Skip to main content
SpringerLink
Log in

Liver, Bile Ducts and Gallbladder

  • Chapter
  • First Online:
Handbook of Practical Immunohistochemistry

  • 4608 Accesses

Abstract

Immunohistochemistry (IHC) is an indispensable tool for pathological diagnosis of both neoplastic and non-neoplastic diseases of the liver and biliary tract. It has a wide spectrum of application ranging from pathogen detection to differentiation of primary from metastatic tumors. The focus of this chapter is to address applications regarding diagnosis and differential diagnosis of liver and biliary tract tumors. Commonly used markers or antibodies are listed in various tables detailing their staining patterns in benign, reactive and neoplastic conditions. Suggested panels of markers are provided to address specific diagnostic challenges such as distinguishing benign vs. malignant biliary proliferation and hepatocellular lesions, differentiating intrahepatic cholangiocarcinoma from extrhepatic cholangiocarinoma and metastatic adenocarcinomas from other organs. A process is defined utilizing an initial screening panel and subsequent confirmatory markers for unknown primary tumors in liver. Photomicrographs are provided to illustrate characteristic staining patterns.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Chu PG, Weiss LM. Modern Immunohistochemistry. New York: Cambridge University Press; 2009.

    Google Scholar 

  2. Dabbs DJ. Immunohistology of the pancreas and hepatobiliary tract. In: Basturk O, Farris AB, Volkan Adsay N, editors. Diagnostic Immunohistochemistry theranostic and genomic applications. Philadelphia, PA: Elsevier Saunders; 2014. p. 508–39.

    Google Scholar 

  3. Taylor C, Cote R. Immunomicroscopy A diagnostic tool for the surgical pathologist. Major Problems in Pathology. 3rd ed. Philadelphia, PA: Saunders Elsevier; 2006.

    Google Scholar 

  4. Geller SA, Dhall D, Alsabeh R. Application of immunohistochemistry to liver and gastrointestinal neoplasms: liver, stomach, colon, and pancreas. Arch Pathol Lab Med. 2008;132(3):490–9.

    PubMed  Google Scholar 

  5. Mills SE. Histology for pathologists. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007. p. 696–7.

    Google Scholar 

  6. Burt AD, Portmann BC, Ferrell LD. MacSween’s pathology of the liver. 5th ed. Philadelphia, PA: Churchill Livingstone Elsevier; 2007. p. 20–45.

    Google Scholar 

  7. De Young BR, Frierson Jr HF, Ly MN, Smith D, Swanson PE. CD31 immunoreactivity in carcinomas and mesotheliomas. Am J Clin Pathol. 1998;110(3):374–7.

    PubMed  Google Scholar 

  8. de Boer WB, Segal A, Frost FA, Sterret GF. Can CD34 discriminate between benign and malignant hepatocytic lesions in fine-needle aspirates and thin core biopsies? Cancer. 2000;90(5):273–8.

    PubMed  Google Scholar 

  9. Gottschalk-Sabag S, Ron N, Glick T. Use of CD34 and factor VIII to diagnose hepatocellular carcinoma on fine needle aspirates. Acta Cytol. 1998;42(3):691–6.

    CAS  PubMed  Google Scholar 

  10. Coston WM, Loera S, Lau SK, et al. Distinction of hepatocellular carcinoma from benign hepatic mimickers using Glypican-3 and CD34 immunohistochemistry. Am J Surg Pathol. 2008;32(3):433–44.

    PubMed  Google Scholar 

  11. Werling RW, Yaziji H, Bacchi CE, Gown AM. 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. 2003;27(3):303–10.

    PubMed  Google Scholar 

  12. Lin F, Shi J, Liu H, et al. Immunohistochemical detection of the von Hippel-Lindau gene product (pVHL) in human tissues and tumors: a useful marker for metastatic renal cell carcinoma and clear cell carcinoma of the ovary and uterus. Am J Clin Pathol. 2008;129(4):592–605.

    CAS  PubMed  Google Scholar 

  13. Shah S, Gupta S, Shet T, et al. Metastatic clear cell variant of hepatocellular carcinoma with an occult hepatic primary. Hepatobiliary Pancreat Dis Int. 2005;4(2):306–7.

    PubMed  Google Scholar 

  14. Maeda T, Kajiyama K, Adachi E, Takenaka K, Sugimachi K, Tsuneyoshi M. The expression of cytokeratins 7, 19, and 20 in primary and metastatic carcinomas of the liver. Mod Pathol. 1996;9(9):901–9.

    CAS  PubMed  Google Scholar 

  15. Rullier A, Le Bail B, Fawaz R, Saric J, Bioulac-Sage P. Cytokeratin 7 and 20 expression in cholangiocarcinomas varies along the biliary tract but still differs from that in colorectal carcinoma metastasis. Am J Surg Pathol. 2000;24(6):870–6.

