Der Pathologe

, Volume 27, Issue 4, pp 244–250 | Cite as

Bedeutung der Immunhistochemie für die Diagnose des Cholangiokarzinoms

Schwerpunkt: Lebertumoren

Zusammenfassung

Dem Immunphänotyp kommt bei der histogenetischen Zuordnung von Karzinomen wachsende Bedeutung zu. Für Cholangiokarzinome (CC) trifft dies zum einen aufgrund der zunehmenden Zahl kleiner diagnostischer Proben mit eingeschränkter morphologischer Aussagekraft zu, zum anderen treten in der Leber eine Vielzahl metastasierter Adenokarzinome mit morphologischen Überlappungen zum CC auf. Zur Immunphänotypisierung von Tumoren können Intermediärfilamente, Glykoproteine, Mukoproteine, Adhäsionsmoleküle und Rezeptoren oder auch Transkriptionsfaktoren und die Proteinprodukte von Tumorsuppressorgenen herangezogen werden. In der vorliegenden Übersicht wird das Expressionmuster des CC und der häufigsten Karzinommetastasen in der Leber für 30 in der Literatur gut dokumentierte Antikörper vergleichend dargestellt. Das typische CC weist folgenden Immunphänotyp auf: Ck 7+, Ck 17+, CD 7+, CDX 2. Wenngleich dieser Phänotyp eine gute Abgrenzung gegenüber den meisten metastasierten Karzinomen erlaubt, zeigen Pankreaskarzinome und CC einen auch entwicklungsgeschichtlich naheliegenden Überlappungsbereich des Immunphänotyps, sodass eine zuverlässige immunhistologische Abgrenzung dieser Tumoren oft nicht möglich ist.

Schüsselwörter

Cholangiokarzinom (CC) Metastase Karzinom Leber Immunhistologie 

The importance of immunohistochemistry for the diagnosis of cholangiocarcinomas

Abstract

The correct diagnosis of intrahepatic cholangiocarcinoma (CC) is often confounded by the small size of the diagnostic specimen and the wide morphological range of carcinomas metastasising to the liver. Expression analysis of cytokeratins, glycoproteins, mucoproteins, adhesion molecules, receptors and transcription factors has been shown to be a valuable adjunct in the typing of carcinomas. For this study, the expression pattern of 30 well documented antibodies to CC and the most common metastatic adenocarcinomas of the liver were studied. CC show a rather distinct immunophenotype with co-expression of CK7, CK17, CD7 and a lack of CDX2. Although this pattern allows the separation of CC from most metastatic carcinomas, pancreatic carcinomas show a broad overlap with this expression pattern.

Keywords

Cholangiocarcinoma Carcinoma Liver Metastasis Immunohistology 

Notes

Interessenkonflikt

Es besteht kein Interessenkonflikt. Der korrespondierende Autor versichert, dass keine Verbindungen mit einer Firma, deren Produkt in dem Artikel genannt ist, oder einer Firma, die ein Konkurrenzprodukt vertreibt, bestehen. Die Präsentation des Themas ist unabhängig und die Darstellung der Inhalte produktneutral.

