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Scoring Systems for Immunohistochemistry in Urothelial Carcinoma

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Urothelial Carcinoma

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2684))

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Abstract

Immunohistochemistry is widely used in diagnostic and scientific analysis of urothelial carcinoma. Objective interpretation of staining results is mandatory for accuracy and comparability in diagnostic and therapeutic patient care as well as research.

Herein we summarize and explain standardized microscopic evaluation and scoring approaches for immunohistochemical stainings. We focus on commonly used and generally feasible approaches for different cellular compartments and comment on their utility in diagnostics and research practice.

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References

  1. Magaki S, Hojat SA, Wei B et al (2019) An introduction to the performance of immunohistochemistry. Methods Mol Biol 1897:289–298. https://doi.org/10.1007/978-1-4939-8935-5_25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Sukswai N, Khoury JD (2019) Immunohistochemistry innovations for diagnosis and tissue-based biomarker detection. Curr Hematol Malig Rep 14(5):368–375. https://doi.org/10.1007/s11899-019-00533-9

    Article  PubMed  Google Scholar 

  3. Amin MB, Trpkov K, Lopez-Beltran A et al (2014) Best practices recommendations in the application of immunohistochemistry in the bladder lesions: report from the International Society of Urologic Pathology consensus conference. Am J Surg Pathol 38(8):e20–e34. https://doi.org/10.1097/PAS.0000000000000240

    Article  PubMed  Google Scholar 

  4. Bellizzi AM (2020) An algorithmic immunohistochemical approach to define tumor type and assign site of origin. Adv Anat Pathol 27(3):114–163. https://doi.org/10.1097/PAP.0000000000000256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Lopez-Beltran A, Marques RC, Montironi R et al (2015) Dysplasia and carcinoma in situ of the urinary bladder. Anal Quant Cytopathol Histpathol 37(1):29–38

    PubMed  Google Scholar 

  6. McKenney JK (2021) Urothelial carcinoma in situ: diagnostic update. Pathology 53(1):86–95. https://doi.org/10.1016/j.pathol.2020.10.001

    Article  PubMed  Google Scholar 

  7. Eckstein M, Cimadamore A, Hartmann A et al (2019) PD-L1 assessment in urothelial carcinoma: a practical approach. Ann Transl Med 7(22):690. https://doi.org/10.21037/atm.2019.10.24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Paver EC, Cooper WA, Colebatch AJ et al (2021) Programmed death ligand-1 (PD-L1) as a predictive marker for immunotherapy in solid tumours: a guide to immunohistochemistry implementation and interpretation. Pathology 53(2):141–156. https://doi.org/10.1016/j.pathol.2020.10.007

    Article  CAS  PubMed  Google Scholar 

  9. Wucherpfennig S, Rose M, Maurer A et al (2021) Evaluation of therapeutic targets in histological subtypes of bladder cancer. Int J Mol Sci 22(21). https://doi.org/10.3390/ijms222111547

  10. Lotan Y, Bagrodia A, Passoni N et al (2013) Prospective evaluation of a molecular marker panel for prediction of recurrence and cancer-specific survival after radical cystectomy. Eur Urol 64(3):465–471. https://doi.org/10.1016/j.eururo.2013.03.043

    Article  CAS  PubMed  Google Scholar 

  11. Calandrella ML, Francesconi S, Caprera C et al (2022) Nectin-4 and DNA mismatch repair proteins expression in upper urinary tract urothelial carcinoma (UTUC) as a model for tumor targeting approaches: an ImGO pilot study. BMC Cancer 22(1):168. https://doi.org/10.1186/s12885-022-09259-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Rizzardi AE, Johnson AT, Vogel RI et al (2012) Quantitative comparison of immunohistochemical staining measured by digital image analysis versus pathologist visual scoring. Diagn Pathol 7:42. https://doi.org/10.1186/1746-1596-7-42

    Article  PubMed  PubMed Central  Google Scholar 

  13. Taylor CR, Levenson RM (2006) Quantification of immunohistochemistry--issues concerning methods, utility and semiquantitative assessment II. Histopathology 49(4):411–424. https://doi.org/10.1111/j.1365-2559.2006.02513.x

    Article  CAS  PubMed  Google Scholar 

  14. Simon R, Sauter G (2002) Tissue microarrays for miniaturized high-throughput molecular profiling of tumors. Exp Hematol 30(12):1365–1372. https://doi.org/10.1016/s0301-472x(02)00965-7

    Article  CAS  PubMed  Google Scholar 

  15. Walker RA (2006) Quantification of immunohistochemistry--issues concerning methods, utility and semiquantitative assessment I. Histopathology 49(4):406–410. https://doi.org/10.1111/j.1365-2559.2006.02514.x

    Article  CAS  PubMed  Google Scholar 

  16. Meyerholz DK, Beck AP (2018) Principles and approaches for reproducible scoring of tissue stains in research. Lab Investig 98(7):844–855. https://doi.org/10.1038/s41374-018-0057-0