    CAS  PubMed  Google Scholar 

  16. Levy M, Lin F, Xu H, et al. S100P, von Hippel-Lindau gene product, and IMP3 serve as a useful immunohistochemical panel in the diagnosis of adenocarcinoma on endoscopic bile duct biopsy. Hum Pathol. 2010;41(9):1210–9.

    CAS  PubMed  Google Scholar 

  17. Shafizadeh N, Ferrell LD, Kakar S. Utility and limitations of glypican-3 expression for the diagnosis of hepatocellular carcinoma at both ends of the differentiation spectrum. Mod Pathol. 2008;21(8):1011–8.

    CAS  PubMed  Google Scholar 

  18. Wang HL, Anatelli F, Zhai QJ, Adley B, Chuang ST, Yang XJ. Glypican-3 as a useful diagnostic marker that distinguishes hepatocellular carcinoma from benign hepatocellular mass lesions. Arch Pathol Lab Med. 2008;132(11):1723–8.

    PubMed  Google Scholar 

  19. Yamauchi N, Watanabe A, Hishinuma M, et al. The glypican 3 oncofetal protein is a promising diagnostic marker for hepatocellular carcinoma. Mod Pathol. 2005;18(12):1591–8.

    CAS  PubMed  Google Scholar 

  20. Abenoza P, Manivel JC, Wick MR, Hagen K, Dehner LP. Hepatoblastoma: an immunohistochemical and ultrastructural study. Hum Pathol. 1987;18(10):1025–35.

    CAS  PubMed  Google Scholar 

  21. Cajaiba MM, Neves JI, Casarotti FF, et al. Hepatoblastomas and liver development: a study of cytokeratin immunoexpression in twenty-nine hepatoblastomas. Pediatr Dev Pathol. 2006;9(3):196–202.

    PubMed  Google Scholar 

  22. López-Terrada D, Gunaratne PH, Adesina AM, et al. Histologic subtypes of hepatoblastoma are characterized by differential canonical Wnt and Notch pathway activation in DLK + precursors. Hum Pathol. 2009;40(6):783–94.

    PubMed  Google Scholar 

  23. Stocker JT. Hepatoblastoma. Semin Diagn Pathol. 1994;11(2): 136–43.

    CAS  PubMed  Google Scholar 

  24. Warfel KA, Hull MT. Hepatoblastomas: an ultrastructural and immunohistochemical study. Ultrastruct Pathol. 1992;16(4):451–61.

    CAS  PubMed  Google Scholar 

  25. Christensen WN, Boitnott JK, Kuhajda FP. Immunoperoxidase staining as a diagnostic aid for hepatocellular carcinoma. Mod Pathol. 1989;2(1):8–12.

    CAS  PubMed  Google Scholar 

  26. Varma V, Cohen C. Immunohistochemical and molecular markers in the diagnosis of hepatocellular carcinoma. Adv Anat Pathol. 2004;11(5):239–49.

    CAS  PubMed  Google Scholar 

  27. Haratake J, Hashimoto H. An immunohistochemical analysis of 13 cases with combined hepatocellular and cholangiocellular carcinoma. Liver. 1995;15(1):9–15.

    CAS  PubMed  Google Scholar 

  28. Fanni D, Nemolato S, Ganga R, et al. Cytokeratin 20-positive hepatocellular carcinoma. Eur J Histochem. 2009;53(4):269–73.

    CAS  PubMed  Google Scholar 

  29. Kakar S, Gown AM, Goodman ZD, Ferrell LD. Best practices in diagnostic immunohistochemistry: hepatocellular carcinoma versus metastatic neoplasms. Arch Pathol Lab Med. 2007; 131(11):1648–54.

    PubMed  Google Scholar 

  30. Krishna M. Diagnosis of metastatic neoplasms: an immunohistochemical approach. Arch Pathol Lab Med. 2010;134(2):207–15.

    PubMed  Google Scholar 

  31. Lau SK, Prakash S, Geller SA, Alsabeh R. Comparative immunohistochemical profile of hepatocellular carcinoma, cholangiocarcinoma, and metastatic adenocarcinoma. Hum Pathol. 2002;33(12):1175–81.

    PubMed  Google Scholar 

  32. Wieczorek TJ, Pinkus JL, Glickman JN, Pinkus GS. Comparison of thyroid transcription factor-1 and hepatocyte antigen immunohistochemical analysis in the differential diagnosis of hepatocellular carcinoma, metastatic adenocarcinoma, renal cell carcinoma, and adrenal cortical carcinoma. Am J Clin Pathol. 2002;118(2): 911–21.

    PubMed  Google Scholar 

  33. Cho MS, Lee SN, Sung SH, Han WS. Sarcomatoid hepatocellular carcinoma with hepatoblastoma-like features in an adult. Pathol Int. 2004;54(6):446–50.

    PubMed  Google Scholar 

  34. Fu Y, Kobayashi S, Kushida Y, et al. Sarcomatoid hepatocellular carcinoma with chondroid variant: case report with immunohistochemical findings. Pathol Int. 2000;50(11):919–22.

