Comparative immunohistochemical characteristics of hepatocellular, cholangiocellular cancer and liver metastases of pancreatic cancer in puncture trephine biopsy of the liver
DOI:
https://doi.org/10.14739/2310-1210.2015.5.53775Keywords:
Cholangiocellular And Hepatocellular Carcinoma, Combined Hepatocellular-Cholangiocarcinoma, Metastases Pancreatic Cancer, Expression Of Immunohistochemical MarkersAbstract
Aim. Differential immunohistochemical parameters of primary liver cancer and liver metastases of ductal pancreatic cancer (DPC) were studied in puncture trephine biopsy of the liver of 23 patients with hepatocellular carcinoma (HCC), 2 patients combined hepato-cholangiocellular cancer (CHCC), 15 patients cholangiocellular cancer (CCC) and 12 patients with metastatic DPC.
Results. It was found that HCC liver is characterized by high levels of expression of HepPar 1 and alpha-fetoprotein, the lack of expression of MUC1 mucins, MUC5AC and CA125, and variable expression of CK8, CK7, SK19 and CK20, which depends on the degree of tumor differentiation and embodiment. Cholangiocellular liver cancer differs from others expressed desmoplastic stroma, high levels of expression of cytokeratins 7 and 19, MUC1 and MUC5AC, lack expression of HepPar 1 and variable expression of alpha-fetoprotein, cytokeratin 8 and20. Insolid and trabecular patterns of CHCC expression of HepRar 1, AFP and CK20 were determined, and in ductual patterne- CK7 and CK19 were determined. CCC and liver metastases of DPC which have the similar microstructure were characterized with the same spectrum characteristic of expressed cytokeratin (SK7, + 19, + 20, +) and mucin (MUC1 + MUC5AC +), and variable expression of CA125 and CA19-9.
Conclusion. Therefore, the differential diagnosis in immunohistochemistry of liver trepanobioptate between CCC and liver metastases of DPC is only possible based on the data of computed tomography or ultrasound examination of the liver and pancreas.
References
Ferlay, J., Soerjomataram, I., Dikshit, R., Dikshit, R., Eser, S., Mathers, C., et al. (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer, 136(5), E359–E386. doi: 10.1002/ijc.29210.
Ferlay J., Shin H.R., Bray F., Forman, D., Mathers, C., Parkin, D. M., et al. (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer., 127(12), 2893–2917. doi: 10.1002/ijc.25516.
Venook, A. P., Papandreou, C., Furuse, J., & de Guevara, L. L. (2010) The incidence and epidemiology of hepatocellular carcinoma: a global and regional perspective. Oncologist, 15, 5–13. doi: 10.1634/theoncologist.2010-S4-05.
Forner A., Reig M.E., de Lope C.R., Bruix J. Current strategy for staging and treatment: the BCLC update and future prospects // Semin Liver Dis. – 2010. – V.30. – P.61–74.
Colombo, M., & Sangiovanni, A. (2015) Treatment of hepatocellular carcinoma: beyond international guidelines. Liver International., 35(1), 129–138. doi: 10.1111/liv.12713.
Bosman, F.T., Carneiro, F., Hruban, R. H., Theise, N. D. (Eds.) (2010) The WHO Classification of Tumours of the Digestive System (IARC WHO Classification of Tumours). WHO
Nakanuma, Y., & Kakuda, Y. (2015) Pathologic classification of cholangiocarcinoma: New concepts. Best Pract Res Clin Gastroenterol., 29(2), 277–293. doi: 10.1016/j.bpg.2015.02.006.
Guedj, N., Bedossa, P., & Paradis, V. (2010) Anatomopathologie des cholangiocarcinomes. Ann Pathol., 30(6), 455–463. doi: 10.1016/j.annpat.2010.10.004.
McKenna, B., & Bihlmeyer, Sh. (2010) Pathology of hepatocellular carcinoma, cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma. Primary Carcinomas of the Liver. J.E. Adviser (Ed). Husband: Cambridge University Press, (p. 16–32).
