Wilentz R E, Geradts J, Maynard R, Offerhaus G J, Kang M, Goggins M, Yeo C J, Kern S E, Hruban R H
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Cancer Res. 1998 Oct 15;58(20):4740-4.
Pancreatic adenocarcinoma develops from histologically identifiable intraductal lesions that undergo a series of architectural, cytological, and genetic changes. Limited genetic evidence recently suggested that the p16 gene plays a role in the progression of these "duct lesions." Duct lesions were identified in pancreata from 33 pancreaticoduodenectomies performed for infiltrating adenocarcinoma. All of these infiltrating adenocarcinomas were previously shown to contain alterations in the p16 gene or its promoter. Monoclonal and polyclonal anti-p16 antibodies were used for histological immunodetection. One hundred twenty-six duct lesions were identified. Nine (30%) of 30 flat, 4 (27%) of 15 papillary, 37 (55%) of 67 papillary with atypia, and 10 (71%) of 14 carcinoma in situ duct lesions showed loss of p16 expression. These included 30% of the flat lesions versus 53% of the nonflat lesions and 29% of the nonatypical lesions versus 58% of the atypical lesions. For both comparisons, the differences were statistically significant (P = 0.036 and P = 0.003, respectively). Loss of p16 expression occurs more frequently, but not exclusively, in higher-grade duct lesions. These data support the hypothesis that pancreatic duct lesions are neoplastic and that they represent the precursors of infiltrating adenocarcinoma. Immunohistochemical detection of p16 provides a new technology to study the genetic alterations in and stages of progression of large numbers of morphologically defined pancreatic duct lesions.
胰腺腺癌由组织学上可识别的导管内病变发展而来，这些病变会经历一系列结构、细胞学和基因变化。最近有限的基因证据表明，p16基因在这些“导管病变”的进展中起作用。在33例因浸润性腺癌而进行胰十二指肠切除术的胰腺中发现了导管病变。所有这些浸润性腺癌先前已显示含有p16基因或其启动子的改变。使用单克隆和多克隆抗p16抗体进行组织学免疫检测。共识别出126个导管病变。30个扁平病变中有9个（30%）、15个乳头状病变中有4个（27%）、67个非典型乳头状病变中有37个（55%）以及14个原位癌导管病变中有10个（71%）显示p16表达缺失。这些包括30%的扁平病变和53%的非扁平病变，以及29%的非非典型病变和58%的非典型病变。对于这两组比较，差异均具有统计学意义（分别为P = 0.036和P = 0.003）。p16表达缺失在更高级别的导管病变中更频繁发生，但并非仅见于此类病变。这些数据支持了胰腺导管病变是肿瘤性的这一假说，并且它们代表浸润性腺癌的前体。p16的免疫组织化学检测提供了一种新技术，用于研究大量形态学上明确的胰腺导管病变的基因改变和进展阶段。
