Immunohistochemistry in the Diagnosis of Primary and Secondary Cancers

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Handbook of Cancer and Immunology

Abstract

In everyday practice, pathologists often have to face the challenging task of labeling primary and secondary malignancies, sometimes on a small amount of cells/tissue, in order to provide diagnostic, prognostic, and predictive information to guide patients’ treatment and follow-up. A correct diagnosis results from collecting, analyzing, and perceiving relevant clinical data along with peculiar morphological features, and in the modern era. Immunohistochemistry (IHC) plays a pivotal role in this process, by assessing the presence or absence of tissue markers in tumor cells at light microscopy, employing the high affinity of a given antibody to its antigen. In this setting, the choice of the most suitable antibodies is meant to confirm or rebut the suspected diagnosis, and must rely on the knowledge of their specific patterns of expression, within a rational algorithm including both first-line and second-line markers. First-line antibodies are used to screen the major tumor categories, and classified accordingly as epithelial, mesenchymal, neuroendocrine, melanocytic, and lymphoid markers. Since no marker is 100% sensitive and specific for a given tumor, current protocols recommend to use panels of selected antibodies. The aim of this chapter is to delineate the most common scenarios in which IHC may be useful, with its inherent advantages and related issues, in order to diagnose primary and secondary cancers.

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References

  • Agaimy A, Specht K, Stoehr R et al (2016) Metastatic malignant melanoma with complete loss of differentiation markers (undifferentiated/dedifferentiated melanoma): analysis of 14 patients emphasizing phenotypic plasticity and the value of molecular testing as surrogate diagnostic marker. Am J Surg Pathol 40:181–191

    Article  PubMed  Google Scholar 

  • Algino KM, Thomason RW, King DE et al (1996) CD20 (pan-B cell antigen) expression on bone marrow derived T cells. Am J Clin Pathol 106:78–81

    Article  CAS  PubMed  Google Scholar 

  • Asa SL, La Rosa S, Mete O (2021) The Spectrum of neuroendocrine neoplasia. A practical approach to diagnosis, classification and therapy. Springer Nature Switzerland AG

    Book  Google Scholar 

  • Asch-Kendrick R, Cimino-Mathews A (2016) The role of GATA3 in breast carcinomas: a review. Hum Pathol 48:37–47

    Article  CAS  PubMed  Google Scholar 

  • Barbareschi M, Roldo C, Zamboni G et al (2004) CDX-2 homeobox gene product expression in neuroendocrine tumors: its role as a marker of intestinal neuroendocrine tumors. Am J Surg Pathol 28:1169–1176

    Article  PubMed  Google Scholar 

  • Beck F, Chawengsaksophak K, Waring P et al (1999) Reprogramming of intestinal differentiation and intercalary regeneration in Cdx2 mutant mice. Proc Natl Acad Sci U S A 96:7318–7323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bejarano PA, Nikiforov YE, Swenson ES et al (2000) Thyroid transcription factor-1, thyroglobulin, cytokeratin 7, and cytokeratin 20 in thyroid neoplasms. Appl Immunohistochem Mol Morphol 8:189–194

    Article  CAS  PubMed  Google Scholar 

  • Bellizzi AM (2013) Assigning site of origin in metastatic neuroendocrine neoplasms: a clinically significant application of diagnostic immunohistochemistry. Adv Anat Pathol 20:285–314

    Article  CAS  PubMed  Google Scholar 

  • Bellizzi AM (2020a) An algorithmic immunohistochemical approach to define tumor type and assign site of origin. Adv Anat Pathol 27:114–163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bellizzi AM (2020b) Immunohistochemistry in the diagnosis and classification of neuroendocrine neoplasms: what can brown do for you? Hum Pathol 96:8–33

    Article  PubMed  Google Scholar 

  • Betts G, Beckett E, Nonaka D (2014) GATA3 shows differential immunohistochemical expression across thyroid and parathyroid lesions. Histopathology 65:288–290

    Article  PubMed  Google Scholar 

  • Bishop JA, Sharma R, Westra WH (2011) PAX8 immunostaining of anaplastic thyroid carcinoma: a reliable means of discerning thyroid origin for undifferentiated tumors of the head and neck. Hum Pathol 42:1873–1877

