Prostate cancer is mostly diagnosed at an early stage; however, some tumors are diagnosed in a metastatic stage as cancer of unknown primary origin. In order to allow specific treatment in the case of prostate cancer presenting as cancer of unknown primary origin, it is important to determine the tumor origin. Prostate-specific antigen is used as a diagnostic marker for prostate cancer but the expression declines with progression to castration-resistant prostate cancer. Aim of this study was to identify the most informative marker constellation, which is able to detect metastatic prostate cancer at high sensitivity. The widely used prostate cancer markers such as prostate-specific antigen, prostate-specific acid phosphatase, androgen receptor, prostate-specific membrane antigen, prostein, and ETS-related gene were investigated for their sensitivity to detect prostatic origin of metastases. Expression of prostate-specific antigen, prostate-specific acid phosphatase, androgen receptor, prostate-specific membrane antigen, prostein, and ETS-related gene was determined on archived tissue specimens consisting of benign prostatic tissue (n=9), primary prostate cancer (n=79), lymph node metastases (n=58), and distant metastases (n=39) using immunohistochemistry. The staining intensity was categorized as negative (0), weak (1), moderate (2), and strong (3). All markers except ETS-related gene were able to detect at least 70% of lymph node metastases and distant metastases, with prostate-specific antigen, androgen receptor, and prostate-specific membrane antigen having the highest sensitivity (97%, 91%, and 94%, respectively). A further increase of the sensitivity up to 98% and 100% could be achieved by the combination of prostate-specific antigen, prostate-specific membrane antigen, or androgen receptor for lymph node metastases and for distant metastases, respectively. The same sensitivity could be reached by combining prostate-specific membrane antigen and prostein. Our data show that a combined staining of at least two prostate markers should be utilized to identify metastases as originating from prostate cancer.
前列腺癌大多数可以早期诊断; 但是，一些前列腺癌在转移期因原发不明的转移癌时才得以诊断。为了能够特异性治疗表现为原发部位不明的前列腺癌病例，确定肿瘤的来源很重要。前列腺特异性抗原PSA被用作前列腺癌的诊断标记物，但是随着前列腺癌进展为去势效果差，PSA的表达也随之降低。本研究目的在于找到最有意义的一组标记物，能够检测到转移性前列腺癌，并且具有较高敏感性。广泛使用的前列腺癌标记物如PSA、PSAP、AR和前列腺特异膜抗原PSMA、prostein和ETS-相关基因，我们应用免疫组织化学方法，使用存档的组织标本，对全部这些抗体在检测前列腺来源转移癌中的敏感性进行了研究，其中包括良性前列腺组织 (n=9)、原发性前列腺癌 (n=79)、淋巴结转移 (n=58)和远处转移 (n=39)。染色阳性强度分为阴性(0)、弱 (1)、中等(2)和强 (3)。全部标记物除了ETS-相关基因外均能在至少70%的淋巴结转移和远处转移中检测到，PSA、AR、PSMA具有较高的敏感性，分别为(97%, 91%, and 94%)。联合应用PSA、PSMA或AR可以进一步将淋巴结转移和远处转移的敏感性分别提高到98% 和100% 。同样的敏感性也可以通过联合应用PSMA和prostein达到。我们的数据表明联合应用至少两种前列腺标记物可以证实源于前列腺癌的转移癌。