    CAS  PubMed  Google Scholar 

  35. Górnicka B, Ziarkiewicz-Wróblewska B, Wróblewski T, et al. Carcinoma, a fibrolamellar variant–immunohistochemical analysis of 4 cases. Hepatogastroenterology. 2005;52(62):519–23.

    PubMed  Google Scholar 

  36. Malouf G, Falissard B, Azoulay D, et al. Is histological diagnosis of primary liver carcinomas with fibrous stroma reproducible among experts? J Clin Pathol. 2009;62(6):519–24.

    CAS  PubMed  Google Scholar 

  37. Ward SC, Huang J, Tickoo SK, Thung SN, Ladanyi M, Klimstra DS. Fibrolamellar carcinoma of the liver exhibits immunohistochemical evidence of both hepatocyte and bile duct differentiation. Mod Pathol. 2010;23(9):1180–90.

    CAS  PubMed  Google Scholar 

  38. Yang GC, Yang GY, Tao LC. Distinguishing well-differentiated hepatocellular carcinoma from benign liver by the physical features of fine-needle aspirates. Mod Pathol. 2004;17(7):798–802.

    PubMed  Google Scholar 

  39. Ushiku T, Shinozaki A, Shibahara J, et al. SALL4 represents fetal gut differentiation of gastric cancer, and is diagnostically useful in distinguishing hepatoid gastric carcinoma from hepatocellular carcinoma. Am J Surg Pathol. 2010;34(4):533–40.

    PubMed  Google Scholar 

  40. Terracciano LM, Glatz K, Mhawech P, et al. Hepatoid adenocarcinoma with liver metastasis mimicking hepatocellular carcinoma. Am J Surg Pathol. 2003;27:1302–12.

    PubMed  Google Scholar 

  41. Van Eyken P. Cytokeratin immunohistochemistry in liver histopatology. Adv Clin Pathol. 2000;4(4):201–11.

    Google Scholar 

  42. Zatloukal K, Stumptner C, Fuchsbichler A, et al. The keratin cytoskeleton in liver diseases. J Pathol. 2004;204(4):367–76.

    CAS  PubMed  Google Scholar 

  43. Yang XR, Xu Y, Shi GM, Fan J, et al. Cytokeratin 10 and cytokeratin 19: predictive markers for poor prognosis in hepatocellular carcinoma patients after curative resection. Clin Cancer Res. 2008;14(12):3850–9.

    CAS  PubMed  Google Scholar 

  44. Lackner C, Gogg-Kamerer M, Zatloukal K, Stumptner C, Brunt EM, Denk H. Ballooned hepatocytes in steatohepatitis: the value of keratin immunohistochemistry for diagnosis. J Hepatol. 2008;48(5):821–8.

    CAS  PubMed  Google Scholar 

  45. Lee MJ, Lee HS, Kim WH, Choi Y, Yang M. Expression of mucins and cytokeratins in primary carcinomas of the digestive system. Mod Pathol. 2003;16(5):403–10.

    PubMed  Google Scholar 

  46. Listrom MB, Dalton LW. Comparison of keratin monoclonal antibodies MAK-6, AE1:AE3, and CAM-5.2. Am J Clin Pathol. 1987;88(3):297–301.

    CAS  PubMed  Google Scholar 

  47. Jain R, Fischer S, Serra S, Chetty R. The use of cytokeratin 19 (CK19) immunohistochemistry in lesions of the pancreas, gastrointestinal tract, and liver. Appl Immunohistochem Mol Morphol. 2010;18(1):9–15.

    CAS  PubMed  Google Scholar 

  48. Lefkowitch JH. Special stains in diagnostic liver pathology. Semin Diagn Pathol. 2006;23(3–4):190–8.

    PubMed  Google Scholar 

  49. Fan Z, van de Rijn M, Montgomery K, Rouse RV. Hep par 1 antibody stain for the differential diagnosis of hepatocellular carcinoma: 676 tumors tested using tissue microarrays and conventional tissue sections. Mod Pathol. 2003;16(2):137–44.

    PubMed  Google Scholar 

  50. Roskams T. The role of immunohistochemistry in diagnosis. Clin Liver Dis. 2002;6(2):571–89.

    PubMed  Google Scholar 

  51. Morrison C, Marsh Jr W, Frankel WL. A comparison of CD10 to pCEA, MOC-31, and hepatocyte for the distinction of malignant tumors in the liver. Mod Pathol. 2002;15(12):1279–87.

    PubMed  Google Scholar 

  52. Porcell AI, De Young BR, Proca DM, Frankel WL. Immunohistochemical analysis of hepatocellular and adenocarcinoma in the liver: MOC31 compares favorably with other putative markers. Mod Pathol. 2000;13(7):77377–8.

    Google Scholar 

  53. Lau SK, Weiss LM, Chu PG. Differential expression of MUC1, MUC2, and MUC5AC in carcinomas of various sites: an immunohistochemical study. Am J Clin Pathol. 2004;122(1):61–9.

