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Br J Cancer. 1999 June; 80(7): 1046–1051.
PMCID: PMC2363041

Cadherin–catenin expression in primary colorectal cancer: a survival analysis


Both cell adhesion and cell signalling events are mediated by components of the cadherin–catenin complex. Loss of expression of the components of this complex have been shown to correlate with invasive behaviour in many tumour types although their exact role in colorectal cancer remains unclear. Immunohistochemical analysis of the expression of components of the cadherin–catenin complex in colorectal cancers from 60 patients was undertaken. Loss of memberanous expression of E-cadherin, α-catenin and β-catenin was demonstrated in 52%, 85% and 40% of tumours respectively. Focal nuclear expression of β-catenin (< 75% of cells per section), usually associated with cytoplasmic expression, was clearly demonstrated in 19 (32%) tumours while widespread nuclear expression (> 75% of tumour cells per section) was seen in 11 (18%) tumours. Loss of membranous α-catenin expression significantly correlated with tumour de-differentiation (P = 0.009). There was a trend towards an association between advanced tumour stage and loss of membranous expression of α-catenin or β-catenin, although these associations were not statistically significant. Univariate analysis revealed that advanced Dukes' stage, tumour de-differentiation, loss of membranous β-catenin expression, cytoplasmic β-catenin expression and widespread nuclear expression of β-catenin all correlated with short survival following apparently curative resection of the primary tumour. However, only Dukes' stage (P = 0.002), tumour grade (P = 0.02) and widespread nuclear expression of β-catenin (P = 0.002) were independent predictors of short survival. Disturbed growth signalling events in colorectal tumours are thought to result in nuclear accumulation of β-catenin. Consequently, tumours with widespread nuclear expression of β-catenin are likely to have severely abnormal growth characteristics, and which therefore might be predictive of short survival in these patients. © 1999 Cancer Research Campaign

Keywords: cadherin–catenin complex, colorectal cancer, β-catenin, nuclear expression

