Hampel O Z, Kattan M W, Yang G, Haidacher S J, Saleh G Y, Thompson T C, Wheeler T M, Marcelli M
Scott Department of Urology, Baylor College of Medicine and Veterans Affairs Medical Center, Houston, Texas, USA.
J Urol. 1998 Jun;159(6):2220-5. doi: 10.1016/S0022-5347(01)63309-3.
We sought to characterize and quantitate the expression of IGFBP-3 in adenocarcinoma of the prostate and to test whether it correlated with tumor differentiation determined by Gleason grade. We also investigated the potential of using IGFBP-3 as a prognostic indicator of clinically localized prostate cancer.
Initially we evaluated the expression of IGFBP-3 in six normal and twenty neoplastic prostates using standard immunohistochemical techniques (study 1). We then obtained radical prostatectomy specimens from twenty-four patients with a preoperative diagnosis of clinically localized prostate adenocarcinoma and five year follow up information, and nine normal prostates from organ donors or from patients undergoing cystoprostatectomy (study 2). All specimens were immunostained with a polyclonal anti-human IGFBP-3 antibody. A single pathologist reviewed all sections and assigned a Gleason grade to each cancer focus. Using computer-assisted video image analysis, we quantified the intensity of IGFBP-3 immunostaining of each cancer focus and of normal controls.
Normal prostatic epithelium showed intense cytoplasmic IGFBP-3 staining. The stromal compartment showed less intense staining, although there were occasional areas with strong immunoreactivity. The cellular distribution of IGFBP-3 staining in prostatic adenocarcinoma was comparable to normal tissue; however, the intensity of detectable staining in neoplastic epithelial cells was significantly decreased. Two foci of prostatic intraepithelial neoplasia (PIN) demonstrated IGFBP-3 immunoreactivity decreased in comparison to normal epithelium, but greater than prostatic adenocarcinoma. Histologically normal epithelium surrounding cancer foci also showed decreased immunostaining for IGFBP-3 compared with normal prostate. The marked decrease in immunostaining intensity of IGFBP-3 in prostate adenocarcinoma was not associated with Gleason grade or with clinical outcome.
Malignant transformation of prostatic epithelium was associated with a significant decrease in the amount of immunoreactive IGFBP-3 (p <0.0001); however, this parameter did not correlate with Gleason grade of the tumor or with patient outcome. The decrease in immunostaining intensity of IGFBP-3 in all Gleason grades and in PIN suggests that lower expression of IGFBP-3 is an early event in prostatic carcinogenesis. The finding that decreased IGFBP-3 immunostaining did not correlate with clinical outcome suggests that this parameter is not a therapy-guiding prognostic indicator for clinically localized prostate cancer.
我们试图对前列腺腺癌中IGFBP - 3的表达进行特征描述和定量分析，并测试其是否与Gleason分级所确定的肿瘤分化相关。我们还研究了将IGFBP - 3用作临床局限性前列腺癌预后指标的潜力。
最初，我们使用标准免疫组织化学技术评估了6个正常前列腺和20个肿瘤性前列腺中IGFBP - 3的表达（研究1）。然后，我们获取了24例术前诊断为临床局限性前列腺腺癌患者的根治性前列腺切除术标本及5年随访信息，以及9个来自器官捐赠者或接受膀胱前列腺切除术患者的正常前列腺（研究2）。所有标本均用多克隆抗人IGFBP - 3抗体进行免疫染色。由一名病理学家审阅所有切片，并为每个癌灶指定Gleason分级。使用计算机辅助视频图像分析，我们对每个癌灶和正常对照的IGFBP - 3免疫染色强度进行了定量分析。
正常前列腺上皮显示强烈的细胞质IGFBP - 3染色。间质部分染色强度较低，尽管偶尔有强免疫反应区域。前列腺腺癌中IGFBP - 3染色的细胞分布与正常组织相当；然而，肿瘤上皮细胞中可检测到的染色强度明显降低。两个前列腺上皮内瘤变（PIN）灶显示IGFBP - 3免疫反应性与正常上皮相比降低，但高于前列腺腺癌。癌灶周围组织学正常的上皮与正常前列腺相比，IGFBP - 3免疫染色也降低。前列腺腺癌中IGFBP - 3免疫染色强度的显著降低与Gleason分级或临床结局无关。
前列腺上皮的恶性转化与免疫反应性IGFBP - 3量的显著降低相关（p <0.0001）；然而，该参数与肿瘤的Gleason分级或患者结局无关。所有Gleason分级和PIN中IGFBP - 3免疫染色强度的降低表明，IGFBP - 3表达降低是前列腺癌发生的早期事件。IGFBP - 3免疫染色降低与临床结局无关的发现表明，该参数不是临床局限性前列腺癌的治疗指导预后指标。
