- Volume 13 Issue 12
DOI QR Code
Altered Distribution and Expression Pattern of E-cadherin in Hepatocellular Carcinomas: Correlations with Prognosis and Clinical Features
- Jiang, Xue-Mei (Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education) ;
- Zhang, Ju-Bo (Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education) ;
- Xiong, Ju (Liver Cancer Institute, Zhongshan Hospital, Fudan University) ;
- Huang, Xiao-Xi (Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education) ;
- Ren, Zheng-Gang (Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education)
- Published : 2012.12.31
Objective: E-cadherin has been identified as a tumor suppressor in many types of carcinoma. However, some studies recently suggested that the role and expression of E-cadherin might be more complex and diverse. In the present study, we evaluated the prognostic value of E-cadherin expression with reference to levels in membranes and cytoplasm, and the membrane/cytoplasm ratio, in hepatocellular carcinomas (HCCs) after curative hepatectomy. Methods: The expression of E-cadherin was assessed by immunohistochemistry in HCC tissue microarrays from 125 patients, and its prognostic values and other clinicopathlogical data were retrospectively analyzed. Patients were followed for a median period of 43.7 months (range 1 to 126 months). Results: Univariate analysis demonstrated that a high membrane/cytoplasm (M/C) ratio of E-cadherin expression was associated with poor overall survival (OS) (P =0.001) and shorter time to recurrence (TTR) (P=0.038), as well as tumor size, intrahepatic metastasis, and TNM stage. In contrast, neither membrane nor cytoplasmic expression of E-cadherin was related with OS and TTR. Furthermore, multivariate analysis confirmed the M/C ratio to be an independent predictor of OS (P=0.031).
Hepatocellular carcinoma;E-cadherin;tumor suppressor
- Tang ZY, Ye SL, Liu YK, et al (2004). A decade's studies on metastasis of hepatocellular carcinoma. J Cancer Res Clin Oncol, 130, 187-96. https://doi.org/10.1007/s00432-003-0511-1
- Thiery JP (2002). Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer, 2, 442-54. https://doi.org/10.1038/nrc822
- Wei Y, Van Nhieu JT, Prigent S, et al (2002). Altered expression of E-cadherin in hepatocellular carcinoma: correlations with genetic alterations, beta-catenin expression, and clinical features. Hepatology, 36, 692-701.
- Wijnhoven BP, Pignatelli M (1999) E-cadherin-catenin: more than a "sticky" molecular complex. Lancet, 354, 356-7. https://doi.org/10.1016/S0140-6736(99)90055-7
- Wong AS, Gumbiner BM (2003). Adhesion-independent mechanism for suppression of tumor cell invasion by E-cadherin. J Cell Biol, 161, 1191-203. https://doi.org/10.1083/jcb.200212033
- Xu HX, Zhu XD, Zhuang PY, et al (2011). Expression and prognostic significance of placental growth factor in hepatocellular carcinoma and peritumoral liver tissue. Int J Cancer, 128, 1559-69. https://doi.org/10.1002/ijc.25492
- Han AC, Peralta-Soler A, Knudsen KA, et al (1997). Differential expression of N-cadherin in pleural mesotheliomas and E-cadherin in lung adenocarcinomas in formalin-fixed, paraffin-embedded tissues. Hum Pathol, 28, 641-5. https://doi.org/10.1016/S0046-8177(97)90171-4
- Ikeda K, Arase Y, Kobayashi M, et al (2003). Significance of multicentric cancer recurrence after potentially curative ablation of hepatocellular carcinoma: a longterm cohort study of 892 patients with viral cirrhosis. J Gastroenterol, 38, 865-76. https://doi.org/10.1007/s00535-003-1163-2
- Jiang WG, Mansel RE (2000). E-cadherin complex and its abnormalities in human breast cancer. Surg Oncol, 9, 151-71. https://doi.org/10.1016/S0960-7404(01)00010-X
- Kavgaci H, Yildiz B, Fidan E, et al (2010). The effects of E-cadherin and bcl-2 on prognosis in patients with breast cancer. Bratisl Lek Listy, 111, 493-7.
- Kensler TW, Qian GS, Chen JG, Groopman JD (2003). Translational strategies for cancer prevention in liver. Nat Rev Cancer, 3, 321-9. https://doi.org/10.1038/nrc1076
- Lewis-Tuffin LJ, Rodriguez F, Giannini C, et al (2010). Misregulated E-cadherin expression associated with an aggressive brain tumor phenotype. PLoS One, 5, e13665. https://doi.org/10.1371/journal.pone.0013665
- Mayer B, Johnson JP, Leitl F, et al (1993). E-cadherin expression in primary and metastatic gastric cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration. Cancer Res, 53, 1690-5.