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Selected References

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  • Andrews NA, Jones AS, Helliwell TR, Kinsella AR. Expression of the E-cadherin-catenin cell adhesion complex in primary squamous cell carcinomas of the head and neck and their nodal metastases. Br J Cancer. 1997;75(10):1474–1480. [PMC free article] [PubMed]
  • Behrens J, von Kries JP, Kühl M, Bruhn L, Wedlich D, Grosschedl R, Birchmeier W. Functional interaction of beta-catenin with the transcription factor LEF-1. Nature. 1996 Aug 15;382(6592):638–642. [PubMed]
  • Dorudi S, Hanby AM, Poulsom R, Northover J, Hart IR. Level of expression of E-cadherin mRNA in colorectal cancer correlates with clinical outcome. Br J Cancer. 1995 Mar;71(3):614–616. [PMC free article] [PubMed]
  • Gagliardi G, Kandemir O, Liu D, Guida M, Benvestito S, Ruers TG, Benjamin IS, Northover JM, Stamp GW, Talbot IC, et al. Changes in E-cadherin immunoreactivity in the adenoma-carcinoma sequence of the large bowel. Virchows Arch. 1995;426(2):149–154. [PubMed]
  • Gumbiner BM. Signal transduction of beta-catenin. Curr Opin Cell Biol. 1995 Oct;7(5):634–640. [PubMed]
  • Hao X, Palazzo JP, Ilyas M, Tomlinson I, Talbot IC. Reduced expression of molecules of the cadherin/catenin complex in the transition from colorectal adenoma to carcinoma. Anticancer Res. 1997 May-Jun;17(3C):2241–2247. [PubMed]
  • Hao X, Tomlinson I, Ilyas M, Palazzo JP, Talbot IC. Reciprocity between membranous and nuclear expression of beta-catenin in colorectal tumours. Virchows Arch. 1997 Sep;431(3):167–172. [PubMed]
  • Hashizume R, Koizumi H, Ihara A, Ohta T, Uchikoshi T. Expression of beta-catenin in normal breast tissue and breast carcinoma: a comparative study with epithelial cadherin and alpha-catenin. Histopathology. 1996 Aug;29(2):139–146. [PubMed]
  • Hinck L, Näthke IS, Papkoff J, Nelson WJ. Dynamics of cadherin/catenin complex formation: novel protein interactions and pathways of complex assembly. J Cell Biol. 1994 Jun;125(6):1327–1340. [PMC free article] [PubMed]
  • Hiscox S, Jiang WG. Expression of E-cadherin, alpha, beta and gamma-catenin in human colorectal cancer. Anticancer Res. 1997 Mar-Apr;17(2B):1349–1354. [PubMed]
  • Inomata M, Ochiai A, Akimoto S, Kitano S, Hirohashi S. Alteration of beta-catenin expression in colonic epithelial cells of familial adenomatous polyposis patients. Cancer Res. 1996 May 1;56(9):2213–2217. [PubMed]
  • Iwao K, Nakamori S, Kameyama M, Imaoka S, Kinoshita M, Fukui T, Ishiguro S, Nakamura Y, Miyoshi Y. Activation of the beta-catenin gene by interstitial deletions involving exon 3 in primary colorectal carcinomas without adenomatous polyposis coli mutations. Cancer Res. 1998 Mar 1;58(5):1021–1026. [PubMed]
  • Jawhari A, Jordan S, Poole S, Browne P, Pignatelli M, Farthing MJ. Abnormal immunoreactivity of the E-cadherin-catenin complex in gastric carcinoma: relationship with patient survival. Gastroenterology. 1997 Jan;112(1):46–54. [PubMed]
  • Jou TS, Stewart DB, Stappert J, Nelson WJ, Marrs JA. Genetic and biochemical dissection of protein linkages in the cadherin-catenin complex. Proc Natl Acad Sci U S A. 1995 May 23;92(11):5067–5071. [PubMed]
  • Kadowaki T, Shiozaki H, Inoue M, Tamura S, Oka H, Doki Y, Iihara K, Matsui S, Iwazawa T, Nagafuchi A, et al. E-cadherin and alpha-catenin expression in human esophageal cancer. Cancer Res. 1994 Jan 1;54(1):291–296. [PubMed]
  • Kinsella AR, Green B, Lepts GC, Hill CL, Bowie G, Taylor BA. The role of the cell-cell adhesion molecule E-cadherin in large bowel tumour cell invasion and metastasis. Br J Cancer. 1993 May;67(5):904–909. [PMC free article] [PubMed]
  • Kinsella AR, Lepts GC, Hill CL, Jones M. Reduced E-cadherin expression correlates with increased invasiveness in colorectal carcinoma cell lines. Clin Exp Metastasis. 1994 Jul;12(4):335–342. [PubMed]
  • Knudsen KA, Soler AP, Johnson KR, Wheelock MJ. Interaction of alpha-actinin with the cadherin/catenin cell-cell adhesion complex via alpha-catenin. J Cell Biol. 1995 Jul;130(1):67–77. [PMC free article] [PubMed]
  • Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW, Vogelstein B, Clevers H. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. Science. 1997 Mar 21;275(5307):1784–1787. [PubMed]
  • Krishnadath KK, Tilanus HW, van Blankenstein M, Hop WC, Kremers ED, Dinjens WN, Bosman FT. Reduced expression of the cadherin-catenin complex in oesophageal adenocarcinoma correlates with poor prognosis. J Pathol. 1997 Jul;182(3):331–338. [PubMed]
  • Matsui S, Shiozaki H, Inoue M, Tamura S, Doki Y, Kadowaki T, Iwazawa T, Shimaya K, Nagafuchi A, Tsukita S, et al. Immunohistochemical evaluation of alpha-catenin expression in human gastric cancer. Virchows Arch. 1994;424(4):375–381. [PubMed]
  • Miller JR, Moon RT. Signal transduction through beta-catenin and specification of cell fate during embryogenesis. Genes Dev. 1996 Oct 15;10(20):2527–2539. [PubMed]
  • Molenaar M, van de Wetering M, Oosterwegel M, Peterson-Maduro J, Godsave S, Korinek V, Roose J, Destrée O, Clevers H. XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos. Cell. 1996 Aug 9;86(3):391–399. [PubMed]
  • Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B, Kinzler KW. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science. 1997 Mar 21;275(5307):1787–1790. [PubMed]
  • Morton RA, Ewing CM, Nagafuchi A, Tsukita S, Isaacs WB. Reduction of E-cadherin levels and deletion of the alpha-catenin gene in human prostate cancer cells. Cancer Res. 1993 Aug 1;53(15):3585–3590. [PubMed]
  • Nagafuchi A, Takeichi M, Tsukita S. The 102 kd cadherin-associated protein: similarity to vinculin and posttranscriptional regulation of expression. Cell. 1991 May 31;65(5):849–857. [PubMed]
  • Ozawa M, Kemler R. Molecular organization of the uvomorulin-catenin complex. J Cell Biol. 1992 Feb;116(4):989–996. [PMC free article] [PubMed]
  • Rubinfeld B, Albert I, Porfiri E, Fiol C, Munemitsu S, Polakis P. Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly. Science. 1996 May 17;272(5264):1023–1026. [PubMed]
  • Rubinfeld B, Albert I, Porfiri E, Munemitsu S, Polakis P. Loss of beta-catenin regulation by the APC tumor suppressor protein correlates with loss of structure due to common somatic mutations of the gene. Cancer Res. 1997 Oct 15;57(20):4624–4630. [PubMed]
  • Shimoyama Y, Nagafuchi A, Fujita S, Gotoh M, Takeichi M, Tsukita S, Hirohashi S. Cadherin dysfunction in a human cancer cell line: possible involvement of loss of alpha-catenin expression in reduced cell-cell adhesiveness. Cancer Res. 1992 Oct 15;52(20):5770–5774. [PubMed]
  • Shiozaki H, Oka H, Inoue M, Tamura S, Monden M. E-cadherin mediated adhesion system in cancer cells. Cancer. 1996 Apr 15;77(8 Suppl):1605–1613. [PubMed]
  • Takayama T, Shiozaki H, Shibamoto S, Oka H, Kimura Y, Tamura S, Inoue M, Monden T, Ito F, Monden M. Beta-catenin expression in human cancers. Am J Pathol. 1996 Jan;148(1):39–46. [PubMed]
  • Takeichi M. Cadherins in cancer: implications for invasion and metastasis. Curr Opin Cell Biol. 1993 Oct;5(5):806–811. [PubMed]
  • Takeichi M. Morphogenetic roles of classic cadherins. Curr Opin Cell Biol. 1995 Oct;7(5):619–627. [PubMed]
  • Valizadeh A, Karayiannakis AJ, el-Hariry I, Kmiot W, Pignatelli M. Expression of E-cadherin-associated molecules (alpha-, beta-, and gamma-catenins and p120) in colorectal polyps. Am J Pathol. 1997 Jun;150(6):1977–1984. [PubMed]
  • Vleminckx K, Vakaet L, Jr, Mareel M, Fiers W, van Roy F. Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell. 1991 Jul 12;66(1):107–119. [PubMed]

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