Rubin M A, Mucci N R, Figurski J, Fecko A, Pienta K J, Day M L
Departments of Pathology, Surgery-Urology Section, University of Michigan, Ann Arbor, MI 48109-0054, USA.
Hum Pathol. 2001 Jul;32(7):690-7. doi: 10.1053/hupa.2001.25902.
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.
E-钙黏蛋白是一种依赖钙离子的细胞黏附分子，它决定胚胎中的上皮发育，并维持成年期分化上皮及内环境稳定。据报道，其异常表达或表达降低与前列腺癌进展相关。前列腺癌中E-钙黏蛋白的表达程度仍存在争议。一些研究报道，随着肿瘤进展和转移，E-钙黏蛋白表达降低。其他研究则未证实这种关系。为解决这些差异，我们开展了一项研究，系统评估广泛前列腺组织中E-钙黏蛋白的表达。在统一条件下，使用高密度组织微阵列（TMA）对良性前列腺组织、临床局限性前列腺癌组织及激素难治性转移性前列腺癌组织进行分析。将临床局限性前列腺癌男性患者的福尔马林固定、石蜡包埋前列腺癌组织以及死于广泛转移、激素难治性前列腺癌男性患者的尸检材料排列成6个高密度TMA块。临床局限性病例中还纳入了良性和萎缩性前列腺组织以及高级别前列腺上皮内瘤变（PIN）。使用免疫球蛋白G1小鼠单克隆抗体（HECD-1；Zymed，旧金山，加利福尼亚州）进行免疫组织化学检测。膜染色记录为低（异常）或高（正常）。如果少于70%的细胞有强膜染色，则E-钙黏蛋白表达被认为异常。共分析了1220个前列腺TMA样本。在757个良性样本的87%、41个高级别PIN样本的80%、325个前列腺癌样本的82%以及97个激素难治性前列腺癌TMA样本的90%中观察到高（正常）E-钙黏蛋白表达。对128例临床局限性前列腺癌病例中的每一例确定E-钙黏蛋白平均表达。异常E-钙黏蛋白表达显示出与手术切缘阳性（P = 0.012）、更高的Gleason评分（P = 0.18）和前列腺特异性抗原（PSA）失败（Kaplan-Meier分析，对数秩检验P = 0.09）相关的统计学趋势。异常E-钙黏蛋白表达与更大肿瘤大小之间存在统计学显著关联（P = 0.01）。未观察到与前列腺外侵犯和精囊侵犯有显著关联。当前研究展示了一种评估前列腺癌中E-钙黏蛋白蛋白表达的广谱方法。仅接受手术治疗的临床局限性前列腺肿瘤显示出高水平的E-钙黏蛋白表达。在手术切缘阳性、Gleason评分较高和PSA失败率较高的肿瘤中鉴定出异常表达。然而，这些趋势无统计学显著性。鉴定出异常E-钙黏蛋白表达与更大肿瘤大小之间存在统计学显著关联。在转移性激素难治性前列腺肿瘤中，E-钙黏蛋白表达广泛，仅有罕见病例有异常表达。因此，本研究结果最符合局限性前列腺癌中E-钙黏蛋白的短暂下调。抗E-钙黏蛋白抗体HECD-1检测显示转移性前列腺癌有强E-钙黏蛋白表达。