    Article  PubMed  Google Scholar 

  17. Hamilton PW, Bankhead P, Wang Y et al (2014) Digital pathology and image analysis in tissue biomarker research. Methods 70(1):59–73. https://doi.org/10.1016/j.ymeth.2014.06.015

    Article  CAS  PubMed  Google Scholar 

  18. Rakha EA, Vougas K, Tan PH (2021) Digital Technology in Diagnostic Breast Pathology and Immunohistochemistry. Pathobiology 89:1–9. https://doi.org/10.1159/000521149

    Article  Google Scholar 

  19. Bencze J, Szarka M, Koti B et al (2021) Comparison of semi-quantitative scoring and artificial intelligence aided digital image analysis of chromogenic immunohistochemistry. Biomolecules 12(1). https://doi.org/10.3390/biom12010019

  20. Rose M, Gaisa NT (2018) Immunohistochemical analysis of urothelial carcinoma tissues for proliferation and differentiation markers. Methods Mol Biol 1655:43–52. https://doi.org/10.1007/978-1-4939-7234-0_4

    Article  CAS  PubMed  Google Scholar 

  21. Kim SW, Roh J, Park CS (2016) Immunohistochemistry for pathologists: protocols, pitfalls, and tips. J Pathol Transl Med 50(6):411–418. https://doi.org/10.4132/jptm.2016.08.08

    Article  PubMed  PubMed Central  Google Scholar 

  22. Helm MF, Lin L (2011) Calculating microscope field area is important for accurately determining melanoma mitotic rate. Dermatol Surg 37(12):1820–1821. https://doi.org/10.1111/j.1524-4725.2011.02196.x

    Article  CAS  PubMed  Google Scholar 

  23. Bagchi S, Yuan R, Engleman EG (2021) Immune checkpoint inhibitors for the treatment of cancer: clinical impact and mechanisms of response and resistance. Annu Rev Pathol 16:223–249. https://doi.org/10.1146/annurev-pathol-042020-042741

    Article  CAS  PubMed  Google Scholar 

  24. Schoenfeld AJ, Hellmann MD (2020) Acquired resistance to immune checkpoint inhibitors. Cancer Cell 37(4):443–455. https://doi.org/10.1016/j.ccell.2020.03.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Bajorin DF, Witjes JA, Gschwend JE et al (2021) Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. N Engl J Med 384(22):2102–2114. https://doi.org/10.1056/NEJMoa2034442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Grivas P, Agarwal N, Pal S et al (2021) Avelumab first-line maintenance in locally advanced or metastatic urothelial carcinoma: applying clinical trial findings to clinical practice. Cancer Treat Rev 97:102187. https://doi.org/10.1016/j.ctrv.2021.102187

    Article  CAS  PubMed  Google Scholar 

  27. Schildhaus HU (2018) [Predictive value of PD-L1 diagnostics]. Pathologe 39(6):498–519. https://doi.org/10.1007/s00292-018-0507-x

  28. Eckstein M, Erben P, Kriegmair MC et al (2019) Performance of the Food and Drug Administration/EMA-approved programmed cell death ligand-1 assays in urothelial carcinoma with emphasis on therapy stratification for first-line use of atezolizumab and pembrolizumab. Eur J Cancer 106:234–243. https://doi.org/10.1016/j.ejca.2018.11.007

    Article  CAS  PubMed  Google Scholar 

  29. Du Z, Lovly CM (2018) Mechanisms of receptor tyrosine kinase activation in cancer. Mol Cancer 17(1):58. https://doi.org/10.1186/s12943-018-0782-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Menard S, Casalini P, Campiglio M et al (2004) Role of HER2/neu in tumor progression and therapy. Cell Mol Life Sci 61(23):2965–2978. https://doi.org/10.1007/s00018-004-4277-7

    Article  CAS  PubMed  Google Scholar 

  31. Raval SH, Singh RD, Joshi DV et al (2016) Recent developments in receptor tyrosine kinases targeted anticancer therapy. Vet World 9(1):80–90. https://doi.org/10.14202/vetworld.2016.80-90

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Turner N, Grose R (2010) Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer 10(2):116–129. https://doi.org/10.1038/nrc2780

    Article  CAS  PubMed  Google Scholar 

  33. Mertens LS, Claps F, Mayr R et al (2022) Prognostic markers in invasive bladder cancer: FGFR3 mutation status versus P53 and KI-67 expression: a multi-center, multi-laboratory analysis in 1058 radical cystectomy patients. Urol Oncol 40(3):110 e111–110 e119. https://doi.org/10.1016/j.urolonc.2021.10.010

    Article  CAS  Google Scholar 

  34. van Rhijn BWG, Mertens LS, Mayr R et al (2020) FGFR3 mutation status and FGFR3 expression in a large bladder cancer cohort treated by radical cystectomy: implications for anti-FGFR3 treatment?(dagger). Eur Urol 78(5):682–687. https://doi.org/10.1016/j.eururo.2020.07.002

