Hobisch A, Culig Z, Radmayr C, Bartsch G, Klocker H, Hittmair A
Department of Urology, University of Innsbruck, Austria.
Cancer Res. 1995 Jul 15;55(14):3068-72.
Nearly all primary prostatic carcinomas have been found to express the androgen receptor (AR) protein, which is the intracellular mediator of androgen action. To gain a better insight into the mechanisms of androgen independence of advanced prostatic carcinoma, it is important to know whether the AR is also present in metastases of androgen-independent tumors. We have assessed the status of the AR and the prostate-specific antigen in 22 metastases of 18 patients with progressive prostate cancer. In 18 cases, the metastases were localized in bone, in 3 cases in the epidural space, and in 1 case in the periosteum. All but one patient had received some kind of endocrine treatment for prostatic carcinoma. Paraffin-embedded tissue sections were stained for the AR following a streptavidinbiotin-peroxidase protocol with the polyclonal antibody PG-21, which is directed against amino acids 1 through 21 of the rat and the human AR. The percentage of AR-positive cells was evaluated on the basis of an arbitrary 4-point scale. All 22 tumor metastases displayed AR positivity. One AR-positive metastatic lesion did not stain for prostate-specific antigen, but in all other metastases, this protein was detected by means of immunohistochemistry. The present study provides evidence that, unlike androgen-independent prostatic carcinoma cell lines, distant prostatic carcinoma metastases do express the AR. These findings indicate that the AR may be involved in the progression of prostate cancer.
几乎所有原发性前列腺癌都已被发现表达雄激素受体(AR)蛋白,该蛋白是雄激素作用的细胞内介质。为了更好地了解晚期前列腺癌雄激素非依赖性的机制,了解AR是否也存在于雄激素非依赖性肿瘤的转移灶中很重要。我们评估了18例进展性前列腺癌患者的22个转移灶中的AR和前列腺特异性抗原的状态。18例转移灶位于骨,3例位于硬膜外腔,1例位于骨膜。除1例患者外,所有患者均接受过某种前列腺癌内分泌治疗。石蜡包埋的组织切片按照链霉亲和素-生物素-过氧化物酶方案,用针对大鼠和人AR的第1至21个氨基酸的多克隆抗体PG-21进行AR染色。根据任意的4分制评估AR阳性细胞的百分比。所有22个肿瘤转移灶均显示AR阳性。1个AR阳性转移灶未检测到前列腺特异性抗原染色,但在所有其他转移灶中,通过免疫组织化学检测到了该蛋白。本研究提供了证据,与雄激素非依赖性前列腺癌细胞系不同,远处前列腺癌转移灶确实表达AR。这些发现表明AR可能参与前列腺癌的进展。