Z Gastroenterol 2017; 55(06): 575-581
DOI: 10.1055/s-0043-102581
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Update on cholangiocarcinoma: potential impact of genomic studies on clinical management

Update zum Cholangiokarzinom: potentieller Einfluss genomischer Studien auf das klinische Management
Dirk Walter
1   Department of Internal Medicine I, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany
,
Sylvia Hartmann
2   Johann Wolfgang Goethe-University Hospital, Dr. Senckenberg Institute of Pathology, Frankfurt, Germany
,
Oliver Waidmann
1   Department of Internal Medicine I, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany
› Author Affiliations
Further Information

Publication History

06 October 2016

25 January 2017

Publication Date:
04 April 2017 (online)

Abstract

The term cholangiocarcinoma (CCA) comprises neoplasms of the intrahepatic, perihilar, and distal bile duct. Five-year survival rates of patients with CCA are below 20 %, and no targeted therapy could prove a benefit in comparison to the standard treatment of cisplatinum and gemcitabine. In recent years, next generation sequencing studies revealed a profound genomic heterogeneity of CCA subtypes potentially affecting the design of future therapy trials. This review provides a concise update on current clinical management of CCA including data of recent genomic studies and differences between CCA subtypes.

Zusammenfassung

Die Entität Cholangiokarzinom (CCA) beinhaltet Neoplasien aus dem intrahepatischen, perihilären und distalen Gallengang. Weniger als 20 % der Patienten mit einem CCA überleben länger als 5 Jahre und bislang konnte keine zielgerichtete Therapie einen Überlebensvorteil gegenüber dem Standard aus Cisplatin und Gemcitabine zeigen. In den letzten Jahren haben Next-Generation-Sequencing Daten beim CCA und seinen Subtypen eine ausgeprägte genetische Heterogenität offenbart, welche die Planung zukünftiger Therapiestudien beeinflussen könnte. Diese Arbeit soll einen kompakten Überblick zur aktuellen Diagnostik und Therapie des CCA geben und in diesem Rahmen auch auf Daten aus Sequenzierungsstudien sowie auf die Unterschiede der CCA-Subtypen eingehen.