    Article  CAS  PubMed  Google Scholar 

  • Cheville JC, Rao S, Iczkowski KA et al (2000) Cytokeratin expression in seminoma of the human testis. Am J Clin Pathol 113:583–588

    Article  CAS  PubMed  Google Scholar 

  • Cimino-Mathews A (2021) Novel uses of immunohistochemistry in breast pathology: interpretation and pitfalls. Mod Pathol 34(Suppl 1):62–77

    Article  CAS  PubMed  Google Scholar 

  • Cimino-Mathews A, Subhawong AP, Illei PB et al (2013) GATA3 expression in breast carcinoma: utility in triple-negative, sarcomatoid, and metastatic carcinomas. Hum Pathol 44:1341–1349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Civitareale D, Castelli MP, Falasca P et al (1993) Thyroid transcription factor 1 activates the promoter of the thyrotropin receptor gene. Mol Endocrinol 7:1589–1595

    CAS  PubMed  Google Scholar 

  • Dabbs DJ (2019) Diagnostic immunohistochemistry. In: Theranostic and genomic applications, 5th edn. Elsevier, Philadelphia

    Google Scholar 

  • Donato R, Cannon BR, Sorci G et al (2013) Functions of S100 proteins. Curr Mol Med 13:24–57

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ellis CL, Chang AG, Cimino-Mathews A et al (2013) GATA-3 immunohistochemistry in the differential diagnosis of adenocarcinoma of the urinary bladder. Am J Surg Pathol 37:1756–1760

    Article  PubMed  Google Scholar 

  • Fahrenkamp AG, Wibbeke C, Winde G et al (1995) Immunohistochemical distribution of chromogranins a and B and secretogranin II in neuroendocrine tumours of the gastrointestinal tract. Virchows Arch 426:361–367

    Article  CAS  PubMed  Google Scholar 

  • Fatima N, Osunkoya AO (2014) GATA3 expression in sarcomatoid urothelial carcinoma of the bladder. Hum Pathol 45:1625–1629

    Article  CAS  PubMed  Google Scholar 

  • Feldman AL, Law ME, Inwards DJ et al (2010) PAX5-positive T-cell anaplastic large cell lymphomas associated with extra copies of the PAX5 gene locus. Mod Pathol 23:593–602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferenczi K, Lastra RR, Farkas T et al (2012) MUM-1 expression differentiates tumors in the PEComa family from clear cell sarcoma and melanoma. Int J Surg Pathol 20:29–36

    Article  PubMed  Google Scholar 

  • Fetsch PA, Marincola FM, Abati A (1999) The new melanoma markers: MART-1 and Melan-A (the NIH experience). Am J Surg Pathol 23:607–610

    Article  CAS  PubMed  Google Scholar 

  • Foucar E (2001) Diagnostic decision-making in anatomic pathology. Am J Clin Pathol 116(Suppl):S21–S33

    PubMed  Google Scholar 

  • Fratoni S, Zanelli M, Zizzo M et al (2020) The broad landscape of follicular lymphoma: part I. Pathologica 112:1–16

    PubMed  PubMed Central  Google Scholar 

  • Herrera GA, Turbat-Herrera EA, Lott RL (1988) S-100 protein expression by primary and metastatic adenocarcinomas. Am J Clin Pathol 89:168–176

    Article  CAS  PubMed  Google Scholar 

  • Hinoi T, Tani M, Lucas PC et al (2001) Loss of CDX2 expression and microsatellite instability are prominent features of large cell minimally differentiated carcinomas of the colon. Am J Pathol 159:2239–2248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Judkins AR, Montone KT, LiVolsi VA et al (1998) Sensitivity and specificity of antibodies on necrotic tumor tissue. Am J Clin Pathol 110:641–646

    Article  CAS  PubMed  Google Scholar 

  • Jungbluth A, Frosina D, Fayad M et al (2018) Cancer testis antigen PRAME is abundantly expressed in metastatic melanoma and other malignancies. Mod Pathol 98:695–711

    Google Scholar 

  • Kandalaft PL, Simon RA, Isacson C et al (2016) Comparative sensitivities and specificities of antibodies to breast markers GCDFP-15, mammaglobin a, and different clones of antibodies to GATA-3: a study of 338 tumors using whole sections. Appl Immunohistochem Mol Morphol 24:609–614