- Montserrat N, Gallardo A, Escuin D, et al (2011). Repression of E-cadherin by SNAIL, ZEB1, and TWIST in invasive ductal carcinomas of the breast: a cooperative effort? Hum Pathol, 42, 103-10. https://doi.org/10.1016/j.humpath.2010.05.019
- Mosesson Y, Mills GB, Yarden Y (2008). Derailed endocytosis: an emerging feature of cancer. Nat Rev Cancer, 8, 835-50. https://doi.org/10.1038/nrc2521
- Poon RT, Fan ST, Ng IO, et al (2000). Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma. Cancer, 89, 500-7. https://doi.org/10.1002/1097-0142(20000801)89:3<500::AID-CNCR4>3.0.CO;2-O
- Qian YB, Zhang JB, Wu WZ, et al (2006). P48 is a predictive marker for outcome of postoperative interferon-alpha treatment in patients with hepatitis B virus infection-related hepatocellular carcinoma. Cancer, 107, 1562-9. https://doi.org/10.1002/cncr.22206
- Regimbeau JM, Abdalla EK, Vauthey JN, et al (2004). Risk factors for early death due to recurrence after liver resection for hepatocellular carcinoma: results of a multicenter study. J Surg Oncol, 85, 36-41. https://doi.org/10.1002/jso.10284
- Ross JS, del Rosario AD, Figge HL, et al (1995). E-cadherin expression in papillary transitional cell carcinoma of the urinary bladder. Hum Pathol, 26, 940-4. https://doi.org/10.1016/0046-8177(95)90081-0
- Shim HS, Yoon BS, Cho NH (2009). Prognostic significance of paired epithelial cell adhesion molecule and E-cadherin in ovarian serous carcinoma. Hum Pathol, 40, 693-8. https://doi.org/10.1016/j.humpath.2008.10.013
- Shirabe K, Kanematsu T, Matsumata T, et al (1991). Factors linked to early recurrence of small hepatocellular carcinoma after hepatectomy: univariate and multivariate analyses. Hepatology, 14, 802-5. https://doi.org/10.1002/hep.1840140510
- Sobin LH (2002). TNM classification of malignant tumors, 6th edn. Geneva, Switzerland: International Union Against Cancer.
- Arulanandam R, Vultur A, Cao J, et al (2009). Cadherin-cadherin engagement promotes cell survival via Rac1/Cdc42 and signal transducer and activator of transcription-3. Mol Cancer Res, 7, 1310-27. https://doi.org/10.1158/1541-7786.MCR-08-0469
- Brunt EM (2000). Grading and staging the histopathological lesions of chronic hepatitis: the Knodell histology activity index and beyond. Hepatology, 31, 241-6. https://doi.org/10.1002/hep.510310136
- Bussemakers MJ, van Bokhoven A, Mees SG, Kemler R, Schalken JA (1993). Molecular cloning and characterization of the human E-cadherin cDNA. Mol Biol Rep, 17, 123-8. https://doi.org/10.1007/BF00996219
- Cespedes MV, Larriba MJ, Pavon MA, et al (2010). Sitedependent E-cadherin cleavage and nuclear translocation in a metastatic colorectal cancer model. Am J Pathol 177: 2067-2079. https://doi.org/10.2353/ajpath.2010.100079
- Comoglio PM, Boccaccio C, Trusolino L (2003). Interactions between growth factor receptors and adhesion molecules: breaking the rules. Curr Opin Cell Biol, 15, 565-71. https://doi.org/10.1016/S0955-0674(03)00096-6
- Cowin P, Rowlands TM, Hatsell SJ (2005). Cadherins and catenins in breast cancer. Curr Opin Cell Biol, 17, 499-508. https://doi.org/10.1016/j.ceb.2005.08.014
- Du GS, Wang JM, Lu JX, et al (2009). Expression of P-aPKCiota, E-cadherin, and beta-catenin related to invasion and metastasis in hepatocellular carcinoma. Ann Surg Oncol, 16, 1578-86. https://doi.org/10.1245/s10434-009-0423-7
- Fransvea E, Angelotti U, Antonaci S, Giannelli G (2008). Blocking transforming growth factor-beta up-regulates E-cadherin and reduces migration and invasion of hepatocellular carcinoma cells. Hepatology, 47, 1557-66. https://doi.org/10.1002/hep.22201
- Garcia S, Martini F, De Micco C, et al (1998). [Prognostic value of E-cadherin expression in hepatocellular carcinoma]. Ann Pathol, 18, 98-102.
- Prognostic Significance of E-Cadherin Expression in Hepatocellular Carcinoma: A Meta-Analysis vol.9, pp.8, 2014, https://doi.org/10.1371/journal.pone.0103952
- Management of hepatocellular carcinoma: Predictive value of immunohistochemical markers for postoperative survival vol.7, pp.1, 2015, https://doi.org/10.4254/wjh.v7.i1.7
- Clinical significance of CD13 and epithelial mesenchymal transition (EMT) markers in hepatocellular carcinoma pp.1465-3621, 2017, https://doi.org/10.1093/jjco/hyx157
- MicroRNA-219-5p Promotes Tumor Growth and Metastasis of Hepatocellular Carcinoma by Regulating Cadherin 1 vol.2018, pp.2314-6141, 2018, https://doi.org/10.1155/2018/4793971