Literatur

  1. 1.
    Ashida K, Terada T, Kitamura Y, Kaibara N (1998) Expression of E-cadherin, alpha-catenin, beta-catenin, and CD44 (standard and variant isoforms) in human cholangiocarcinoma: an immunohistochemical study. Hepatology 27(4): 974–982CrossRefPubMedGoogle Scholar
  2. 2.
    Chu PG, Arber DA, Weiss LM (2003) Expression of T/NK-cell and plasma cell antigens in nonhematopoietic epithelioid neoplasms. An immunohistochemical study of 447 cases. Am J Clin Pathol 120(1): 64–70CrossRefPubMedGoogle Scholar
  3. 3.
    Chu PG, Schwarz RE, Lau SK et al. (2005) Immunohistochemical staining in the diagnosis of pancreatobiliary and ampulla of Vater adenocarcinoma: application of CDX2, CK17, MUC1, and MUC2. Am J Surg Pathol 29(3): 359–367CrossRefPubMedGoogle Scholar
  4. 4.
    Dennis JL, Hvidsten TR, Wit EC et al. (2005) Markers of adenocarcinoma characteristic of the site of origin: development of a diagnostic algorithm. Clin Cancer Res 11(10): 3766–3772CrossRefPubMedGoogle Scholar
  5. 5.
    Han JH, Kang Y, Shin HC et al. (2003) Mammaglobin expression in lymph nodes is an important marker of metastatic breast carcinoma. Arch Pathol Lab Med 127(10): 1330–1334PubMedGoogle Scholar
  6. 6.
    Hornick JL, Lauwers GY, Odze RD (2005) Immunohistochemistry can help distinguish metastatic pancreatic adenocarcinomas from bile duct adenomas and hamartomas of the liver. Am J Surg Pathol 29(3): 381–389CrossRefPubMedGoogle Scholar
  7. 7.
    Immunoquery – Datenbankabfrage (Stand 01.11.2005): http://www.ipox.org
  8. 8.
    Ishikawa A, Sasaki M, Ohira S et al. (2004) Aberrant expression of CDX2 is closely related to the intestinal metaplasia and MUC2 expression in intraductal papillary neoplasm of the liver in hepatolithiasis. Lab Invest 84(5): 629–638CrossRefPubMedGoogle Scholar
  9. 9.
    Kende AI, Carr NJ, Sobin LH (2003) Expression of cytokeratins 7 and 20 in carcinomas of the gastrointestinal tract. Histopathology 42: 137–140CrossRefPubMedGoogle Scholar
  10. 10.
    Khan SA, Thomas HC, Davidson BR, Taylor-Robinson SD (2005) Cholangiocarcinoma. Lancet 366(9493): 1303–1314CrossRefPubMedGoogle Scholar
  11. 11.
    Lau SK, Prakash S, Geller SA, Alsabeh R (2002) Comparative immunohistochemical profile of hepatocellular carcinoma, cholangiocarcinoma, and metastatic adenocarcinoma. Hum Pathol 33(12): 1175–1181CrossRefPubMedGoogle Scholar
  12. 12.
    Lau SK, Weiss LM, Chu PG (2004) Differential expression of MUC1, MUC2, and MUC5AC in carcinomas of various sites: an immunohistochemical study. Am J Clin Pathol 122(1): 61–69CrossRefPubMedGoogle Scholar
  13. 13.
    Lugli A, Tornillo L, Mirlacher M et al. (1994) Hepatocyte paraffin 1 expression in human normal and neoplastic tissues: tissue microarray analysis on 3,940 tissue samples. Am J Clin Pathol 122(5): 721–727CrossRefGoogle Scholar
  14. 14.
    Morrison C, Marsh W Jr, Frankel WL (2002) A comparison of CD10 to pCEA, MOC-31, and hepatocyte for the distinction of malignant tumors in the liver. Mod Pathol 15(12): 1279–1287CrossRefPubMedGoogle Scholar
  15. 15.
    Nash JW, Morrison C, Frankel WL (2003) 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 127(12): 1591–1595PubMedGoogle Scholar
  16. 16.
    Rakha EA, Boyce RW, Abd El-Rehim D et al. (2005) Expression of mucins (MUC1, MUC2, MUC3, MUC4, MUC5AC and MUC6) and their prognostic significance in human breast cancer. Mod Pathol 18(10): 1295–1304CrossRefPubMedGoogle Scholar
  17. 17.
    Rullier A, Le Bail B, Fawaz R et al. (2000) 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 24(6): 870–876CrossRefPubMedGoogle Scholar
  18. 18.
    Sasaki A, Kawano K, Aramaki M et al. (1999) Immunohistochemical expression of cytokeratins in intrahepatic cholangiocarcinoma and metastatic adenocarcinoma of the liver. J Surg Oncol 70(2): 103–108CrossRefPubMedGoogle Scholar
  19. 19.
    Shimonishi T, Miyazaki K, Nakanuma Y (2000) Cytokeratin profile relates to histological subtypes and intrahepatic location of intrahepatic cholangiocarcinoma and primary sites of metastatic adenocarcinoma of liver. Histopathology 37(1): 55–63CrossRefPubMedGoogle Scholar
  20. 20.
    Tan G, Yilmaz A, De Young BR et al. (2004) Immunohistochemical analysis of biliary tract lesions. Appl Immunohistochem Mol Morphol 12(3): 193–197PubMedGoogle Scholar
  21. 21.
    Tannapfel A, Weinans L, Geissler F et al. (2000) Mutations of p53 tumor suppressor gene, apoptosis, and proliferation in intrahepatic cholangiocellular carcinoma of the liver. Dig Dis Sci 45(2): 317–324CrossRefPubMedGoogle Scholar
  22. 22.
    Tickoo SK, Zee SY, Obiekwe S et al. (2002) Combined hepatocellular-cholangiocarcinoma: a histopathologic, immunohistochemical, and in situ hybridization study. Am J Surg Pathol 26(8): 989–997CrossRefPubMedGoogle Scholar
  23. 23.
    Torbenson M, Kannangai R, Abraham S et al. (2004) Concurrent evaluation of p53, beta-catenin, and alpha-fetoprotein expression in human hepatocellular carcinoma. Am J Clin Pathol 122(3): 377–382CrossRefPubMedGoogle Scholar
  24. 24.
    Vlasoff DM, Baschinsky DY, Frankel WL (2002) Cytokeratin 5/6 immunostaining in hepatobiliary and pancreatic neoplasms. Appl Immunohistochem Mol Morphol 10(2): 147–151CrossRefPubMedGoogle Scholar
  25. 25.
    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(3): 303–310CrossRefPubMedGoogle Scholar

Copyright information

© Springer Medizin Verlag 2006

Authors and Affiliations

  1. 1.Institut für PathologieMedizinische HochschuleHannover

Personalised recommendations