    Article  CAS  PubMed  Google Scholar 

  • Kang Y, Pekmezci M, Flope AL et al (2014) Diagnostic utility of SOX10 to distinguish malignant peripheral nerve sheath tumor from synovial sarcoma, including intraneural synovial sarcoma. Mod Pathol 27:55–61

    Article  CAS  PubMed  Google Scholar 

  • Kei S, Adeyi OA (2020) Practical application of lineage-specific immunohistochemistry markers: transcription factors (sometimes) behaving badly. Arch Pathol Lab Med 144:626–643

    Article  PubMed  Google Scholar 

  • Klimstra DS, Klöppel G, La Rosa S et al (2019) Classification of neuroendocrine neoplasms of the digestive system. In: WHO Classification of Tumours Editorial Board (ed) Digestive system tumours. WHO classification of tumours series, vol vol. 1, 5th edn. International Agency for Research on Cancer, Lyon

    Google Scholar 

  • Kriegsmann M, Kriegsmann K, Harms A et al (2018) Expression of HMB45, MelanA and SOX10 is rare in non-small cell lung cancer. Diagn Pathol 13:68

    Article  PubMed Central  Google Scholar 

  • Latchman DS (1997) Transcription factors: an overview. Int J Biochem Cell Biol 29:1305–1312

    Article  CAS  PubMed  Google Scholar 

  • Laury AR, Perets R, Piao H et al (2011) A comprehensive analysis of PAX8 expression in human epithelial tumors. Am J Surg Pathol 35:816–826

    Article  PubMed  Google Scholar 

  • Levy C, Khaled M, Fisher DE (2006) MITF: master regulator of melanocyte development and melanoma oncogene. Trends Mol Med 12:406–414

    Article  CAS  PubMed  Google Scholar 

  • Lezcano C, Jungbluth AA, Nehal KS et al (2018) PRAME expression in melanocytic tumors. Am J Surg Pathol 42:1456–1465

    Article  PubMed  PubMed Central  Google Scholar 

  • Lezcano C, Pulitzer M, Moy AP et al (2020) Immunohistochemistry for PRAME in the distinction of nodal nevi from metastatic melanoma. Am J Surg Pathol 44:503–508

    Article  PubMed  PubMed Central  Google Scholar 

  • Lin F, Liu H (2014) Immunohistochemistry in undifferentiated neoplasm/tumor of uncertain origin. Arch Pathol Lab Med 138:1583–1610

    Article  PubMed  Google Scholar 

  • Lloyd RV, Osamura RY, Klöppel G et al (2017) WHO classification of tumours of endocrine organs. International Agency for Research on Cancer, Lyon

    Google Scholar 

  • Long KB, Srivastava A, Hirsch MS et al (2010) PAX8 expression in well-differentiated pancreatic endocrine tumors: correlation with clinicopathologic features and comparison with gastrointestinal and pulmonary carcinoid tumors. Am J Surg Pathol 34:723–729

    Article  PubMed  Google Scholar 

  • Mariño-Enríquez A, Wang WL, Roy A et al (2011) Epithelioid inflammatory myofibroblastic sarcoma: an aggressive intra-abdominal variant of inflammatory myofibroblastic tumor with nuclear membrane or perinuclear ALK. Am J Surg Pathol 35:135–144

    Article  PubMed  Google Scholar 

  • Miettinen M, Cupo W (1993) Neural cell adhesion molecule distribution in soft tissue tumors. Hum Pathol 24:62–66

    Article  CAS  PubMed  Google Scholar 

  • 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 38:13–22

    Article  PubMed  PubMed Central  Google Scholar 

  • Miettinen M, McCue PA, Sarlomo-Rikala M et al (2015) Sox10–a marker for not only schwannian and melanocytic neoplasms but also myoepithelial cell tumors of soft tissue: a systematic analysis of 5134 tumors. Am J Surg Pathol 39:826–835

    Article  PubMed  PubMed Central  Google Scholar 

  • Mohanty SK, Sharma S, Pradhan D et al (2018) Microphthalmia-associated transcription factor (MiTF): promiscuous staining patterns in fibrohistiocytic lesions is a potential pitfall. Pathol Res Pract 214:821–825

    Article  CAS  PubMed  Google Scholar 

  • Moll R, Franke WW, Schiller DL et al (1982) The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell 31:11–24

