Expression of epidermal growth factor receptor correlates with disease relapse and progression to androgen-independence in human prostate cancer.
Expression of epidermal growth factor receptor correlates with disease relapse and progression to androgen-independence in human prostate cancer.
复制标题
DOI：
--
复制
发表时间：
2002-11
期刊：
影响因子：
--
通讯作者：
G. Di Lorenzo;G. Tortora;F. D'armiento;G. de Rosa;S. Staibano;R. Autorino;M. D’armiento;M. De Lauren
中科院分区：
文献类型：
--
作者：
G. Di Lorenzo;G. Tortora;F. D'armiento;G. de Rosa;S. Staibano;R. Autorino;M. D’armiento;M. De Lauren
转化生长因子α-表皮生长因子受体（EGFR）自分泌途径与前列腺癌细胞生长有关。与EGFR密切相关的受体c-erbB-2的扩增和/或过表达最近参与了前列腺癌的进展。我们研究了EGFR和c-erbB-2在原发性雄激素依赖性和晚期雄激素非依赖性前列腺癌中的表达及其作为疾病进展标志物的潜在作用。实验设计通过免疫组化评价74例前列腺癌患者的EGFR和c-erbB-2表达，这些患者具有以下特征：29例患者（第1组）接受根治性前列腺切除术治疗; 29例患者（第2组）接受促黄体生成素释放激素类似物和抗雄激素治疗，随后接受根治性前列腺切除术; 16例患者患有难治性转移性疾病。在我们评估的所有患者中：EGFR和/或c-erbB-2表达与临床病理参数之间的关联;以及在单变量分析（Kaplan-Meier乘积极限法）和多变量分析（考克斯比例风险回归模型）中根据EGFR和c-erbB-2表达的无病生存。结果29例乳腺癌中12例EGFR表达阳性（41.4%）第1组患者，29例中有22例（75.9%）第2组患者（P < 0.0005），16/16例（100%）转移性患者而c-erbB-2在第1组29例中11例（37.9%）、第2组29例中10例（34.5%）、转移组16例中9例（56.3%）表达。在所有患者组中，EGFR表达与高Gleason评分（P < 0.01）和EGFR表达与高血清前列腺特异性抗原值（P < 0.02）之间存在显著相关性。在58例根治性乳腺癌患者中，34例EGFR阳性患者中有23例（67.6%）复发，而24例EGFR阴性患者中只有2例（8.3%）复发（P < 0.00004）。c-erbB-2表达与复发无明显相关性（P = 0.07）。在考克斯多变量分析中，EGFR表达是唯一对无病生存期有独立预后影响的参数（相对危险度，11.23; P = 0.0014）。结论：EGFR在前列腺癌的自然病程中表达增加。与疾病进展和前列腺癌难治性疾病的相关性表明，EGFR靶向药物可能在前列腺癌中具有治疗意义。
PURPOSE The transforming growth factor alpha-epidermal growth factor receptor (EGFR) autocrine pathway has been implicated in prostate cancer cell growth. Amplification and/or overexpression of c-erbB-2, a receptor closely related to the EGFR, has been recently involved in prostate cancer progression. We investigated EGFR and c-erbB-2 expression in primary androgen-dependent and in advanced androgen-independent prostate cancer and their potential role as markers of disease progression. EXPERIMENTAL DESIGN EGFR and c-erbB-2 expression were evaluated by immunohistochemistry in a consecutive series of 74 prostate cancer patients with the following characteristics: 29 patients (group 1) treated with radical prostatectomy; 29 patients (group 2) treated with luteinizing hormone-releasing hormone analogues and antiandrogen therapy followed by radical prostatectomy; and 16 patients with hormone-refractory metastatic disease. In all patients we evaluated: association between EGFR and/or c-erbB-2 expression and clinicopathological parameters; and disease-free survival according to EGFR and c-erbB-2 expression in univariate analysis (Kaplan-Meier product-limit method) and in multivariate analysis (Cox proportional hazards regression model). RESULTS EGFR expression was found in 12 of 29 (41.4%) group 1 patients, in 22 of 29 (75.9%) group 2 patients (P < 0.0005), and in 16 of 16 (100%) metastatic patients (P < 0.005), whereas c-erbB-2 expression was found in 11 of 29 (37.9%) group 1, in 10 of 29 (34.5%) group 2 patients, and in 9 of 16 (56.3%) metastatic patients. A significant association was found between EGFR expression and a high Gleason score (P < 0.01) and between EGFR expression and higher serum prostate-specific antigen values (P < 0.02) in all groups of patients. Among the 58 patients treated with radical prostatectomy, 23 of 34 EGFR-positive patients (67.6%) relapsed, whereas only 2 of 24 EGFR-negative patients (8.3%) relapsed (P < 0.00004). c-erbB-2 expression did not significantly correlate with disease relapse (P = 0.07). In a Cox multivariate analysis, the only parameter with an independent prognostic effect on disease-free survival was EGFR expression (relative hazard, 11.23; P = 0.0014). CONCLUSIONS EGFR expression increases during the natural history of prostate cancer. Correlation with disease progression and hormone-refractory disease suggests that EGFR-targeted drugs could be of therapeutic relevance in prostate cancer.