    PubMed  Google Scholar 

  54. Hornick JL, Fletcher CD. PEComa: what do we know so far? Histopathology. 2006;48(1):75–82.

    CAS  PubMed  Google Scholar 

  55. Tryggvason G, Blöndal S, Goldin RD, Albrechtsen J, Björnsson J, Jónasson JG. Epithelioid angiomyolipoma of the liver: case report and review of the literature. APMIS. 2004;112(9):612–6.

    PubMed  Google Scholar 

  56. Krings G, Ramachandran R, Jain D, et al. Immunohistochemical pitfalls and the importance of glypican 3 and arginase in the diagnosis of scirrhous hepatocellular carcinoma. Mod Pathol. 2013;26(6):782–91.

    CAS  PubMed  Google Scholar 

  57. Fujiwara M, Kwok S, Yano H, Pai RK. Arginase-1 is a more sensitive marker of hepatic differentiation than HepPar-1 and glypican-3 in fine-needle aspiration biopsies. Cancer Cytopathol. 2012;120(4):230–7.

    CAS  PubMed  Google Scholar 

  58. Fatima N, Cohen C, Siddiqui MT. Arginase-1: a highly specific marker separating pancreatic adenocarcinoma from hepatocellular carcinoma. Acta Cytol. 2014;58(1):83–8.

    CAS  PubMed  Google Scholar 

  59. McKnight R, Nassar A, Cohen C, Siddiqui MT. Arginase-1: a novel immunohistochemical marker of hepatocellular differentiation in fine needle aspiration cytology. Cancer Cytopathol. 2012;120(4):223–9.

    CAS  PubMed  Google Scholar 

  60. Radwan NA, Ahmed NS. The diagnostic value of arginase-1 immunostaining in differentiating hepatocellular carcinoma from metastatic carcinoma and cholangiocarcinoma as compared to HepPar-1. Diagn Pathol. 2012;7:149.

    PubMed Central  PubMed  Google Scholar 

  61. Timek DT, Shi J, Liu H, Lin F. Arginase-1, HepPar-1, and Glypican-3 are the most effective panel of markers in distinguishing hepatocellular carcinoma from metastatic tumor on fine-needle aspiration specimens. Am J Clin Pathol. 2012;138(2):203–10.

    PubMed  Google Scholar 

  62. Haraguchi Y, Takiguchi M, Amaya Y, Kawamoto S, Matsuda I, Mori M. Molecular cloning and nucleotide sequence of cDNA for human liver arginase. Proc Natl Acad Sci USA. 1987;84(2):412–5.

    PubMed Central  CAS  PubMed  Google Scholar 

  63. Tretiakova M, Antic T, Westerhoff M, et al. Diagnostic utility of CD10 in benign and malignant extrahepatic bile duct lesions. Am J Surg Pathol. 2012;36(1):101–8.

    PubMed  Google Scholar 

  64. Schmidt MT, Himmelfarb EA, Shafi H, Lin F, Xu H, Wang HL. Use of IMP3, S100P, and pVHL immunopanel to aid in the interpretation of bile duct biopsies with atypical histology or suspicious for malignancy. Appl Immunohistochem Mol Morphol. 2012;20:478–87.

    CAS  PubMed  Google Scholar 

  65. Findeis-Hosey JJ, Xu H. Insulin-like growth factor II-messenger RNA-binding protein-3 and lung cancer. Biotech Histochem. 2012;87(1):24–9.

    CAS  PubMed  Google Scholar 

  66. Wang ZB, Yuan J, Chen W, Wei LX. Transcription factor ERG is a specific and sensitive diagnostic marker for hepatic angiosarcoma. World J Gastroenterol. 2014;20(13):3672–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  67. Guy CD, Suzuki A, Burchette JL, et al. Costaining for keratins 8/18 plus ubiquitin improves detection of hepatocyte injury in nonalcoholic fatty liver disease. Hum Pathol. 2012;43(6):790–800.

    PubMed Central  CAS  PubMed  Google Scholar 

  68. Turanyi E, Dezso K, Csomor J, Schaff Z, Paku S, Nagy P. Immunohistochemical classification of ductular reactions in human liver. Histopathology. 2010;57(4):607–14.

    PubMed  Google Scholar 

  69. Bateman AC, Hubscher SG. Cytokeratin expression as an aid to diagnosis in medical liver biopsies. Histopathology. 2010;56(4):412–25.

    Google Scholar 

  70. Okabe H, Beppu T, Hayashi H, et al. Hepatic stellate cells may relate to progression of intrahepatic cholangiocarcinoma. Ann Surg Oncol. 2009;16(9):2555–64.

    PubMed  Google Scholar 

  71. Snover D. Immunohistochemical analysis in steatohepatitis: does it have a role in diagnosis and management? Am J Clin Pathol. 2005;123(4):491–3.