    Article  CAS  PubMed  Google Scholar 

  • Moll R, Divo M, Langbein L (2008) The human keratins: biology and pathology. Histochem Cell Biol 129:705–733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morgenstern DA, Gibson S, Sebire NJ et al (2009) PAX5 expression in rhabdomyosarcoma. Am J Surg Pathol 33:1575–1577

    Article  PubMed  Google Scholar 

  • Moskaluk CA, Zhang H, Powell SM et al (2003) Cdx2 protein expression in normal and malignant human tissues: an immunohistochemical survey using tissue microarrays. Mod Pathol 16:913–919

    Article  PubMed  Google Scholar 

  • Nonaka D, Tang Y, Chiriboga L et al (2008) Diagnostic utility of thyroid transcription factors Pax8 and TTF-2 (FoxE1) in thyroid epithelial neoplasms. Mod Pathol 21:192–200

    Article  CAS  PubMed  Google Scholar 

  • O’Connell FP, Pinkus JL, Pinkus GS (2004) CD138 (syndecan-1), a plasma cell marker immunohistochemical profile in hematopoietic and nonhematopoietic neoplasms. Am J Clin Pathol 121:254–263

    Article  PubMed  Google Scholar 

  • O’Malley DP, Dogan A, Fedoriw Y et al (2019) American registry of pathology expert opinions: immunohistochemical evaluation of classic Hodgkin lymphoma. Ann Diagn Pathol 39:105–110

    Article  PubMed  Google Scholar 

  • Ordonez NG (2012a) Value of thyroid transcription factor-1 immunostaining in tumor diagnosis: a review and update. Appl Immunohistochem Mol Morphol 20:429–444

    Article  CAS  PubMed  Google Scholar 

  • Ordonez NG (2012b) Value of PAX 8 immunostaining in tumor diagnosis: a review and update. Adv Anat Pathol 19:140–151

    Article  CAS  PubMed  Google Scholar 

  • Ordonez NG (2013a) Broad-spectrum immunohistochemical epithelial markers: a review. Hum Pathol 44:1195–1215

    Article  CAS  PubMed  Google Scholar 

  • Ordonez NG (2013b) Value of GATA3 immunostaining in tumor diagnosis: a review. Adv Anat Pathol 20:352

    Article  CAS  PubMed  Google Scholar 

  • Ozcan A, Shen SS, Hamilton C et al (2011) PAX 8 expression in non-neoplastic tissues, primary tumors, and metastatic tumors: a comprehensive immunohistochemical study. Mod Pathol 24:751–764

    Article  CAS  PubMed  Google Scholar 

  • Patient RK, McGhee JD (2002) The GATA family (vertebrates and invertebrates). Curr Opin Genet Dev 12:416–422

    Article  CAS  PubMed  Google Scholar 

  • Pena GP, Andrade-Filho JS (2009) How does a pathologist make a diagnosis? Arch Pathol Lab Med 133:124–132

    Article  PubMed  Google Scholar 

  • Piehl MR, Gould VE, Warren WH et al (1988) Immunohistochemical identification of exocrine and neuroendocrine subsets of large cell lung carcinomas. Pathol Res Pract 183:675–682

    Article  CAS  PubMed  Google Scholar 

  • Pileri SA, Grogan TM, Harris NL et al (2002) Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases. Histopathology 41:1–29

    Article  CAS  PubMed  Google Scholar 

  • Rekhtman N, Ang DC, Sima CS et al (2011) Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens. Mod Pathol 24:1348–1359

    Article  PubMed  Google Scholar 

  • Ronchi A, Zito Marino F et al (2022) Diagnostic performance of melanocytic markers for immunocytochemical evaluation of lymph-node melanoma metastases on cytological samples. J Clin Pathol 75:45–49

    Article  CAS  PubMed  Google Scholar 

  • Rosenbaum JN, Guo Z, Baus RM et al (2015) INSM1: a novel immunohistochemical and molecular marker for neuroendocrine and neuroepithelial neoplasms. Am J Clin Pathol 144:579–591

    Article  CAS  PubMed  Google Scholar 

  • Saliba E, Bhawan J (2021) Aberrant expression of Immunohistochemical markers in malignant melanoma: a review. Dermatopathology (Basel) 8:359–370

    Article  PubMed  Google Scholar 

  • Sanguedolce F, Landriscina M, Ambrosi A et al (2018) Bladder metastases from breast cancer: managing the unexpected. A systematic review. Urol Int 101:125–131

