Shah R, Mucci N R, Amin A, Macoska J A, Rubin M A
Department of Pathology, Section of Urology, University of Michigan, Ann Arbor, Michigan, USA.
Am J Pathol. 2001 May;158(5):1767-73. doi: 10.1016/S0002-9440(10)64132-6.
Postatrophic hyperplasia (PAH) of the prostate gland often demonstrates overlapping histological features with prostatic adenocarcinoma (PCA). These features include small acinar growth and enlarged nuclei with prominent nucleoli. Recent work has demonstrated that PAH is a proliferative, noninvoluting lesion. PAH is also histologically distinct from simple atrophy (SA), which has intermediate- to large-sized glands, minimal cytoplasm, and inconspicuous nuclei. However, despite overlapping features between PAH and PCA, high-grade prostatic intraepithelial neoplasm (HGPIN) is still considered the only direct neoplastic precursor to PCA. HGPIN resembles PCA in its topographic distribution, cytological appearance, and molecular alterations including chromosome 8p loss and chromosome 8 centromeric gain. To examine the hypothesis that PAH is the earliest histologically distinct precursor to HGPIN or PCA, the frequency, distribution, proliferative state, and chromosome 8 gain of benign prostate, SA, PAH, HGPIN, and PCA were analyzed. Forty radical prostatectomy specimens from men with clinically localized PCA were systematically analyzed. Proliferation was determined by Ki-67 immunohistochemistry (MIB-1) on formalin-fixed, paraffin-embedded tissue and quantified by digital image analysis from a total of 5,510 sample areas with benign, SA, PAH, HGPIN, and PCA. A tissue microarray was constructed to evaluate 8c gain using interphase fluorescence in situ hybridization. SA foci (n = 129) and PAH foci (n = 114) were identified in the 40 cases of which 74% (95 of 129) and 88% (100 of 114) were seen in the peripheral zone, respectively (P = 0.006). PAH and SA were identified adjacent to PCA in 28% (32 of 114) and 14% (18 of 129) of foci examined, respectively (P = 0.007). The median number of proliferating nuclei increased significantly from benign (1.20%), SA (2.67%), PAH (3.62%), HGPIN (6.14%), to PCA (12.00%) (P < 0.001). The median percentage of nuclei with more than three centromeric probe signals (chromosome 8c gain) for SA, HGPIN, PAH, and PCA were 2.1, 2.8, 4.0, and 6.0%, respectively, as compared to benign prostate with 1.3% (P = 0.006). In conclusion, the present study identified a strong topographic association between PAH and PCA. PAH is also seen often to be closely associated with chronic inflammation. Proliferation of PAH is significantly greater than benign prostatic epithelium and SA but less than HGPIN or PCA. Gain of 8c is significantly greater in PAH than benign prostate, SA, and even HGPIN. These findings demonstrate a strong association between PAH and PCA, supporting its role as a neoplastic precursor.
前列腺萎缩后增生（PAH）常表现出与前列腺腺癌（PCA）重叠的组织学特征。这些特征包括小腺泡生长以及核增大伴明显核仁。最近的研究表明，PAH是一种增殖性、非退化性病变。PAH在组织学上也与单纯萎缩（SA）不同，SA具有中等大小至大尺寸的腺管、极少的细胞质以及不明显的细胞核。然而，尽管PAH和PCA存在重叠特征，但高级别前列腺上皮内瘤变（HGPIN）仍被认为是PCA唯一直接的肿瘤前体。HGPIN在其拓扑分布、细胞学外观以及分子改变（包括8号染色体短臂缺失和8号染色体着丝粒增加）方面与PCA相似。为了检验PAH是HGPIN或PCA最早在组织学上有明显区别的前体这一假设，对良性前列腺、SA、PAH、HGPIN和PCA的频率、分布、增殖状态以及8号染色体增加情况进行了分析。对40例临床局限性PCA男性患者的根治性前列腺切除术标本进行了系统分析。通过对福尔马林固定、石蜡包埋组织进行Ki-67免疫组织化学（MIB-1）检测来确定增殖情况，并通过数字图像分析对总共5510个具有良性、SA、PAH、HGPIN和PCA的样本区域进行定量分析。构建组织微阵列以使用间期荧光原位杂交评估8号染色体着丝粒增加情况。在40例病例中识别出SA灶（n = 129）和PAH灶（n = 114），其中分别有74%（129例中的95例）和88%（114例中的100例）见于外周区（P = 0.006）。在分别检查的PAH和SA灶中，分别有28%（114例中的32例）和14%（129例中的18例）与PCA相邻（P = 0.007）。增殖细胞核的中位数从良性（1.20%）、SA（2.67%）、PAH（3.62%）、HGPIN（6.14%）到PCA（12.00%）显著增加（P < 0.001）。与良性前列腺的1.3%相比，SA、HGPIN、PAH和PCA中具有超过三个着丝粒探针信号（8号染色体着丝粒增加）的细胞核中位数百分比分别为2.1%、2.8%、4.0%和6.0%（P = 0.006）。总之，本研究确定了PAH与PCA之间存在很强的拓扑学关联。PAH也常被发现与慢性炎症密切相关。PAH的增殖明显大于良性前列腺上皮和SA，但小于HGPIN或PCA。PAH中8号染色体着丝粒增加明显大于良性前列腺、SA，甚至HGPIN。这些发现表明PAH与PCA之间存在很强的关联，支持其作为肿瘤前体的作用。
