Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1999 May 1;80(3-4):477–482. doi: 10.1038/sj.bjc.6690381

α-Catenin expression has prognostic value in local and locally advanced prostate cancer

S Aaltomaa 1, P Lipponen 2, M Ala-Opas 1, M Eskelinen 3, V-M Kosma 2,4
PMCID: PMC2362305  PMID: 10408856

Abstract

Normally functioning cell–cell adhesion plays an important role in the maintenance of tissue architecture and cell cohesion. E-cadherin is an important adhesion molecule of epithelial cells. In many types of cancer the expression of E-cadherin is reduced leading to increased risk of disease progression. α-Catenin is one of the intracellular elements of the E-cadherin–catenin complex. The abnormalities in the expression of α-catenin seem to associate with malignant cellular features and disease progression in prostate cancer. To further analyse the significance of α-catenin expression, we studied 215 cases of prostate cancer by immunohistochemistry and the results were related to other known prognostic factors and patient survival during a mean follow-up period of 13 years. α-Catenin expression was down-regulated in 19% of the cases and 3% of the tumours were totally α-catenin-negative. The abnormal α-catenin expression and cytoplasmic signal were significantly linked with high T-category, metastatic disease, high Gleason score, perineural growth, high mitotic rate, high S phase fraction and DNA aneuploidy (P < 0.05 for all). In the survival analysis, reduced α-catenin expression (P = 0.06) and cytoplasmic signal (P = 0.04) were related to unfavourable patient outcome. In the multivariate analysis, including TM-classification and Gleason score, α-catenin expression had independent prognostic value in T1–2 M0 tumors. In the M0 tumours, abnormal α-catenin signal was independently associated with recurrence-free survival as well. The results indicate that down-regulation of α-catenin is related to several malignant cellular features, and it seems to have prognostic significance in the early phases of cancer progression. We suggest that α-catenin expression can provide prognostic information in early prostate cancer. © 1999 Cancer Research Campaign