    Article  PubMed  Google Scholar 

  • Sanguedolce F, Russo D, Calò B et al (2019) Diagnostic and prognostic roles of CK20 in the pathology of urothelial lesions. A systematic review. Pathol Res Pract 215:152413

    Article  CAS  PubMed  Google Scholar 

  • Sanguedolce F, Zanelli M, Ascani S et al (2021) PD-L1 as a prognostic and predictive biomarker in neuroendocrine tumors of the lung: state of the art and future perspectives. Minerva Resp Med 60:36–51

    Google Scholar 

  • Schmitz K, Brugger W, Weiss B et al (1999) Clonal selection of CD20-negative non-Hodgkin’s lymphoma cells after treatment with anti-CD20 antibody rituximab. Br J Haematol 106:571–572

    Article  CAS  PubMed  Google Scholar 

  • See SHC, Finkelman BS, Yeldandi AV (2020) The diagnostic utility of PRAME and p16 in distinguishing nodal nevi from nodal metastatic melanoma. Pathol Res Pract 216:153105

    Article  CAS  PubMed  Google Scholar 

  • Selves J, Long-Mira E, Mathieu MC et al (2018) Immunohistochemistry for diagnosis of metastatic carcinomas of unknown primary site. Cancers (Basel) 10:108

    Article  PubMed  Google Scholar 

  • Stopyra GA, Warhol MJ, Multhaupt HA (2001) Cytokeratin 20 immunoreactivity in renal oncocytomas. J Histochem Cytochem 49:919–920

    Article  CAS  PubMed  Google Scholar 

  • Suzuki K, Kobayashi Y, Katoh R et al (1998) Identification of thyroid transcription factor-1 in C cells and parathyroid cells. Endocrinology 139:3014–3017

    Article  CAS  PubMed  Google Scholar 

  • Svajdler M, Mezencev R, Saskova B et al (2019) Triple marker composed of p16, CD56, and TTF1 shows higher sensitivity than INSM1 for diagnosis of pulmonary small cell carcinoma: proposal for a rational immunohistochemical algorithm for diagnosis of small cell carcinoma in small biopsy and cytology specimens. Hum Pathol 85:58–64

    Article  CAS  PubMed  Google Scholar 

  • Tacha D, Zhou D, Cheng L (2011) Expression of PAX8 in normal and neoplastic tissues: a comprehensive immunohistochemical study. Appl Immunohistochem Mol Morphol 19:293–299

    Article  CAS  PubMed  Google Scholar 

  • Thoene S, Rawat VPS, Heilmeier B et al (2009) The homeobox gene CDX2 is aberrantly expressed and associated with an inferior prognosis in patients with acute lymphoblastic leukemia. Leukemia 23:649–655

    Article  CAS  PubMed  Google Scholar 

  • Tong GX, Weeden EM, Hamele-Bena D et al (2008) Expression of PAX8 in nephrogenic adenoma and clear cell adenocarcinoma of the lower urinary tract: evidence of related histogenesis? Am J Surg Pathol 32:1380–1387

    Article  PubMed  Google Scholar 

  • Tong GX, Yu WM, Beaubier NT et al (2009) Expression of PAX8 in normal and neoplastic renal tissues: an immunohistochemical study. Mod Pathol 22:1218–1227

    Article  CAS  PubMed  Google Scholar 

  • Toriyama A, Mori T, Sekine S et al (2014) Utility of PAX8 mouse monoclonal antibody in the diagnosis of thyroid, thymic, pleural and lung tumours: a comparison with polyclonal PAX8 antibody. Histopathology 65:465–472

    Article  PubMed  Google Scholar 

  • Tornillo L, Moch H, Diener PA et al (2004) CDX-2 immunostaining in primary and secondary ovarian carcinomas. J Clin Pathol 57:641–643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tuffaha MSA, Guski H, Kristiansen G (2018) Immunohistochemistry in tumor diagnostics. Springer International Publishing AG

    Book  Google Scholar 

  • Uccella S, Asa SL, Mete O (2021) Metastatic neuroendocrine neoplasms of unknown primary site. In: Asa SL, La Rosa S, Mete O (eds) The Spectrum of neuroendocrine neoplasia. A practical approach to diagnosis, classification and therapy. Springer Nature Switzerland AG