Suriawinata, A. A., & Thung, S. N. (Eds.) (2011) Liver Pathology. An Atlas and Cоncise Guide. N. Y.: demosMEDICAL.
Tumanskiy, V. A. & Zubko, M. D. (2014) Gepatocellyulyarnaya karcinoma: osobennosti mikrostruktury i e′kspressii HepPar-1. alfa-fetoproteina. tsitokeratinov 7 i 20 [Hepatocellular carcinoma: microstructure and expression features of hepatocyte marker, alpha-fetoprotein, cytokeratins 7 and 20 in hepatocellular carcinoma and cholangiocellular carcinoma]. Patologіya, 1(30), 45–50. [in Ukrainian].
Ferrel, L., & Kakar, S. (2013) Tumors of the Liver. Biliary Tree and Gallbladder. Diagnostic histopathology of tumors. Ch.D.M. Fletcher (Ed.). (Vol. 4), (p. 477–530). Saunders: Philadelphia.
Tumanskiy, V. A., & Zubko, M. D. (2014) Characteristic of expression levels of HepPar-1, alpha-fetoprotein, cytokeratin 7 and 20 by cells of cholangiocellular cancer in trephine biopsy of the liver. Zaporozhskij medicinskij zhurnal, 5(86), 55–58. [in Ukrainian].
Schlageter, M., Terracciano, L. M., D’Angelo, S., & Sorrentino, P. (2014) Histopathology of hepatocellular carcinoma. World J Gastroenterol., 20(43), 15955–15964. doi: 10.3748/wjg.v20.i43.15955.
Zhang, F., Chen, X. P., Zhang, W., Dong, H. H., Xiang, S., Zhang, W. G., & Zhang, B. X. (2008) Combined hepatocellular cholangiocarcinoma originating from hepatic progenitor cells: immunohistochemical and double-fluorescence immunostaining evidence. Histopathology, 52, 224–232. doi: 10.1111/j.1365-2559.2007.02929.x.
Rizvi, S., & Gores, G. J. (2013) Pathogenesis, Diagnosis, and Management of Cholangiocarcinoma. Gastroenterology, 145(6), 1215–1229. doi: 10.1053/j.gastro.2013.10.013.
Komuta, M., Govaere, O., Vandecaveye, V., Akiba, J., Van Steenbergen, W., Verslype, C., et al. (2012) Histological Diversity in Cholangiocellular Carcinoma Reflects the Different Cholangiocyte Phenotypes. Hepathology, 55, 876–1888. doi: 10.1002/hep.25595.
Karabork, A., Kaygusuz, G., & Ekinci, C. (2010) The best immunohistochemical panel for differentiating hepatocellular carcinoma from metastatic adenocarcinoma. Pathol Res Pract., 206(8), 572–577. doi: 10.1016/j.prp.2010.03.004.
Pozharisski, K. M., Granov, D. A., Ten, V. P., Kudaibergenova, A. G., Leenman, E. E., & Rasskazov, A. I. (2008) Znachenie immunogistokhimii dlya izucheniya novoobrazovanij pecheni: differencialnyj diagnoz, prognosticheskie markery [The importance of immunohistochemistry in hepatic neoplasia research: differential analysis, prognostic markers]. Voprosy onkologii, 4, 417–433. [in Russian].
Geller, S. A., & Petrovic, L. M. (2009) Primary and Metastatic Malignant Tumors of the Liver. Biopsy Interpretation of the Liver. Lippincott Williams & Wilkins (LWW).
Lugli, A., Tornillo, L., Mirlacher, M., Bundi, M., Sauter, G., & Terracciano, L. M. (2004) Hepatocyte paraffin 1 expression in human normal and neoplastic tissues: tissue microarray analysis on 3,940 tissue samples. Am J Clin Pathol., 122, 721–727.
Radwan, N. A., & Ahmed, N. S. (2012) The diagnostic value of arginase-1 immunostaining in differentiating hepatocellular carcinoma from metastatic carcinoma and cholangiocarcinoma as compared to HepPar-1. Diagn Pathol., 7, 149. doi: 10.1186/1746-1596-7-149.
