Expression of Molecular Differentiation Markers Does Not Correlate with Histological Differentiation Grade in Intrahepatic Cholangiocarcinoma

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2016 Jun 10

PMID 27280413

Citations 4

Authors

Celine Demarez

Catherine Hubert

Christine Sempoux

Frederic P Lemaigre

Affiliations

Soon will be listed here.

Abstract

The differentiation status of tumor cells, defined by histomorphological criteria, is a prognostic factor for survival of patients affected with intrahepatic cholangiocarcinoma (ICC). To strengthen the value of morphological differentiation criteria, we wished to correlate histopathological differentiation grade with expression of molecular biliary differentiation markers and of microRNAs previously shown to be dysregulated in ICC. We analysed a series of tumors that were histologically classified as well, moderately or poorly differentiated, and investigated the expression of cytokeratin 7, 19 and 903 (CK7, CK19, CK903), SRY-related HMG box transcription factors 4 and 9 (SOX4, SOX9), osteopontin (OPN), Hepatocyte Nuclear Factor-1 beta (HNF1β), Yes-associated protein (YAP), Epithelial cell adhesion molecule (EPCAM), Mucin 1 (MUC1) and N-cadherin (NCAD) by qRT-PCR and immunostaining, and of miR-31, miR-135b, miR-132, miR-200c, miR-221 and miR-222. Unexpectedly, except for subcellular location of SOX9 and OPN, no correlation was found between the expression levels of these molecular markers and histopathological differentiation grade. Therefore, our data point toward necessary caution when investigating the evolution and prognosis of ICC on the basis of cell differentiation criteria.

Citing Articles

IL-13 as Target to Reduce Cholestasis and Dysbiosis in Knockout Mice.

Hahn L, Helmrich N, Herebian D, Mayatepek E, Drebber U, Domann E Cells. 2020; 9(9).

PMID: 32846954 PMC: 7564366. DOI: 10.3390/cells9091949.

Circulating osteopontin per tumor volume as a prognostic biomarker for resectable intrahepatic cholangiocarcinoma.

Zhou K, Liu W, Yang L, Sun Y, Hu J, Chen F Hepatobiliary Surg Nutr. 2020; 8(6):582-596.

PMID: 31929985 PMC: 6943027. DOI: 10.21037/hbsn.2019.03.14.

Notch Inhibition Promotes Differentiation of Liver Progenitor Cells into Hepatocytes via Repression in Zebrafish.

Russell J, Ko S, Monga S, Shin D Stem Cells Int. 2019; 2019:8451282.

PMID: 30992706 PMC: 6434270. DOI: 10.1155/2019/8451282.

Deregulated MicroRNAs in Biliary Tract Cancer: Functional Targets and Potential Biomarkers.

Mayr C, Beyreis M, Wagner A, Pichler M, Neureiter D, Kiesslich T Biomed Res Int. 2016; 2016:4805270.

PMID: 27957497 PMC: 5120202. DOI: 10.1155/2016/4805270.

References

Coffinier C, Gresh L, Fiette L, Tronche F, Schutz G, Babinet C . Bile system morphogenesis defects and liver dysfunction upon targeted deletion of HNF1beta. Development. 2002; 129(8):1829-38. DOI: 10.1242/dev.129.8.1829. View

Aishima S, Asayama Y, Taguchi K, Sugimachi K, Shirabe K, Shimada M . The utility of keratin 903 as a new prognostic marker in mass-forming-type intrahepatic cholangiocarcinoma. Mod Pathol. 2002; 15(11):1181-90. DOI: 10.1097/01.MP.0000032537.82380.69. View

Uenishi T, Kubo S, Yamamoto T, Shuto T, Ogawa M, Tanaka H . Cytokeratin 19 expression in hepatocellular carcinoma predicts early postoperative recurrence. Cancer Sci. 2003; 94(10):851-7. PMC: 11160230. DOI: 10.1111/j.1349-7006.2003.tb01366.x. View

Terashi T, Aishima S, Taguchi K, Asayama Y, Sugimachi K, Matsuura S . Decreased expression of osteopontin is related to tumor aggressiveness and clinical outcome of intrahepatic cholangiocarcinoma. Liver Int. 2004; 24(1):38-45. DOI: 10.1111/j.1478-3231.2004.00886.x. View

Meng F, Henson R, Lang M, Wehbe H, Maheshwari S, Mendell J . Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. Gastroenterology. 2006; 130(7):2113-29. DOI: 10.1053/j.gastro.2006.02.057. View

von Ahlfen S, Missel A, Bendrat K, Schlumpberger M . Determinants of RNA quality from FFPE samples. PLoS One. 2007; 2(12):e1261. PMC: 2092395. DOI: 10.1371/journal.pone.0001261. View

