK-positive lung cancer. Clin Cancer Res 15(9):3143–9.Google Scholar
Terata, K, Saito, H, Nanjo, H, Hiroshima, Y, Ito, S, Narita, K, Akagami, Y, Nakamura, R, Konno, H, Ito, A, Motoyama, S, Minamiya, Y 2017. Novel rapid-immunohistochemistry using an alternating current electric field for intraoperative diagnosis of sentinel lymph nodes in breast cancer. Sci Rep 7:2810.CrossRefGoogle ScholarPubMed
Van der Loos, CM 1999. Immunoenzyme multiple staining methods. First edition. Garland Science.Google Scholar
Vartanian, RK, Leung, JK, Davis, JE, Kim, YB, Owen, DA 1998. A novel Alcian yellow-toluidine blue (Leung) stain for Helicobacter species: Comparison with standard stains, a cost-effectiveness analysis, and supplemental utilities. Mod Pathol 11(1):72–8.Google Scholar
Wolff, AC, Hammond, MEH, Allison, KH, Harvey, BE, Mangu, PB, Bartlett, JMS, Bilous, M, Ellis, IO, Fitzgibbons, P, Hanna, W, Jenkins, RB, Press, MF, Spears, PA, Vance, GH, Viale, G, McShane, LM, Dowsett, M 2018. Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol 36(20):2105–22.Google Scholar
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 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(1):118–45.Google Scholar
Yatabe, Y, Dacic, S, Borczuk, AC, Warth, A, Russell, PA, Lantuejoul, S, Beasley, MB, Thunnissen, E, Pelosi, G, Rekhtman, N, Bubendorf, L, Mino-Kenudson, M, Yoshida, A, Geisinger, KR, Noguchi, M, Chirieac, LR, Bolting, J, Chung, JH, Chou, TY, Chen, G, Poleri, C, Lopez-Rios, F, Papotti, M, Sholl, LM, Roden, AC, Travis, WD, Hirsch, FR, Kerr, KM, Tsao, MS, Nicholson, AG, Wistuba, I, Moreira, AL 2019. Best practices recommendations for diagnostic immunohistochemistry in lung cancer. J Thorac Onco 14(3):377–407.Google Scholar
Yu, J, Kane, S, Wu, J, Benedettini, E, Li, D, Reeves, C, Innocenti, G, Wetzel, R, Crosby, K, Becker, A, Ferrante, M, Cheung, WC, Hong, X, Chirieac, LR, Sholl, LM, Haack, H, Smith, BL, Polakiewicz, RD, Tan, Y, Gu, TL, Loda, M, Zhou, X, Comb, MJ 2009. Mutation-specific antibodies for the detection of EGFR mutations in non-small-cell lung cancer. Clin Cancer Res 15(9):3023–8.Google Scholar
Zhuo, M, Zheng, Q, Zhao, J, Wu, M, An, T, Wang, Y, Li, J, Wang, S, Zhong, J, Yang, X, Chen, H, Jia, B, Dong, Z, Gao, E, Wang, J, Wang, Z 2017. Survival difference between EGFR Del19 and L858 R mutant advanced non-small cell lung cancer patients receiving gefitinib: A propensity score matching analysis. Chin J Cancer Res 29(6):553–60.Google Scholar

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