Koehne de Gonzalez, A. K., Salomao, M. A., & Lagana, S. M. (2015) Current concepts in the immunohistochemical evaluation of liver tumors. World J Hepatol., 7(10), 1403–1411. doi: 10.4254/wjh.v7.i10.1403.
Krings, G., Ramachandran, R., Jain, D., Wu, T. T., Yeh, M. M., Torbenson, M., & Kakar, S. (2013) Immunohistochemical pitfalls and the importance of glypican 3 and arginase in the diagnosis of scirrhous hepatocellular carcinoma. Mod Pathol., 26, 782–791. doi: 10.1038/modpathol.2012.243.
Mounajjed, T., Zhang, L., & Wu, T. T. (2013) Glypican-3 expression in gastrointestinal and pancreatic epithelial neoplasms. Hum Pathol., 44, 542–550. doi: 10.1016/j.humpath.2012.06.016.
Ishchenko, V. G. (2012) Profilaktyka ta likuvannia metastatychnoho urazhennia pechinky pry kolorektalnomu raku (Avtoref. dis… dokt. med. nauk) [Prevention and treatment of metastatic liver disease in colorectal cancer. Dr. med. sci. diss.] Doneck. [in Ukrainian].
(2009) The International Consensus Group for Hepatocellular Neoplasia.Pathologic diagnosis of early hepatocellular carcinoma: a report of the international consensus group for hepatocellular neoplasia. Hepatology, 49, 658–664. doi: 10.1002/hep.22709.
Basturk, О., Farris III, А. В., & Adsay, N. V. (2010) Immunohistology of the Pancreas, Biliary Tract and Liver. Diagnostic immunohistochemistry: theranostic and genomic applications. D.J. Dabbs (Ed), (p. 541–592). Philadelphia: Saunders/Elsevier.
Wee, А. (2005) Distinction between Well-Differentiated Hepatocellular Carcinoma and Benign Hepatocellular Nodular Lesions, Using Fine-Needle Aspiration Biopsy. Handbook of Immunohistochemistry and in situ Hybridization of Human Carcinomas, 3, 247–259.
Lau, S. K., Prakash, S., Geller, S. A., & Alsabeh, R. (2003) Comparative immunohistochemical profile of hepatocellular carcinoma, cholangiocarcinoma, and metastatic adenocarcinoma. Hum. Pathol., 33, 1175–1181. doi: 10.1053/hupa.2002.130104.
Gusarev, S. A. (2006) Patologoanatomicheskaya kharakteristika pervichnogo i metastaticheskogo raka pecheni (Avtoref. dis…kand. med. nauk) [Pathologic characteristics of primary and metastatic liver cancer. Dr. med. sci. diss.]. Moscow [in Russian].
Ryu, H. S., Lee, K., Shin, E.,Kim, S. H., Jing, J., Jung, H. Y., et al. (2012) Comparative analysis of immunohistochemical markers for differential diagnosis of hepatocelluar carcinoma and cholangiocarcinoma. Tumori., 98(4), 478–484. doi: 10.1700/1146.12643.
Durnez, A., Verslype, C., Nevens, F., Fevery, J., Aerts, R., Pirenne, J., et al. (2006) The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma. A possible progenitor cell origin. Histopathology, 49, 138–151.
Matsuura, S., Aishima, S., Taguchi, K., Asayama, Y., Terashi, T., Honda, H., & Tsuneyoshi, M. (2005) 'Scirrhous' type hepatocellular carcinomas: a special reference to expression of cytokeratin 7 and hepatocyte paraffin. Histopathology, 47(4), 382–390. doi: 10.1111/j.1365-2559.2005.02230.x.
Sugiki, T., Yamamoto, M., Taka, K., & Nakano, M. (2009) Specific characteristics of scirrhous hepatocellular carcinoma. Hepatogastroenterology, 56(93), 1086–1089.