 
  • References

  • 1 Deoliveira ML. Schulick RD. Nimura Y. et al. New staging system and a registry for perihilar cholangiocarcinoma. Hepatology 2011; 53: 1363-1371
  • 2 Nakeeb A. Pitt HA. Sohn TA. et al. Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors. Ann Surg 1996; 224: 463-473
  • 3 Kaatsch P. Spix C. Katalinic A. et al. Krebs in Deutschland 2011/2012. Berlin: Robert Koch-Institut (Hrsg) und die Gesellschaft der epidemiologischen Krebsregister in Deutschland e.V. (Hrsg); 2015
  • 4 Brandi G. Farioli A. Astolfi A. et al. Genetic heterogeneity in cholangiocarcinoma: a major challenge for targeted therapies. Oncotarget 2015; 6: 14744-14753
  • 5 Sirica AE. Gores GJ. Desmoplastic stroma and cholangiocarcinoma: clinical implications and therapeutic targeting. Hepatology 2014; 59: 2397-2402
  • 6 Bridgewater J. Galle PR. Khan SA. et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol 2014; 60: 1268-1289
  • 7 DeOliveira ML. Cunningham SC. Cameron JL. et al. Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution. Ann Surg 2007; 245: 755-762
  • 8 Welzel TM. McGlynn KA. Hsing AW. et al. Impact of classification of hilar cholangiocarcinomas (Klatskin tumors) on the incidence of intra- and extrahepatic cholangiocarcinoma in the United States. J Natl Cancer Inst 2006; 98: 873-875
  • 9 Njei B. Changing pattern of epidemiology in intrahepatic cholangiocarcinoma. Hepatology 2014; 60: 1107-1108
  • 10 von Hahn T. Ciesek S. Wegener G. et al. Epidemiological trends in incidence and mortality of hepatobiliary cancers in Germany. Scand J Gastroenterol 2011; 46: 1092-1098
  • 11 Khan SA. Emadossadaty S. Ladep NG. et al. Rising trends in cholangiocarcinoma: is the ICD classification system misleading us?. J Hepatol 2012; 56: 848-854
  • 12 Broomé U. Olsson R. Lööf L. et al. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut 1996; 38: 610-615
  • 13 Farrant JM. Hayllar KM. Wilkinson ML. et al. Natural history and prognostic variables in primary sclerosing cholangitis. Gastroenterology 1991; 100: 1710-1717
  • 14 Welzel TM. Graubard BI. El-Serag HB. et al. Risk factors for intrahepatic and extrahepatic cholangiocarcinoma in the United States: a population-based case-control study. Clin Gastroenterol Hepatol 2007; 5: 1221-1228
  • 15 Shin HR. Oh JK. Masuyer E. et al. Epidemiology of cholangiocarcinoma: an update focusing on risk factors. Cancer Sci 2010; 101: 579-585
  • 16 Albert J. Waidmann O. Welzel T. Das Gallengangskarzinom: Von neuen Erkenntnissen der Epidemiologie zur Früherkennung. Dtsch Med Wochenschr 2015; 140: 1431-1434
  • 17 Komuta M. Govaere O. Vandecaveye V. et al. Histological diversity in cholangiocellular carcinoma reflects the different cholangiocyte phenotypes. Hepatology 2012; 55: 1876-1888
  • 18 Komuta M. Spee B. Vander Borght S. et al. Clinicopathological study on cholangiolocellular carcinoma suggesting hepatic progenitor cell origin. Hepatology 2008; 47: 1544-1556
  • 19 Fan B. Malato Y. Calvisi DF. et al. Cholangiocarcinomas can originate from hepatocytes in mice. J Clin Invest 2012; 122: 2911-2915
  • 20 Cardinale V. Carpino G. Reid L. et al. Multiple cells of origin in cholangiocarcinoma underlie biological, epidemiological and clinical heterogeneity. World J Gastrointest Oncol 2012; 4: 94-102
  • 21 Yamasaki S. Intrahepatic cholangiocarcinoma: macroscopic type and stage classification. J Hepatobiliary Pancreat Surg 2003; 10: 288-291
  • 22 Bosman FT. Carneiro F. Hruban RH. et al. eds WHO Classification of Tumours of the Digestive System. 4th ed. WHO Press; 2010
  • 23 Sato Y. Sasaki M. Harada K. et al. Pathological diagnosis of flat epithelial lesions of the biliary tract with emphasis on biliary intraepithelial neoplasia. J Gastroenterol 2014; 49: 64-72