    Article  CAS  PubMed  Google Scholar 

  35. Sung JY, Sun JM, Chang Jeong B et al (2014) FGFR3 overexpression is prognostic of adverse outcome for muscle-invasive bladder carcinoma treated with adjuvant chemotherapy. Urol Oncol 32(1):49 e23–49 e31. https://doi.org/10.1016/j.urolonc.2013.07.015

    Article  CAS  PubMed  Google Scholar 

  36. Bednova O, Leyton JV (2020) Targeted molecular therapeutics for bladder cancer-a new option beyond the mixed fortunes of immune checkpoint inhibitors? Int J Mol Sci 21(19). https://doi.org/10.3390/ijms21197268

  37. Tomlinson DC, Baldo O, Harnden P et al (2007) FGFR3 protein expression and its relationship to mutation status and prognostic variables in bladder cancer. J Pathol 213(1):91–98. https://doi.org/10.1002/path.2207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Singh D, Attri BK, Gill RK et al (2016) Review on EGFR inhibitors: critical updates. Mini Rev Med Chem 16(14):1134–1166. https://doi.org/10.2174/1389557516666160321114917

    Article  CAS  PubMed  Google Scholar 

  39. Chong CR, Janne PA (2013) The quest to overcome resistance to EGFR-targeted therapies in cancer. Nat Med 19(11):1389–1400. https://doi.org/10.1038/nm.3388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Rebouissou S, Bernard-Pierrot I, de Reynies A et al (2014) EGFR as a potential therapeutic target for a subset of muscle-invasive bladder cancers presenting a basal-like phenotype. Sci Transl Med 6(244):244ra291. https://doi.org/10.1126/scitranslmed.3008970

    Article  CAS  Google Scholar 

  41. Rose M, Maurer A, Wirtz J et al (2020) EGFR activity addiction facilitates anti-ERBB based combination treatment of squamous bladder cancer. Oncogene 39(44):6856–6870. https://doi.org/10.1038/s41388-020-01465-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Hofman P (2021) EGFR status assessment for better care of early stage non-small cell lung carcinoma: what is changing in the daily practice of pathologists? Cell 10(8). https://doi.org/10.3390/cells10082157

  43. Pirker R (2012) EGFR-directed monoclonal antibodies in non-small cell lung cancer: how to predict efficacy? Transl Lung Cancer Res 1(4):269–275. https://doi.org/10.3978/j.issn.2218-6751.2012.10.09

    Article  PubMed  PubMed Central  Google Scholar 

  44. Shiogama K, Wongsiri T, Mizutani Y et al (2013) High-sensitivity epidermal growth factor receptor immunostaining for colorectal carcinomas, compared with EGFR PharmDx: a study of diagnostic accuracy. Int J Clin Exp Pathol 6(1):24–30

    CAS  PubMed  Google Scholar 

  45. Pirker R, Pereira JR, von Pawel J et al (2012) EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study. Lancet Oncol 13(1):33–42. https://doi.org/10.1016/S1470-2045(11)70318-7

    Article  CAS  PubMed  Google Scholar 

  46. Ross JS, Fletcher JA, Bloom KJ et al (2004) Targeted therapy in breast cancer: the HER-2/neu gene and protein. Mol Cell Proteomics 3(4):379–398. https://doi.org/10.1074/mcp.R400001-MCP200

    Article  CAS  PubMed  Google Scholar 

  47. Liedtke C, Kiesel L (2012) Breast cancer molecular subtypes – modern therapeutic concepts for targeted therapy of a heterogeneous entity. Maturitas 73(4):288–294. https://doi.org/10.1016/j.maturitas.2012.08.006

    Article  CAS  PubMed  Google Scholar 

  48. Nelson E (2014) HER2/neu: an increasingly important therapeutic target. Part 3: clinical applications and investigations. Clin Investig 4:791–823. https://doi.org/10.4155/cli.14.63

    Article  CAS  Google Scholar 

  49. Mollica V, Rizzo A, Montironi R et al (2020) Current strategies and novel therapeutic approaches for metastatic urothelial carcinoma. Cancers (Basel) 12(6). https://doi.org/10.3390/cancers12061449

  50. Patelli G, Zeppellini A, Spina F et al (2022) The evolving panorama of HER2-targeted treatments in metastatic urothelial cancer: a systematic review and future perspectives. Cancer Treat Rev 104:102351. https://doi.org/10.1016/j.ctrv.2022.102351

    Article  CAS  PubMed  Google Scholar 

  51. Mollica V, Maggio I, Lopez-Beltran A et al (2020) Combination therapy in advanced urothelial cancer: the role of PARP, HER-2 and mTOR inhibitors. Expert Rev Anticancer Ther 20(9):755–763. https://doi.org/10.1080/14737140.2020.1807334

