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Expression patterns of potential therapeutic targets in prostate cancer
Author(s) -
Zellweger Tobias,
Ninck Christoph,
Bloch Michael,
Mirlacher Martina,
Koivisto Pasi A.,
Helin Heikki J.,
Mihatsch Michael J.,
Gasser Thomas C.,
Bubendorf Lukas
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20615
Subject(s) - prostate cancer , medicine , prostate , cancer , immunohistochemistry , tissue microarray , hyperplasia , intraepithelial neoplasia , cancer research , metastasis , oncology , androgen receptor , pca3 , androgen , hormonal therapy , tumor progression , hormone
Androgen withdrawal is the only effective therapy for patients with advanced prostate cancer, but progression to androgen independence ultimately occurs in almost all patients. Novel therapeutic strategies targeting molecular mechanisms that mediate resistance to hormonal and chemotherapeutic treatment are highly warranted. Here, we aimed to evaluate the expression of potential therapeutic targets in advanced prostate cancer. A tissue microarray (TMA) containing samples from 535 tissue blocks was constructed, including benign prostatic hyperplasia as controls ( n = 65), prostatic intraepithelial neoplasia (PIN; n = 78), clinically localized prostate cancers ( n = 181), as well as hormone‐refractory local recurrences ( n = 120) and distant metastases ( n = 91). The expression of 13 different proteins was analyzed using immunohistochemistry (Bcl‐2, p53, ILK, Syndecan‐1, MUC‐1, EGFR, HER2/neu, HSP‐90, Ep‐CAM, MMP‐2, CD‐10, CD‐117 and Ki67). Significant overexpression in hormone‐refractory prostate cancer and metastatic tissue compared to localized prostate cancer was found for Ki67 (64% vs . 9%), Bcl‐2 (11% vs . 1%), p53 (35% vs . 4%), Syndecan‐1 (38% vs . 3%), EGFR (16% vs . 1%) and HER2/neu (16% vs . 0%). Overexpression of CD‐117 was restricted to 1 single metastasis. All other markers did not show relevant differences in expression between subgroups. Taken together, p53, Bcl‐2, Syndecan‐1, EGFR and HER2/neu are preferentially expressed in hormone‐refractory and metastatic prostate cancer. Selected inhibition of these targets might offer a strategy to treat advanced tumors and prevent further progression. Treatment decisions should not be based on findings in primary tumors but rather on tissues from recurrent or metastatic lesions.