    PubMed  Google Scholar 

  72. Svegliati Baroni G, D’Ambrosio L, Ferretti G, et al. Fibrogenic effect of oxidative stress on rat hepatic stellate cells. J Hepatol. 1999;27(3):868–75.

    Google Scholar 

  73. Tomanovic NR, Boricic IV, Brasanac DC, Stojsic ZM, Delic DS, Brmbolic BJ. Activated liver stellate cells in chronic viral C hepatitis: histopathological and immunohistochemical study. J Gastrointestin Liver Dis. 2009;18(2):163–7.

    PubMed  Google Scholar 

  74. Lee CT, Zhang L, Mounajjed T, Wu TT. High mobility group AT-hook 2 is overexpressed in hepatoblastoma. Hum Pathol. 2013;44(5):802–10.

    CAS  PubMed  Google Scholar 

  75. Bioulac-Sage P, Balabaud C, Bedossa P, et al. Pathological diagnosis of liver cell adenoma and focal nodular hyperplasia: Bordeaux update. J Hepatol. 2007;46(3):521–7.

    CAS  PubMed  Google Scholar 

  76. Bioulac-Sage P, Balabaud C, Zucman-Rossi J. Subtype classification of hepatocellular adenoma. Dig Surg. 2010;27(1):39–45.

    CAS  PubMed  Google Scholar 

  77. Bioulac-Sage P, Blanc JF, Rebouissou S, et al. Genotype phenotype classification of hepatocellular adenoma. World J Gastroenterol. 2007;13(19):2649–54.

    PubMed Central  CAS  PubMed  Google Scholar 

  78. Bioulac-Sage P, Laumonier H, Couchy G, et al. Hepatocellular adenoma management and phenotypic classification: the Bordeaux experience. Hepatology. 2009;50(2):481–9.

    PubMed  Google Scholar 

  79. Bioulac-Sage P, Laumonier H, Laurent C, et al. Hepatocellular adenoma: what is new in 2008. Hepatol Int. 2008;2(3):316–21.

    PubMed Central  PubMed  Google Scholar 

  80. Chen ZM, Crone KG, Watson MA, Pfeifer JD, Wang HL. Identification of a unique gene expression signature that differentiates hepatocellular adenoma from well-differentiated hepatocellular carcinoma. Am J Surg Pathol. 2005;29(12):1600–8.

    PubMed  Google Scholar 

  81. Cohen C, Lawson D, DeRose PB. Sex and androgenic steroid receptor expression in hepatic adenomas. Hum Pathol. 1998;29(12):1428–32.

    CAS  PubMed  Google Scholar 

  82. Micchelli ST, Vivekanandan P, Boitnott JK, Pawlik TM, Choti MA, Torbenson M. Malignant transformation of hepatic adenomas. Mod Pathol. 2008;21(4):491–7.

    CAS  PubMed  Google Scholar 

  83. Torbenson M, Lee JH, Choti M, et al. Hepatic adenomas: analysis of sex steroid receptor status and the Wnt signaling pathway. Mod Pathol. 2002;15(3):189–96.

    PubMed  Google Scholar 

  84. Zucman-Rossi J, Jeannot E, Nhieu JT, et al. Genotype-phenotype correlation in hepatocellular adenoma: new classification and relationship with HCC. Hepatology. 2006;43(3):515–24.

    CAS  PubMed  Google Scholar 

  85. Ahmad I, Iyer A, Marginean CE, et al. Diagnostic use of cytokeratins, CD34, and neuronal cell adhesion molecule staining in focal nodular hyperplasia and hepatic adenoma. Hum Pathol. 2009;40(5):726–34.

    CAS  PubMed  Google Scholar 

  86. Rebouissou S, Bioulac-Sage P, Zucman-Rossi J. Molecular pathogenesis of focal nodular hyperplasia and hepatocellular adenoma. J Hepatol. 2008;48(1):163–70.

    CAS  PubMed  Google Scholar 

  87. Bioulac-Sage P, Cubel G, Taouji S, et al. Immunohistochemical markers on needle biopsies are helpful for the diagnosis of focal nodular hyperplasia and hepatocellular adenoma subtypes. Am J Surg Pathol. 2012;36(11):1691–9.

    PubMed  Google Scholar 

  88. Balabaud C, Al-Rabih WR, Chen PJ, et al. Focal nodular hyperplasia and hepatocellular adenoma around the world viewed through the scope of the immunopathological classification. Int J Hepatol. 2013;2013:268625.

    PubMed Central  PubMed  Google Scholar 

  89. Chen Ban K, Singh H, Krishnan R, Fong SH. Comparison of the expression of beta-catenin in hepatocellular carcinoma in areas with high and low levels of exposure to aflatoxin B1. J Surg Oncol. 2004;86(3):157–63.

    PubMed  Google Scholar 

  90. Torbenson M, Kannangai R, Abraham S, Sahin F, Choti M, Wang J. Concurrent evaluation of p53, beta-catenin, and alpha-fetoprotein expression in human hepatocellular carcinoma. Am J Clin Pathol. 2004;122(3):377–82.

