Correlation of epithelial-mesenchymal transition and CK19 expression in hepatocellular carcinoma.

HALE KIRIMLIOGLU

Abstract


ABSTRACT

Objective: Hepatocellular carcinomas are one of the leading cause of death throughout the world with a high recurrence rate and metastatic potential. The relationship between the prognosis and immunoexpression of cytokeratin 19 has been shown in hepatocellular carcinomas. Recently, EMT  has been shown to be an important mechanism contributing to cancer invasion and metastasis in epithelial-derived cancers , including Hepatocellular carcinoma. We aimed to  investigate the relationship between  the CK19 positivity with a poor prognosis in HCC and E-cadherin and vimentin as the EMT indicator proteins.

Materials and Methods: The cytokeratin-19, vimentin and E-cadherin expression of 41 HCC tissue samples was examined by immunohistochemical staining.

 

Results:

The E-cadherin expression was negatively  and vimentin expression positively corralated with CK19 positivity (p<0,05).

 

Conclusion : Previous studies implicated that both the CK19 positive HCCs and the HCCs having reduced expression of E-cad and gain vimentin expression have  poor prognosis with increased risk of recurrence and metastasis. In our study the correlation between the CK19 positivity and EMT may suggest that those tumors are originated form progenitor cells. The tumors originated from progenitor cells may have higher EMT, this may be related with the carcinogenesis of this HCC subtype.

 


Keywords


Hepatocellular carcinoma _ Cytokeratin -19 _Epithelial–mesenchymal transition

References


Wang G, et al. A comparison of Twist and E-cadherin protein expression in primary non-small-cell lung carcinoma and corresponding metastases. Eur J Cardiothorac Surg. 2011;39(6): 1028–32.

Kim DY, Joo JK, Park YK, et al. E-cadherin Expression in early gastric carcinoma and correlation with lymph node metastasis. J Surg Oncol. 2007;96:429–435.

van Oort IM, Tomita K, van Bokhoven A, et al. The prognostic value of E-cadherin and the cadherin-associated molecules alpha-, beta-, gammacatenin and P120ctn in prostate cancer specific survival: A long-term follow-up study. Prostate. 2007;67:1432–1438.

Zheng G, et al. Disruption of E-cadherin by matrix metalloproteinase directly mediates epithelial-mesenchymal transition downstream of transforming growth factor-beta1 in renal tubular epithelial cells. Am J Pathol. 2009;175(2):580–91.

Soini Y, et al. Transcription factors zeb1, twist and snai1 in breast carcinoma. BMC Cancer. 2011;11:73.

Behrens J, et al. Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell–cell adhesion. J Cell Biol. 1989;108(6):2435–47.

Thiery JP, et al. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139(5):871–90.

Myong NH. Loss of E-cadherin and acquisition of vimentin in epithelial-mesenchymal transition are noble indicators of uterine cervix cancer progression. Korean J Pathol. 2012;46(4):341–8.

Li LP, et al. Subcellular proteomics revealed the epithelial-mesenchymal transition phenotype in lung cancer. Proteomics. 2011; 11(3):429–39.

Soltermann A, et al. Prognostic significance of epithelial-mesenchymal and mesenchymal-epithelial transition protein expression in non-small cell lung cancer. Clin Cancer Res. 2008;14(22):7430–7.

Yang Fei, MSc, Xu-Shun Liu, MSc, Feng Wang, MSc, Wei Wang, MSc, Sheng-Li Liu, MSc. E-cadherin Expression in Normal and Abnormal Tissue Specimens From Patients With Pancreatic Carcinoma . Science. August 2010 Volume 41 Number 8:473-77.

van Zijl F, et al. A human model of epithelial to mesenchymal transition to monitor drug efficacy in hepatocellular carcinoma progression. Mol Cancer Ther. 2011;10(5):850–60.

Yi ZY, et al. Vascular endothelial growth factor receptor-1 activation mediates epithelial to mesenchymal transition in hepatocellular carcinoma cells. J Invest Surg. 2011;24(2):67–76.

Kim J, et al. Epithelial-mesenchymal transition gene signature to predict clinical outcome of hepatocellular carcinoma. Cancer Sci.2010;101(6):1521–8.

Xiaolu Z, Huijun Z, Wei W, Shu Z, Yixin Z, Guoxin M. Abnormal expression of EMT-related proteins, S100A4, vimentin and E-cadherin, is correlated with clinicopathological features

and prognosis in HCC. Med Oncol (2014) 31:970.