Park, S. Y., Roh, S. J., Kim, Y. N., Kim, S. Z., Park, H. S., Jang, K. Y., et al. (2009) Expression of MUC1, MUC2, MUC5AC and MUC6 in cholangiocarcinoma: prognostic impact. Oncol Rep., 22(3), 649–657. doi: 10.3892/or_00000485.
Makoto Osanai. (2005) Expression of Carbohydrate Antigens in Pancreatic Cancer. Handbook of Immunohistochemistry and in situ Hybridization of Human Carcinomas, 3, 341–350. doi:10.1016/S1874-5784(05)80039-X.
Streppel, M. M., Vincent, А., Mukherjee, R., Campbell, N. R., Chen, S. H., Konstantopoulos, K., et al. (2012) Mucin 16 (cancer antigen 125) expression in human tissues and cell lines and correlation with clinical outcome in adenocarcinomas of the pancreas, esophagus, stomach, and colon. Human Pathology, 43, 1755–1763. doi: 10.1016/j.humpath.2012.01.005.
Dennis, J. L., Hvidsten, T. R., Wit, E. C., Komorowski, J., Bell, A. K., Downie, I., et al. (2005) Markers of adenocarcinoma characteristic of the site of origin: development of a diagnostic algorithm. Clin Cancer Res., 11(10), 3766–3772. doi: 10.1158/1078-0432.CCR-04-2236.
Higashi, M., Yamada, N., Yokoyama, S., Kitamoto, S., Tabata, K., Koriyama, C., et al. (2012) Pathobiological implications of MUC16/CA125 expression in intrahepatic cholangiocarcinoma-mass forming type. Pathobiology, 79(2), 101–106. doi: 10.1159/000335164.
Werling, R. W., Yaziji, H., Bacchi, C. E., & Gown, A. M. (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), 303–310. doi:10.1097/00000478-200303000-00003.
Kaimaktchiev, V., Terracciano, L., Tornillo, L., Spichtin, H., Stoios, D., Bundi, M., et al. (2004) The homeobox intestinal differentiation factor CDX2 is selectively expressed in gastrointestinal adenocarcinomas. Modern Pathology, 17, 1392–1399.
Babichenko, I. I. & Kovyazin, V. A. (2008) Novyye metody immunogistokhimicheskoj diagnostiki opukholevogo rosta [New methods of immunohistochemical diagnostic of tumor growth]. Moscow. [in Russian].
Suriawinata, A. A., & Thung, S. N. (2011) Liver pathology: an atlas and concise guide. N. Y.: demosMEDICAL.
Cardinale, V., Bragazzi, M. C., Carpino, G., Torrice, A., Fraveto, A., Gentile, R., et al. (2013) Cholangiocarcinoma: increasing burden of classifications. Hepatobiliary Surg Nutr, 2(5), 272–780. doi: 10.3978/j.issn.2304-3881.2013.10.02.
Massani, M., Stecca, T., Fabris, L., Caratozzolo, E., Ruffolo, C., Furlanetto, A., et al. (2013) Isolation and characterization of biliary epithelial and stromal cells from resected human cholangiocarcinoma: a novel in vitro model to study tumor-stroma interactions. Oncol Rep., 30, 1143–1148. doi: 10.3892/or.2013.2568.
Apte, M. V., Park, S., Phillips, P.A., Santucci, N., Goldstein, D., Kumar, R. K., et al. (2004) Desmoplastic Reaction in Pancreatic Cancer. Role of Pancreatic Stellate Cells. Pancreas, 29, 179–187.
Tumanskiy, V. A., Evseyev, A. V., & Kovalenko, I. S. (2015) Kolichestvennye pokazateli e′kspressii stromal′nykh markerov v podzheludochnoj zheleze pri protokovoj adenokartsinome i khronicheskom pankreatite [Quantitative indexes of stromal markers expression in the pancreatic ductal adenocarcinoma and chronic pancreatitis]. Patologіya, 2(34), 26–30. [in Ukrainian].
Downloads
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)