    CAS  PubMed  Google Scholar 

  91. Batheja N, Suriawinata A, Saxena R, Ionescu G, Schwartz M, Thung SN. Expression of p53 and PCNA in cholangiocarcinoma and primary sclerosing cholangitis. Mod Pathol. 2000;13(12):1265–8.

    CAS  PubMed  Google Scholar 

  92. Peroukides S, Bravou V, Alexopoulos A, Varakis J, Kalofonos H, Papadaki H. Survivin overexpression in HCC and liver cirrhosis differentially correlates with p-STAT3 and E-cadherin. Histol Histopathol. 2010;25(3):299–307.

    CAS  PubMed  Google Scholar 

  93. Xie L, Jessurun J, Manivel JC, Pambuccian SE. Hepatic epithelioid angiomyolipoma with trabecular growth pattern: a mimic of hepatocellular carcinoma on fine needle aspiration cytology. Diagn Cytopathol. 2012;40(7):639–50.

    PubMed  Google Scholar 

  94. Tátrai P, Somorácz A, Batmunkh E, et al. Agrin and CD34 immunohistochemistry for the discrimination of benign versus malignant hepatocellular lesions. Am J Surg Pathol. 2009;33(6):874–85.

    PubMed  Google Scholar 

  95. Zhang MF, Zhang ZY, Fu J, Yang YF, Yun JP. Correlation between expression of p53, p21/WAF1, and MDM2 proteins and their prognostic significance in primary hepatocellular carcinoma. J Transl Med. 2009;7:110.

    PubMed Central  CAS  PubMed  Google Scholar 

  96. Lopez-Terrada D, Alaggio R, de Davila MT, et al. Towards an international pediatric liver tumor consensus classification: proceeding of the Los Angeles COG liver tumors symposium. Mod Pathol. 2014;27(3):472–91.

    PubMed  Google Scholar 

  97. Kanamoto M, Yoshizumi T, Ikegami T, et al. Cholangiolocellular carcinoma containing hepatocellular carcinoma and cholangiocellular carcinoma, extremely rare tumor of the liver:a case report. J Med Invest. 2008;55(1–2):161–5.

    PubMed  Google Scholar 

  98. Kang YK, Kim WH, Jang JJ. Expression of G1-S modulators (p53, p16, p27, cyclin D1, Rb) and Smad4/Dpc4 in intrahepatic cholangiocarcinoma. Hum Pathol. 2002;33(9):877–83.

    CAS  PubMed  Google Scholar 

  99. Mosnier JF, Kandel C, Cazals-Hatem D, et al. N-cadherin serves as diagnostic biomarker in intrahepatic and perihilar cholangiocarcinomas. Mod Pathol. 2009;22(2):182–90.

    CAS  PubMed  Google Scholar 

  100. Nakanuma Y, Harada K, Ishikawa A, Zen Y, Sasaki M. Anatomic and molecular pathology of intrahepatic cholangiocarcinoma. J Hepatobiliary Pancreat Surg. 2003;10(4):265–81.

    PubMed  Google Scholar 

  101. Rizzi PM, Ryder SD, Portmann B, Ramage JK, Naoumov NV, Williams R. p53 protein overexpression in cholangiocarcinoma arising in primary sclerosing cholangitis. Gut. 1996;38(2):265–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  102. Röcken C, Pross M, Brucks U, Ridwelski K, Roessner A. Cholangiocarcinoma occurring in a liver with multiple bile duct hamartomas (von Meyenburg complexes). Arch Pathol Lab Med. 2000;124(11):1704–6.

    PubMed  Google Scholar 

  103. Nash JW, Morrison C, Frankel WL. The utility of estrogen receptor and progesterone receptor immunohistochemistry in the distinction of metastatic breast carcinoma from other tumors in the liver. Arch Pathol Lab Med. 2003;127(12):1591–5.

    CAS  PubMed  Google Scholar 

  104. Hruban RH, Pitman MB, Klimstra DS. AFIP atlast of tumor pathology; tumors of the pancreas. Vol Fourth Series. Fascicle 6 ed. Washington, DC: American Registry of Pathology; 2007.

    Google Scholar 

  105. Bioulac-Sage P, Rebouissou S, Thomas C, et al. Hepatocellular adenoma subtype classification using molecular markers and immunohistochemistry. Hepatology. 2007;46(3):740–8.

    CAS  PubMed  Google Scholar 

  106. Shi J, Liu H, Wang HL, Prichard JW, Lin F. Diagnostic utility of von Hippel-Lindau gene product, maspin, IMP3, and S100P in adenocarcinoma of the gallbladder. Hum Pathol. 2013;44(4): 503–11.

    CAS  PubMed  Google Scholar 

  107. Findeis-Hosey JJ, Yang Q, Spaulding BO, Wang HL, Xu H. IMP3 expression is correlated with histologic grade of lung adenocarcinoma. Hum Pathol. 2010;41(4):477–84.