    Article  CAS  PubMed  Google Scholar 

  52. Jorgensen JT, Winther H, Askaa J et al (2021) A companion diagnostic with significant clinical impact in treatment of breast and gastric cancer. Front Oncol 11:676939. https://doi.org/10.3389/fonc.2021.676939

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Hofmann M, Stoss O, Shi D et al (2008) Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 52(7):797–805. https://doi.org/10.1111/j.1365-2559.2008.03028.x

    Article  CAS  PubMed  Google Scholar 

  54. Tsuda H, Sasano H, Akiyama F et al (2002) Evaluation of interobserver agreement in scoring immunohistochemical results of HER-2/neu (c-erbB-2) expression detected by HercepTest, Nichirei polyclonal antibody, CB11 and TAB250 in breast carcinoma. Pathol Int 52(2):126–134. https://doi.org/10.1046/j.1440-1827.2002.01327.x

    Article  CAS  PubMed  Google Scholar 

  55. Nadal R, Bellmunt J (2019) Management of metastatic bladder cancer. Cancer Treat Rev 76:10–21. https://doi.org/10.1016/j.ctrv.2019.04.002

    Article  CAS  PubMed  Google Scholar 

  56. Challita-Eid PM, Satpayev D, Yang P et al (2016) Enfortumab vedotin antibody-drug conjugate targeting nectin-4 is a highly potent therapeutic agent in multiple preclinical cancer models. Cancer Res 76(10):3003–3013. https://doi.org/10.1158/0008-5472.CAN-15-1313

    Article  CAS  PubMed  Google Scholar 

  57. Coleman JF, Hansel DE (2009) Utility of diagnostic and prognostic markers in urothelial carcinoma of the bladder. Adv Anat Pathol 16(2):67–78. https://doi.org/10.1097/PAP.0b013e318199f89e

    Article  CAS  PubMed  Google Scholar 

  58. Desai S, Lim SD, Jimenez RE et al (2000) Relationship of cytokeratin 20 and CD44 protein expression with WHO/ISUP grade in pTa and pT1 papillary urothelial neoplasia. Mod Pathol 13(12):1315–1323. https://doi.org/10.1038/modpathol.3880241

    Article  CAS  PubMed  Google Scholar 

  59. McKenney JK, Desai S, Cohen C et al (2001) Discriminatory immunohistochemical staining of urothelial carcinoma in situ and non-neoplastic urothelium: an analysis of cytokeratin 20, p53, and CD44 antigens. Am J Surg Pathol 25(8):1074–1078. https://doi.org/10.1097/00000478-200108000-00013

    Article  CAS  PubMed  Google Scholar 

  60. Kaufmann O, Volmerig J, Dietel M (2000) Uroplakin III is a highly specific and moderately sensitive immunohistochemical marker for primary and metastatic urothelial carcinomas. Am J Clin Pathol 113(5):683–687. https://doi.org/10.1309/PYQC-17CB-063T-Q07J

    Article  CAS  PubMed  Google Scholar 

  61. Hoang LL, Tacha DE, Qi W et al (2014) A newly developed uroplakin II antibody with increased sensitivity in urothelial carcinoma of the bladder. Arch Pathol Lab Med 138(7):943–949. https://doi.org/10.5858/arpa.2013-0221-OA

    Article  CAS  PubMed  Google Scholar 

  62. Moll R, Wu XR, Lin JH et al (1995) Uroplakins, specific membrane proteins of urothelial umbrella cells, as histological markers of metastatic transitional cell carcinomas. Am J Pathol 147(5):1383–1397

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Li W, Liang Y, Deavers MT et al (2014) Uroplakin II is a more sensitive immunohistochemical marker than uroplakin III in urothelial carcinoma and its variants. Am J Clin Pathol 142(6):864–871. https://doi.org/10.1309/AJCP1J0JPJBPSUXF

    Article  PubMed  Google Scholar 

  64. Schweizer J, Bowden PE, Coulombe PA et al (2006) New consensus nomenclature for mammalian keratins. J Cell Biol 174(2):169–174. https://doi.org/10.1083/jcb.200603161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Moll R, Divo M, Langbein L (2008) The human keratins: biology and pathology. Histochem Cell Biol 129(6):705–733. https://doi.org/10.1007/s00418-008-0435-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Gulmann C, Paner GP, Parakh RS et al (2013) Immunohistochemical profile to distinguish urothelial from squamous differentiation in carcinomas of urothelial tract. Hum Pathol 44(2):164–172. https://doi.org/10.1016/j.humpath.2012.05.018

    Article  CAS  PubMed  Google Scholar 

  67. Zupancic D, Romih R (2021) Immunohistochemistry as a paramount tool in research of normal urothelium, bladder cancer and bladder pain syndrome. Eur J Histochem 65(2). https://doi.org/10.4081/ejh.2021.3242