Keywords: α-catenin, prostate neoplasm, prognosis

Full Text

The Full Text of this article is available as a PDF (138.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Behrens J., Mareel M. M., Van Roy F. M., Birchmeier W. Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion. J Cell Biol. 1989 Jun;108(6):2435–2447. doi: 10.1083/jcb.108.6.2435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Breen E., Steele G., Jr, Mercurio A. M. Role of the E-cadherin/alpha-catenin complex in modulating cell-cell and cell-matrix adhesive properties of invasive colon carcinoma cells. Ann Surg Oncol. 1995 Sep;2(5):378–385. doi: 10.1007/BF02306369. [DOI] [PubMed] [Google Scholar]
  3. Crundwell M. C., Arkell D. G., Gearty J., Phillips S. M. Genetic alterations in incidentally diagnosed, transitional zone prostate cancer: a seven year follow-up. J Urol. 1997 Oct;158(4):1568–1575. [PubMed] [Google Scholar]
  4. Frixen U. H., Behrens J., Sachs M., Eberle G., Voss B., Warda A., Löchner D., Birchmeier W. E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol. 1991 Apr;113(1):173–185. doi: 10.1083/jcb.113.1.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gumbiner B. M., McCrea P. D. Catenins as mediators of the cytoplasmic functions of cadherins. J Cell Sci Suppl. 1993;17:155–158. doi: 10.1242/jcs.1993.supplement_17.22. [DOI] [PubMed] [Google Scholar]
  6. Isaacs W. B. Molecular genetics of prostate cancer. Cancer Surv. 1995;25:357–379. [PubMed] [Google Scholar]
  7. Morton R. A., Ewing C. M., Nagafuchi A., Tsukita S., Isaacs W. B. 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] [Google Scholar]
  8. Morton R. A., Jr, Ewing C. M., Watkins J. J., Isaacs W. B. The E-cadherin cell-cell adhesion pathway in urologic malignancies. World J Urol. 1995;13(6):364–368. doi: 10.1007/BF00191218. [DOI] [PubMed] [Google Scholar]
  9. Murant S. J., Handley J., Stower M., Reid N., Cussenot O., Maitland N. J. Co-ordinated changes in expression of cell adhesion molecules in prostate cancer. Eur J Cancer. 1997 Feb;33(2):263–271. doi: 10.1016/s0959-8049(96)00418-2. [DOI] [PubMed] [Google Scholar]
  10. Paul R., Ewing C. M., Jarrard D. F., Isaacs W. B. The cadherin cell-cell adhesion pathway in prostate cancer progression. Br J Urol. 1997 Mar;79 (Suppl 1):37–43. doi: 10.1111/j.1464-410x.1997.tb00799.x. [DOI] [PubMed] [Google Scholar]
  11. Richmond P. J., Karayiannakis A. J., Nagafuchi A., Kaisary A. V., Pignatelli M. Aberrant E-cadherin and alpha-catenin expression in prostate cancer: correlation with patient survival. Cancer Res. 1997 Aug 1;57(15):3189–3193. [PubMed] [Google Scholar]
  12. Rimm D. L., Sinard J. H., Morrow J. S. Reduced alpha-catenin and E-cadherin expression in breast cancer. Lab Invest. 1995 May;72(5):506–512. [PubMed] [Google Scholar]
  13. Shimazui T., Bringuier P. P., van Berkel H., Ruijter E., Akaza H., Debruyne F. M., Oosterwijk E., Schalken J. A. Decreased expression of alpha-catenin is associated with poor prognosis of patients with localized renal cell carcinoma. Int J Cancer. 1997 Oct 21;74(5):523–528. doi: 10.1002/(sici)1097-0215(19971021)74:5<523::aid-ijc8>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
  14. Shimazui T., Schalken J. A., Giroldi L. A., Jansen C. F., Akaza H., Koiso K., Debruyne F. M., Bringuier P. P. Prognostic value of cadherin-associated molecules (alpha-, beta-, and gamma-catenins and p120cas) in bladder tumors. Cancer Res. 1996 Sep 15;56(18):4154–4158. [PubMed] [Google Scholar]
  15. Umbas R., Isaacs W. B., Bringuier P. P., Schaafsma H. E., Karthaus H. F., Oosterhof G. O., Debruyne F. M., Schalken J. A. Decreased E-cadherin expression is associated with poor prognosis in patients with prostate cancer. Cancer Res. 1994 Jul 15;54(14):3929–3933. [PubMed] [Google Scholar]
  16. Umbas R., Isaacs W. B., Bringuier P. P., Xue Y., Debruyne F. M., Schalken J. A. Relation between aberrant alpha-catenin expression and loss of E-cadherin function in prostate cancer. Int J Cancer. 1997 Aug 22;74(4):374–377. doi: 10.1002/(sici)1097-0215(19970822)74:4<374::aid-ijc2>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
  17. Vermeulen S., Van Marck V., Van Hoorde L., Van Roy F., Bracke M., Mareel M. Regulation of the invasion suppressor function of the cadherin/catenin complex. Pathol Res Pract. 1996 Jul;192(7):694–707. doi: 10.1016/S0344-0338(96)80091-4. [DOI] [PubMed] [Google Scholar]
  18. Vesalainen S., Lipponen P., Talja M., Syrjänen K. Mitotic activity and prognosis in prostatic adenocarcinoma. Prostate. 1995 Feb;26(2):80–86. doi: 10.1002/pros.2990260204. [DOI] [PubMed] [Google Scholar]
  19. Vesalainen S., Nordling S., Lipponen P., Talja M., Syrjänen K. Progression and survival in prostatic adenocarcinoma: a comparison of clinical stage, Gleason grade, S-phase fraction and DNA ploidy. Br J Cancer. 1994 Aug;70(2):309–314. doi: 10.1038/bjc.1994.298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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. doi: 10.1016/0092-8674(91)90143-m. [DOI] [PubMed] [Google Scholar]
  21. Zschiesche W., Schönborn I., Behrens J., Herrenknecht K., Hartveit F., Lilleng P., Birchmeier W. Expression of E-cadherin and catenins in invasive mammary carcinomas. Anticancer Res. 1997 Jan-Feb;17(1B):561–567. [PubMed] [Google Scholar]
  22. van der Wurff A. A., Vermeulen S. J., van der Linden E. P., Mareel M. M., Bosman F. T., Arends J. W. Patterns of alpha- and beta-catenin and E-cadherin expression in colorectal adenomas and carcinomas. J Pathol. 1997 Jul;182(3):325–330. doi: 10.1002/(SICI)1096-9896(199707)182:3<325::AID-PATH865>3.0.CO;2-Y. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES