E-cadherin is a
calcium 2+-dependent
cell-adhesion molecule that determines epithelial development in the embryo and maintains adult differentiated epithelium and homeostasis. Aberrant or decreased expression has been reported to be associated with prostate
carcinoma progression. The degree of
E-cadherin expression in
prostate cancer remains controversial. Some studies have reported decreased expression of
E-cadherin as
tumors advance and metastasize. Other studies have not demonstrated this relationship. To address these variations, we undertook a study to systematically evaluate
E-cadherin expression in a broad range of prostate tissue. Benign prostate, clinically localized
prostate cancer, and
hormone-refractory metastatic
prostate cancer were analyzed under uniform conditions using high-density tissue microarrays (TMA).
Formalin-fixed,
paraffin-embedded prostate
carcinoma from men with clinically localized prostate
carcinoma and autopsy material from men who died of widely metastatic,
hormone-refractory prostate
carcinoma were arrayed into 6 high-density TMA blocks. Benign and atrophic prostate tissue and high-grade
prostatic intraepithelial neoplasia (PIN) were also included from the clinically localized cases. Immunohistochemistry was performed using the
immunoglobulin G1 mouse
monoclonal antibody (HECD-1; Zymed, San Francisco, CA). Membranous staining was recorded as low (aberrant) or high (normal).
E-cadherin expression was considered aberrant if less than 70% of the cells had strong membranous staining. A total of 1,220 prostate TMA samples were analyzed. High (normal)
E-cadherin expression was seen in 87% of 757 benign, 80% of 41 high-grade PIN, 82% of 325 prostate
carcinoma and 90% of 97
hormone-refractory prostate
carcinoma TMA samples. Mean
E-cadherin expression was determined for each of the 128 clinically localized
prostate cancer cases. Aberrant
E-cadherin expression showed a statistical trend toward an association with
positive surgical margins (P =.012), higher Gleason score (P =.18), and
prostate-specific antigen (PSA) failure (Kaplan-Meier analysis, log-rank P =.09). There was a statistically significant association between aberrant
E-cadherin expression and larger
tumor size (P =.01). No significant associations were seen with extraprostatic extension and seminal vesicle invasion. The current study shows a broad-spectrum approach to evaluating
E-cadherin protein expression in prostate
carcinoma. Clinically localized prostate
tumors, treated with surgery alone, show a high level of
E-cadherin expression. Aberrant expression was identified in
tumors with
positive surgical margins, higher Gleason score, and a higher rate of PSA failure. However, these trends were not statistically significant. A statically significant association between aberrant
E-cadherin expression and larger
tumor size was identified. In the metastatic
hormone-refractory prostate
tumors,
E-cadherin expression was vastly expressed, and only rare cases had aberrant expression. Therefore, the findings of this study are most consistent with a transient down-regulation of
E-cadherin in localized
prostate cancer. Metastatic
prostate cancer shows strong
E-cadherin expression as determined by anti-
E-cadherin antibody HECD-1.