Xiao Guang-Qian, Unger Pamela, Yang Qi, Kinoshita Yayoi, Singh Kyra, McMahon Loralee, Nastiuk Kent, Sha Kai, Krolewski John, Burstein David
Departments of Pathology, University of Rochester Medical Center, Rochester, New York, United States of America.
Departments of Pathology, Lenox Hill Hospital, New York, New York, United States of America.
PLoS One. 2015 Mar 25;10(3):e0121318. doi: 10.1371/journal.pone.0121318. eCollection 2015.
PLZF is a transcription repressor, which plays a critical role in development, spermatogenesis and oncogenesis. Down-regulation of PLZF has been found in various tumor cell lines. There has been virtually no tissue study on the expression of PLZF in prostate cancer (PCa). PCa is a heterogeneous disease, most of which are indolent and non-lethal. Currently there are no biomarkers that distinguish indolent from aggressive PCa; therefore there is an urgent need for such markers to provide clinical decision support. This study aimed to investigate the expression of PLZF by immunohistochemistry in different grade as well as metastatic PCa and to correlate the alteration of PLZF expression with PCa aggressiveness. We studied a total of 83 primary PCa from biopsies, 43 metastatic PCa and 8 paired primary and metastatic PCa from radical prostatectomies with lymph node dissection. Our results demonstrated that PLZF was strongly expressed in almost all (~100%) benign luminal cells (n=77) and low grade (Gleason pattern 3) PCa (n=70) and weak or absent (100%) in basal cells (n=70). Decreased or lost expression of PLZF was evidenced in 26% of high-grade (Gleason 4 and 5) primary PCa (n=70) and 84% metastatic PCa (n=43). The primary high grade PCa in the prostatectomies shared similar PLZF loss/decrease and histomorphology to that of paired parallel lymph node metastases. These data demonstrated that down-regulation of PLZF is an important molecular process for tumor progression and loss of PLZF expression detected by routine immunohistochemistry is a promising and valuable biomarker for PCa aggressiveness and metastasis in the personalized care of PCa.
早幼粒细胞白血病锌指蛋白（PLZF）是一种转录抑制因子，在发育、精子发生和肿瘤发生过程中发挥关键作用。在多种肿瘤细胞系中均发现PLZF表达下调。目前关于PLZF在前列腺癌（PCa）中的表达几乎没有组织学研究。PCa是一种异质性疾病，大多数为惰性且非致死性。目前尚无区分惰性PCa和侵袭性PCa的生物标志物；因此迫切需要此类标志物来提供临床决策支持。本研究旨在通过免疫组织化学法研究不同分级以及转移性PCa中PLZF的表达情况，并将PLZF表达的改变与PCa的侵袭性相关联。我们共研究了83例活检获得的原发性PCa、43例转移性PCa以及8例来自根治性前列腺切除术并伴有淋巴结清扫的原发性与转移性PCa配对样本。我们的结果表明，PLZF在几乎所有（约100%）良性管腔细胞（n = 77）和低级别（Gleason模式3）PCa（n = 70）中强烈表达，而在基底细胞（n = 70）中弱表达或无表达（100%）。在26%的高级别（Gleason 4和5）原发性PCa（n = 70）和84%的转移性PCa（n = 43）中，PLZF表达降低或缺失。前列腺切除术中的原发性高级别PCa与配对的平行淋巴结转移灶具有相似的PLZF缺失/降低情况和组织形态学特征。这些数据表明，PLZF下调是肿瘤进展的重要分子过程，通过常规免疫组织化学检测到的PLZF表达缺失是PCa个性化治疗中PCa侵袭性和转移的一个有前景且有价值的生物标志物。