Yoneda N, Sato Y, Kitao A, Ikeda H, Sawada-Kitamura S, Miyakoshi M, Harada K, Sasaki M, Matsui O, Nakanuma Y. 4,448.indd 2360 2014/8/20 20:28:46 Epidermal growth factor induces cytokeratin 19 expression accompanied by increased growth abilities in human hepatocellular carcinoma. Laboratory Investigation 2011; 91: 262- 272.

Berasain C, Latasa MU, Urtasun R, Goñi S, Elizalde M, Garcia- Irigoyen O, Azcona M, Prieto J, Ávila MA. Epidermal growth factor receptor (EGFR) crosstalks in liver cancer. Cancers 2011; 3: 2444-2461.

Uenishi T, Kubo S, Yamamoto T, Shuto T, Ogawa M, Tanaka H, Tanaka S, Kaneda K, Hirohashi K. Cytokeratin 19 expression in hepatocellular carcinoma predicts early postoperative recurrence.

Cancer Sci 2003; 94: 851-857.

Wu PC, Fang JW, Lau VK, Lai CL, Lo CK, Lau JY. Classification of hepatocellular carcinoma according to hepatocellular and biliary differentiation markers. Clinical and biological implications Am J Pathol 1996; 149: 1167-1175.

Ding SJ, Li Y, Tan YX, Jiang MR, Tian B, Liu YK, Shao XX, Ye SL, Wu JR, Zeng R, Wang HY, Tang ZY, Xia QC. From proteomic analysis to clinical significance: overexpression of cytokeratin 19 correlates with hepatocellular carcinoma metastasis. Mol Cell Proteomics 2004; 3: 73-81.

Roayaie S, Minguez B, Sole M, Battiston C, van Laarhoven S, Fiel MI, Di Feo A, Hoshida Y, Yea Y, Toffanin S, Ramos A, Martignetti JA, Mazzaferro V, Bruix J, Waxman S, Schwartz M, Meyerson

M, Friedman SL, Llovet JM. Pivotal role of mTOR signaling in hepatocellular carcinoma. Gastroenterology 2008; 135: 1972-1983.

Onder TT, Gupta PB, Mani SA, Yang J, Lander ES, Weinberg RA. Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Res. 2008; 68(10):3645–54.

Nakagawaa H, Hikibac Y, Hirataa Y, Font-Burgadab J, Sakamotoc K, Hayakawaa Y, Taniguchib K, Umemurab A, Kinoshitaa H, Sakitania K, Nishikawad Y, Hiranoa K, Ikenouee T, Ijichia H, Dharb D, Shibataf W, Akanumac M, Koikea K, Karinb M, Maedaf S. Loss of liver E-cadherin induces sclerosing cholangitis and promotes carcinogenesis. Proc Natl Acad Sci USA 2014; 111(3); 1090–1095.

Yamada S, Okumura N, Wei L, Fuchs BC, Fujii T, Sugimoto H, Nomoto S, Takeda S, Tanabe KK, Kodera Y.Ann Surg Oncol 2014; 21:3882–3890.

Libbrecht L, Desmet V, Van Damme B, Roskams T. Epithelial to Mesenchymal Transition is Associated with Shorter Disease-Free Survival in Hepatocellular Carcinoma. The immunohistochemical phenotype of dysplastic foci in human liver: correlation with putative progenitor cells. J Hepatol. 2000;11:76–84.

Yamamoto T, Uenishi T, Ogawa M, Ichikawa T, Hai S, Sakabe K, Tanaka S, Kato H, Mikami S, Ikebe T, Tanaka H, Ito S, Kaneda K, Hirohashi K, Kubo S. Immunohistologic attempt to find carcinogenesis from hepatic progenitor cell in hepatocellular carcinoma. Dig Surg. 2005;11:364–370.

Lee CW, Kuo WL, Yu MC, Chen TC, Tsai CN, Lee WC, Chen MF. . The expression of cytokeratin 19 in lymph nodes was a poor prognostic factor for hepatocellular carcinoma after hepatic resection. World J Surg Oncol. 2013; 11: 136.

Yoneda N, Sato K, Kitao A, Ikeda H, Sawada-Kitamura S, Miyakos M, Harada K, Sasaki M, Matsui O, Nakanuma Y. Epidermal growth factor induces cytokeratin 19 expression accompanied by increased growth abilities in human hepatocellular carcinoma. Lab Invest 2011; 91: 262-272


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