Bostwick D G
Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
Cancer. 1996 Jul 15;78(2):330-6. doi: 10.1002/(SICI)1097-0142(19960715)78:2<330::AID-CNCR22>3.0.CO;2-W.
The search for the precursor of prostatic adenocarcinoma has focused in recent years on two histopathologic findings: high grade prostatic intraepithelial neoplasia (PIN) and atypical adenomatous hyperplasia (AAH). This article describes the diagnostic criteria and clinical significance of PIN and AAH.
PIN is the most likely precursor of prostate carcinoma. The continuum that culminates in high grade PIN and early invasive carcinoma is characterized by progressive basal cell layer disruption, loss of markers of secretory differentiation, nuclear and nucleolar abnormalities, increasing proliferative potential, increasing microvessel density, variation in DNA content, and allelic loss. Clinical studies suggest that PIN predates carcinoma by 10 years or more, with low grade PIN first appearing in men in their 30s. AAH is usually found in the transition zone, and shows a weak and inconclusive link to well differentiated adenocarcinoma of the transition zone.
The significance of recognizing PIN is based on its strong association with prostatic carcinoma. PIN coexists with carcinoma in most cases, but retains an intact or fragmented basal cell layer, unlike carcinoma, which lacks a basal cell layer. High grade PIN in biopsies predicts the presence of carcinoma in subsequent biopsies, and PIN provides the highest risk ratio of all known predictive factors. This finding indicates the need for repeat biopsy and follow-up when PIN is identified in a biopsy, especially in patients with an elevated serum prostate specific antigen concentration. PIN also offers promise as an intermediate endpoint in studies of chemoprevention of prostatic carcinoma. Unlike PIN, AAH is weakly linked to carcinoma, and current data indicate that no follow-up is necessary for patients with this finding.
近年来，前列腺腺癌前驱病变的研究主要集中在两项组织病理学发现上：高级别前列腺上皮内瘤变（PIN）和非典型腺瘤样增生（AAH）。本文介绍了PIN和AAH的诊断标准及临床意义。
PIN最有可能是前列腺癌的前驱病变。发展为高级别PIN和早期浸润性癌的连续过程的特征为基底细胞层逐渐破坏、分泌分化标志物丧失、核及核仁异常、增殖潜能增加、微血管密度增加、DNA含量变异和等位基因缺失。临床研究表明，PIN比癌早出现10年或更久，低级别PIN最早出现在30多岁的男性中。AAH通常见于移行带，与移行带高分化腺癌的联系微弱且不明确。
认识PIN的意义在于其与前列腺癌的密切关联。在大多数情况下，PIN与癌共存，但与癌不同，PIN保留完整或破碎的基底细胞层，而癌缺乏基底细胞层。活检中发现高级别PIN预示后续活检中存在癌，且PIN是所有已知预测因素中风险比最高的。这一发现表明，活检中发现PIN时，尤其是血清前列腺特异性抗原浓度升高的患者，需要重复活检及随访。PIN在前列腺癌化学预防研究中也有望作为中间终点。与PIN不同，AAH与癌的联系较弱，目前数据表明，发现AAH的患者无需随访。