  • 24 Chan-On W. Nairismägi ML. Ong CK. et al. Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers. Nat Genet 2013; 45: 1474-1478
  • 25 Fujimoto A. Furuta M. Shiraishi Y. et al. Whole-genome mutational landscape of liver cancers displaying biliary phenotype reveals hepatitis impact and molecular diversity. Nat Commun 2015; 6: 6120
  • 26 Andersen JB. Spee B. Blechacz BR. et al. Genomic and genetic characterization of cholangiocarcinoma identifies therapeutic targets for tyrosine kinase inhibitors. Gastroenterology 2012; 142: 1021-1031
  • 27 Sia D. Hoshida Y. Villanueva A. et al. Integrative molecular analysis of intrahepatic cholangiocarcinoma reveals 2 classes that have different outcomes. Gastroenterology 2013; 144: 829-840
  • 28 Simbolo M. Fassan M. Ruzzenente A. et al. Multigene mutational profiling of cholangiocarcinomas identifies actionable molecular subgroups. Oncotarget 2014; 5: 2839-2852
  • 29 Arai Y. Totoki Y. Hosoda F. et al. Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma. Hepatology 2014; 59: 1427-1434
  • 30 Bailey P. Chang DK. Nones K. et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature 2016; 531: 47-52
  • 31 Guinney J. Dienstmann R. Wang X. et al. The consensus molecular subtypes of colorectal cancer. Nat Med 2015; 21: 1350-1356
  • 32 Andersen JB. Molecular pathogenesis of intrahepatic cholangiocarcinoma. J Hepatobiliary Pancreat Sci 2015; 22: 101-113
  • 33 Gerlinger M. Rowan AJ. Horswell S. et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 2012; 366: 883-892
  • 34 Zhang J. Fujimoto J. Zhang J. et al. Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing. Science 2014; 346: 256-259
  • 35 Yates LR. Gerstung M. Knappskog S. et al. Subclonal diversification of primary breast cancer revealed by multiregion sequencing. Nat Med 2015; 21: 751-759
  • 36 Kim TM. Jung SH. An CH. et al. Subclonal genomic architectures of primary and metastatic colorectal cancer based on intratumoral genetic heterogeneity. Clin Cancer Res 2015; 21: 4461-4472
  • 37 Valls C. Gumà A. Puig I. et al. Intrahepatic peripheral cholangiocarcinoma: CT evaluation. Abdom Imaging 2000; 25: 490-496
  • 38 Charatcharoenwitthaya P. Enders FB. Halling KC. et al. Utility of serum tumor markers, imaging, and biliary cytology for detecting cholangiocarcinoma in primary sclerosing cholangitis. Hepatology 2008; 48: 1106-1117
  • 39 Navaneethan U. Njei B. Lourdusamy V. et al. Comparative effectiveness of biliary brush cytology and intraductal biopsy for detection of malignant biliary strictures: a systematic review and meta-analysis. Gastrointest Endosc 2015; 81: 168-176
  • 40 Walter D. Peveling-Oberhag J. Schulze F. et al. Intraductal biopsies in indeterminate biliary stricture: evaluation of histopathological criteria in fluoroscopy- vs. cholangioscopy guided technique. Dig Liver Dis 2016; 48: 765-770
  • 41 Navaneethan U. Hasan MK. Lourdusamy V. et al. Single-operator cholangioscopy and targeted biopsies in the diagnosis of indeterminate biliary strictures: a systematic review. Gastrointest Endosc 2015; 82: 608-614
  • 42 Navaneethan U. Njei B. Venkatesh PGK. et al. Fluorescence in situ hybridization for diagnosis of cholangiocarcinoma in primary sclerosing cholangitis: a systematic review and meta-analysis. Gastrointest Endosc 2014; 79: 943-950
  • 43 Walter D. Herrmann E. Winkelmann R. et al. Role of CD15 expression in dysplastic and neoplastic tissue of the bile duct – a potential novel tool for differential diagnosis of indeterminate biliary stricture. Histopathology 2016; 69: 962-970
