Terada T, Nakanuma Y
Second Department of Pathology, Kanazawa University School of Medicine, Japan.
Virchows Arch A Pathol Anat Histopathol. 1992;420(4):327-35. doi: 10.1007/BF01600212.
We evaluated cell proliferative activity and expression of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9) and DU-PAN-2 in various bile duct lesions in livers with hepatoliths, using histochemical and immunohistochemical methods. Histologically, the bile duct lesions were divisible into hyperplasia, dysplasia, adenocarcinoma in situ and invasive adenocarcinoma. All cases showed mucosal hyperplasia in stone-bearing bile ducts. Livers with invasive adenocarcinoma frequently contained adenocarcinoma in situ and dysplasia, and livers with adenocarcinoma in situ occasionally harboured dysplasia. Proliferating cell nuclear antigen (PCNA) labelling index was low in hyperplasia (mean +/- SD = 20.5 +/- 8.7%), intermediate in dysplasia (35.4 +/- 15.9%), and high in adenocarcinoma in situ (46.4 +/- 9.3%). The mean number of argyrophilic nucleolar organizer regions (AgNORs) was low in hyperplasia (1.52), intermediate in dysplasia (2.26) and high in adenocarcinoma in situ (2.69). There was a significant positive correlation between PCNA labelling index and AgNORs count. CEA was expressed on invasive adenocarcinoma cells and adenocarcinoma in situ cells in most cases and on dysplastic cells in about a half, while CEA was never present in hyperplastic epithelia. Expression of CA 19-9 was low in adenocarcinoma, intermediate in dysplasia and rather high in hyperplasia. There was no significant difference in DU-PAN-2 expression among these bile duct lesions. These data suggest that cell replicative activity is low in hyperplasia, intermediate in dysplasia and high in adenocarcinoma in situ, and that CEA appears in the following order: dysplasia, adenocarcinoma in situ, invasive adenocarcinoma. We suggest that carcinogenesis in biliary epithelial in livers with stones is a multi-step process through hyperplasia, dysplasia and adenocarcinoma in situ to invasive adenocarcinoma.
我们采用组织化学和免疫组织化学方法，评估了肝内胆管结石患者肝脏各种胆管病变中细胞增殖活性以及癌胚抗原（CEA）、糖类抗原19-9（CA 19-9）和DU-PAN-2的表达情况。组织学上，胆管病变可分为增生、发育异常、原位腺癌和浸润性腺癌。所有病例在含结石的胆管中均表现为黏膜增生。浸润性腺癌的肝脏常伴有原位腺癌和发育异常，原位腺癌的肝脏偶尔伴有发育异常。增殖细胞核抗原（PCNA）标记指数在增生中较低（均值±标准差=20.5±8.7%），在发育异常中为中等水平（35.4±15.9%），在原位腺癌中较高（46.4±9.3%）。嗜银核仁组织区（AgNORs）的平均数量在增生中较低（1.52），在发育异常中为中等水平（2.26），在原位腺癌中较高（2.69）。PCNA标记指数与AgNORs计数之间存在显著正相关。大多数情况下，CEA在浸润性腺癌细胞和原位腺癌细胞中表达，约一半的发育异常细胞中也有表达，而增生上皮中从未出现CEA。CA 19-9在腺癌中的表达较低，在发育异常中为中等水平，在增生中较高。这些胆管病变中DU-PAN-2的表达无显著差异。这些数据表明，细胞复制活性在增生中较低，在发育异常中为中等水平，在原位腺癌中较高，且CEA按以下顺序出现：发育异常、原位腺癌、浸润性腺癌。我们认为，结石性肝病中胆管上皮的癌变是一个通过增生（hyperplasia）、发育异常（dysplasia）和原位腺癌（adenocarcinoma in situ）到浸润性腺癌的多步骤过程。