Mosnier J, Kandel C, Cazals-Hatem D, Bou-Hanna C, Gournay J, Jarry A . N-cadherin serves as diagnostic biomarker in intrahepatic and perihilar cholangiocarcinomas. Mod Pathol. 2008; 22(2):182-90. DOI: 10.1038/modpathol.2008.123. View

Chen L, Yan H, Yang W, Hu L, Yu L, Liu Q . The role of microRNA expression pattern in human intrahepatic cholangiocarcinoma. J Hepatol. 2008; 50(2):358-69. DOI: 10.1016/j.jhep.2008.09.015. View

Antoniou A, Raynaud P, Cordi S, Zong Y, Tronche F, Stanger B . Intrahepatic bile ducts develop according to a new mode of tubulogenesis regulated by the transcription factor SOX9. Gastroenterology. 2009; 136(7):2325-33. PMC: 2743481. DOI: 10.1053/j.gastro.2009.02.051. View

10.

Kawahigashi Y, Mishima T, Mizuguchi Y, Arima Y, Yokomuro S, Kanda T . MicroRNA profiling of human intrahepatic cholangiocarcinoma cell lines reveals biliary epithelial cell-specific microRNAs. J Nippon Med Sch. 2009; 76(4):188-97. DOI: 10.1272/jnms.76.188. View

11.

Sirica A, Dumur C, Campbell D, Almenara J, Ogunwobi O, Dewitt J . Intrahepatic cholangiocarcinoma progression: prognostic factors and basic mechanisms. Clin Gastroenterol Hepatol. 2009; 7(11 Suppl):S68-78. PMC: 3795391. DOI: 10.1016/j.cgh.2009.08.023. View

12.

Chakravarty G, Rider B, Mondal D . Cytoplasmic compartmentalization of SOX9 abrogates the growth arrest response of breast cancer cells that can be rescued by trichostatin A treatment. Cancer Biol Ther. 2010; 11(1):71-83. DOI: 10.4161/cbt.11.1.13952. View

13.

Fan L, He F, Liu H, Zhu J, Liu Y, Yin Z . CD133: a potential indicator for differentiation and prognosis of human cholangiocarcinoma. BMC Cancer. 2011; 11:320. PMC: 3161038. DOI: 10.1186/1471-2407-11-320. View

14.

Mazur P, Riener M, Jochum W, Kristiansen G, Weber A, Schmid R . Expression and clinicopathological significance of notch signaling and cell-fate genes in biliary tract cancer. Am J Gastroenterol. 2011; 107(1):126-35. DOI: 10.1038/ajg.2011.305. View

15.

Khan S, Emadossadaty S, G Ladep N, Thomas H, Elliott P, Taylor-Robinson S . Rising trends in cholangiocarcinoma: is the ICD classification system misleading us?. J Hepatol. 2011; 56(4):848-54. DOI: 10.1016/j.jhep.2011.11.015. View

16.

Karakatsanis A, Papaconstantinou I, Gazouli M, Lyberopoulou A, Polymeneas G, Voros D . Expression of microRNAs, miR-21, miR-31, miR-122, miR-145, miR-146a, miR-200c, miR-221, miR-222, and miR-223 in patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma and its prognostic significance. Mol Carcinog. 2012; 52(4):297-303. DOI: 10.1002/mc.21864. View

17.

Papaconstantinou I, Karakatsanis A, Gazouli M, Polymeneas G, Voros D . The role of microRNAs in liver cancer. Eur J Gastroenterol Hepatol. 2012; 24(3):223-8. DOI: 10.1097/MEG.0b013e3283505063. View

18.

Wang X, Heegaard N, Orum H . MicroRNAs in liver disease. Gastroenterology. 2012; 142(7):1431-43. PMC: 6311104. DOI: 10.1053/j.gastro.2012.04.007. View

19.

Razumilava N, Gores G . Classification, diagnosis, and management of cholangiocarcinoma. Clin Gastroenterol Hepatol. 2012; 11(1):13-21.e1. PMC: 3596004. DOI: 10.1016/j.cgh.2012.09.009. View

20.

Munoz-Garrido P, Garcia-Fernandez de Barrena M, Hijona E, Carracedo M, Marin J, Bujanda L . MicroRNAs in biliary diseases. World J Gastroenterol. 2012; 18(43):6189-96. PMC: 3501766. DOI: 10.3748/wjg.v18.i43.6189. View