  68. Edgecombe A, Nguyen BN, Djordjevic B et al (2012) Utility of cytokeratin 5/6, cytokeratin 20, and p16 in the diagnosis of reactive urothelial atypia and noninvasive component of urothelial neoplasia. Appl Immunohistochem Mol Morphol 20(3):264–271. https://doi.org/10.1097/PAI.0b013e3182351ed3

    Article  CAS  PubMed  Google Scholar 

  69. Alston ELJ, Zynger DL (2019) Does the addition of AMACR to CK20 help to diagnose challenging cases of urothelial carcinoma in situ? Diagn Pathol 14(1):91. https://doi.org/10.1186/s13000-019-0871-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Bassily NH, Vallorosi CJ, Akdas G et al (2000) Coordinate expression of cytokeratins 7 and 20 in prostate adenocarcinoma and bladder urothelial carcinoma. Am J Clin Pathol 113(3):383–388. https://doi.org/10.1309/G1RA-EU9X-X6VV-3W79

    Article  CAS  PubMed  Google Scholar 

  71. Otto W, Denzinger S, Fritsche HM et al (2013) Introduction and first clinical application of a simplified immunohistochemical validation system confirms prognostic impact of KI-67 and CK20 for stage T1 urothelial bladder carcinoma: single-center analysis of eight biomarkers in a series of three hundred six patients. Clin Genitourin Cancer 11(4):537–544. https://doi.org/10.1016/j.clgc.2013.05.001

    Article  PubMed  Google Scholar 

  72. Dadhania V, Zhang M, Zhang L et al (2016) Meta-analysis of the luminal and basal subtypes of bladder cancer and the identification of signature immunohistochemical markers for clinical use. EBioMedicine 12:105–117. https://doi.org/10.1016/j.ebiom.2016.08.036

    Article  PubMed  PubMed Central  Google Scholar 

  73. Queipo FJ, Unamunzaga GM, Negro BF et al (2022) Immunohistochemistry subtyping of urothelial carcinoma is feasible in the daily practice. Virchows Arch 481(2):191–200. https://doi.org/10.1007/s00428-022-03361-0

    Article  CAS  PubMed  Google Scholar 

  74. Babu S, Kim NW, Wu M et al (2021) Keratin 17 is a novel cytologic biomarker for urothelial carcinoma diagnosis. Am J Clin Pathol 156(5):926–933. https://doi.org/10.1093/ajcp/aqab050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Aron M, Luthringer DJ, McKenney JK et al (2013) Utility of a triple antibody cocktail intraurothelial neoplasm-3 (IUN-3-CK20/CD44s/p53) and alpha-methylacyl-CoA racemase (AMACR) in the distinction of urothelial carcinoma in situ (CIS) and reactive urothelial atypia. Am J Surg Pathol 37(12):1815–1823. https://doi.org/10.1097/PAS.0000000000000114

    Article  PubMed  Google Scholar 

  76. Park S, Reuter VE, Hansel DE (2019) Non-urothelial carcinomas of the bladder. Histopathology 74(1):97–111. https://doi.org/10.1111/his.13719

    Article  PubMed  Google Scholar 

  77. Wang G, Yuan R, Zhou C et al (2021) Urinary large cell neuroendocrine carcinoma: a Clinicopathologic analysis of 22 cases. Am J Surg Pathol 45(10):1399–1408. https://doi.org/10.1097/PAS.0000000000001740

    Article  PubMed  PubMed Central  Google Scholar 

  78. Urinary and male genital tumours (2022). WHO classification of tumours series, vol 8, 5th edn. International Agency for Research on Cancer, Lyon

    Google Scholar 

  79. Bellizzi AM (2020) Immunohistochemistry in the diagnosis and classification of neuroendocrine neoplasms: what can brown do for you? Hum Pathol 96:8–33. https://doi.org/10.1016/j.humpath.2019.12.002

    Article  PubMed  Google Scholar 

  80. Robinson-Bennett B, Han A (2006) 30 – Role of immunohistochemistry in elucidating lung cancer metastatic to the ovary from primary ovarian carcinoma. In: Hayat MA (ed) Handbook of immunohistochemistry and in situ hybridization of human carcinomas, vol 4. Academic Press, pp 537–545. https://doi.org/10.1016/S1874-5784(05)80116-3

    Chapter  Google Scholar 

  81. Rahmani AH, Babiker AY, AlWanian WM et al (2015) Association of cytokeratin and vimentin protein in the genesis of transitional cell carcinoma of urinary bladder patients. Dis Markers 2015:204759. https://doi.org/10.1155/2015/204759

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Agaimy A, Hartmann A, Trpkov K et al (2021) Undifferentiated and dedifferentiated urological carcinomas: lessons learned from the recent developments. Semin Diagn Pathol 38(6):152–162. https://doi.org/10.1053/j.semdp.2021.09.004