  • 44 Keira Y. Takasawa A. Murata M. et al. An immunohistochemical marker panel including claudin-18, maspin, and p53 improves diagnostic accuracy of bile duct neoplasms in surgical and presurgical biopsy specimens. Virchows Arch 2015; 466: 265-277
  • 45 Chen L. Huang K. Himmelfarb EA. et al. Diagnostic value of maspin in distinguishing adenocarcinoma from benign biliary epithelium on endoscopic bile duct biopsy. Hum Pathol 2015; 46: 1647-1654
  • 46 Erdogan D. Kloek JJ. ten Kate FJW. et al. Immunoglobulin G4-related sclerosing cholangitis in patients resected for presumed malignant bile duct strictures. Br J Surg 2008; 95: 727-734
  • 47 Domagk D. Poremba C. Dietl KH. et al. Endoscopic transpapillary biopsies and intraductal ultrasonography in the diagnostics of bile duct strictures: a prospective study. Gut 2002; 51: 240-244
  • 48 Juntermanns B. Kaiser GM. Reis H. et al. Klatskin-mimicking lesions: still a diagnostical and therapeutical dilemma?. Hepatogastroenterology 2011; 58: 265-269
  • 49 Chamberlain RS. Nashed C. Sakpal SV. et al. Eosinophilic cholangitis and cholangiopathy: a sheep in wolves clothing. HPB Surg 2010; 2010: 906496
  • 50 Walter D. Hartmann S. Herrmann E. et al. Eosinophilic cholangitis is a potentially underdiagnosed etiology in indeterminate biliary stricture.. World J Gastroenterol. 2017; 23: 1044
  • 51 Juntermanns B. Sotiropoulos GC. Radunz S. et al. Comparison of the sixth and the seventh editions of the UICC classification for perihilar cholangiocarcinoma. Ann Surg Oncol 2013; 20: 277-284
  • 52 Bismuth H. Corlette MB. Intrahepatic cholangioenteric anastomosis in carcinoma of the hilus of the liver. Surg Gynecol Obstet 1975; 140: 170-178
  • 53 Plentz RR. Malek NP. Clinical presentation, risk factors and staging systems of cholangiocarcinoma. Best Pract Res Clin Gastroenterol 2015; 29: 245-252
  • 54 Weber SM. Ribero D. O’Reilly EM. et al. Intrahepatic cholangiocarcinoma: expert consensus statement. HPB (Oxford) 2015; 17: 669-680
  • 55 Stein A. Arnold D. Bridgewater J. et al. Adjuvant chemotherapy with gemcitabine and cisplatin compared to observation after curative intent resection of cholangiocarcinoma and muscle invasive gallbladder carcinoma (ACTICCA-1 trial) – a randomized, multidisciplinary, multinational phase III trial. BMC Cancer 2015; 15: 564
  • 56 Valle J. Wasan H. Palmer DH. et al. Cisplatin plus Gemcitabine versus Gemcitabine for Biliary Tract Cancer.. N Engl J Med. Massachusetts Medical Society 2010; 362: 1273-1281
  • 57 Okusaka T. Nakachi K. Fukutomi A. et al. Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan. Br J Cancer 2010; 103: 469-474
  • 58 Lamarca A. Hubner RA. Ryder DW. et al. Second-line chemotherapy in advanced biliary cancer: a systematic review. Ann Oncol 2014; 25: 2328-2338
  • 59 Walter T. Horgan AM. McNamara M. et al. Feasibility and benefits of second-line chemotherapy in advanced biliary tract cancer: a large retrospective study. Eur J Cancer 2013; 49: 329-335
  • 60 Li J. Li T. Sun P. et al. Covered versus uncovered self-expandable metal stents for managing malignant distal biliary obstruction: a meta-analysis. PLoS One 2016; 11: e0149066
  • 61 Lu Y. Liu L. Wu J. et al. Efficacy and safety of photodynamic therapy for unresectable cholangiocarcinoma: a meta-analysis. Clin Res Hepatol Gastroenterol 2015; 39: 718-724
  • 62 Patel J. Rizk N. Kahaleh M. Role of photodynamic therapy and intraductal radiofrequency ablation in cholangiocarcinoma. Best Pract Res Clin Gastroenterol 2015; 29: 309-318
  • 63 Tal AO. Vermehren J. Friedrich-Rust M. et al. Intraductal endoscopic radiofrequency ablation for the treatment of hilar non-resectable malignant bile duct obstruction. World J Gastrointest Endosc 2014; 6: 13-19
  • 64 Chapman PB. Hauschild A. Robert C. et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011; 364: 2507-2516
