Expression of the Cellular Adhesion Molecule E-Cadherin Is Reduced or Absent in High-Grade Prostate Cancer

H. Rainy Umbas, Tilly W. Aalders, Frans M.J. Debruyne, Jack A. Schalken

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575 Citations (Scopus)

Abstract

E-cadherin is a Ca2+-dependent cell adhesion molecule which plays an important role in normal growth and development via mediation of homotypic, homophilic cell-cell interaction. Recent studies suggest that E-cadherin may be important in neoplastic progression as well, partic-ularly as a suppressor of invasion. We have previously demonstrated that the invasive phenotype of rat prostate cancer cells is associated with the decreased expression of E-cadherin (M. J. G. Bussemakers, R. J. A. Van Moorselaar, L. A. Giroldi, T. Ichikawa, J. T. Isaacs, F. M. J. Debruyne, and J. A. Schalken, Cancer Res., 52:2916-2922,1992). This is of particular interest, since the locus to which the human E-cadherin gene is mapped is frequently involved in allelic loss in prostate cancer (B. S. Carter, C. M. Ewing, W. S. Ward, B. F. Treiger, T. W. Aalders, J. A. Schalken, J. I. Epstein, and W. B. Isaacs, Proc. Natl. Acad. Sci. USA, £7:8751-8755,1990; U. S. Bergerheim, K. Kunimi, V. P. Collins, and P. Ekman, Genes, Chromosomes Cancer, 3: 215-220, 1991). Impaired E-cadherin function is likely to be associated with aberrant expression of the protein. We therefore analyzed E-cadherin expression in situ by immunohistochemistry in nonmalignant and malignant specimens of human prostatic tissue. Of 92 tumor samples of either primary or metastatic deposits of prostate cancer, 46 had reduced or absent E-cadherin staining when compared to nonmalignant prostate, which uniformly stained strongly positive. There was a statistically significant correlation between the decreased expression of E-cadherin and loss of tumor differentiation. Additionally, certain rumors within a histologi-cally similar group could be distinguished by the presence of mixed populations of E-cadherin-negative and -positive cells. The percentage of tumors with aberrant E-cadherin staining increased when clinically localized tumors were compared to either tumors with extensive local progression or metastatic deposits of prostate cancer, suggesting a cor-relation between loss of E-cadherin and tumor progression. Taken to-gether, these findings suggest that further exploration of E-cadherin as a candidate invasion suppressor molecule in human prostate cancer is warranted.

Original languageEnglish
Pages (from-to)5104-5109
Number of pages6
JournalCancer Research
Volume52
Issue number18
Publication statusPublished - Sep 1992

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