Expression of epidermal growth factor receptor correlates with disease relapse and progression to androgen-independence in human prostate cancer

Giuseppe Di Lorenzo, Giampaolo Tortora, Francesco P. D'Armiento, Gaetano De Rosa, Stefania Staibano, Riccardo Autorino, Massimo D'Armiento, Michele De Laurentiis, Sabino De Placido, Giuseppe Catalano, A. Raffaele Bianco, Fortunato Ciardiello

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Abstract

Purpose: The transforming growth factor α-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.

Original languageEnglish
Pages (from-to)3438-3444
Number of pages7
JournalClinical Cancer Research
Volume8
Issue number11
Publication statusPublished - Nov 1 2002

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Di Lorenzo, G., Tortora, G., D'Armiento, F. P., De Rosa, G., Staibano, S., Autorino, R., D'Armiento, M., De Laurentiis, M., De Placido, S., Catalano, G., Bianco, A. R., & Ciardiello, F. (2002). Expression of epidermal growth factor receptor correlates with disease relapse and progression to androgen-independence in human prostate cancer. Clinical Cancer Research, 8(11), 3438-3444.