    CAS  PubMed  Google Scholar 

  108. Shibahara H, Tamada S, Goto M, et al. Pathologic features of mucin-producing bile duct tumors: two histopathologic categories as counterparts of pancreatic intraductal papillary-mucinous neoplasms. Am J Surg Pathol. 2004;28(3):327–38.

    PubMed  Google Scholar 

  109. Zhou H, Schaefer N, Wolff M, Fischer HP. Carcinoma of the ampulla of Vater: comparative histologic/immunohistochemical classification and follow-up. Am J Surg Pathol. 2004;28(7):875–82.

    PubMed  Google Scholar 

  110. Lok T, Chen L, Lin F, Wang HL. Immunohistochemical distinction between intrahepatic cholangiocarcinoma and pancreatic ductal adenocarcinoma. Hum Pathol. 2014;45(2):394–400.

    CAS  PubMed  Google Scholar 

  111. Di Tommaso L, Destro A, Seok JY, et al. The application of markers (HSP70 GPC3 and GS) in liver biopsies is useful for detection of hepatocellular carcinoma. J Hepatol. 2009;50(4):746–54.

    PubMed  Google Scholar 

  112. Weinreb I, Cunningham KS, Perez-Ordoñez B, Hwang DM. CD10 is expressed in most epithelioid hemangioendotheliomas: a potential diagnostic pitfall. Arch Pathol Lab Med. 2009;133(12):1965–8.

    PubMed  Google Scholar 

  113. Yesim G, Gupse T, Zafer U, Ahmet A. Mesenchymal hamartoma of the liver in adulthood: immunohistochemical profiles, clinical and histopathological features in two patients. J Hepatobiliary Pancreat Surg. 2005;12(6):502–7.

    PubMed  Google Scholar 

  114. Doi H, Horiike N, Hiraoka A, et al. Primary hepatic marginal zone B cell lymphoma of mucosa-associated lymphoma of mucosa-associated lymphoid tissue type: case report and review of the literature. Int J Hematol. 2008;88(4):418. 23.

    PubMed  Google Scholar 

  115. Anagnostopoulos G, Sakorafas GH, Grigoriadis K, Kostopoulos P. Malignant fibrous histiocytoma of the liver: a case report and review of the literature. Mt Sinai J Med. 2005;72(1):50–2.

    PubMed  Google Scholar 

  116. Fujita S, Lauwers GY. Primary hepatic malignant fibrous histiocytoma: report of a case and review of the literature. Pathol Int. 1998;48(3):225–9.

    CAS  PubMed  Google Scholar 

  117. Chu PG, Schwarz RE, Lau SK, Lau SK, Yen Y, Weiss LM. Immunohistochemical staining in the diagnosis of pancreatobiliary and ampulla of Vater adenocarcinoma: application of CDX2, CK17, MUC1, and MUC2. Am J Surg Pathol. 2005;29(3):359–67.

    PubMed  Google Scholar 

  118. Lin F, Shi J, Liu H, et al. Diagnostic utility of S100P and von Hippel-Lindau gene product (pVHL) in pancreatic adenocarcinoma-with implication of their roles in early tumorigenesis. Am J Surg Pathol. 2008;32(1):78–91.

    PubMed  Google Scholar 

  119. Lu D, Vohra P, Chu PG, et al. An oncofetal protein IMP3: a new molecular marker for the detection of esophageal adenocarcinoma and high-grade dysplasia. Am J Surg Pathol. 2009;33(4):521–5.

    PubMed  Google Scholar 

  120. Di Tommaso L, Franchi G, Park YN, et al. Diagnostic value of HSP70, glypican 3, and glutamine synthetase in hepatocellular nodules in cirrhosis. Hepatology. 2007;45(3):725–34.

    PubMed  Google Scholar 

  121. Hytiroglou P, Theise ND. Differential diagnosis of hepatocellular nodular lesions. Semin Diagn Pathol. 1998;15(4):285–99.

    CAS  PubMed  Google Scholar 

  122. Libbrecht L, Severi T, Cassiman D, et al. Glycipan-3 expression distinguishes small hepatocellular carcinomas from cirrhosis, dysplastic nodules, and focal nodular hyperplasia-like nodules. Am J Surg Pathol. 2006;30(11):1405–11.

    PubMed  Google Scholar 

  123. Roskams T, Kojiro M. Pathology of early hepatocellular carcinoma: conventional and molecular diagnosis. Semin Liver Dis. 2010;30(1):17–25.

    PubMed  Google Scholar 

  124. Masood S, West AB, Barwick KW. Expression of steroid hormone receptors in benign hepatic tumors. An immunocytochemical study. Arch Pathol Lab Med. 1992;116(12):1355–9.

    CAS  PubMed  Google Scholar 

  125. Yamamoto M, Nakajo S, Tahara E. Immunohistochemical analysis of estrogen receptors in human gallbladder. Acta Pathol Jpn. 1990;40(1):14–21.