    Article  PubMed  Google Scholar 

  83. Sjodahl G, Jackson CL, Bartlett JM et al (2019) Molecular profiling in muscle-invasive bladder cancer: more than the sum of its parts. J Pathol 247(5):563–573. https://doi.org/10.1002/path.5230

    Article  PubMed  Google Scholar 

  84. Liu CY, Lin HH, Tang MJ et al (2015) Vimentin contributes to epithelial-mesenchymal transition cancer cell mechanics by mediating cytoskeletal organization and focal adhesion maturation. Oncotarget 6(18):15966–15983. https://doi.org/10.18632/oncotarget.3862

    Article  PubMed  PubMed Central  Google Scholar 

  85. Aurilio G, Cimadamore A, Mazzucchelli R et al (2020) Androgen receptor signaling pathway in prostate cancer: from genetics to clinical applications. Cells 9(12). https://doi.org/10.3390/cells9122653

  86. AlFakeeh A, Brezden-Masley C (2018) Overcoming endocrine resistance in hormone receptor-positive breast cancer. Curr Oncol 25(Suppl 1):S18–S27. https://doi.org/10.3747/co.25.3752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Nofech-Mozes S, Vella ET, Dhesy-Thind S et al (2012) Systematic review on hormone receptor testing in breast cancer. Appl Immunohistochem Mol Morphol 20(3):214–263. https://doi.org/10.1097/PAI.0b013e318234aa12

    Article  CAS  PubMed  Google Scholar 

  88. Miyamoto KK, McSherry SA, Dent GA et al (1993) Immunohistochemistry of the androgen receptor in human benign and malignant prostate tissue. J Urol 149(5):1015–1019. https://doi.org/10.1016/s0022-5347(17)36284-5

    Article  CAS  PubMed  Google Scholar 

  89. Mizushima T, Jiang G, Kawahara T et al (2020) Androgen receptor signaling reduces the efficacy of bacillus Calmette-Guerin therapy for bladder cancer via modulating Rab27b-induced exocytosis. Mol Cancer Ther 19(9):1930–1942. https://doi.org/10.1158/1535-7163.MCT-20-0050

    Article  CAS  PubMed  Google Scholar 

  90. Creta M, Celentano G, Napolitano L et al (2021) Inhibition of androgen signalling improves the outcomes of therapies for bladder cancer: results from a systematic review of preclinical and clinical evidence and meta-analysis of clinical studies. Diagnostics (Basel) 11(2). https://doi.org/10.3390/diagnostics11020351

  91. Remmele W, Hildebrand U, Hienz HA et al (1986) Comparative histological, histochemical, immunohistochemical and biochemical studies on oestrogen receptors, lectin receptors, and Barr bodies in human breast cancer. Virchows Arch A Pathol Anat Histopathol 409(2):127–147. https://doi.org/10.1007/BF00708323

    Article  CAS  PubMed  Google Scholar 

  92. Mohsin SK, Weiss H, Havighurst T et al (2004) Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study. Mod Pathol 17(12):1545–1554. https://doi.org/10.1038/modpathol.3800229

    Article  CAS  PubMed  Google Scholar 

  93. Harvey JM, Clark GM, Osborne CK 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(5):1474–1481. https://doi.org/10.1200/JCO.1999.17.5.1474

    Article  CAS  PubMed  Google Scholar 

  94. Allred DC, Harvey JM, Berardo M et al (1998) Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 11(2):155–168

    CAS  PubMed  Google Scholar 

  95. Svrcek M, Lascols O, Cohen R et al (2019) MSI/MMR-deficient tumor diagnosis: which standard for screening and for diagnosis? Diagnostic modalities for the colon and other sites: differences between tumors. Bull Cancer 106(2):119–128. https://doi.org/10.1016/j.bulcan.2018.12.008

    Article  PubMed  Google Scholar 

  96. Baretti M, Le DT (2018) DNA mismatch repair in cancer. Pharmacol Ther 189:45–62. https://doi.org/10.1016/j.pharmthera.2018.04.004

    Article  CAS  PubMed  Google Scholar 

  97. Marcus L, Lemery SJ, Keegan P et al (2019) FDA approval summary: pembrolizumab for the treatment of microsatellite instability-high solid tumors. Clin Cancer Res 25(13):3753–3758. https://doi.org/10.1158/1078-0432.CCR-18-4070

    Article  CAS  PubMed  Google Scholar 

  98. Roupret M, Yates DR, Comperat E et al (2008) Upper urinary tract urothelial cell carcinomas and other urological malignancies involved in the hereditary nonpolyposis colorectal cancer (Lynch syndrome) tumor spectrum. Eur Urol 54(6):1226–1236. https://doi.org/10.1016/j.eururo.2008.08.008

    Article  PubMed  Google Scholar 

  99. Catto JW, Xinarianos G, Burton JL et al (2003) Differential expression of hMLH1 and hMSH2 is related to bladder cancer grade, stage and prognosis but not microsatellite instability. Int J Cancer 105(4):484–490. https://doi.org/10.1002/ijc.11109

    Article  CAS  PubMed  Google Scholar 

  100. Evrard C, Tachon G, Randrian V et al (2019) Microsatellite instability: diagnosis, heterogeneity, discordance, and clinical impact in colorectal cancer. Cancers (Basel) 11(10). https://doi.org/10.3390/cancers11101567

  101. Pai RK, Pai RK (2016) A practical approach to the evaluation of gastrointestinal tract carcinomas for lynch syndrome. Am J Surg Pathol 40(4):e17–e34. https://doi.org/10.1097/PAS.0000000000000620

    Article  PubMed  Google Scholar 

  102. Chen W, Frankel WL (2019) A practical guide to biomarkers for the evaluation of colorectal cancer. Mod Pathol 32(Suppl 1):1–15. https://doi.org/10.1038/s41379-018-0136-1

    Article  CAS  PubMed  Google Scholar 

  103. Sarode VR, Robinson L (2019) Screening for lynch syndrome by immunohistochemistry of mismatch repair proteins: significance of indeterminate result and correlation with mutational studies. Arch Pathol Lab Med 143(10):1225–1233. https://doi.org/10.5858/arpa.2018-0201-OA

    Article  CAS  PubMed  Google Scholar 

  104. Olave MC, Graham RP (2022) Mismatch repair deficiency: the what, how and why it is important. Genes Chromosomes Cancer 61(6):314–321. https://doi.org/10.1002/gcc.23015

    Article  CAS  PubMed  Google Scholar 

  105. Bateman AC (2021) DNA mismatch repair protein immunohistochemistry – an illustrated guide. Histopathology 79(2):128–138. https://doi.org/10.1111/his.14367

    Article  PubMed  Google Scholar 

  106. Overbeek LI, Ligtenberg MJ, Willems RW et al (2008) Interpretation of immunohistochemistry for mismatch repair proteins is only reliable in a specialized setting. Am J Surg Pathol 32(8):1246–1251. https://doi.org/10.1097/pas.0b013e31816401bb

    Article  PubMed  Google Scholar 

  107. Markow M, Chen W, Frankel WL (2017) Immunohistochemical pitfalls: common mistakes in the evaluation of lynch syndrome. Surg Pathol Clin 10(4):977–1007. https://doi.org/10.1016/j.path.2017.07.012

    Article  PubMed  Google Scholar 

  108. Zhang C, Liu J, Xu D et al (2020) Gain-of-function mutant p53 in cancer progression and therapy. J Mol Cell Biol 12(9):674–687. https://doi.org/10.1093/jmcb/mjaa040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Hodgson A, Xu B, Downes MR (2017) p53 immunohistochemistry in high-grade urothelial carcinoma of the bladder is prognostically significant. Histopathology 71(2):296–304. https://doi.org/10.1111/his.13225

    Article  PubMed  Google Scholar 

  110. Rindi G, Mete O, Uccella S et al (2022) Overview of the 2022 WHO classification of neuroendocrine neoplasms. Endocr Pathol 33(1):115–154. https://doi.org/10.1007/s12022-022-09708-2

    Article  CAS  PubMed  Google Scholar 

  111. Yemelyanova A, Vang R, Kshirsagar M et al (2011) Immunohistochemical staining patterns of p53 can serve as a surrogate marker for TP53 mutations in ovarian carcinoma: an immunohistochemical and nucleotide sequencing analysis. Mod Pathol 24(9):1248–1253. https://doi.org/10.1038/modpathol.2011.85

    Article  CAS  PubMed  Google Scholar 

  112. Kobel M, Ronnett BM, Singh N et al (2019) Interpretation of P53 immunohistochemistry in endometrial carcinomas: toward increased reproducibility. Int J Gynecol Pathol 38(Suppl 1):S123–S131. https://doi.org/10.1097/PGP.0000000000000488

    Article  CAS  PubMed  Google Scholar 

  113. Hodgson A, van Rhijn BWG, Kim SS et al (2020) Reassessment of p53 immunohistochemistry thresholds in invasive high grade bladder cancer shows a better correlation with TP53 and FGFR3 mutations. Pathol Res Pract 216(11):153186. https://doi.org/10.1016/j.prp.2020.153186

    Article  CAS  PubMed  Google Scholar 

  114. Bertz S, Otto W, Denzinger S et al (2014) Combination of CK20 and Ki-67 immunostaining analysis predicts recurrence, progression, and cancer-specific survival in pT1 urothelial bladder cancer. Eur Urol 65(1):218–226. https://doi.org/10.1016/j.eururo.2012.05.033

    Article  CAS  PubMed  Google Scholar 

  115. Scholzen T, Gerdes J (2000) The Ki-67 protein: from the known and the unknown. J Cell Physiol 182(3):311–322. https://doi.org/10.1002/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9