    Google Scholar 

  • Vidarsdottir H, Tran L, Nodin B et al (2019) Immunohistochemical profiles in primary lung cancers and epithelial pulmonary metastases. Hum Pathol 84:221–230

    Article  CAS  PubMed  Google Scholar 

  • Weider M, Wegner M (2017) SoxE factors: transcriptional regulators of neural differentiation and nervous system development. Semin Cell Dev Biol 63:35–42

    Article  CAS  PubMed  Google Scholar 

  • Weissferdt A, Moran CA (2011) Pax8 expression in thymic epithelial neoplasms: an immunohistochemical analysis. Am J Surg Pathol 35:1305–1310

    Article  PubMed  Google Scholar 

  • Weissferdt A, Tang X, Wistuba II et al (2013) Comparative immunohistochemical analysis of pulmonary and thymic neuroendocrine carcinomas using PAX8 and TTF-1. Mod Pathol 26:1554–1560

    Article  CAS  PubMed  Google Scholar 

  • Weissferdt A, Phan A, Suster S et al (2014) Adrenocortical carcinoma: a comprehensive immunohistochemical study of 40 cases. Appl Immunohistochem Mol Morphol 22:24–30

    Article  CAS  PubMed  Google Scholar 

  • Weissinger SE, Keil P, Silvers DN et al (2014) A diagnostic algorithm to distinguish desmoplastic from spindle cell melanoma. Mod Pathol 27:524–534

    Article  CAS  PubMed  Google Scholar 

  • Werling RW, Yaziji H, Bacchi CE, Gown AM (2003) CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas. Am J Surg Pathol 27:303–310

    Article  PubMed  Google Scholar 

  • WHO Classification of Tumours Editorial Board (2021) Thoracic tumours [Internet]. WHO classification of tumours series, 5th edn, vol 5. International Agency for Research on Cancer, Lyon [cited 2022 Dec 19]. Available from: https://tumourclassification.iarc.who.int/chapters/35

  • Wiedenmann B, Kuhn C, Schwechheimer K et al (1987) Synaptophysin identified in metastases of neuroendocrine tumors by immunocytochemistry and immunoblotting. Am J Clin Pathol 88:560–569

    Article  CAS  PubMed  Google Scholar 

  • Wilson BS, Lloyd RV (1984) Detection of chromogranin in neuroendocrine cells with a monoclonal antibody. Am J Pathol 115:458–468

    CAS  PubMed  PubMed Central  Google Scholar 

  • **ng D, Banet N, Sharma R et al (2018) Aberrant Pax-8 expression in well-differentiated papillary mesothelioma and malignant mesothelioma of the peritoneum: a clinicopathologic study. Hum Pathol 72:160–166

    Article  CAS  PubMed  Google Scholar 

  • Yatabe Y, Dacic S, Borczuk AC et al (2019) Best practices recommendations for diagnostic immunohistochemistry in lung cancer. J Thorac Oncol 14:377–407

    Article  CAS  PubMed  Google Scholar 

  • Yoshida A, Makise N, Wakai S et al (2018) INSM1 expression and its diagnostic significance in extraskeletal myxoid chondrosarcoma. Mod Pathol 31:744–752

    Article  CAS  PubMed  Google Scholar 

  • Zanelli M, Sanguedolce F, Palicelli A et al (2021) EBV-driven lymphoproliferative disorders and lymphomas of the gastrointestinal tract: a spectrum of entities with a common denominator (part 1). Cancers (Basel) 13:4578

    Article  CAS  PubMed  Google Scholar 

  • Zhang L, Whitsett JA, Stripp BR (1997) Regulation of Clara cell secretory protein gene transcription by thyroid transcription factor-1. Biochim Biophys Acta 1350:359–367

    Article  CAS  PubMed  Google Scholar 

  • Zhao C, Vinh TN, McManus K et al (2009) Identification of the most sensitive and robust immunohistochemical markers in different categories of ovarian sex cord-stromal tumors. Am J Surg Pathol 33:354–366

    Article  PubMed  Google Scholar 

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Sanguedolce, F., Zanelli, M. (2022). Immunohistochemistry in the Diagnosis of Primary and Secondary Cancers. In: Rezaei, N. (eds) Handbook of Cancer and Immunology. Springer, Cham. https://doi.org/10.1007/978-3-030-80962-1_129-1

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