  • 65 Chen JS. Hsu C. Chiang NJ. et al. A KRAS mutation status-stratified randomized phase II trial of gemcitabine and oxaliplatin alone or in combination with cetuximab in advanced biliary tract cancer. Ann Oncol 2015; 26: 943-949
  • 66 Schadendorf D. Hodi FS. Robert C. et al. Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. J Clin Oncol 2015; 33: 1889-1894
  • 67 Garon EB. Rizvi NA. Hui R. et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 2015; 372: 2018-2028
  • 68 Borghaei H. Paz-Ares L. Horn L. et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 2015; 373: 1627-1639
  • 69 Hodi FS. O’Day SJ. McDermott DF. et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363: 711-723
  • 70 Le D. Uram J. Wang H. et al. PD-1 blockade in mismatch repair deficient non-colorectal gastrointestinal cancers | ASCO 2016. J Clin Oncol 34 2016 (suppl 4S; abstr 195)
  • 71 Churi CR. Shroff R. Wang Y. et al. Mutation profiling in cholangiocarcinoma: prognostic and therapeutic implications. PLoS One 2014; 9: e115383
  • 72 Ross JS. Wang K. Gay L. et al. New routes to targeted therapy of intrahepatic cholangiocarcinomas revealed by next-generation sequencing. Oncologist 2014; 19: 235-242
  • 73 Jiao Y. Pawlik TM. Anders RA. et al. Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas. Nat Genet 2013; 45: 1470-1473
  • 74 Zhu AX. Borger DR. Kim Y. et al. Genomic profiling of intrahepatic cholangiocarcinoma: refining prognosis and identifying therapeutic targets. Ann Surg Oncol 2014; 21: 3827-3834
  • 75 Borad MJ. Champion MD. Egan JB. et al. Integrated genomic characterization reveals novel, therapeutically relevant drug targets in FGFR and EGFR pathways in sporadic intrahepatic cholangiocarcinoma. PLoS Genet 2014; 10: e1004135
  • 76 Sia D. Losic B. Moeini A. et al. Massive parallel sequencing uncovers actionable FGFR2-PPHLN1 fusion and ARAF mutations in intrahepatic cholangiocarcinoma. Nat Commun 2015; 6: 6087
  • 77 Jang S. Chun SM. Hong SM. et al. High throughput molecular profiling reveals differential mutation patterns in intrahepatic cholangiocarcinomas arising in chronic advanced liver diseases. Mod Pathol 2014; 27: 731-739
  • 78 Zou S. Li J. Zhou H. et al. Mutational landscape of intrahepatic cholangiocarcinoma. Nat Commun 2014; 5: 2696
  • 79 Wang P. Dong Q. Zhang C. et al. Mutations in isocitrate dehydrogenase 1 and 2 occur frequently in intrahepatic cholangiocarcinomas and share hypermethylation targets with glioblastomas. Oncogene 2013; 32: 3091
  • 80 Gao Q. Zhao YJ. Wang XY. et al. Activating mutations in PTPN3 promote cholangiocarcinoma cell proliferation and migration and are associated with tumor recurrence in patients. Gastroenterology 2014; 146: 1397-1407
  • 81 Wu YM. Su F. Kalyana-Sundaram S. et al. Identification of targetable FGFR gene fusions in diverse cancers. Cancer Discov 2013; 3: 636
  • 82 Graham RP. Barr Fritcher EG. Pestova E. et al. Fibroblast growth factor receptor 2 translocations in intrahepatic cholangiocarcinoma. Hum Pathol 2014; 45: 1630-1638
  • 83 Kipp BR. Voss JS. Kerr SE. et al. Isocitrate dehydrogenase 1 and 2 mutations in cholangiocarcinoma. Hum Pathol 2012; 43: 1552-1558
  • 84 Moeini A. Sia D. Bardeesy N. et al. Molecular pathogenesis and targeted therapies for intrahepatic cholangiocarcinoma. Clin Cancer Res 2016; 22: 291-300
  • 85 Xie D. Ren Z. Fan J. et al. Genetic profiling of intrahepatic cholangiocarcinoma and its clinical implication in targeted therapy. Am J Cancer Res 2016; 6: 577
  • 86 Walter D. Döring C. Feldhahn M. et al. Intratumoral heterogeneity of intrahepatic cholangiocarcinoma. Oncotarget 2017; DOI: 10.18632/oncotarget.14844. [Epub ahead of print]