    Article  CAS  PubMed  Google Scholar 

  116. Wang L, Zhou M, Feng C et al (2016) Prognostic value of Ki67 and p63 expressions in bladder cancer patients who underwent radical cystectomy. Int Urol Nephrol 48(4):495–501. https://doi.org/10.1007/s11255-015-1197-4

    Article  CAS  PubMed  Google Scholar 

  117. Shui R, Yu B, Bi R et al (2015) An interobserver reproducibility analysis of Ki67 visual assessment in breast cancer. PLoS One 10(5):e0125131. https://doi.org/10.1371/journal.pone.0125131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Nielsen TO, Leung SCY, Rimm DL et al (2021) Assessment of Ki67 in breast cancer: updated recommendations from the international Ki67 in Breast Cancer Working Group. J Natl Cancer Inst 113(7):808–819. https://doi.org/10.1093/jnci/djaa201

    Article  CAS  PubMed  Google Scholar 

  119. Joulin V, Bories D, Eleouet JF et al (1991) A T-cell specific TCR delta DNA binding protein is a member of the human GATA family. EMBO J 10(7):1809–1816. https://doi.org/10.1002/j.1460-2075.1991.tb07706.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Ordonez NG (2013) Value of GATA3 immunostaining in tumor diagnosis: a review. Adv Anat Pathol 20(5):352–360. https://doi.org/10.1097/PAP.0b013e3182a28a68

    Article  CAS  PubMed  Google Scholar 

  121. Miettinen M, McCue PA, Sarlomo-Rikala M et al (2014) GATA3: a multispecific but potentially useful marker in surgical pathology: a systematic analysis of 2500 epithelial and nonepithelial tumors. Am J Surg Pathol 38(1):13–22. https://doi.org/10.1097/PAS.0b013e3182a0218f

    Article  PubMed  PubMed Central  Google Scholar 

  122. Lerner SP, McConkey DJ, Hoadley KA et al (2016) Bladder cancer molecular taxonomy: summary from a consensus meeting. Bladder Cancer 2(1):37–47. https://doi.org/10.3233/BLC-150037

    Article  PubMed  PubMed Central  Google Scholar 

  123. Budwit-Novotny DA, McCarty KS, Cox EB et al (1986) Immunohistochemical analyses of estrogen receptor in endometrial adenocarcinoma using a monoclonal antibody. Cancer Res 46(10):5419–5425

    CAS  PubMed  Google Scholar 

  124. Flanagan MB, Dabbs DJ, Brufsky AM et al (2008) Histopathologic variables predict Oncotype DX recurrence score. Mod Pathol 21(10):1255–1261. https://doi.org/10.1038/modpathol.2008.54

    Article  CAS  PubMed  Google Scholar 

  125. Tarantino P, Hamilton E, Tolaney SM et al (2020) HER2-low breast cancer: pathological and clinical landscape. J Clin Oncol 38(17):1951–1962. https://doi.org/10.1200/JCO.19.02488

    Article  CAS  PubMed  Google Scholar 

  126. Remmele W, Stegner HE (1987) [Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue]. Pathologe 8(3):138–140

    Google Scholar 

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Authors and Affiliations

  1. Institute of Pathology, RWTH Aachen University, Aachen, Germany

    Mark-Sebastian Bösherz

  2. Department of Pathology, GROW – School for Oncology and Reproduction, Maastricht University, Medical Centre+, Maastricht, The Netherlands

    Iryna V. Samarska

  3. Institute of Pathology, University Hospital, RWTH Aachen University, Aachen, Germany

    Nadine T. Gaisa

  4. German Study Group of Bladder Cancer (DFBK e.V.), Munich, Germany

    Nadine T. Gaisa

Authors
  1. Mark-Sebastian Bösherz
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  2. Iryna V. Samarska
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  3. Nadine T. Gaisa
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Correspondence to Mark-Sebastian Bösherz .

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Editors and Affiliations

  1. Department of Urology, Medical Faculty and University Hospital, Heinrich-Heine-University Duesseldorf, Düsseldorf, Germany

    Michèle J. Hoffmann

  2. Institute of Pathology, University Hospital, RWTH Aachen University, Aachen, Germany

    Nadine T. Gaisa

  3. Department of Urology, University Hospital Rechts der Isar, Technical University Munich, Munich, Germany

    Roman Nawroth

  4. Department of Urology, Helios Hospital, Bad Saarow, Germany

    Thorsten H. Ecke

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Bösherz, MS., Samarska, I.V., Gaisa, N.T. (2023). Scoring Systems for Immunohistochemistry in Urothelial Carcinoma. In: Hoffmann, M.J., Gaisa, N.T., Nawroth, R., Ecke, T.H. (eds) Urothelial Carcinoma. Methods in Molecular Biology, vol 2684. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3291-8_1

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  • DOI: https://doi.org/10.1007/978-1-0716-3291-8_1

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