    CAS  PubMed  Google Scholar 

  126. Esheba GE, Longacre TA, Atkins KA, Higgins JP. Expression of the urothelial differentiation markers GATA3 and placental S100 (S100P) in female genital tract transitional cell proliferations. Am J Surg Pathol. 2009;33(3):347–53.

    PubMed  Google Scholar 

  127. Nagata S, Ajioka Y, Nishikura K, et al. Co-expression of gastric and biliary phenotype in pyloric-gland type adenoma of the gallbladder: immunohistochemical analysis of mucin profile and CD10. Oncol Rep. 2007;17(4):721–9.

    CAS  PubMed  Google Scholar 

  128. Harder J, Waiz O, Otto F, et al. EGFR and HER2 expression in advanced biliary tract cancer. World J Gastroenterol. 2009;15(36):4511–7.

    PubMed Central  PubMed  Google Scholar 

  129. Kandil DH, Cooper K. Glypican-3: a novel diagnostic marker for hepatocellular carcinoma and more. Adv Anat Pathol. 2009;16(2): 125–9.

    CAS  PubMed  Google Scholar 

  130. Machado I, Noguera R, Santonja N, et al. Immunohistochemical study as a tool in differential diagnosis of pediatric malignant rhabdoid tumor. Appl Immunohistochem Mol Morphol. 2010; 18(2):150–8.

    PubMed  Google Scholar 

  131. Yuri T, Danbara N, Shikata N, et al. Malignant rhabdoid tumor of the liver: case report and literature review. Pathol Int. 2004;54(8):623–9.

    PubMed  Google Scholar 

  132. Guglielmi A, Frameglia M, Iuzzolino P, et al. Solitary fibrous tumor of the liver with CD 34 positivity and hypoglycemia. J Hepatobiliary Pancreat Surg. 1998;5(2):212–6.

    CAS  PubMed  Google Scholar 

  133. Jarmay K, Gallai M, Karacsony G, et al. Decorin and actin expression and distribution in patients with chronic hepatitis C following interferon-alpha-2b-treatment. J Hepatol. 2000;32(6):993–1002.

    CAS  PubMed  Google Scholar 

  134. Knittel T, Kobold D, Saile B, et al. Rat liver myofibroblasts and hepatic stellate cells: different cell populations of the fibroblast lineage with fibrogenic potential. Gastroenterology. 1999;117:1205–21.

    CAS  PubMed  Google Scholar 

  135. Moreira RK. Hepatic stellate cells and liver fibrosis. Arch Pathol Lab Med. 2007;131(11):1728–34.

    CAS  PubMed  Google Scholar 

  136. Gu K, Shah V, Ma C, Zhang L, Yang M. Cytoplasmic immunoreactivity of thyroid transcription factor-1 (clone 8G7G3/1) in hepatocytes: true positivity or cross-reaction? Am J Clin Pathol. 2007;128(3):382–8.

    CAS  PubMed  Google Scholar 

  137. Pan CC, Chen PC, Tsay SH, Chiang H. Cytoplasmic immunoreactivity for thyroid transcription factor-1 in hepatocellular carcinoma. A comparative immunohistochemical analysis of four commercial antibodies using a tissue array technique. Am J Clin Pathol. 2004;121(3):343–49.

    CAS  PubMed  Google Scholar 

  138. Van Rossen E, Vander Borght S, van Grunsven LA, et al. Vinculin and cellular retinol-binding protein-1 are markers for quiescent and activated hepatic stellate cells in formalin-fixed paraffin embedded human liver. Histochem Cell Biol. 2009;131(3):313–25.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Immunohistochemistry, Geisinger Medical Center, 100 N. Academy Avenue, Danville, PA, 17822, USA

    Zongming E. Chen MD, PhD

  2. Pathology and Laboratory Medicine, Geisinger Medical Center, Danville, PA, USA

    Zongming E. Chen MD, PhD, Jeffrey Prichard DO & Fan Lin MD, PhD

  3. Surgical Pathology, Geisinger Medical Center, Danville, PA, USA

    Jeffrey Prichard DO

  4. Anatomic Pathology, Geisinger Medical Center, Danville, PA, USA

    Fan Lin MD, PhD

Authors
  1. Zongming E. Chen MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeffrey Prichard DO
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fan Lin MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zongming E. Chen MD, PhD .

Editor information

Editors and Affiliations

  1. Laboratory Medicine, Geisinger Health System, Danville, Pennsylvania, USA

    Fan Lin

  2. Laboratory Medicine, Geisinger Medical Center, Danville, Pennsylvania, USA

    Jeffrey Prichard

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this chapter

Cite this chapter

Chen, Z.E., Prichard, J., Lin, F. (2015). Liver, Bile Ducts and Gallbladder. In: Lin, F., Prichard, J. (eds) Handbook of Practical Immunohistochemistry. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1578-1_26

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-1578-1_26

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-1577-4

  • Online ISBN: 978-1-4939-1578-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation